Distribution of Soft Tissue Sarcoma by Age and Histology

Pediatric soft tissue sarcomas are a heterogenous group of malignant tumors that originate from primitive mesenchymal tissue and account for 6% of all childhood tumors (rhabdomyosarcomas, 3%; other soft tissue sarcomas, 3%).[2]

The distribution of soft tissue sarcomas by histology and age, on the basis of the Surveillance, Epidemiology, and End Results (SEER) Program information from 2000 to 2015, is depicted in Table 1. The distribution of histological subtypes by age is also shown in Figure 2.

NRSTS are more common in adolescents and adults.[5] Most of the information regarding treatment and natural history of the disease in younger patients has been based on adult studies. The distributions of these tumors by age according to stage (Figure 1), histological subtype (Figure 2), and tumor site (Figure 3) are shown below.[6]

Figure 1. The distribution of nonrhabdomyosarcomatous soft tissue sarcomas by age according to stage.

Figure 2. The distribution of nonrhabdomyosarcomatous soft tissue sarcomas by age according to histological subtype.

Figure 3. The distribution of nonrhabdomyosarcomatous soft tissue sarcomas by age according to tumor site.

Risk Factors

Some genetic factors and external exposures have been associated with the development of NRSTS, including the following:

• Genetic factors:

  -

  Li-Fraumeni syndrome: Patients with Li-Fraumeni syndrome (usually resulting from heritable cancer-associated changes of the TP53 tumor suppressor gene) have an increased risk of developing soft tissue tumors (mostly NRSTS), bone sarcomas, breast cancer, brain tumors, and acute leukemia.[7,8]

  -

  Familial adenomatous polyposis: Patients with familial adenomatous polyposis are at increased risk of developing desmoid-type fibromatosis.[9]

  -

  RB1 gene: Germline mutations of the RB1 gene have been associated with an increased risk of developing soft tissue sarcoma, particularly leiomyosarcoma, and the risk appears higher among those younger than 1 year who were treated with alkylating agents.[10,11]

  -

  SMARCB1 gene: Germline mutations or deletions of the SMARCB1 (INI1) gene are associated with an increased risk of developing extrarenal rhabdoid tumors.[12]

  -

  Neurofibromatosis type 1: Approximately 4% of patients with neurofibromatosis type 1 develop malignant peripheral nerve sheath tumors, which usually develop after a long latency; some patients develop multiple lesions.[13-15]

  -

  Werner syndrome: Werner syndrome is characterized by spontaneous chromosomal instability, resulting in increased susceptibility to cancer and premature aging. An excess of soft tissue sarcomas has been reported in patients with Werner syndrome.[16]

  -

  Tuberous sclerosis complex: Tuberous sclerosis complex is associated with the development of various tumors showing perivascular epithelioid cell differentiation (PEComas), including lymphangioleiomyomatosis and hepatic and renal angiomyolipomas.[17-19]

  -

  Adenosine deaminase-deficient severe combined immunodeficiency: Patients with adenosine deaminase-deficient severe combined immunodeficiency have been reported to be at increased risk of developing multicentric dermatofibrosarcoma protuberans, which usually presents at an average age of 8.9 years.[20]

• External exposures:

  -

  Radiation: Some NRSTS (particularly malignant fibrous histiocytoma) can develop within a previously irradiated site.[21-25]

  -

  Epstein-Barr virus infection in patients with AIDS: Some NRSTS (e.g., leiomyosarcoma) have been linked to Epstein-Barr virus infection in patients with AIDS.[21,26]

Clinical Presentation

Although NRSTS can develop in any part of the body, they arise most commonly in the trunk and extremities.[27-29] These neoplasms can present initially as an asymptomatic solid mass, or they may be symptomatic because of local invasion of adjacent anatomical structures. Although rare, these tumors can arise in brain tissue and are treated according to the histological type.[30]

Systemic symptoms (e.g., fever, weight loss, and night sweats) are rare. Hypoglycemia and hypophosphatemic rickets have been reported in cases of hemangiopericytoma (now identified as a solitary fibrous tumor in the revised World Health Organization classification system), whereas hyperglycemia has been noted in patients with fibrosarcoma of the lung.[31]

Diagnostic and Staging Evaluation

When a suspicious lesion is identified, it is crucial that a complete workup, followed by adequate biopsy be performed. The lesion is imaged before initiating any intervention using the following procedures:

• Plain films. Plain films can be used to rule out bone involvement and detect calcifications that may be seen in soft tissue tumors such as extraskeletal osteosarcoma or synovial sarcoma.
• Chest computed tomography (CT). Chest CT is essential to assess the presence of metastases.
• Abdominal CT or magnetic resonance imaging (MRI). Abdominal CT or MRI can be used to image intra-abdominal tumors, such as liposarcoma.
• Extremity MRI. MRI is essential for extremity lesions.
• Positron emission tomography (PET) scan and bone scan.

  -

  Rhabdomyosarcoma. In children with rhabdomyosarcoma, PET-CT was better than conventional imaging in identifying nodal, bone, bone marrow, and soft tissue disease. The authors of this imaging comparison study suggested that bone scans with technetium Tc 99m might be eliminated as a staging procedure.[32]

  -

  Other soft tissue sarcomas. In a retrospective study, 46 PET scans were completed in 25 pediatric patients with soft tissue sarcoma.[33] The positive predictive value of finding metastatic disease was 89%, and the negative predictive value was 67%. A small study of nine patients with NRSTS suggested that PET-CT was more accurate and cost-effective than either modality alone in identifying distant metastatic disease.[34] The use of this modality in pediatric NRSTS has not been studied prospectively.

  In a prospective study of pediatric patients with sarcoma who underwent sentinel lymph node biopsy, 28 patients were examined. Sentinel lymph node biopsy was positive in 7 of the 28 patients, including 3 patients who had negative PET-CT scans. The findings from the sentinel lymph node biopsies resulted in altering therapy in all 7 patients in whom metastatic disease was determined by sentinel lymph node biopsy. In addition, three of the seven patients with proven malignant sentinel nodes (43%) had cross-sectional and functional imaging (PET) that were negative. PET-CT overestimated and suggested nodal involvement in more patients than what was confirmed by sentinel lymph node biopsy. As indicated by previous reports, epithelioid sarcoma and clear cell sarcoma were the two nonrhabdomyosarcomatous tumors included in this study.[35]

The imaging characteristics of some tumors can be highly suggestive of that particular diagnosis. For example, the imaging characteristics of pediatric low-grade fibromyxoid sarcoma and alveolar soft part sarcoma have been described and can aid in the diagnosis of these rare neoplasms.[36]

Prognosis and Prognostic Factors

The prognosis of NRSTS varies greatly depending on the following factors:[69-71]

• Site of the primary tumor.
• Tumor size.
• Tumor grade. For more information, see the Prognostic Significance of Tumor Grading section.
• Tumor histology.
• Depth of tumor invasion.
• Presence of metastases and site of the metastatic tumor.
• Resectability of the tumor.
• Use of radiation therapy.

In a review of a large adult series of NRSTS, patients with superficial extremity sarcomas had a better prognosis than did patients with deep tumors. Thus, in addition to grade and size, the depth of invasion of the tumor should be considered.[72]

Several adult and pediatric series have shown that patients with large or invasive tumors have a significantly worse prognosis than do those with small, noninvasive tumors. A retrospective review of soft tissue sarcomas in children and adolescents suggests that the 5 cm cutoff used for adults with soft tissue sarcoma may not be ideal for smaller children, especially infants. The review identified an interaction between tumor diameter and body surface area.[73] This relationship has been questioned and requires further study to determine the therapeutic implications of the observation.[74]

Some pediatric NRSTS are associated with a better outcome. For instance, patients with infantile fibrosarcoma who present in infancy and younger than 5 years have an excellent prognosis. This excellent outcome occurs because surgery alone can cure a significant number of these patients, the tumor is highly chemosensitive, and the tumor responds well to larotrectinib, a specific tropomyosin receptor kinase inhibitor.[21,75]

Soft tissue sarcomas in older children and adolescents often behave similarly to those in adult patients.[21,76] A large, prospective, multinational Children's Oncology Group study (ARST0332 [NCT00346164]) enrolled newly diagnosed patients younger than 30 years. Patients were assigned to treatment on the basis of their risk group (defined by the presence of metastasis, tumor resectability and margins, and tumor size and grade; see Figure 4).[77][Level of evidence B4]

Figure 4. Risk group and treatment assignment for the Children’s Oncology Group ARST0332 trial. Reprinted from The Lancet Oncology, Volume 21 (Issue 1), Spunt SL, Million L, Chi YY, et al., A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study, Pages 145–161, Copyright © 2020, with permission from Elsevier.

Each patient was assigned to one of three risk groups and one of four treatment groups. The risk groups were as follows:[77]

1. Low risk: Nonmetastatic R0 (resection was complete with negative microscopic margins) or R1 (microscopically positive margins) low-grade tumor, or ≤5 cm R1 high-grade tumor.
2. Intermediate risk: Nonmetastatic R0 or R1 >5 cm high-grade tumor, or unresected tumor of any size or grade.
3. High risk: Metastatic tumor.

The treatment groups were as follows:

1. Surgery alone.
2. Radiation therapy (55.8 Gy).
3. Chemoradiation therapy (chemotherapy and 55.8 Gy radiation therapy).
4. Neoadjuvant chemoradiation therapy (chemotherapy and 45 Gy radiation therapy, then surgery and radiation therapy boost based on margins with continued chemotherapy).

Chemotherapy included six cycles of ifosfamide (3 g/m² per dose) administered intravenously on days 1 through 3 and five cycles of doxorubicin (37.5 mg/m² per dose) administered intravenously on days 1 to 2 every 3 weeks, with the sequence adjusted on the basis of the timing of surgery or radiation therapy.

For the 550 patients enrolled, 529 evaluable patients were included in the analysis; the survival results are shown in Table 3.

Pediatric patients with unresected localized NRSTS have a poor outcome. Only about one-third of patients treated with multimodality therapy remain disease free.[69,78]; [79,80][Level of evidence C1] In an Italian review of 30 patients with NRSTS at visceral sites, only ten patients survived at 5 years. Unfavorable prognostic factors included inability to achieve complete resection, large tumor size, tumor invasion, histological subtype, and lung-pleura sites.[81][Level of evidence C1]

The European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) conducted a prospective trial for patients younger than 21 years with NRSTS. They reported an analysis of 206 patients with synovial sarcoma and 363 with adult-type NRSTS. Treatment was administered after assignment of patients to risk groups (see Figure 5).[82] With a median follow-up of 80 months (interquartile range, 54.3–111.3) for the 467 surviving patients, the 5-year event-free survival (EFS) rate was 73.7% (95% CI, 69.7%–77.2%) and the overall survival (OS) rate was 83.8% (95% CI, 80.3%–86.7%). The survival by treatment groups are shown in Table 4.[82]

Figure 5. Treatment plan for patients with synovial sarcoma or adult-type non-rhabdomyosarcoma soft tissue sarcomas. Patients were divided into four treatment groups based on surgical stage, tumour size, nodal involvement, tumour grade (according to the Fédération Nationale des Centres de Lutte Contre le Cancer grading system for adult-type non-rhabdomyosarcoma soft tissue sarcomas), and tumour site (for synovial sarcoma). I+D = ifosfamide (3.0 g/m² per day intravenously for 3 days) plus doxorubicin (37.5 mg/m² intravenously per day for 2 days). I = ifosfamide (3.0 g/m² intravenously per day for 2 days). IRS = Intergroup Rhabdomyosarcoma Study. N1 = nodal involvement. S = delayed surgery. Reprinted from The Lancet Child & Adolescent Health, Volume 5, Issue 8, Ferrari A, van Noesel MM, Brennan B, et al., Paediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG), Pages 546-558, Copyright 2021, with permission from Elsevier.

The authors concluded that adjuvant therapy could safely be omitted in the group of patients assigned to surgery alone. They also concluded that improving the outcome for patients with high-risk, initially resected, adult-type NRSTS and those with initially unresected disease remains a major clinical challenge.[82]

In a pooled analysis from U.S. and European pediatric centers, outcome was better for patients whose tumor removal procedure was deemed complete than for patients whose tumor removal was incomplete. Outcome was better for patients who received radiation therapy than for patients who did not.[79][Level of evidence C1]

Because long-term morbidity must be minimized while disease-free survival is maximized, the ideal therapy for each patient must be carefully and individually determined using these prognostic factors before initiating therapy.[28,83-87]

Related Summaries

For information about other types of sarcoma, see the following summaries:

• Childhood Rhabdomyosarcoma Treatment.
• Childhood Vascular Tumors Treatment.
• Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment (extraosseous Ewing, peripheral neuroepithelioma, and Askin tumors).
• Childhood Gastrointestinal Stromal Tumors Treatment.
• Soft Tissue Sarcoma Treatment.

References

1. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PMC free article: PMC4136455] [PubMed: 24853691]
2. National Cancer Institute; National Childhood Cancer Registry: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed August 4, 2022.
3. Hawkins DS, Black JO, Orbach D, et al.: Nonrhabdomyosarcoma soft-tissue sarcomas. In: Blaney SM, Helman LJ, Adamson PC, eds.: Pizzo and Poplack's Pediatric Oncology. 8th ed. Wolters Kluwer, 2020, pp 721-46.
4. Surveillance, Epidemiology, and End Results (SEER) Program: SEER*Stat Database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2017 Sub (1973-2015 varying) - Linked To County Attributes - Total U.S., 1969-2016 Counties [Database]. National Cancer Institute, DCCPS, Surveillance Research Program, released April 2018, based on the November 2017 submission. Available online. Last accessed October 12, 2022.
5. Weiss SW, Goldblum JR: General considerations. In: Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. Mosby, 2008, pp 1-14.
6. Ferrari A, Sultan I, Huang TT, et al.: Soft tissue sarcoma across the age spectrum: a population-based study from the Surveillance Epidemiology and End Results database. Pediatr Blood Cancer 57 (6): 943-9, 2011. [PMC free article: PMC4261144] [PubMed: 21793180]
7. Chang F, Syrjänen S, Syrjänen K: Implications of the p53 tumor-suppressor gene in clinical oncology. J Clin Oncol 13 (4): 1009-22, 1995. [PubMed: 7707100]
8. Plon SE, Malkin D: Childhood cancer and hereditary. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 7th ed. Lippincott Williams and Wilkins, 2015, pp 13-31.
9. Groen EJ, Roos A, Muntinghe FL, et al.: Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol 15 (9): 2439-50, 2008. [PMC free article: PMC2518080] [PubMed: 18612695]
10. Kleinerman RA, Tucker MA, Abramson DH, et al.: Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma. J Natl Cancer Inst 99 (1): 24-31, 2007. [PubMed: 17202110]
11. Wong JR, Morton LM, Tucker MA, et al.: Risk of subsequent malignant neoplasms in long-term hereditary retinoblastoma survivors after chemotherapy and radiotherapy. J Clin Oncol 32 (29): 3284-90, 2014. [PMC free article: PMC4178525] [PubMed: 25185089]
12. Eaton KW, Tooke LS, Wainwright LM, et al.: Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatr Blood Cancer 56 (1): 7-15, 2011. [PMC free article: PMC3086793] [PubMed: 21108436]
13. Weiss SW, Goldblum JR: Benign tumors of peripheral nerves. In: Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. Mosby, 2008, pp 825-901.
14. deCou JM, Rao BN, Parham DM, et al.: Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience. Ann Surg Oncol 2 (6): 524-9, 1995. [PubMed: 8591083]
15. Stark AM, Buhl R, Hugo HH, et al.: Malignant peripheral nerve sheath tumours--report of 8 cases and review of the literature. Acta Neurochir (Wien) 143 (4): 357-63; discussion 363-4, 2001. [PubMed: 11437289]
16. Goto M, Miller RW, Ishikawa Y, et al.: Excess of rare cancers in Werner syndrome (adult progeria). Cancer Epidemiol Biomarkers Prev 5 (4): 239-46, 1996. [PubMed: 8722214]
17. Fricke BL, Donnelly LF, Casper KA, et al.: Frequency and imaging appearance of hepatic angiomyolipomas in pediatric and adult patients with tuberous sclerosis. AJR Am J Roentgenol 182 (4): 1027-30, 2004. [PubMed: 15039181]
18. Adriaensen ME, Schaefer-Prokop CM, Duyndam DA, et al.: Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex. Clin Radiol 66 (7): 625-8, 2011. [PubMed: 21459371]
19. Hornick JL, Fletcher CD: PEComa: what do we know so far? Histopathology 48 (1): 75-82, 2006. [PubMed: 16359539]
20. Kesserwan C, Sokolic R, Cowen EW, et al.: Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency. J Allergy Clin Immunol 129 (3): 762-769.e1, 2012. [PMC free article: PMC3294021] [PubMed: 22153773]
21. Spunt SL, Million L, Coffin C: The nonrhabdomyosarcoma soft tissue sarcoma. In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 7th ed. Lippincott Williams and Wilkins, 2015, pp 827-54.
22. Weiss SW, Goldblum JR: Malignant fibrous histiocytoma (pleomorphic undifferentiated sarcoma). In: Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. Mosby, 2008, pp 403-27.
23. Tukenova M, Guibout C, Hawkins M, et al.: Radiation therapy and late mortality from second sarcoma, carcinoma, and hematological malignancies after a solid cancer in childhood. Int J Radiat Oncol Biol Phys 80 (2): 339-46, 2011. [PubMed: 20646844]
24. Bartkowiak D, Humble N, Suhr P, et al.: Second cancer after radiotherapy, 1981-2007. Radiother Oncol 105 (1): 122-6, 2012. [PubMed: 21993405]
25. Casey DL, Friedman DN, Moskowitz CS, et al.: Second cancer risk in childhood cancer survivors treated with intensity-modulated radiation therapy (IMRT). Pediatr Blood Cancer 62 (2): 311-316, 2015. [PubMed: 25328040]
26. McClain KL, Leach CT, Jenson HB, et al.: Association of Epstein-Barr virus with leiomyosarcomas in children with AIDS. N Engl J Med 332 (1): 12-8, 1995. [PubMed: 7990860]
27. Dillon P, Maurer H, Jenkins J, et al.: A prospective study of nonrhabdomyosarcoma soft tissue sarcomas in the pediatric age group. J Pediatr Surg 27 (2): 241-4; discussion 244-5, 1992. [PubMed: 1314309]
28. Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec. [PubMed: 8284572]
29. Zeytoonjian T, Mankin HJ, Gebhardt MC, et al.: Distal lower extremity sarcomas: frequency of occurrence and patient survival rate. Foot Ankle Int 25 (5): 325-30, 2004. [PubMed: 15134614]
30. Benesch M, von Bueren AO, Dantonello T, et al.: Primary intracranial soft tissue sarcoma in children and adolescents: a cooperative analysis of the European CWS and HIT study groups. J Neurooncol 111 (3): 337-45, 2013. [PubMed: 23229762]
31. Weiss SW, Goldblum JR: Miscellaneous tumors of intermediate malignancy. In: Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. Mosby, 2008, pp 1093-1160.
32. Federico SM, Spunt SL, Krasin MJ, et al.: Comparison of PET-CT and conventional imaging in staging pediatric rhabdomyosarcoma. Pediatr Blood Cancer 60 (7): 1128-34, 2013. [PMC free article: PMC4266929] [PubMed: 23255260]
33. Mody RJ, Bui C, Hutchinson RJ, et al.: FDG PET imaging of childhood sarcomas. Pediatr Blood Cancer 54 (2): 222-7, 2010. [PMC free article: PMC2794959] [PubMed: 19890901]
34. Tateishi U, Hosono A, Makimoto A, et al.: Accuracy of 18F fluorodeoxyglucose positron emission tomography/computed tomography in staging of pediatric sarcomas. J Pediatr Hematol Oncol 29 (9): 608-12, 2007. [PubMed: 17805034]
35. Wagner LM, Kremer N, Gelfand MJ, et al.: Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentinel lymph node biopsy versus fludeoxyglucose positron emission tomography imaging-A prospective trial. Cancer 123 (1): 155-160, 2017. [PubMed: 27563842]
36. Sargar K, Kao SC, Spunt SL, et al.: MRI and CT of Low-Grade Fibromyxoid Sarcoma in Children: A Report From Children's Oncology Group Study ARST0332. AJR Am J Roentgenol 205 (2): 414-20, 2015. [PMC free article: PMC4570741] [PubMed: 26204295]
37. Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. Mosby, 2008.
38. Recommendations for the reporting of soft tissue sarcomas. Association of Directors of Anatomic and Surgical Pathology. Mod Pathol 11 (12): 1257-61, 1998. [PubMed: 9872660]
39. Strauss DC, Qureshi YA, Hayes AJ, et al.: The role of core needle biopsy in the diagnosis of suspected soft tissue tumours. J Surg Oncol 102 (5): 523-9, 2010. [PubMed: 20872955]
40. Chowdhury T, Barnacle A, Haque S, et al.: Ultrasound-guided core needle biopsy for the diagnosis of rhabdomyosarcoma in childhood. Pediatr Blood Cancer 53 (3): 356-60, 2009. [PubMed: 19418540]
41. Tuttle R, Kane JM: Biopsy techniques for soft tissue and bowel sarcomas. J Surg Oncol 111 (5): 504-12, 2015. [PubMed: 25663366]
42. Coffin CM, Dehner LP, O'Shea PA: Pediatric Soft Tissue Tumors: A Clinical, Pathological, and Therapeutic Approach. Williams and Wilkins, 1997.
43. Smith LM, Watterson J, Scott SM: Medical and surgical management of pediatric soft tissue tumors. In: Coffin CM, Dehner LP, O'Shea PA: Pediatric Soft Tissue Tumors: A Clinical, Pathological, and Therapeutic Approach. Williams and Wilkins, 1997, pp 360-71.
44. Neville HL, Andrassy RJ, Lally KP, et al.: Lymphatic mapping with sentinel node biopsy in pediatric patients. J Pediatr Surg 35 (6): 961-4, 2000. [PubMed: 10873044]
45. Neville HL, Raney RB, Andrassy RJ, et al.: Multidisciplinary management of pediatric soft-tissue sarcoma. Oncology (Huntingt) 14 (10): 1471-81; discussion 1482-6, 1489-90, 2000. [PubMed: 11098512]
46. Kayton ML, Delgado R, Busam K, et al.: Experience with 31 sentinel lymph node biopsies for sarcomas and carcinomas in pediatric patients. Cancer 112 (9): 2052-9, 2008. [PubMed: 18338809]
47. Dall'Igna P, De Corti F, Alaggio R, et al.: Sentinel node biopsy in pediatric patients: the experience in a single institution. Eur J Pediatr Surg 24 (6): 482-7, 2014. [PubMed: 25478665]
48. Parida L, Morrisson GT, Shammas A, et al.: Role of lymphoscintigraphy and sentinel lymph node biopsy in the management of pediatric melanoma and sarcoma. Pediatr Surg Int 28 (6): 571-8, 2012. [PMC free article: PMC3608674] [PubMed: 22526545]
49. Alcorn KM, Deans KJ, Congeni A, et al.: Sentinel lymph node biopsy in pediatric soft tissue sarcoma patients: utility and concordance with imaging. J Pediatr Surg 48 (9): 1903-6, 2013. [PubMed: 24074665]
50. Chui CH, Spunt SL, Liu T, et al.: Is reexcision in pediatric nonrhabdomyosarcoma soft tissue sarcoma necessary after an initial unplanned resection? J Pediatr Surg 37 (10): 1424-9, 2002. [PubMed: 12378447]
51. Cecchetto G, Guglielmi M, Inserra A, et al.: Primary re-excision: the Italian experience in patients with localized soft-tissue sarcomas. Pediatr Surg Int 17 (7): 532-4, 2001. [PubMed: 11666052]
52. Qureshi YA, Huddy JR, Miller JD, et al.: Unplanned excision of soft tissue sarcoma results in increased rates of local recurrence despite full further oncological treatment. Ann Surg Oncol 19 (3): 871-7, 2012. [PubMed: 21792512]
53. Sandberg AA: Translocations in malignant tumors. Am J Pathol 159 (6): 1979-80, 2001. [PMC free article: PMC1850575] [PubMed: 11733346]
54. Slater O, Shipley J: Clinical relevance of molecular genetics to paediatric sarcomas. J Clin Pathol 60 (11): 1187-94, 2007. [PMC free article: PMC2095484] [PubMed: 17468291]
55. Mertens F, Antonescu CR, Hohenberger P, et al.: Translocation-related sarcomas. Semin Oncol 36 (4): 312-23, 2009. [PubMed: 19664492]
56. Romeo S, Dei Tos AP: Clinical application of molecular pathology in sarcomas. Curr Opin Oncol 23 (4): 379-84, 2011. [PubMed: 21577110]
57. Schaefer IM, Cote GM, Hornick JL: Contemporary Sarcoma Diagnosis, Genetics, and Genomics. J Clin Oncol 36 (2): 101-110, 2018. [PubMed: 29220288]
58. Ladanyi M, Lui MY, Antonescu CR, et al.: The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 20 (1): 48-57, 2001. [PubMed: 11244503]
59. Ladanyi M: The emerging molecular genetics of sarcoma translocations. Diagn Mol Pathol 4 (3): 162-73, 1995. [PubMed: 7493135]
60. Williams A, Bartle G, Sumathi VP, et al.: Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: useful diagnostic tools in cases with unusual histological features. Virchows Arch 458 (3): 291-300, 2011. [PubMed: 21279521]
61. Antonescu CR, Dal Cin P, Nafa K, et al.: EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer 46 (12): 1051-60, 2007. [PubMed: 17724745]
62. Hisaoka M, Ishida T, Kuo TT, et al.: Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am J Surg Pathol 32 (3): 452-60, 2008. [PubMed: 18300804]
63. Barnoud R, Sabourin JC, Pasquier D, et al.: Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors. Am J Surg Pathol 24 (6): 830-6, 2000. [PubMed: 10843285]
64. Wang LL, Perlman EJ, Vujanic GM, et al.: Desmoplastic small round cell tumor of the kidney in childhood. Am J Surg Pathol 31 (4): 576-84, 2007. [PubMed: 17414105]
65. Errani C, Zhang L, Sung YS, et al.: A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer 50 (8): 644-53, 2011. [PMC free article: PMC3264678] [PubMed: 21584898]
66. Haller F, Knopf J, Ackermann A, et al.: Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern. J Pathol 238 (5): 700-10, 2016. [PubMed: 26863915]
67. Jain S, Xu R, Prieto VG, et al.: Molecular classification of soft tissue sarcomas and its clinical applications. Int J Clin Exp Pathol 3 (4): 416-28, 2010. [PMC free article: PMC2872748] [PubMed: 20490332]
68. Agaimy A, Bieg M, Michal M, et al.: Recurrent Somatic PDGFRB Mutations in Sporadic Infantile/Solitary Adult Myofibromas But Not in Angioleiomyomas and Myopericytomas. Am J Surg Pathol 41 (2): 195-203, 2017. [PubMed: 27776010]
69. Spunt SL, Hill DA, Motosue AM, et al.: Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma. J Clin Oncol 20 (15): 3225-35, 2002. [PubMed: 12149295]
70. Spunt SL, Poquette CA, Hurt YS, et al.: Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: an analysis of 121 patients treated at St Jude Children's Research Hospital. J Clin Oncol 17 (12): 3697-705, 1999. [PubMed: 10577841]
71. Ferrari A, Casanova M, Collini P, et al.: Adult-type soft tissue sarcomas in pediatric-age patients: experience at the Istituto Nazionale Tumori in Milan. J Clin Oncol 23 (18): 4021-30, 2005. [PubMed: 15767645]
72. Brooks AD, Heslin MJ, Leung DH, et al.: Superficial extremity soft tissue sarcoma: an analysis of prognostic factors. Ann Surg Oncol 5 (1): 41-7, 1998 Jan-Feb. [PubMed: 9524707]
73. Ferrari A, Miceli R, Meazza C, et al.: Soft tissue sarcomas of childhood and adolescence: the prognostic role of tumor size in relation to patient body size. J Clin Oncol 27 (3): 371-6, 2009. [PubMed: 19064986]
74. Rodeberg DA, Stoner JA, Garcia-Henriquez N, et al.: Tumor volume and patient weight as predictors of outcome in children with intermediate risk rhabdomyosarcoma: a report from the Children's Oncology Group. Cancer 117 (11): 2541-50, 2011. [PMC free article: PMC3117103] [PubMed: 24048802]
75. Hong DS, DuBois SG, Kummar S, et al.: Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 21 (4): 531-540, 2020. [PMC free article: PMC7497841] [PubMed: 32105622]
76. Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 4th ed. Mosby, 2001.
77. Spunt SL, Million L, Chi YY, et al.: A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol 21 (1): 145-161, 2020. [PMC free article: PMC6946838] [PubMed: 31786124]
78. O'Sullivan B, Davis AM, Turcotte R, et al.: Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 359 (9325): 2235-41, 2002. [PubMed: 12103287]
79. Ferrari A, Miceli R, Rey A, et al.: Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups. Eur J Cancer 47 (5): 724-31, 2011. [PMC free article: PMC3539303] [PubMed: 21145727]
80. Smith KB, Indelicato DJ, Knapik JA, et al.: Definitive radiotherapy for unresectable pediatric and young adult nonrhabdomyosarcoma soft tissue sarcoma. Pediatr Blood Cancer 57 (2): 247-51, 2011. [PubMed: 21671361]
81. Ferrari A, Magni C, Bergamaschi L, et al.: Pediatric nonrhabdomyosarcoma soft tissue sarcomas arising at visceral sites. Pediatr Blood Cancer 64 (9): , 2017. [PubMed: 28233470]
82. Ferrari A, van Noesel MM, Brennan B, et al.: Paediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG). Lancet Child Adolesc Health 5 (8): 546-558, 2021. [PubMed: 34214481]
83. Dillon PW, Whalen TV, Azizkhan RG, et al.: Neonatal soft tissue sarcomas: the influence of pathology on treatment and survival. Children's Cancer Group Surgical Committee. J Pediatr Surg 30 (7): 1038-41, 1995. [PubMed: 7472928]
84. Pappo AS, Fontanesi J, Luo X, et al.: Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience. J Clin Oncol 12 (11): 2360-6, 1994. [PubMed: 7964951]
85. Marcus KC, Grier HE, Shamberger RC, et al.: Childhood soft tissue sarcoma: a 20-year experience. J Pediatr 131 (4): 603-7, 1997. [PubMed: 9386667]
86. Pratt CB, Pappo AS, Gieser P, et al.: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 17 (4): 1219, 1999. [PubMed: 10561182]
87. Pratt CB, Maurer HM, Gieser P, et al.: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30 (4): 201-9, 1998. [PubMed: 9473754]

World Health Organization (WHO) Classification of Soft Tissue Tumors

The WHO classification system for cancer represents the common nomenclature for cancer worldwide. In the United States, it has been adopted by the American Joint Committee on Cancer (AJCC) for sarcoma staging and the College of American Pathologists (CAP) cancer protocols for bone and soft tissue sarcomas. The fifth edition of the WHO Classification of Soft Tissue and Bone Tumors was published in 2020.[1]

The grading of soft tissue tumors has always been a controversial issue. The 2020 WHO classification represents the consensus of several soft tissue pathologists and geneticists, as well as a medical oncologist, radiologist, and surgeon. This edition further integrates morphology and genetic information into the classification. For example, a new category of tumors called NTRK-rearranged spindle cell neoplasms was included, but infantile fibrosarcoma was excluded from this group. This classification also defined the undifferentiated small cell sarcomas of bone and soft tissue by separating Ewing sarcoma from entities such as CIC-rearranged sarcomas, BCOR-rearranged sarcomas, and EWSR1 gene fusions involving non-ETS partner genes. Ewing sarcoma is now in the same area rather than in the bone tumor section to reflect the variable presentation sites and the variety of translocations associated with this entity.[1]

1. Adipocytic tumors.

   1. Benign.

      • Lipoma.
      • Lipomatosis.
      • Lipomatosis of nerve.
      • Lipoblastoma/lipoblastomatosis.
      • Angiolipoma.
      • Myolipoma.
      • Chondroid lipoma.
      • Extrarenal angiomyolipoma.
      • Extra-adrenal myelolipoma.
      • Spindle cell/pleomorphic lipoma.
      • Hibernoma.
   2. Intermediate (locally aggressive).

      • Atypical lipomatous tumor/well-differentiated liposarcoma.
   3. Malignant.

      • Dedifferentiated liposarcoma.
      • Myxoid liposarcoma.
      • Pleomorphic liposarcoma.
      • Liposarcoma, not otherwise specified (NOS).
2. Chondro-osseous tumors.

   • Soft tissue chondroma.
   • Extraskeletal mesenchymal chondrosarcoma.[2]
   • Extraskeletal osteosarcoma.
3. Fibroblastic/myofibroblastic tumors.

   1. Benign.

      • Nodular fasciitis.
      • Proliferative fasciitis.
      • Proliferative myositis.
      • Myositis ossificans.
      • Fibro-osseous pseudotumor of digits.
      • Ischemic fasciitis.
      • Elastofibroma.
      • Fibrous hamartoma of infancy.
      • Fibromatosis colli.
      • Juvenile hyaline fibromatosis.
      • Inclusion body fibromatosis.
      • Fibroma of tendon sheath.
      • Desmoplastic fibroblastoma.
      • Mammary-type myofibroblastoma.
      • Calcifying aponeurotic fibroma.
      • Angiomyofibroblastoma.
      • Cellular angiofibroma.
      • Nuchal-type fibroma.
      • Gardner fibroma.
      • Calcifying fibrous tumor.
   2. Intermediate (locally aggressive).

      • Palmar/plantar fibromatosis.
      • Desmoid-type fibromatosis (previously called desmoid tumor or aggressive fibromatoses).
      • Lipofibromatosis.
      • Giant cell fibroblastoma.
   3. Intermediate (rarely metastasizing).

      • Dermatofibrosarcoma protuberans.

        -

        Fibrosarcomatous dermatofibrosarcoma protuberans.

        -

        Pigmented dermatofibrosarcoma protuberans.

      • Solitary fibrous tumor.

        -

        Solitary fibrous tumor, malignant.

      • Inflammatory myofibroblastic tumor.
      • Low-grade myofibroblastic sarcoma.
      • Myxoinflammatory fibroblastic sarcoma/atypical myxoinflammatory fibroblastic tumor.
      • Infantile fibrosarcoma.[3]
   4. Malignant.

      • Adult fibrosarcoma.
      • Myxofibrosarcoma.
      • Low-grade fibromyxoid sarcoma.[4]
      • Sclerosing epithelioid fibrosarcoma.
4. Skeletal muscle tumors.

   • Rhabdomyoma.
   • Rhabdomyosarcoma (embryonal, spindle cell/sclerosing, alveolar, and pleomorphic forms). For more information, see Childhood Rhabdomyosarcoma Treatment.
5. Smooth muscle tumors.

   1. Benign.

      • Deep leiomyoma.
   2. Malignant.

      • Leiomyosarcoma (excluding skin).
      Angioleiomyoma was reclassified under perivascular tumors.
6. So-called fibrohistiocytic tumors.

   1. Benign.

      • Tenosynovial giant cell tumor.

        -

        Localized type.

        -

        Diffuse type.

        -

        Malignant.

      • Deep benign fibrous histiocytoma.
   2. Intermediate (rarely metastasizing).

      • Plexiform fibrohistiocytic tumor.
      • Giant cell tumor of soft tissue.
      The malignant counterpart of so-called fibrohistiocytic tumors, formerly known as malignant fibrous histiocytoma and its subtypes was renamed undifferentiated sarcoma and was previously classified under the undifferentiated/unclassified sarcomas section.
7. Nerve sheath tumors.

   1. Benign.

      • Schwannoma (including variants).
      • Melanotic schwannoma.
      • Neurofibroma (including variants).

        -

        Plexiform neurofibroma.

      • Perineurioma.

        -

        Malignant perineurioma.

      • Granular cell tumor.
      • Dermal nerve sheath myxoma.
      • Solitary circumscribed neuroma.
      • Ectopic meningioma.
      • Nasal glial heterotopia.
      • Benign Triton tumor.
      • Hybrid nerve sheath tumor.
   2. Malignant.

      • Malignant peripheral nerve sheath tumor.
      • Epithelioid malignant peripheral nerve sheath tumor.
      • Malignant Triton tumor.
      • Malignant granular cell tumor.
      • Ectomesenchymoma.
8. Pericytic (perivascular) tumors.

   • Glomus tumor (and variants).

     -

     Glomangiomatosis.

     -

     Malignant glomus tumor.

   • Myopericytoma.

     -

     Myofibroma (hemangiopericytoma are now included in recent WHO classification).

     -

     Myofibromatosis.

     -

     Infantile myofibromatosis.

   • Angioleiomyoma.
9. Tumors of uncertain differentiation.

   1. Benign.

      • Acral fibromyxoma.
      • Intramuscular myxoma (including cellular variant).
      • Juxta-articular myxoma.
      • Deep (aggressive) angiomyxoma.
      • Pleomorphic hyalinizing angiectatic tumor.
      • Ectopic hamartomatous thymoma.
   2. Intermediate (locally aggressive).

      • Hemosiderotic fibrolipomatous tumor.
   3. Intermediate (rarely metastasizing).

      • Atypical fibroxanthoma.
      • Angiomatoid fibrous histiocytoma.
      • Ossifying fibromyxoid tumor.

        -

        Ossifying fibromyxoid tumor, malignant.

      • Mixed tumor NOS.
      • Mixed tumor NOS, malignant.
      • Myoepithelioma.
      • Myoepithelial carcinoma.
      • Phosphaturic mesenchymal tumor, benign.
      • Phosphaturic mesenchymal tumor, malignant.
   4. Malignant.

      • Synovial sarcoma NOS.

        -

        Synovial sarcoma, spindle cell.

        -

        Synovial sarcoma, biphasic.

      • Epithelioid sarcoma.
      • Alveolar soft part sarcoma.
      • Clear cell sarcoma of soft tissue.
      • Extraskeletal myxoid chondrosarcoma.
      • Extraskeletal Ewing sarcoma. (Refer to the PDQ summary on Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment for more information.)
      • Desmoplastic small round cell tumor.
      • Extrarenal rhabdoid tumor.
      • Neoplasms with perivascular epithelioid cell differentiation (PEComa).

        -

        PEComa NOS, benign.

        -

        PEComa NOS, malignant.

      • Intimal sarcoma.
10. Undifferentiated/unclassified sarcomas.

    • Undifferentiated spindle cell sarcoma.
    • Undifferentiated pleomorphic sarcoma.
    • Undifferentiated round cell sarcoma.
    • Undifferentiated epithelioid sarcoma.
    • Undifferentiated sarcoma NOS.[5]
    Genetic subgroups are emerging within this family and this work is ongoing:

    • Undifferentiated round cell and spindle cell sarcoma.
      In this group, EWSR1 is involved in non-ETS fusions with genes such as PATZ1, POU5F1, SMARCA5, NFATC2, or SP3. Another recurrent rearrangement involves the CIC::DUX4 fusion gene resulting in the chimeric CIC::DUX4 protein, which upregulates genes of the PEA3 subclass of ETS family.
      It is unclear whether these cases represent one or more separate entities, or whether they are better classified as variants of Ewing sarcoma. For more information, see the Genomics of Ewing Sarcoma section in Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment.
    • Undifferentiated pleomorphic sarcoma.
      Undifferentiated pleomorphic sarcoma was most often called malignant fibrous histiocytoma in the past. Historically, this entity has been difficult to evaluate because of the shifting diagnostic criteria. Analysis of 70 cases diagnosed as malignant fibrous histiocytosis of no specific type, storiform or pleomorphic malignant fibrous histiocytoma, pleomorphic sarcoma or undifferentiated pleomorphic sarcoma showed a highly complex karyotype with no specific recurrent aberrations.[6]
      Undifferentiated sarcomas with 12q13–15 amplification, including MDM2 and CDK4, are best classified as dedifferentiated liposarcomas;[6] the relationship between this tumor and the family of undifferentiated/unclassified tumors with spindle cell morphology remains relatively undefined.
11. Vascular tumors.

    1. Benign.

       • Hemangioma. For more information, see Childhood Vascular Tumors Treatment.

         -

         Synovial.

         -

         Venous.

         -

         Arteriovenous hemangioma/malformation.

         -

         Intramuscular.

       • Epithelioid hemangioma.
       • Angiomatosis.
       • Lymphangioma.
    2. Intermediate (locally aggressive).

       • Kaposiform hemangioendothelioma.
    3. Intermediate (rarely metastasizing).

       • Retiform hemangioendothelioma.
       • Papillary intralymphatic angioendothelioma.
       • Composite hemangioendothelioma.
       • Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma.
       • Kaposi sarcoma.
    4. Malignant.

       • Epithelioid hemangioendothelioma.
       • Angiosarcoma of the soft tissue.

With the increased use of next-generation sequencing techniques and heightened awareness of recently approved tyrosine kinase inhibitors that target NTRK and other genes, newer subgroups of pediatric soft tissue lesions that are characterized by kinase fusions have been identified and share a similar morphological spectrum. It is important to identify these rare entities because some of them might be amenable to therapeutic targeting with novel agents. Some examples of these lesions are described below.[7]

• Lipofibromatosis-like neural tumors are superficial tumors that commonly affect children, and the cells are immunoreactive for S100. These tumors commonly have NTRK1 fusions but rarely harbor RET or ALK fusions.
• Spindle cell tumors with S100 and CD34 positivity that resemble intermediate-grade malignant peripheral nerve sheath tumors predominate in children and young adults and can affect bone and soft tissues. They have fusions in various genes, including RAF1, BRAF, NTRK1, and NTRK2.
• Infantile fibrosarcoma–like lesions morphologically resemble infantile fibrosarcoma and most commonly affect patients younger than 2 years. They have a predilection for intraabdominal sites. They often exhibit alternate fusions, involving genes such as BRAF, NTRK1, and MET.
• Spindle cell sarcomas with hemangiopericytic and myopericytic patterns can affect children and have NTRK1 fusions.
• RAF1 fusion–positive spindle cell sarcomas can be seen in children and adults and often arise in the trunk. They rarely behave aggressively.
• BRAF fusion–positive soft tissue tumors have been associated with infantile fibrosarcoma–like variants or spindle cell sarcomas that resemble malignant peripheral nerve sheath tumors. They have been reported in children and often involve the abdominal cavity.
• RET fusion–positive tumors predominantly affect children and have a similar phenotype to NTRK fusion–positive tumors. They can display fibroblastic and neural-like differentiation. These tumors are sensitive to the highly selective small-molecule RET inhibitor selpercatinib.[8]

References

1. WHO Classification of Tumours Editorial Board: WHO Classification of Tumours. Volume 3: Soft Tissue and Bone Tumours. 5th ed., IARC Press, 2020.
2. Dantonello TM, Int-Veen C, Leuschner I, et al.: Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults: experiences of the CWS and COSS study groups. Cancer 112 (11): 2424-31, 2008. [PubMed: 18438777]
3. Steelman C, Katzenstein H, Parham D, et al.: Unusual presentation of congenital infantile fibrosarcoma in seven infants with molecular-genetic analysis. Fetal Pediatr Pathol 30 (5): 329-37, 2011. [PubMed: 21843073]
4. Evans HL: Low-grade fibromyxoid sarcoma: a clinicopathologic study of 33 cases with long-term follow-up. Am J Surg Pathol 35 (10): 1450-62, 2011. [PubMed: 21921785]
5. Alaggio R, Collini P, Randall RL, et al.: Undifferentiated high-grade pleomorphic sarcomas in children: a clinicopathologic study of 10 cases and review of literature. Pediatr Dev Pathol 13 (3): 209-17, 2010 May-Jun. [PubMed: 20055602]
6. Le Guellec S, Chibon F, Ouali M, et al.: Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas? Am J Surg Pathol 38 (3): 293-304, 2014. [PubMed: 24525499]
7. Antonescu CR: Emerging soft tissue tumors with kinase fusions: An overview of the recent literature with an emphasis on diagnostic criteria. Genes Chromosomes Cancer 59 (8): 437-444, 2020. [PMC free article: PMC8323076] [PubMed: 32243019]
8. Ortiz MV, Gerdemann U, Raju SG, et al.: Activity of the Highly Specific RET Inhibitor Selpercatinib (LOXO-292) in Pediatric Patients With Tumors Harboring RET Gene Alterations. JCO Precis Oncol 4: , 2020. [PMC free article: PMC7450975] [PubMed: 32923911]

Intergroup Rhabdomyosarcoma Study Staging System

TNM Staging System

The eighth edition of the AJCC Cancer Staging Manual has designated staging by the four criteria of tumor size, nodal status, histologic grade, and metastasis and by anatomic primary tumor site (head and neck; trunk and extremities; abdomen and thoracic visceral organs; retroperitoneum; and unusual histologies and sites) (see Tables 5, 6, 7, and 8).[3-7] For information on unusual histologies and sites, see the AJCC Cancer Staging Manual.[7]

Soft Tissue Sarcoma Tumor Pathological Grading System

In most cases, accurate histopathological classification alone of soft tissue sarcomas does not yield optimal information about their clinical behavior. Therefore, several histological parameters are evaluated in the grading process, including the following:

• Degree of cellularity.
• Cellular pleomorphism.
• Mitotic activity.
• Degree of necrosis.
• Invasive growth.

This process is used to improve the correlation between histological findings and clinical outcome.[9] In children, grading of soft tissue sarcoma is complicated by certain factors, such as prognosis, patient age, extent of surgical resection, and ability to metastasize. For example, children younger than 4 years with infantile fibrosarcoma and hemangiopericytoma have a good prognosis, and angiomatoid fibrous histiocytoma and dermatofibrosarcoma protuberans can recur locally if incompletely excised but usually do not metastasize.

Testing the validity of a grading system within the pediatric population is difficult because of the rarity of these neoplasms. In March 1986, the Pediatric Oncology Group (POG) conducted a prospective study on pediatric soft tissue sarcomas other than rhabdomyosarcoma and devised the POG grading system. Analysis of outcome for patients with localized soft tissue sarcomas other than rhabdomyosarcoma demonstrated that patients with grade 3 tumors fared significantly worse than those with grade 1 or grade 2 lesions. This finding suggests that this system can accurately predict the clinical behavior of NRSTS.[9-11]

The grading systems developed by the POG and the French Federation of Comprehensive Cancer Centers (Fédération Nationale des Centres de Lutte Contre Le Cancer [FNCLCC]) Sarcoma Group are described below.

Prognostic Significance of Tumor Grading

The POG and FNCLCC grading systems have proven to be of prognostic value in pediatric and adult NRSTS.[14-18] In a study of 130 tumors from children and adolescents with NRSTS enrolled in three prospective clinical trials, a correlation was found between the POG-assigned grade and the FNCLCC-assigned grade. However, grading did not correlate in all cases; 44 patients whose tumors received discrepant grades (POG grade 3, FNCLCC grade 1 or 2) had outcomes between concurrent grade 3 and grades 1 and 2. A mitotic index of 10 or greater emerged as an important prognostic factor.[19]

The Children's Oncology Group (COG) ARST0332 (NCT00346164) trial compared the POG and FNCLCC pathologic grading systems as part of a prospective risk-based strategy. The study found that, in addition to tumor depth and invasiveness, the FNCLCC grade was strongly associated with event-free survival and overall survival.[20] The closed COG ARST1321 (NCT02180867) trial used the FNCLCC system to assign histological grade.

References

1. American Joint Committee on Cancer: AJCC Cancer Staging Manual. 6th ed. Springer, 2002.
2. Maurer HM, Beltangady M, Gehan EA, et al.: The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 61 (2): 209-20, 1988. [PubMed: 3275486]
3. O'Sullivan B, Maki RG, Agulnik M, et al.: Soft tissue sarcoma of the head and neck. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 499-505.
4. Yoon SS, Maki RG, Asare EA, et al.: Soft tissue sarcoma of the trunk and extremities. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 507-15.
5. Raut CP, Maki RG, Baldini EH, et al.: Soft tissue sarcoma of the abdomen and thoracic visceral organs. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 517-21.
6. Pollock RE, Maki RG, Baldini EH, et al.: Soft tissue sarcoma of the retroperitoneum. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 531-7.
7. Maki RG, Folpe AL, Guadagnolo BA, et al.: Soft tissue sarcoma - unusual histologies and sites. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 539-45.
8. Waxweiler TV, Rusthoven CG, Proper MS, et al.: Non-Rhabdomyosarcoma Soft Tissue Sarcomas in Children: A Surveillance, Epidemiology, and End Results Analysis Validating COG Risk Stratifications. Int J Radiat Oncol Biol Phys 92 (2): 339-48, 2015. [PubMed: 25968827]
9. Parham DM, Webber BL, Jenkins JJ, et al.: Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: formulation of a simplified system for grading. Mod Pathol 8 (7): 705-10, 1995. [PubMed: 8539226]
10. Recommendations for the reporting of soft tissue sarcomas. Association of Directors of Anatomic and Surgical Pathology. Mod Pathol 11 (12): 1257-61, 1998. [PubMed: 9872660]
11. Skytting B, Meis-Kindblom JM, Larsson O, et al.: Synovial sarcoma--identification of favorable and unfavorable histologic types: a Scandinavian sarcoma group study of 104 cases. Acta Orthop Scand 70 (6): 543-54, 1999. [PubMed: 10665717]
12. Coindre JM, Terrier P, Guillou L, et al.: Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 91 (10): 1914-26, 2001. [PubMed: 11346874]
13. Guillou L, Coindre JM, Bonichon F, et al.: Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 15 (1): 350-62, 1997. [PubMed: 8996162]
14. Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec. [PubMed: 8284572]
15. Pisters PW, Leung DH, Woodruff J, et al.: Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 14 (5): 1679-89, 1996. [PubMed: 8622088]
16. Coindre JM, Terrier P, Bui NB, et al.: Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol 14 (3): 869-77, 1996. [PubMed: 8622035]
17. Pappo AS, Fontanesi J, Luo X, et al.: Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience. J Clin Oncol 12 (11): 2360-6, 1994. [PubMed: 7964951]
18. Pratt CB, Maurer HM, Gieser P, et al.: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30 (4): 201-9, 1998. [PubMed: 9473754]
19. Khoury JD, Coffin CM, Spunt SL, et al.: Grading of nonrhabdomyosarcoma soft tissue sarcoma in children and adolescents: a comparison of parameters used for the Fédération Nationale des Centers de Lutte Contre le Cancer and Pediatric Oncology Group Systems. Cancer 116 (9): 2266-74, 2010. [PMC free article: PMC2987713] [PubMed: 20166208]
20. Spunt SL, Million L, Chi YY, et al.: A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol 21 (1): 145-161, 2020. [PMC free article: PMC6946838] [PubMed: 31786124]

Surgery

Surgical resection of the primary tumor is the predominant therapy for most NRSTS. In the COG ARST0332 (NCT00346164) study, approximately 37% of patients younger than 30 years were treated with surgery alone.[1] Another 36% of patients had surgical resection after neoadjuvant chemoradiation therapy. Involvement of a surgeon with special expertise in the resection of soft tissue sarcomas is highly desirable.

After an appropriate biopsy and pathological diagnosis, every attempt is made to resect the primary tumor. Completeness of resection predicts outcome. In the COG ARST0332 study, complete resections with negative microscopic margins (R0) resulted in the best outcomes, with 5-year EFS rates of 84%. Resection with positive microscopic margins (R1) led to an EFS rate of 66%. Resection with gross residual disease (R2) led to an EFS rate of 49%. The 5-year OS rates were 93% for R0, 80% for R1, and 63% for R2 resections.[1] For patients treated with surgery only, the 5-year EFS rates were 96% for patients with low-grade tumors who had R0 resections, 81% for patients with low-grade tumors who had R1 resections, and 84% for patients with high-grade tumors that were smaller than 5 cm and had R0 resections.

The timing of surgery depends on an assessment of the feasibility and morbidity of surgery. In the COG ARST0332 study, the outcomes were nearly identical for intermediate-risk patients who achieved an R0 or R1 resection with up-front surgery or surgery after neoadjuvant chemoradiation therapy (70% vs. 71%, respectively). An R0 resection was more likely to occur after neoadjuvant therapy.[1] These observations are true even for high-grade tumors, where ability to achieve R0 or R1 resection was the major predictor of EFS. Treatment with neoadjuvant chemoradiation therapy resulted in lower doses of radiation therapy and achieved greater rates of R0 resection.[2] Resectability should be determined at the time of diagnosis, with an emphasis on achieving negative margins without loss of form or function.

If the initial operation fails to achieve pathologically negative tissue margins or if the initial surgery was done without the knowledge that cancer was present, a re-excision of the affected area is performed to obtain clear, but not necessarily wide, margins.[3-6] This surgical tenet is true even if no mass is detected by magnetic resonance imaging after initial surgery.[7]; [8][Level of evidence C1]

Regional lymph node metastases at diagnosis are unusual and are most often seen in patients with epithelioid and clear cell sarcomas.[9,10] Sentinel lymph node biopsy as a staging procedure in soft tissue sarcoma remains controversial. However, in adults with clear cell sarcoma and epithelioid sarcoma, it may help in the management of selected cases. There are insufficient data to support the use of sentinel lymph node biopsy in the management of pediatric patients with other NRSTS.[11-16]

Radiation Therapy

Considerations for radiation therapy are based on the potential for surgery, with or without chemotherapy, to obtain local control without loss of critical organs or significant functional, cosmetic, or psychological impairment. This will vary according to the following:

• Patient variables (e.g., age and sex).
• Tumor variables (e.g., histopathology, site, size, and grade).
• Use of surgery and margin status.
• Expectations for radiation-induced morbidities (e.g., impaired bone or muscle development, organ damage, or subsequent neoplasm).

Radiation therapy can be given preoperatively or postoperatively. It can also be used as definitive therapy in rare situations in which surgical resection is not performed.[17] Radiation field size and dose will be based on patient and tumor variables and the surgical procedure.[18] Radiation therapy was associated with improved OS compared with surgery alone when delivered preoperatively or postoperatively.[19]

Preoperative radiation therapy has been associated with excellent local control rates.[20-22] The advantages of this approach include treating smaller tissue volumes without the need to treat a postsurgical bed and somewhat lower radiation doses because relative hypoxia from surgical disruption of vasculature and scarring is not present. Preoperative radiation therapy has been associated with an increased rate of wound complications in adults, primarily in lower extremity tumors; however, the degree of these complications is questionable.[23] Conversely, preoperative radiation therapy may lead to less fibrosis than with postoperative approaches, perhaps because of the smaller treatment volume and dose.[24] Radiation technique can impact normal tissue sparing. Compared with 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy offers the potential to decrease radiation dose to skin and epiphysis when irradiating extremity sarcomas.[25]

Retroperitoneal sarcomas are unique in that radiosensitivity of the bowel to injury makes postoperative radiation therapy less desirable.[26,27] Postoperative adhesions and bowel immobility can increase the risk of damage from any given radiation dose. This contrasts with the preoperative approach in which the tumor often displaces bowel outside of the radiation field, and any exposed bowel is more mobile, which decreases exposure to specific bowel segments.

Radiation therapy can also be given postoperatively. In general, radiation is indicated for patients with inadequate surgical margins and for larger, high-grade tumors.[28,29] This is particularly important in high-grade tumors with tumor margins smaller than 1 cm.[30,31]; [32][Level of evidence C3] With combined R0 (negative margin) surgery and radiation therapy, local control of the primary tumor can be achieved in about 90% of patients with extremity sarcomas, 70% to 75% of patients with retroperitoneal sarcomas, and 80% of patients overall.[33-37]

Brachytherapy and intraoperative radiation may be applicable in select situations.[34,38,39]; [40][Level of evidence C2]

Radiation volume and dose depend on the patient, tumor, and surgical variables noted above, as well as the following:

• Patient age and growth potential.
• Ability to avoid critical organs, epiphyseal plates, and lymphatics (but not the neurovascular bundles that are relatively radiation tolerant).
• Functional/cosmetic outcome.

Radiation doses are typically 45 Gy to 50 Gy preoperatively, with consideration for postoperative boost of 10 Gy to 20 Gy if resection margins are microscopically or grossly positive, or planned brachytherapy if the resection is predicted to be subtotal. In addition, even in the preoperative setting, an additional boost of radiation at a dose of 60 Gy can be considered for areas of the tumor predicted to be at risk of residual microscopic disease (e.g., areas of tumor adjacent to critical normal tissues) that cannot be resected with adequate margins. This can be accomplished with a simultaneously integrated boost dose (i.e., higher dose area within the larger lower dose volume) or administered with a small field of radiation after the initial volume is treated with a dose of 45 Gy to 50 Gy. It also must be acknowledged that data documenting the efficacy of a postoperative boost to areas with microscopically positive margins are lacking.[41] The postoperative radiation dose is 55 Gy to 60 Gy for R0 resections, up to 65 Gy for R1 resections (microscopic positive margins), and higher when unresectable gross residual disease exists depending on overall treatment goals (e.g., definitive local control vs. palliation).

Radiation margins are typically 2 cm to 4 cm longitudinally and encompass fascial planes axially.[42,43]

Chemotherapy

The role of postoperative chemotherapy remains unclear.[44]

Evidence (lack of clarity regarding postoperative chemotherapy):

1. A meta-analysis of data from all randomized trials of adults with soft tissue sarcoma observed the following:[45]

   • Recurrence-free survival was better with postoperative chemotherapy for patients with high-grade tumors larger than 5 cm.
2. In a European trial, adults with completely resected soft tissue sarcoma were randomly assigned to observation or postoperative chemotherapy with ifosfamide and doxorubicin.[46][Level of evidence A1]

   • Postoperative chemotherapy was not associated with improved EFS or OS.
   • It is difficult to extrapolate this trial to pediatric patients because the trial included: 1) a wide variety of histologies; 2) a relatively low dose of ifosfamide; 3) patients assigned to chemotherapy had definitive radiation delayed until completion of chemotherapy; and 4) almost one-half of the patients in the trial had intermediate-grade tumors.
   • In the discussion section, the authors merged their patients with previously published series, including those from the European meta-analysis, and concluded that the results suggested a benefit for postoperative chemotherapy.
3. The largest prospective pediatric trial failed to demonstrate any benefit with postoperative vincristine, dactinomycin, cyclophosphamide, and doxorubicin.[33]
4. Doxorubicin and ifosfamide were used in the risk-based COG ARST0332 (NCT00346164) trial.[1][Level of evidence C1]

   • Although this was not a randomized study, results at 2.6 years showed that patients with high-risk (>5 cm and high grade), grossly resected, nonmetastatic tumors who were treated with radiation therapy and postoperative doxorubicin and ifosfamide had a 5-year EFS rate of 67.2% and an OS rate of 78%.
   • In patients with metastatic disease treated with preoperative chemotherapy and radiation therapy, the estimated 5-year EFS rate was 21.2%, and the OS rate was 35.5%.

Targeted Therapy

The use of angiogenesis and mammalian target of rapamycin (mTOR) inhibitors has been explored in the treatment of adult soft tissue sarcomas but not in pediatrics.

Evidence (targeted therapy in adults with soft tissue sarcoma):

1. In a trial of 711 adult patients who achieved a response or stable disease after chemotherapy, patients were randomly assigned to receive ridaforolimus or placebo.[47]

   • The administration of ridaforolimus was associated with a 3-week improvement in progression-free survival (PFS) when compared with placebo.
2. In another trial of 371 randomly assigned adult patients with metastatic soft tissue sarcoma that progressed after chemotherapy, pazopanib was compared with placebo.[48]

   • The median PFS for the pazopanib arm was 4.6 months compared with 1.6 months for the placebo arm. OS was not different between the two arms.
3. In a study of 182 previously treated adult patients with recurrent liposarcoma, leiomyosarcoma, synovial sarcoma, and other sarcomas, patients were randomly assigned to receive regorafenib or placebo.[49]

   • Patients with nonadipocytic tumors who were treated with regorafenib had significant improvements in PFS when compared with patients who were treated with placebo.

The COG and NRG Oncology cancer consortia conducted a randomized trial of pazopanib added to neoadjuvant chemotherapy (doxorubicin and ifosfamide) and preoperative radiation therapy in pediatric and adult patients with NRSTS. Patients whose tumors were larger than 5 cm and had intermediate- or high-grade disease were eligible. The end point of the trial was pathological tumor response after adjuvant therapy. Study entry was closed early because the planned interim analysis showed that the pathological response boundary was crossed. Eighty-one patients were enrolled, but only 42 (52%) were available for response data (17 patients from each group discontinued therapy for either progression, unacceptable toxicity, or patient or physician choice).[50]

• Four of 18 patients (22%) in the control group had greater than 90% necrosis at resection, compared with 14 of 24 patients (58%) in the group treated with pazopanib, meeting the criteria for early stopping of the study.
• Toxicity was greater in the pazopanib group, mainly resulting from increased myelosuppression. Wound complications were also more frequent in the pazopanib group.
• Longer follow-up is needed to report differences in OS or EFS.

References

1. Spunt SL, Million L, Chi YY, et al.: A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol 21 (1): 145-161, 2020. [PMC free article: PMC6946838] [PubMed: 31786124]
2. Million L, Hayes-Jordan A, Chi YY, et al.: Local Control For High-Grade Nonrhabdomyosarcoma Soft Tissue Sarcoma Assigned to Radiation Therapy on ARST0332: A Report From the Childrens Oncology Group. Int J Radiat Oncol Biol Phys 110 (3): 821-830, 2021. [PMC free article: PMC8767764] [PubMed: 33548339]
3. Sugiura H, Takahashi M, Katagiri H, et al.: Additional wide resection of malignant soft tissue tumors. Clin Orthop (394): 201-10, 2002. [PubMed: 11795735]
4. Cecchetto G, Guglielmi M, Inserra A, et al.: Primary re-excision: the Italian experience in patients with localized soft-tissue sarcomas. Pediatr Surg Int 17 (7): 532-4, 2001. [PubMed: 11666052]
5. Chui CH, Spunt SL, Liu T, et al.: Is reexcision in pediatric nonrhabdomyosarcoma soft tissue sarcoma necessary after an initial unplanned resection? J Pediatr Surg 37 (10): 1424-9, 2002. [PubMed: 12378447]
6. Paulino AC, Ritchie J, Wen BC: The value of postoperative radiotherapy in childhood nonrhabdomyosarcoma soft tissue sarcoma. Pediatr Blood Cancer 43 (5): 587-93, 2004. [PubMed: 15382277]
7. Kaste SC, Hill A, Conley L, et al.: Magnetic resonance imaging after incomplete resection of soft tissue sarcoma. Clin Orthop (397): 204-11, 2002. [PubMed: 11953612]
8. Chandrasekar CR, Wafa H, Grimer RJ, et al.: The effect of an unplanned excision of a soft-tissue sarcoma on prognosis. J Bone Joint Surg Br 90 (2): 203-8, 2008. [PubMed: 18256089]
9. Daigeler A, Kuhnen C, Moritz R, et al.: Lymph node metastases in soft tissue sarcomas: a single center analysis of 1,597 patients. Langenbecks Arch Surg 394 (2): 321-9, 2009. [PubMed: 18594854]
10. Mazeron JJ, Suit HD: Lymph nodes as sites of metastases from sarcomas of soft tissue. Cancer 60 (8): 1800-8, 1987. [PubMed: 3308055]
11. Neville HL, Andrassy RJ, Lally KP, et al.: Lymphatic mapping with sentinel node biopsy in pediatric patients. J Pediatr Surg 35 (6): 961-4, 2000. [PubMed: 10873044]
12. Neville HL, Raney RB, Andrassy RJ, et al.: Multidisciplinary management of pediatric soft-tissue sarcoma. Oncology (Huntingt) 14 (10): 1471-81; discussion 1482-6, 1489-90, 2000. [PubMed: 11098512]
13. Kayton ML, Delgado R, Busam K, et al.: Experience with 31 sentinel lymph node biopsies for sarcomas and carcinomas in pediatric patients. Cancer 112 (9): 2052-9, 2008. [PubMed: 18338809]
14. Dall'Igna P, De Corti F, Alaggio R, et al.: Sentinel node biopsy in pediatric patients: the experience in a single institution. Eur J Pediatr Surg 24 (6): 482-7, 2014. [PubMed: 25478665]
15. Parida L, Morrisson GT, Shammas A, et al.: Role of lymphoscintigraphy and sentinel lymph node biopsy in the management of pediatric melanoma and sarcoma. Pediatr Surg Int 28 (6): 571-8, 2012. [PMC free article: PMC3608674] [PubMed: 22526545]
16. Alcorn KM, Deans KJ, Congeni A, et al.: Sentinel lymph node biopsy in pediatric soft tissue sarcoma patients: utility and concordance with imaging. J Pediatr Surg 48 (9): 1903-6, 2013. [PubMed: 24074665]
17. Haas RL, Gronchi A, van de Sande MAJ, et al.: Perioperative Management of Extremity Soft Tissue Sarcomas. J Clin Oncol 36 (2): 118-124, 2018. [PubMed: 29220299]
18. Crompton JG, Ogura K, Bernthal NM, et al.: Local Control of Soft Tissue and Bone Sarcomas. J Clin Oncol 36 (2): 111-117, 2018. [PubMed: 29220297]
19. Nussbaum DP, Rushing CN, Lane WO, et al.: Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: a case-control, propensity score-matched analysis of a nationwide clinical oncology database. Lancet Oncol 17 (7): 966-975, 2016. [PubMed: 27210906]
20. Virkus WW, Mollabashy A, Reith JD, et al.: Preoperative radiotherapy in the treatment of soft tissue sarcomas. Clin Orthop (397): 177-89, 2002. [PubMed: 11953609]
21. Zagars GK, Ballo MT, Pisters PW, et al.: Preoperative vs. postoperative radiation therapy for soft tissue sarcoma: a retrospective comparative evaluation of disease outcome. Int J Radiat Oncol Biol Phys 56 (2): 482-8, 2003. [PubMed: 12738324]
22. Dickie C, Parent A, Griffin AM, et al.: The value of adaptive preoperative radiotherapy in management of soft tissue sarcoma. Radiother Oncol 122 (3): 458-463, 2017. [PubMed: 28169043]
23. O'Sullivan B, Davis AM, Turcotte R, et al.: Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 359 (9325): 2235-41, 2002. [PubMed: 12103287]
24. Davis AM, O'Sullivan B, Turcotte R, et al.: Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother Oncol 75 (1): 48-53, 2005. [PubMed: 15948265]
25. Rao AD, Chen Q, Million L, et al.: Preoperative Intensity Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High-Grade Extremity Sarcomas in Children: Analysis of the Children's Oncology Group Study ARST0332. Int J Radiat Oncol Biol Phys 103 (1): 38-44, 2019. [PubMed: 30213752]
26. Baldini EH, Wang D, Haas RL, et al.: Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel. Int J Radiat Oncol Biol Phys 92 (3): 602-12, 2015. [PubMed: 26068493]
27. Bishop AJ, Zagars GK, Torres KE, et al.: Combined Modality Management of Retroperitoneal Sarcomas: A Single-Institution Series of 121 Patients. Int J Radiat Oncol Biol Phys 93 (1): 158-65, 2015. [PMC free article: PMC4928583] [PubMed: 26130233]
28. Marcus KC, Grier HE, Shamberger RC, et al.: Childhood soft tissue sarcoma: a 20-year experience. J Pediatr 131 (4): 603-7, 1997. [PubMed: 9386667]
29. Delaney TF, Kepka L, Goldberg SI, et al.: Radiation therapy for control of soft-tissue sarcomas resected with positive margins. Int J Radiat Oncol Biol Phys 67 (5): 1460-9, 2007. [PubMed: 17394945]
30. Blakely ML, Spurbeck WW, Pappo AS, et al.: The impact of margin of resection on outcome in pediatric nonrhabdomyosarcoma soft tissue sarcoma. J Pediatr Surg 34 (5): 672-5, 1999. [PubMed: 10359161]
31. Skytting B: Synovial sarcoma. A Scandinavian Sarcoma Group project. Acta Orthop Scand Suppl 291: 1-28, 2000. [PubMed: 10862210]
32. Hua C, Gray JM, Merchant TE, et al.: Treatment planning and delivery of external beam radiotherapy for pediatric sarcoma: the St. Jude Children's Research Hospital experience. Int J Radiat Oncol Biol Phys 70 (5): 1598-606, 2008. [PubMed: 18234441]
33. Pratt CB, Pappo AS, Gieser P, et al.: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 17 (4): 1219, 1999. [PubMed: 10561182]
34. Merchant TE, Parsh N, del Valle PL, et al.: Brachytherapy for pediatric soft-tissue sarcoma. Int J Radiat Oncol Biol Phys 46 (2): 427-32, 2000. [PubMed: 10661350]
35. Karakousis CP, Driscoll DL: Treatment and local control of primary extremity soft tissue sarcomas. J Surg Oncol 71 (3): 155-61, 1999. [PubMed: 10404131]
36. Zagars GK, Ballo MT, Pisters PW, et al.: Prognostic factors for disease-specific survival after first relapse of soft-tissue sarcoma: analysis of 402 patients with disease relapse after initial conservative surgery and radiotherapy. Int J Radiat Oncol Biol Phys 57 (3): 739-47, 2003. [PubMed: 14529779]
37. Raut CP, Miceli R, Strauss DC, et al.: External validation of a multi-institutional retroperitoneal sarcoma nomogram. Cancer 122 (9): 1417-24, 2016. [PubMed: 26916507]
38. Schomberg PJ, Gunderson LL, Moir CR, et al.: Intraoperative electron irradiation in the management of pediatric malignancies. Cancer 79 (11): 2251-6, 1997. [PubMed: 9179074]
39. Nag S, Shasha D, Janjan N, et al.: The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas. Int J Radiat Oncol Biol Phys 49 (4): 1033-43, 2001. [PubMed: 11240245]
40. Viani GA, Novaes PE, Jacinto AA, et al.: High-dose-rate brachytherapy for soft tissue sarcoma in children: a single institution experience. Radiat Oncol 3: 9, 2008. [PMC free article: PMC2359754] [PubMed: 18423047]
41. Al Yami A, Griffin AM, Ferguson PC, et al.: Positive surgical margins in soft tissue sarcoma treated with preoperative radiation: is a postoperative boost necessary? Int J Radiat Oncol Biol Phys 77 (4): 1191-7, 2010. [PubMed: 20056340]
42. Wang D, Bosch W, Kirsch DG, et al.: Variation in the gross tumor volume and clinical target volume for preoperative radiotherapy of primary large high-grade soft tissue sarcoma of the extremity among RTOG sarcoma radiation oncologists. Int J Radiat Oncol Biol Phys 81 (5): e775-80, 2011. [PMC free article: PMC3099246] [PubMed: 21277104]
43. Bahig H, Roberge D, Bosch W, et al.: Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity. Int J Radiat Oncol Biol Phys 86 (2): 298-303, 2013. [PMC free article: PMC3646910] [PubMed: 23474110]
44. Ferrari A: Role of chemotherapy in pediatric nonrhabdomyosarcoma soft-tissue sarcomas. Expert Rev Anticancer Ther 8 (6): 929-38, 2008. [PubMed: 18533802]
45. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 350 (9092): 1647-54, 1997. [PubMed: 9400508]
46. Woll PJ, Reichardt P, Le Cesne A, et al.: Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol 13 (10): 1045-54, 2012. [PubMed: 22954508]
47. Demetri GD, Chawla SP, Ray-Coquard I, et al.: Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy. J Clin Oncol 31 (19): 2485-92, 2013. [PubMed: 23715582]
48. van der Graaf WT, Blay JY, Chawla SP, et al.: Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 379 (9829): 1879-86, 2012. [PubMed: 22595799]
49. Mir O, Brodowicz T, Italiano A, et al.: Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol 17 (12): 1732-1742, 2016. [PubMed: 27751846]
50. Weiss AR, Chen YL, Scharschmidt TJ, et al.: Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol 21 (8): 1110-1122, 2020. [PMC free article: PMC7745646] [PubMed: 32702309]

References

1. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PMC free article: PMC4136455] [PubMed: 24853691]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed June 7, 2022.
3. Suit H, Spiro I: Radiation as a therapeutic modality in sarcomas of the soft tissue. Hematol Oncol Clin North Am 9 (4): 733-46, 1995. [PubMed: 7490238]
4. Hawkins DS, Black JO, Orbach D, et al.: Nonrhabdomyosarcoma soft-tissue sarcomas. In: Blaney SM, Helman LJ, Adamson PC, eds.: Pizzo and Poplack's Pediatric Oncology. 8th ed. Wolters Kluwer, 2020, pp 721-46.

Adipocytic Tumors

Adipocytic tumors account for less than 10% of soft tissue lesions in patients younger than 20 years. The most common adipocytic tumors in children are lipomas and lipoblastomas.

Table 11 summarizes the adipocytic neoplasms seen in pediatric patients and includes information about their corresponding clinico-pathological and molecular features.[1]

Chondro-osseous Tumors

Chondro-osseous tumors include the following subtypes:

• Soft tissue chondroma.
• Extraskeletal mesenchymal chondrosarcoma.
• Extraskeletal osteosarcoma.

Fibroblastic/Myofibroblastic Tumors

Fibroblastic/myofibroblastic tumors include the following subtypes:

1. Fibroblastic/myofibroblastic tumors.

   1. Intermediate (locally aggressive).

      • Palmar/plantar fibromatosis.
      • Desmoid-type fibromatosis (previously called desmoid tumor or aggressive fibromatoses).
      • Lipofibromatosis.
      • Giant cell fibroblastoma.
   2. Intermediate (rarely metastasizing).

      • Dermatofibrosarcoma protuberans.
      • Solitary fibrous tumor.
      • Inflammatory myofibroblastic tumor.
      • Low-grade myofibroblastic sarcoma.
      • Myxoinflammatory fibroblastic sarcoma/atypical myxoinflammatory fibroblastic tumor.
      • Infantile fibrosarcoma.
   3. Malignant.

      • Adult fibrosarcoma.
      • Myxofibrosarcoma.
      • Low-grade fibromyxoid sarcoma.
      • Sclerosing epithelioid fibrosarcoma.

Skeletal Muscle Tumors

Smooth Muscle Tumors

So-called Fibrohistiocytic Tumors

So-called fibrohistiocytic tumors include the following subtypes:

• Plexiform fibrohistiocytic tumor.
• Giant cell tumor of soft tissue.

Nerve Sheath Tumors

Pericytic (Perivascular) Tumors

Tumors of Uncertain Differentiation

Tumors of uncertain differentiation include the following subtypes:

• Myxoma NOS (benign).
• Synovial sarcoma NOS (spindle cell and biphasic varieties).
• Epithelioid sarcoma.
• Alveolar soft part sarcoma.
• Clear cell sarcoma of soft tissue.
• Extraskeletal myxoid chondrosarcoma.
• Extraskeletal Ewing sarcoma.
• Desmoplastic small round cell tumor.
• Extrarenal rhabdoid tumor.
• Neoplasms with perivascular epithelioid cell differentiation (PEComa) (PEComa NOS, malignant).

Undifferentiated/Unclassified Sarcoma

From 1972 to 2006, patients with undifferentiated soft tissue sarcoma were eligible for participation in rhabdomyosarcoma trials coordinated by the IRS group and the COG. The rationale was that patients with undifferentiated soft tissue sarcoma had sites of disease and outcomes that were similar to those in patients with alveolar rhabdomyosarcoma. Therapeutic trials for adults with soft tissue sarcoma include patients with undifferentiated soft tissue sarcoma and other histologies, which are treated similarly, using ifosfamide and doxorubicin, and sometimes with other chemotherapy agents, surgery, and radiation therapy.

In the COG ARST0332 (NCT00346164) trial, patients with high-grade undifferentiated sarcoma were treated with an ifosfamide- and doxorubicin-based regimen. Results for the patients with high-grade undifferentiated sarcoma were reported together with all high-grade soft tissue sarcomas in the trial. The estimated 5-year EFS rate was 64% and the OS rate was 77% for sarcomas classified as high grade by the Fédération Nationale des Centres de Lutte Contre le Cancer.[229][Level of evidence C1]

In a report of 32 patients with undifferentiated soft tissue sarcomas who were enrolled on the ARST0332 (NCT00346164) trial, the median age at enrollment was 13.6 years, and two-thirds of the patients were male. The most common primary sites were the paraspinal region and extremities. Five patients presented with metastatic disease.[361]

• The 5-year EFS rate was 71%, and the OS rate was 83%.
• Of the nine children with low-risk disease (localized low-grade resected disease or localized high-grade disease <5 cm resected with negative margins) who were treated with surgery or radiation therapy only, the 5-year EFS rate was 65% and the OS rate was 100%, suggesting that patients with recurrent disease can be salvaged with additional therapy.
• The remaining 23 patients had either intermediate-risk disease (resected high-grade tumor >5 cm, unresected high-grade tumor >5 cm) or high-risk disease (metastasis to lymph nodes or distant sites) and were treated with chemoradiation therapy and delayed surgery when feasible. The 5-year EFS rate was 73%, and the OS estimate was 77%.
• Copy number aberrations were common, most frequently involving loss of 1p (25%), gain of 1q (25%), gain of chromosome 8 (25%), and gain of chromosome 2 (16%). These alterations were more commonly seen in patients with intermediate-risk or high-risk tumors, and there was a strong association between loss of chromosome 1p or gain of chromosome 1q and inferior clinical outcomes. Co-occurrence of 1q gain and 1p loss was associated with a particularly poor clinical outcome (5-year EFS and OS rates of 20%). Next-generation sequencing identified oncogenic fusions in eight of ten samples, which included BCOR and CIC rearrangements, as well as COL1A1::PDGFB, KIAA1549::BRAF, and SAMD5::SASH1 fusions.

Vascular Tumors

Vascular tumors vary from hemangiomas, which are always considered benign, to angiosarcomas, which are highly malignant.[368] Malignant vascular tumors include the following subtypes:

• Epithelioid hemangioendothelioma.
• Angiosarcoma of the soft tissue.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Putra J, Al-Ibraheemi A: Adipocytic tumors in Children: A contemporary review. Semin Diagn Pathol 36 (2): 95-104, 2019. [PubMed: 30850231]
2. Coffin CM, Alaggio R: Adipose and myxoid tumors of childhood and adolescence. Pediatr Dev Pathol 15 (1 Suppl): 239-54, 2012. [PubMed: 22420730]
3. Dehner LP, Gru AA: Nonepithelial Tumors and Tumor-like Lesions of the Skin and Subcutis in Children. Pediatr Dev Pathol 21 (2): 150-207, 2018 Mar-Apr. [PubMed: 29607758]
4. Yozu M, Symmans P, Dray M, et al.: Muir-Torre syndrome-associated pleomorphic liposarcoma arising in a previous radiation field. Virchows Arch 462 (3): 355-60, 2013. [PubMed: 23299928]
5. Palit A, Inamadar AC: Circumferential skin folds in a child: a case of Michelin tire baby syndrome. Indian J Dermatol Venereol Leprol 73 (1): 49-51, 2007 Jan-Feb. [PubMed: 17314450]
6. Goucha S, Khaled A, Zéglaoui F, et al.: Nevus lipomatosus cutaneous superficialis: Report of eight cases. Dermatol Ther (Heidelb) 1 (2): 25-30, 2011. [PMC free article: PMC3437641] [PubMed: 22984661]
7. Ferrari A, Casanova M, Collini P, et al.: Adult-type soft tissue sarcomas in pediatric-age patients: experience at the Istituto Nazionale Tumori in Milan. J Clin Oncol 23 (18): 4021-30, 2005. [PubMed: 15767645]
8. Stanelle EJ, Christison-Lagay ER, Sidebotham EL, et al.: Prognostic factors and survival in pediatric and adolescent liposarcoma. Sarcoma 2012: 870910, 2012. [PMC free article: PMC3443598] [PubMed: 22991488]
9. Alaggio R, Coffin CM, Weiss SW, et al.: Liposarcomas in young patients: a study of 82 cases occurring in patients younger than 22 years of age. Am J Surg Pathol 33 (5): 645-58, 2009. [PubMed: 19194281]
10. Baday YI, Navai SA, Hicks MJ, et al.: Pediatric liposarcoma: A case series and literature review. Pediatr Blood Cancer 68 (12): e29327, 2021. [PubMed: 34520106]
11. Fletcher CDM, Bridge JA, Hogendoorn P, et al., eds.: WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. IARC Press, 2013.
12. Sreekantaiah C, Karakousis CP, Leong SP, et al.: Cytogenetic findings in liposarcoma correlate with histopathologic subtypes. Cancer 69 (10): 2484-95, 1992. [PubMed: 1568170]
13. Kanojia D, Nagata Y, Garg M, et al.: Genomic landscape of liposarcoma. Oncotarget 6 (40): 42429-44, 2015. [PMC free article: PMC4767443] [PubMed: 26643872]
14. Powers MP, Wang WL, Hernandez VS, et al.: Detection of myxoid liposarcoma-associated FUS-DDIT3 rearrangement variants including a newly identified breakpoint using an optimized RT-PCR assay. Mod Pathol 23 (10): 1307-15, 2010. [PubMed: 20581806]
15. Han J, Murthy R, Wood B, et al.: ER stress signalling through eIF2α and CHOP, but not IRE1α, attenuates adipogenesis in mice. Diabetologia 56 (4): 911-24, 2013. [PMC free article: PMC3606029] [PubMed: 23314846]
16. Peng R, Li N, Lan T, et al.: Liposarcoma in children and young adults: a clinicopathologic and molecular study of 23 cases in one of the largest institutions of China. Virchows Arch 479 (3): 537-549, 2021. [PubMed: 33738541]
17. Barretina J, Taylor BS, Banerji S, et al.: Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet 42 (8): 715-21, 2010. [PMC free article: PMC2911503] [PubMed: 20601955]
18. Creytens D, Folpe AL, Koelsche C, et al.: Myxoid pleomorphic liposarcoma-a clinicopathologic, immunohistochemical, molecular genetic and epigenetic study of 12 cases, suggesting a possible relationship with conventional pleomorphic liposarcoma. Mod Pathol 34 (11): 2043-2049, 2021. [PubMed: 34168281]
19. Hofvander J, Jo VY, Ghanei I, et al.: Comprehensive genetic analysis of a paediatric pleomorphic myxoid liposarcoma reveals near-haploidization and loss of the RB1 gene. Histopathology 69 (1): 141-147, 2016. [PubMed: 26647907]
20. Sinclair TJ, Thorson CM, Alvarez E, et al.: Pleomorphic myxoid liposarcoma in an adolescent with Li-Fraumeni syndrome. Pediatr Surg Int 33 (5): 631-635, 2017. [PubMed: 28160093]
21. Francom CR, Leoniak SM, Lovell MA, et al.: Head and neck pleomorphic myxoid liposarcoma in a child with Li-Fraumeni syndrome. Int J Pediatr Otorhinolaryngol 123: 191-194, 2019. [PubMed: 31129458]
22. Zare SY, Leivo M, Fadare O: Recurrent Pleomorphic Myxoid Liposarcoma in a Patient With Li-Fraumeni Syndrome. Int J Surg Pathol 28 (2): 225-228, 2020. [PubMed: 31559875]
23. Sugiura H, Takahashi M, Katagiri H, et al.: Additional wide resection of malignant soft tissue tumors. Clin Orthop (394): 201-10, 2002. [PubMed: 11795735]
24. Cecchetto G, Guglielmi M, Inserra A, et al.: Primary re-excision: the Italian experience in patients with localized soft-tissue sarcomas. Pediatr Surg Int 17 (7): 532-4, 2001. [PubMed: 11666052]
25. Chui CH, Spunt SL, Liu T, et al.: Is reexcision in pediatric nonrhabdomyosarcoma soft tissue sarcoma necessary after an initial unplanned resection? J Pediatr Surg 37 (10): 1424-9, 2002. [PubMed: 12378447]
26. Bahig H, Roberge D, Bosch W, et al.: Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity. Int J Radiat Oncol Biol Phys 86 (2): 298-303, 2013. [PMC free article: PMC3646910] [PubMed: 23474110]
27. Baldini EH, Wang D, Haas RL, et al.: Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel. Int J Radiat Oncol Biol Phys 92 (3): 602-12, 2015. [PubMed: 26068493]
28. La Quaglia MP, Spiro SA, Ghavimi F, et al.: Liposarcoma in patients younger than or equal to 22 years of age. Cancer 72 (10): 3114-9, 1993. [PubMed: 8221578]
29. Lee ATJ, Thway K, Huang PH, et al.: Clinical and Molecular Spectrum of Liposarcoma. J Clin Oncol 36 (2): 151-159, 2018. [PMC free article: PMC5759315] [PubMed: 29220294]
30. Beane JD, Yang JC, White D, et al.: Efficacy of adjuvant radiation therapy in the treatment of soft tissue sarcoma of the extremity: 20-year follow-up of a randomized prospective trial. Ann Surg Oncol 21 (8): 2484-9, 2014. [PMC free article: PMC6293463] [PubMed: 24756814]
31. Ferrari A, Casanova M, Spreafico F, et al.: Childhood liposarcoma: a single-institutional twenty-year experience. Pediatr Hematol Oncol 16 (5): 415-21, 1999 Sep-Oct. [PubMed: 10505317]
32. Cecchetto G, Alaggio R, Dall'Igna P, et al.: Localized unresectable non-rhabdo soft tissue sarcomas of the extremities in pediatric age: results from the Italian studies. Cancer 104 (9): 2006-12, 2005. [PubMed: 16161038]
33. Huh WW, Yuen C, Munsell M, et al.: Liposarcoma in children and young adults: a multi-institutional experience. Pediatr Blood Cancer 57 (7): 1142-6, 2011. [PMC free article: PMC3134599] [PubMed: 21394894]
34. Gronchi A, Bui BN, Bonvalot S, et al.: Phase II clinical trial of neoadjuvant trabectedin in patients with advanced localized myxoid liposarcoma. Ann Oncol 23 (3): 771-6, 2012. [PubMed: 21642514]
35. Demetri GD, von Mehren M, Jones RL, et al.: Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. J Clin Oncol 34 (8): 786-93, 2016. [PMC free article: PMC5070559] [PubMed: 26371143]
36. Baruchel S, Pappo A, Krailo M, et al.: A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: a report from the Children's Oncology Group. Eur J Cancer 48 (4): 579-85, 2012. [PubMed: 22088484]
37. Demetri GD, Schöffski P, Grignani G, et al.: Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine. J Clin Oncol 35 (30): 3433-3439, 2017. [PubMed: 28854066]
38. Schafer ES, Rau RE, Berg S, et al.: A phase 1 study of eribulin mesylate (E7389), a novel microtubule-targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314). Pediatr Blood Cancer 65 (8): e27066, 2018. [PMC free article: PMC6019176] [PubMed: 29719113]
39. Wang L, Motoi T, Khanin R, et al.: Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data. Genes Chromosomes Cancer 51 (2): 127-39, 2012. [PMC free article: PMC3235801] [PubMed: 22034177]
40. Nyquist KB, Panagopoulos I, Thorsen J, et al.: Whole-transcriptome sequencing identifies novel IRF2BP2-CDX1 fusion gene brought about by translocation t(1;5)(q42;q32) in mesenchymal chondrosarcoma. PLoS One 7 (11): e49705, 2012. [PMC free article: PMC3504151] [PubMed: 23185413]
41. Frezza AM, Cesari M, Baumhoer D, et al.: Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study. Eur J Cancer 51 (3): 374-81, 2015. [PubMed: 25529371]
42. Schneiderman BA, Kliethermes SA, Nystrom LM: Survival in Mesenchymal Chondrosarcoma Varies Based on Age and Tumor Location: A Survival Analysis of the SEER Database. Clin Orthop Relat Res 475 (3): 799-805, 2017. [PMC free article: PMC5289165] [PubMed: 26975384]
43. Kawaguchi S, Weiss I, Lin PP, et al.: Radiation therapy is associated with fewer recurrences in mesenchymal chondrosarcoma. Clin Orthop Relat Res 472 (3): 856-64, 2014. [PMC free article: PMC3916617] [PubMed: 23709273]
44. Dantonello TM, Int-Veen C, Leuschner I, et al.: Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults: experiences of the CWS and COSS study groups. Cancer 112 (11): 2424-31, 2008. [PubMed: 18438777]
45. Bishop MW, Somerville JM, Bahrami A, et al.: Mesenchymal Chondrosarcoma in Children and Young Adults: A Single Institution Retrospective Review. Sarcoma 2015: 608279, 2015. [PMC free article: PMC4469840] [PubMed: 26146478]
46. Morioka H, Takahashi S, Araki N, et al.: Results of sub-analysis of a phase 2 study on trabectedin treatment for extraskeletal myxoid chondrosarcoma and mesenchymal chondrosarcoma. BMC Cancer 16: 479, 2016. [PMC free article: PMC4946242] [PubMed: 27418251]
47. Thampi S, Matthay KK, Boscardin WJ, et al.: Clinical Features and Outcomes Differ between Skeletal and Extraskeletal Osteosarcoma. Sarcoma 2014: 902620, 2014. [PMC free article: PMC4175789] [PubMed: 25294959]
48. Jour G, Wang L, Middha S, et al.: The molecular landscape of extraskeletal osteosarcoma: A clinicopathological and molecular biomarker study. J Pathol Clin Res 2 (1): 9-20, 2016. [PMC free article: PMC4858130] [PubMed: 27499911]
49. Sordillo PP, Hajdu SI, Magill GB, et al.: Extraosseous osteogenic sarcoma. A review of 48 patients. Cancer 51 (4): 727-34, 1983. [PubMed: 6571801]
50. Paludo J, Fritchie K, Haddox CL, et al.: Extraskeletal Osteosarcoma: Outcomes and the Role of Chemotherapy. Am J Clin Oncol 41 (9): 832-837, 2018. [PMC free article: PMC5732098] [PubMed: 28622153]
51. Longhi A, Bielack SS, Grimer R, et al.: Extraskeletal osteosarcoma: A European Musculoskeletal Oncology Society study on 266 patients. Eur J Cancer 74: 9-16, 2017. [PubMed: 28167373]
52. Nieuwenhuis MH, Casparie M, Mathus-Vliegen LM, et al.: A nation-wide study comparing sporadic and familial adenomatous polyposis-related desmoid-type fibromatoses. Int J Cancer 129 (1): 256-61, 2011. [PubMed: 20830713]
53. Rossato M, Rigotti M, Grazia M, et al.: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) and familial adenomatous polyposis (FAP). Acta Ophthalmol Scand 74 (4): 338-42, 1996. [PubMed: 8883546]
54. Baker RH, Heinemann MH, Miller HH, et al.: Hyperpigmented lesions of the retinal pigment epithelium in familial adenomatous polyposis. Am J Med Genet 31 (2): 427-35, 1988. [PubMed: 2852900]
55. Kattentidt Mouravieva AA, Geurts-Giele IR, de Krijger RR, et al.: Identification of Familial Adenomatous Polyposis carriers among children with desmoid tumours. Eur J Cancer 48 (12): 1867-74, 2012. [PubMed: 22305464]
56. Wang WL, Nero C, Pappo A, et al.: CTNNB1 genotyping and APC screening in pediatric desmoid tumors: a proposed algorithm. Pediatr Dev Pathol 15 (5): 361-7, 2012 Sep-Oct. [PubMed: 22372443]
57. Lewis JJ, Boland PJ, Leung DH, et al.: The enigma of desmoid tumors. Ann Surg 229 (6): 866-72; discussion 872-3, 1999. [PMC free article: PMC1420834] [PubMed: 10363901]
58. Lazar AJ, Tuvin D, Hajibashi S, et al.: Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol 173 (5): 1518-27, 2008. [PMC free article: PMC2570141] [PubMed: 18832571]
59. Faulkner LB, Hajdu SI, Kher U, et al.: Pediatric desmoid tumor: retrospective analysis of 63 cases. J Clin Oncol 13 (11): 2813-8, 1995. [PubMed: 7595743]
60. Gounder MM, Mahoney MR, Van Tine BA, et al.: Sorafenib for Advanced and Refractory Desmoid Tumors. N Engl J Med 379 (25): 2417-2428, 2018. [PMC free article: PMC6447029] [PubMed: 30575484]
61. Merchant NB, Lewis JJ, Woodruff JM, et al.: Extremity and trunk desmoid tumors: a multifactorial analysis of outcome. Cancer 86 (10): 2045-52, 1999. [PubMed: 10570430]
62. Honeyman JN, Theilen TM, Knowles MA, et al.: Desmoid fibromatosis in children and adolescents: a conservative approach to management. J Pediatr Surg 48 (1): 62-6, 2013. [PubMed: 23331794]
63. Bonvalot S, Ternès N, Fiore M, et al.: Spontaneous regression of primary abdominal wall desmoid tumors: more common than previously thought. Ann Surg Oncol 20 (13): 4096-102, 2013. [PubMed: 24052312]
64. Bonvalot S, Eldweny H, Haddad V, et al.: Extra-abdominal primary fibromatosis: Aggressive management could be avoided in a subgroup of patients. Eur J Surg Oncol 34 (4): 462-8, 2008. [PubMed: 17709227]
65. Merchant TE, Nguyen D, Walter AW, et al.: Long-term results with radiation therapy for pediatric desmoid tumors. Int J Radiat Oncol Biol Phys 47 (5): 1267-71, 2000. [PubMed: 10889380]
66. Zelefsky MJ, Harrison LB, Shiu MH, et al.: Combined surgical resection and iridium 192 implantation for locally advanced and recurrent desmoid tumors. Cancer 67 (2): 380-4, 1991. [PubMed: 1985733]
67. Weiss AJ, Lackman RD: Low-dose chemotherapy of desmoid tumors. Cancer 64 (6): 1192-4, 1989. [PubMed: 2766217]
68. Klein WA, Miller HH, Anderson M, et al.: The use of indomethacin, sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial polyposis. Cancer 60 (12): 2863-8, 1987. [PubMed: 2824015]
69. Soto-Miranda MA, Sandoval JA, Rao B, et al.: Surgical treatment of pediatric desmoid tumors. A 12-year, single-center experience. Ann Surg Oncol 20 (11): 3384-90, 2013. [PubMed: 23838914]
70. Desmoid Tumor Working Group: The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients. Eur J Cancer 127: 96-107, 2020. [PubMed: 32004793]
71. Penel N, Le Cesne A, Bonvalot S, et al.: Surgical versus non-surgical approach in primary desmoid-type fibromatosis patients: A nationwide prospective cohort from the French Sarcoma Group. Eur J Cancer 83: 125-131, 2017. [PubMed: 28735069]
72. Orbach D, Brennan B, Bisogno G, et al.: The EpSSG NRSTS 2005 treatment protocol for desmoid-type fibromatosis in children: an international prospective case series. Lancet Child Adolesc Health 1 (4): 284-292, 2017. [PubMed: 30169184]
73. Gladdy RA, Gupta AA: If Active Surveillance is the Standard of Care for Desmoid Patients, When Should Intervention be Considered? Ann Surg Oncol 26 (13): 4185-4187, 2019. [PubMed: 31552615]
74. Skapek SX, Ferguson WS, Granowetter L, et al.: Vinblastine and methotrexate for desmoid fibromatosis in children: results of a Pediatric Oncology Group Phase II Trial. J Clin Oncol 25 (5): 501-6, 2007. [PubMed: 17290057]
75. Gega M, Yanagi H, Yoshikawa R, et al.: Successful chemotherapeutic modality of doxorubicin plus dacarbazine for the treatment of desmoid tumors in association with familial adenomatous polyposis. J Clin Oncol 24 (1): 102-5, 2006. [PubMed: 16382119]
76. Constantinidou A, Jones RL, Scurr M, et al.: Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis. Eur J Cancer 45 (17): 2930-4, 2009. [PubMed: 19767198]
77. Ananth P, Werger A, Voss S, et al.: Liposomal doxorubicin: Effective treatment for pediatric desmoid fibromatosis. Pediatr Blood Cancer 64 (7): , 2017. [PubMed: 27905688]
78. Ferrari A, Orbach D, Affinita MC, et al.: Evidence of hydroxyurea activity in children with pretreated desmoid-type fibromatosis: A new option in the armamentarium of systemic therapies. Pediatr Blood Cancer 66 (1): e27472, 2019. [PubMed: 30270493]
79. Agresta L, Kim H, Turpin BK, et al.: Pazopanib therapy for desmoid tumors in adolescent and young adult patients. Pediatr Blood Cancer 65 (6): e26968, 2018. [PubMed: 29384266]
80. Toulmonde M, Pulido M, Ray-Coquard I, et al.: Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study. Lancet Oncol 20 (9): 1263-1272, 2019. [PubMed: 31331699]
81. Shang H, Braggio D, Lee YJ, et al.: Targeting the Notch pathway: A potential therapeutic approach for desmoid tumors. Cancer 121 (22): 4088-96, 2015. [PMC free article: PMC4635059] [PubMed: 26349011]
82. Kummar S, O'Sullivan Coyne G, Do KT, et al.: Clinical Activity of the γ-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors (Aggressive Fibromatosis). J Clin Oncol 35 (14): 1561-1569, 2017. [PMC free article: PMC5455706] [PubMed: 28350521]
83. Takahashi T, Prensner JR, Robson CD, et al.: Safety and efficacy of gamma-secretase inhibitor nirogacestat (PF-03084014) in desmoid tumor: Report of four pediatric/young adult cases. Pediatr Blood Cancer 67 (10): e28636, 2020. [PubMed: 32762028]
84. Meazza C, Bisogno G, Gronchi A, et al.: Aggressive fibromatosis in children and adolescents: the Italian experience. Cancer 116 (1): 233-40, 2010. [PubMed: 19950127]
85. Hansmann A, Adolph C, Vogel T, et al.: High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors. Cancer 100 (3): 612-20, 2004. [PubMed: 14745880]
86. Skapek SX, Anderson JR, Hill DA, et al.: Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: results of a Children's Oncology Group (COG) phase II study. Pediatr Blood Cancer 60 (7): 1108-12, 2013. [PMC free article: PMC4646066] [PubMed: 23281268]
87. Rutenberg MS, Indelicato DJ, Knapik JA, et al.: External-beam radiotherapy for pediatric and young adult desmoid tumors. Pediatr Blood Cancer 57 (3): 435-42, 2011. [PubMed: 21744472]
88. Buckley PG, Mantripragada KK, Benetkiewicz M, et al.: A full-coverage, high-resolution human chromosome 22 genomic microarray for clinical and research applications. Hum Mol Genet 11 (25): 3221-9, 2002. [PubMed: 12444106]
89. Valdivielso-Ramos M, Torrelo A, Campos M, et al.: Pediatric dermatofibrosarcoma protuberans in Madrid, Spain: multi-institutional outcomes. Pediatr Dermatol 31 (6): 676-82, 2014 Nov-Dec. [PubMed: 25424208]
90. Gooskens SL, Oranje AP, van Adrichem LN, et al.: Imatinib mesylate for children with dermatofibrosarcoma protuberans (DFSP). Pediatr Blood Cancer 55 (2): 369-73, 2010. [PubMed: 20582941]
91. Rubio GA, Alvarado A, Gerth DJ, et al.: Incidence and Outcomes of Dermatofibrosarcoma Protuberans in the US Pediatric Population. J Craniofac Surg 28 (1): 182-184, 2017. [PubMed: 27922973]
92. Meguerditchian AN, Wang J, Lema B, et al.: Wide excision or Mohs micrographic surgery for the treatment of primary dermatofibrosarcoma protuberans. Am J Clin Oncol 33 (3): 300-3, 2010. [PubMed: 19858696]
93. Brennan B, Zanetti I, De Salvo GL, et al.: Dermatofibrosarcoma protuberans in children and adolescents: The European Paediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005). Pediatr Blood Cancer 67 (10): e28351, 2020. [PubMed: 32558231]
94. Dagan R, Morris CG, Zlotecki RA, et al.: Radiotherapy in the treatment of dermatofibrosarcoma protuberans. Am J Clin Oncol 28 (6): 537-9, 2005. [PubMed: 16317260]
95. Sun LM, Wang CJ, Huang CC, et al.: Dermatofibrosarcoma protuberans: treatment results of 35 cases. Radiother Oncol 57 (2): 175-81, 2000. [PubMed: 11054521]
96. Price VE, Fletcher JA, Zielenska M, et al.: Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans. Pediatr Blood Cancer 44 (5): 511-5, 2005. [PubMed: 15503291]
97. McArthur GA, Demetri GD, van Oosterom A, et al.: Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225. J Clin Oncol 23 (4): 866-73, 2005. [PubMed: 15681532]
98. Rutkowski P, Van Glabbeke M, Rankin CJ, et al.: Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol 28 (10): 1772-9, 2010. [PMC free article: PMC3040044] [PubMed: 20194851]
99. Navarrete-Dechent C, Mori S, Barker CA, et al.: Imatinib Treatment for Locally Advanced or Metastatic Dermatofibrosarcoma Protuberans: A Systematic Review. JAMA Dermatol 155 (3): 361-369, 2019. [PMC free article: PMC8909640] [PubMed: 30601909]
100. Miller SJ, Alam M, Andersen JS, et al.: Dermatofibrosarcoma protuberans. J Natl Compr Canc Netw 10 (3): 312-8, 2012. [PubMed: 22393193]
101. Kovach SJ, Fischer AC, Katzman PJ, et al.: Inflammatory myofibroblastic tumors. J Surg Oncol 94 (5): 385-91, 2006. [PubMed: 16967468]
102. Brodlie M, Barwick SC, Wood KM, et al.: Inflammatory myofibroblastic tumours of the respiratory tract: paediatric case series with varying clinical presentations. J Laryngol Otol 125 (8): 865-8, 2011. [PubMed: 21481297]
103. Xiao Y, Zhou S, Ma C, et al.: Radiological and histopathological features of hepatic inflammatory myofibroblastic tumour: analysis of 10 cases. Clin Radiol 68 (11): 1114-20, 2013. [PubMed: 23876410]
104. Karnak I, Senocak ME, Ciftci AO, et al.: Inflammatory myofibroblastic tumor in children: diagnosis and treatment. J Pediatr Surg 36 (6): 908-12, 2001. [PubMed: 11381424]
105. Collin M, Charles A, Barker A, et al.: Inflammatory myofibroblastic tumour of the bladder in children: a review. J Pediatr Urol 11 (5): 239-45, 2015. [PubMed: 25982020]
106. Mariño-Enríquez A, Wang WL, Roy A, et al.: Epithelioid inflammatory myofibroblastic sarcoma: An aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. Am J Surg Pathol 35 (1): 135-44, 2011. [PubMed: 21164297]
107. Lee JC, Li CF, Huang HY, et al.: ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1-ALK fusions in epithelioid inflammatory myofibroblastic sarcoma. J Pathol 241 (3): 316-323, 2017. [PMC free article: PMC5337428] [PubMed: 27874193]
108. Trahair T, Gifford AJ, Fordham A, et al.: Crizotinib and Surgery for Long-Term Disease Control in Children and Adolescents With ALK-Positive Inflammatory Myofibroblastic Tumors. JCO Precis Oncol 3: , 2019. [PMC free article: PMC7446396] [PubMed: 32914017]
109. Coffin CM, Hornick JL, Fletcher CD: Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 31 (4): 509-20, 2007. [PubMed: 17414097]
110. Lovly CM, Gupta A, Lipson D, et al.: Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions. Cancer Discov 4 (8): 889-95, 2014. [PMC free article: PMC4125481] [PubMed: 24875859]
111. Casanova M, Brennan B, Alaggio R, et al.: Inflammatory myofibroblastic tumor: The experience of the European pediatric Soft Tissue Sarcoma Study Group (EpSSG). Eur J Cancer 127: 123-129, 2020. [PubMed: 32007712]
112. Yu L, Liu J, Lao IW, et al.: Epithelioid inflammatory myofibroblastic sarcoma: a clinicopathological, immunohistochemical and molecular cytogenetic analysis of five additional cases and review of the literature. Diagn Pathol 11 (1): 67, 2016. [PMC free article: PMC4962498] [PubMed: 27460384]
113. Devaney KO, Lafeir DJ, Triantafyllou A, et al.: Inflammatory myofibroblastic tumors of the head and neck: evaluation of clinicopathologic and prognostic features. Eur Arch Otorhinolaryngol 269 (12): 2461-5, 2012. [PubMed: 22588194]
114. Mehta B, Mascarenhas L, Zhou S, et al.: Inflammatory myofibroblastic tumors in childhood. Pediatr Hematol Oncol 30 (7): 640-5, 2013. [PubMed: 23988029]
115. Kube S, Vokuhl C, Dantonello T, et al.: Inflammatory myofibroblastic tumors-A retrospective analysis of the Cooperative Weichteilsarkom Studiengruppe. Pediatr Blood Cancer 65 (6): e27012, 2018. [PubMed: 29480552]
116. Favini F, Resti AG, Collini P, et al.: Inflammatory myofibroblastic tumor of the conjunctiva: response to chemotherapy with low-dose methotrexate and vinorelbine. Pediatr Blood Cancer 54 (3): 483-5, 2010. [PubMed: 19890966]
117. Doski JJ, Priebe CJ, Driessnack M, et al.: Corticosteroids in the management of unresected plasma cell granuloma (inflammatory pseudotumor) of the lung. J Pediatr Surg 26 (9): 1064-6, 1991. [PubMed: 1941485]
118. Diop B, Konate I, Ka S, et al.: Mesenteric myofibroblastic tumor: NSAID therapy after incomplete resection. J Visc Surg 148 (4): e311-4, 2011. [PubMed: 21872549]
119. Dalton BG, Thomas PG, Sharp NE, et al.: Inflammatory myofibroblastic tumors in children. J Pediatr Surg 51 (4): 541-4, 2016. [PubMed: 26732283]
120. Butrynski JE, D'Adamo DR, Hornick JL, et al.: Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med 363 (18): 1727-33, 2010. [PMC free article: PMC3014292] [PubMed: 20979472]
121. Mossé YP, Lim MS, Voss SD, et al.: Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol 14 (6): 472-80, 2013. [PMC free article: PMC3730818] [PubMed: 23598171]
122. Gaudichon J, Jeanne-Pasquier C, Deparis M, et al.: Complete and Repeated Response of a Metastatic ALK-rearranged Inflammatory Myofibroblastic Tumor to Crizotinib in a Teenage Girl. J Pediatr Hematol Oncol 38 (4): 308-11, 2016. [PubMed: 26808369]
123. Mossé YP, Voss SD, Lim MS, et al.: Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children's Oncology Group Study. J Clin Oncol 35 (28): 3215-3221, 2017. [PMC free article: PMC5617123] [PubMed: 28787259]
124. Nishio M, Murakami H, Horiike A, et al.: Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors. J Thorac Oncol 10 (7): 1058-66, 2015. [PMC free article: PMC4467585] [PubMed: 26020125]
125. Brivio E, Zwaan CM: ALK inhibition in two emblematic cases of pediatric inflammatory myofibroblastic tumor: Efficacy and side effects. Pediatr Blood Cancer 66 (5): e27645, 2019. [PubMed: 30697903]
126. Fischer M, Moreno L, Ziegler DS, et al.: Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Lancet Oncol 22 (12): 1764-1776, 2021. [PubMed: 34780709]
127. Sulkowski JP, Raval MV, Browne M: Margin status and multimodal therapy in infantile fibrosarcoma. Pediatr Surg Int 29 (8): 771-6, 2013. [PubMed: 23765394]
128. Hirschfeld R, Welch JJG, Harrison DJ, et al.: Two cases of humoral hypercalcemia of malignancy complicating infantile fibrosarcoma. Pediatr Blood Cancer 64 (10): , 2017. [PubMed: 28371408]
129. Kao YC, Fletcher CDM, Alaggio R, et al.: Recurrent BRAF Gene Fusions in a Subset of Pediatric Spindle Cell Sarcomas: Expanding the Genetic Spectrum of Tumors With Overlapping Features With Infantile Fibrosarcoma. Am J Surg Pathol 42 (1): 28-38, 2018. [PMC free article: PMC5730460] [PubMed: 28877062]
130. Wegert J, Vokuhl C, Collord G, et al.: Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants. Nat Commun 9 (1): 2378, 2018. [PMC free article: PMC6006309] [PubMed: 29915264]
131. Tan SY, Al-Ibraheemi A, Ahrens WA, et al.: ALK rearrangements in infantile fibrosarcoma-like spindle cell tumours of soft tissue and kidney. Histopathology 80 (4): 698-707, 2022. [PubMed: 34843129]
132. Orbach D, Rey A, Cecchetto G, et al.: Infantile fibrosarcoma: management based on the European experience. J Clin Oncol 28 (2): 318-23, 2010. [PubMed: 19917847]
133. Orbach D, Brennan B, De Paoli A, et al.: Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience. Eur J Cancer 57: 1-9, 2016. [PubMed: 26849118]
134. Hawkins DS, Black JO, Orbach D, et al.: Nonrhabdomyosarcoma soft-tissue sarcomas. In: Blaney SM, Helman LJ, Adamson PC, eds.: Pizzo and Poplack's Pediatric Oncology. 8th ed. Wolters Kluwer, 2020, pp 721-46.
135. Loh ML, Ahn P, Perez-Atayde AR, et al.: Treatment of infantile fibrosarcoma with chemotherapy and surgery: results from the Dana-Farber Cancer Institute and Children's Hospital, Boston. J Pediatr Hematol Oncol 24 (9): 722-6, 2002. [PubMed: 12468912]
136. Akyüz C, Küpeli S, Varan A, et al.: Infantile fibrosarcoma: retrospective analysis of eleven patients. Tumori 97 (2): 166-9, 2011 Mar-Apr. [PubMed: 21617710]
137. Gallego S, Pericas N, Barber I, et al.: Infantile fibrosarcoma of the retroperitoneum: a site of unfavorable prognosis? Pediatr Hematol Oncol 28 (5): 451-3, 2011. [PubMed: 21345076]
138. Parida L, Fernandez-Pineda I, Uffman JK, et al.: Clinical management of infantile fibrosarcoma: a retrospective single-institution review. Pediatr Surg Int 29 (7): 703-8, 2013. [PMC free article: PMC4825685] [PubMed: 23708972]
139. Mody RJ, Wu YM, Lonigro RJ, et al.: Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth. JAMA 314 (9): 913-25, 2015. [PMC free article: PMC4758114] [PubMed: 26325560]
140. Wong V, Pavlick D, Brennan T, et al.: Evaluation of a Congenital Infantile Fibrosarcoma by Comprehensive Genomic Profiling Reveals an LMNA-NTRK1 Gene Fusion Responsive to Crizotinib. J Natl Cancer Inst 108 (1): , 2016. [PubMed: 26563356]
141. Laetsch TW, DuBois SG, Mascarenhas L, et al.: Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol 19 (5): 705-714, 2018. [PMC free article: PMC5949072] [PubMed: 29606586]
142. Kummar S, Lassen UN: TRK Inhibition: A New Tumor-Agnostic Treatment Strategy. Target Oncol 13 (5): 545-556, 2018. [PubMed: 30276762]
143. Drilon A, Laetsch TW, Kummar S, et al.: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378 (8): 731-739, 2018. [PMC free article: PMC5857389] [PubMed: 29466156]
144. DuBois SG, Laetsch TW, Federman N, et al.: The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer 124 (21): 4241-4247, 2018. [PMC free article: PMC6263791] [PubMed: 30204247]
145. Hong DS, DuBois SG, Kummar S, et al.: Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 21 (4): 531-540, 2020. [PMC free article: PMC7497841] [PubMed: 32105622]
146. Drilon A, Nagasubramanian R, Blake JF, et al.: A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov 7 (9): 963-972, 2017. [PMC free article: PMC5581710] [PubMed: 28578312]
147. Yanagisawa R, Noguchi M, Fujita K, et al.: Preoperative Treatment With Pazopanib in a Case of Chemotherapy-Resistant Infantile Fibrosarcoma. Pediatr Blood Cancer 63 (2): 348-51, 2016. [PubMed: 26375879]
148. Madden NP, Spicer RD, Allibone EB, et al.: Spontaneous regression of neonatal fibrosarcoma. Br J Cancer Suppl 18: S72-5, 1992. [PMC free article: PMC2149666] [PubMed: 1503930]
149. Evans HL: Low-grade fibromyxoid sarcoma: a clinicopathologic study of 33 cases with long-term follow-up. Am J Surg Pathol 35 (10): 1450-62, 2011. [PubMed: 21921785]
150. Guillou L, Benhattar J, Gengler C, et al.: Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. Am J Surg Pathol 31 (9): 1387-402, 2007. [PubMed: 17721195]
151. Scheer M, Vokuhl C, Veit-Friedrich I, et al.: Low-grade fibromyxoid sarcoma: A report of the Cooperative Weichteilsarkom Studiengruppe (CWS). Pediatr Blood Cancer 67 (2): e28009, 2020. [PubMed: 31736251]
152. Mohamed M, Fisher C, Thway K: Low-grade fibromyxoid sarcoma: Clinical, morphologic and genetic features. Ann Diagn Pathol 28: 60-67, 2017. [PubMed: 28648941]
153. O'Sullivan MJ, Sirgi KE, Dehner LP: Low-grade fibrosarcoma (hyalinizing spindle cell tumor with giant rosettes) with pulmonary metastases at presentation: case report and review of the literature. Int J Surg Pathol 10 (3): 211-6, 2002. [PubMed: 12232578]
154. Folpe AL, Lane KL, Paull G, et al.: Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes: a clinicopathologic study of 73 cases supporting their identity and assessing the impact of high-grade areas. Am J Surg Pathol 24 (10): 1353-60, 2000. [PubMed: 11023096]
155. Sargar K, Kao SC, Spunt SL, et al.: MRI and CT of Low-Grade Fibromyxoid Sarcoma in Children: A Report From Children's Oncology Group Study ARST0332. AJR Am J Roentgenol 205 (2): 414-20, 2015. [PMC free article: PMC4570741] [PubMed: 26204295]
156. Maretty-Nielsen K, Baerentzen S, Keller J, et al.: Low-Grade Fibromyxoid Sarcoma: Incidence, Treatment Strategy of Metastases, and Clinical Significance of the FUS Gene. Sarcoma 2013: 256280, 2013. [PMC free article: PMC3683502] [PubMed: 23818812]
157. Prieto-Granada C, Zhang L, Chen HW, et al.: A genetic dichotomy between pure sclerosing epithelioid fibrosarcoma (SEF) and hybrid SEF/low-grade fibromyxoid sarcoma: a pathologic and molecular study of 18 cases. Genes Chromosomes Cancer 54 (1): 28-38, 2015. [PMC free article: PMC4232448] [PubMed: 25231134]
158. Chew W, Benson C, Thway K, et al.: Clinical Characteristics and efficacy of chemotherapy in sclerosing epithelioid fibrosarcoma. Med Oncol 35 (11): 138, 2018. [PMC free article: PMC6132781] [PubMed: 30187231]
159. Arbajian E, Puls F, Antonescu CR, et al.: In-depth Genetic Analysis of Sclerosing Epithelioid Fibrosarcoma Reveals Recurrent Genomic Alterations and Potential Treatment Targets. Clin Cancer Res 23 (23): 7426-7434, 2017. [PubMed: 28939748]
160. Arbajian E, Puls F, Magnusson L, et al.: Recurrent EWSR1-CREB3L1 gene fusions in sclerosing epithelioid fibrosarcoma. Am J Surg Pathol 38 (6): 801-8, 2014. [PubMed: 24441665]
161. Dewaele B, Libbrecht L, Levy G, et al.: A novel EWS-CREB3L3 gene fusion in a mesenteric sclerosing epithelioid fibrosarcoma. Genes Chromosomes Cancer 56 (9): 695-699, 2017. [PubMed: 28569045]
162. Porteus C, Gan Q, Gong Y, et al.: Sclerosing epithelioid fibrosarcoma: cytologic characterization with histologic, immunohistologic, molecular, and clinical correlation of 8 cases. J Am Soc Cytopathol 9 (6): 513-519, 2020 Nov - Dec. [PubMed: 32624384]
163. Puls F, Agaimy A, Flucke U, et al.: Recurrent Fusions Between YAP1 and KMT2A in Morphologically Distinct Neoplasms Within the Spectrum of Low-grade Fibromyxoid Sarcoma and Sclerosing Epithelioid Fibrosarcoma. Am J Surg Pathol 44 (5): 594-606, 2020. [PubMed: 31913156]
164. Warmke LM, Meis JM: Sclerosing Epithelioid Fibrosarcoma: A Distinct Sarcoma With Aggressive Features. Am J Surg Pathol 45 (3): 317-328, 2021. [PubMed: 32769431]
165. Pollock BH, Jenson HB, Leach CT, et al.: Risk factors for pediatric human immunodeficiency virus-related malignancy. JAMA 289 (18): 2393-9, 2003. [PubMed: 12746363]
166. Kleinerman RA, Tucker MA, Abramson DH, et al.: Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma. J Natl Cancer Inst 99 (1): 24-31, 2007. [PubMed: 17202110]
167. Samuels BL, Chawla S, Patel S, et al.: Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol 24 (6): 1703-9, 2013. [PubMed: 23385197]
168. Enzinger FM, Zhang RY: Plexiform fibrohistiocytic tumor presenting in children and young adults. An analysis of 65 cases. Am J Surg Pathol 12 (11): 818-26, 1988. [PubMed: 2847569]
169. Black J, Coffin CM, Dehner LP: Fibrohistiocytic tumors and related neoplasms in children and adolescents. Pediatr Dev Pathol 15 (1 Suppl): 181-210, 2012. [PubMed: 22420728]
170. Moosavi C, Jha P, Fanburg-Smith JC: An update on plexiform fibrohistiocytic tumor and addition of 66 new cases from the Armed Forces Institute of Pathology, in honor of Franz M. Enzinger, MD. Ann Diagn Pathol 11 (5): 313-9, 2007. [PubMed: 17870015]
171. Billings SD, Folpe AL: Cutaneous and subcutaneous fibrohistiocytic tumors of intermediate malignancy: an update. Am J Dermatopathol 26 (2): 141-55, 2004. [PubMed: 15024197]
172. Remstein ED, Arndt CA, Nascimento AG: Plexiform fibrohistiocytic tumor: clinicopathologic analysis of 22 cases. Am J Surg Pathol 23 (6): 662-70, 1999. [PubMed: 10366148]
173. Salomao DR, Nascimento AG: Plexiform fibrohistiocytic tumor with systemic metastases: a case report. Am J Surg Pathol 21 (4): 469-76, 1997. [PubMed: 9130995]
174. Redlich GC, Montgomery KD, Allgood GA, et al.: Plexiform fibrohistiocytic tumor with a clonal cytogenetic anomaly. Cancer Genet Cytogenet 108 (2): 141-3, 1999. [PubMed: 9973942]
175. Luzar B, Calonje E: Cutaneous fibrohistiocytic tumours - an update. Histopathology 56 (1): 148-65, 2010. [PubMed: 20055912]
176. Carli M, Ferrari A, Mattke A, et al.: Pediatric malignant peripheral nerve sheath tumor: the Italian and German soft tissue sarcoma cooperative group. J Clin Oncol 23 (33): 8422-30, 2005. [PubMed: 16293873]
177. Malbari F, Spira M, B Knight P, et al.: Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis: Impact of Family History. J Pediatr Hematol Oncol 40 (6): e359-e363, 2018. [PubMed: 29683959]
178. Agresta L, Salloum R, Hummel TR, et al.: Malignant peripheral nerve sheath tumor: Transformation in a patient with neurofibromatosis type 2. Pediatr Blood Cancer 66 (2): e27520, 2019. [PubMed: 30408304]
179. Zhang M, Wang Y, Jones S, et al.: Somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors. Nat Genet 46 (11): 1170-2, 2014. [PMC free article: PMC4383254] [PubMed: 25305755]
180. Röhrich M, Koelsche C, Schrimpf D, et al.: Methylation-based classification of benign and malignant peripheral nerve sheath tumors. Acta Neuropathol 131 (6): 877-87, 2016. [PubMed: 26857854]
181. Kaplan HG, Rostad S, Ross JS, et al.: Genomic Profiling in Patients With Malignant Peripheral Nerve Sheath Tumors Reveals Multiple Pathways With Targetable Mutations. J Natl Compr Canc Netw 16 (8): 967-974, 2018. [PubMed: 30099373]
182. Hagel C, Zils U, Peiper M, et al.: Histopathology and clinical outcome of NF1-associated vs. sporadic malignant peripheral nerve sheath tumors. J Neurooncol 82 (2): 187-92, 2007. [PubMed: 17111191]
183. Zou C, Smith KD, Liu J, et al.: Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. Ann Surg 249 (6): 1014-22, 2009. [PubMed: 19474676]
184. Okada K, Hasegawa T, Tajino T, et al.: Clinical relevance of pathological grades of malignant peripheral nerve sheath tumor: a multi-institution TMTS study of 56 cases in Northern Japan. Ann Surg Oncol 14 (2): 597-604, 2007. [PubMed: 17103076]
185. Amirian ES, Goodman JC, New P, et al.: Pediatric and adult malignant peripheral nerve sheath tumors: an analysis of data from the surveillance, epidemiology, and end results program. J Neurooncol 116 (3): 609-16, 2014. [PubMed: 24390465]
186. Valentin T, Le Cesne A, Ray-Coquard I, et al.: Management and prognosis of malignant peripheral nerve sheath tumors: The experience of the French Sarcoma Group (GSF-GETO). Eur J Cancer 56: 77-84, 2016. [PubMed: 26824706]
187. Høland M, Kolberg M, Danielsen SA, et al.: Inferior survival for patients with malignant peripheral nerve sheath tumors defined by aberrant TP53. Mod Pathol 31 (11): 1694-1707, 2018. [PubMed: 29946184]
188. Krawczyk MA, Karpinsky G, Izycka-Swieszewska E, et al.: Immunohistochemical assessment of cyclin D1 and p53 is associated with survival in childhood malignant peripheral nerve sheath tumor. Cancer Biomark 24 (3): 351-361, 2019. [PubMed: 30883338]
189. Martin E, Coert JH, Flucke UE, et al.: Neurofibromatosis-associated malignant peripheral nerve sheath tumors in children have a worse prognosis: A nationwide cohort study. Pediatr Blood Cancer 67 (4): e28138, 2020. [PubMed: 31889416]
190. Bergamaschi L, Bisogno G, Manzitti C, et al.: Salvage rates and prognostic factors after relapse in children and adolescents with malignant peripheral nerve sheath tumors. Pediatr Blood Cancer 65 (2): , 2018. [PubMed: 28926683]
191. Meister MT, Scheer M, Hallmen E, et al.: Malignant peripheral nerve sheath tumors in children, adolescents, and young adults: Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry. J Surg Oncol 122 (7): 1337-1347, 2020. [PubMed: 32812260]
192. Ferrari A, Bisogno G, Macaluso A, et al.: Soft-tissue sarcomas in children and adolescents with neurofibromatosis type 1. Cancer 109 (7): 1406-12, 2007. [PubMed: 17330850]
193. van Noesel MM, Orbach D, Brennan B, et al.: Outcome and prognostic factors in pediatric malignant peripheral nerve sheath tumors: An analysis of the European Pediatric Soft Tissue Sarcoma Group (EpSSG) NRSTS-2005 prospective study. Pediatr Blood Cancer 66 (10): e27833, 2019. [PubMed: 31241238]
194. Higham CS, Steinberg SM, Dombi E, et al.: SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors. Sarcoma 2017: 8685638, 2017. [PMC free article: PMC5613633] [PubMed: 29138631]
195. Al-Ezzi E, Gounder M, Watson G, et al.: Selinexor, a First in Class, Nuclear Export Inhibitor for the Treatment of Advanced Malignant Peripheral Nerve Sheath Tumor. Oncologist 26 (4): e710-e714, 2021. [PMC free article: PMC8018316] [PubMed: 33512749]
196. Okur FV, Oguz A, Karadeniz C, et al.: Malignant triton tumor of the pelvis in a 2-year-old boy. J Pediatr Hematol Oncol 28 (3): 173-6, 2006. [PubMed: 16679944]
197. Griffin BB, Chou PM, George D, et al.: Malignant Ectomesenchymoma: Series Analysis of a Histologically and Genetically Heterogeneous Tumor. Int J Surg Pathol 26 (3): 200-212, 2018. [PubMed: 28994342]
198. Huang SC, Alaggio R, Sung YS, et al.: Frequent HRAS Mutations in Malignant Ectomesenchymoma: Overlapping Genetic Abnormalities With Embryonal Rhabdomyosarcoma. Am J Surg Pathol 40 (7): 876-85, 2016. [PMC free article: PMC4905780] [PubMed: 26872011]
199. Dantonello TM, Leuschner I, Vokuhl C, et al.: Malignant ectomesenchymoma in children and adolescents: report from the Cooperative Weichteilsarkom Studiengruppe (CWS). Pediatr Blood Cancer 60 (2): 224-9, 2013. [PubMed: 22535600]
200. Rodriguez-Galindo C, Ramsey K, Jenkins JJ, et al.: Hemangiopericytoma in children and infants. Cancer 88 (1): 198-204, 2000. [PubMed: 10618624]
201. Ferrari A, Casanova M, Bisogno G, et al.: Hemangiopericytoma in pediatric ages: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 92 (10): 2692-8, 2001. [PubMed: 11745205]
202. Bien E, Stachowicz-Stencel T, Godzinski J, et al.: Retrospective multi-institutional study on hemangiopericytoma in Polish children. Pediatr Int 51 (1): 19-24, 2009. [PubMed: 19371273]
203. Weiss SW, Goldblum JR: Enzinger and Weiss's Soft Tissue Tumors. 5th ed. Mosby, 2008.
204. Fernandez-Pineda I, Parida L, Jenkins JJ, et al.: Childhood hemangiopericytoma: review of St Jude Children's Research Hospital. J Pediatr Hematol Oncol 33 (5): 356-9, 2011. [PubMed: 21602721]
205. Haller F, Knopf J, Ackermann A, et al.: Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern. J Pathol 238 (5): 700-10, 2016. [PubMed: 26863915]
206. Doebele RC, Davis LE, Vaishnavi A, et al.: An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov 5 (10): 1049-57, 2015. [PMC free article: PMC4635026] [PubMed: 26216294]
207. Wiswell TE, Davis J, Cunningham BE, et al.: Infantile myofibromatosis: the most common fibrous tumor of infancy. J Pediatr Surg 23 (4): 315-8, 1988. [PubMed: 3385581]
208. Chung EB, Enzinger FM: Infantile myofibromatosis. Cancer 48 (8): 1807-18, 1981. [PubMed: 7284977]
209. Modi N: Congenital generalised fibromatosis. Arch Dis Child 57 (11): 881-2, 1982. [PMC free article: PMC1628023] [PubMed: 7149764]
210. Levine E, Fréneaux P, Schleiermacher G, et al.: Risk-adapted therapy for infantile myofibromatosis in children. Pediatr Blood Cancer 59 (1): 115-20, 2012. [PubMed: 22038698]
211. Larralde M, Hoffner MV, Boggio P, et al.: Infantile myofibromatosis: report of nine patients. Pediatr Dermatol 27 (1): 29-33, 2010 Jan-Feb. [PubMed: 20199406]
212. Cheung YH, Gayden T, Campeau PM, et al.: A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am J Hum Genet 92 (6): 996-1000, 2013. [PMC free article: PMC3675240] [PubMed: 23731537]
213. Martignetti JA, Tian L, Li D, et al.: Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am J Hum Genet 92 (6): 1001-7, 2013. [PMC free article: PMC3675260] [PubMed: 23731542]
214. Murray N, Hanna B, Graf N, et al.: The spectrum of infantile myofibromatosis includes both non-penetrance and adult recurrence. Eur J Med Genet 60 (7): 353-358, 2017. [PubMed: 28286173]
215. Dachy G, de Krijger RR, Fraitag S, et al.: Association of PDGFRB Mutations With Pediatric Myofibroma and Myofibromatosis. JAMA Dermatol 155 (8): 946-950, 2019. [PMC free article: PMC6487901] [PubMed: 31017643]
216. Hettmer S, Dachy G, Seitz G, et al.: Genetic testing and surveillance in infantile myofibromatosis: a report from the SIOPE Host Genome Working Group. Fam Cancer 20 (4): 327-336, 2021. [PMC free article: PMC8484085] [PubMed: 32888134]
217. Agaimy A, Bieg M, Michal M, et al.: Recurrent Somatic PDGFRB Mutations in Sporadic Infantile/Solitary Adult Myofibromas But Not in Angioleiomyomas and Myopericytomas. Am J Surg Pathol 41 (2): 195-203, 2017. [PubMed: 27776010]
218. Arts FA, Sciot R, Brichard B, et al.: PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis. Hum Mol Genet 26 (10): 1801-1810, 2017. [PubMed: 28334876]
219. Gopal M, Chahal G, Al-Rifai Z, et al.: Infantile myofibromatosis. Pediatr Surg Int 24 (3): 287-91, 2008. [PubMed: 18074145]
220. Weaver MS, Navid F, Huppmann A, et al.: Vincristine and Dactinomycin in Infantile Myofibromatosis With a Review of Treatment Options. J Pediatr Hematol Oncol 37 (3): 237-41, 2015. [PubMed: 25389917]
221. Weller JM, Keil VC, Gielen GH, et al.: PDGRFB mutation-associated myofibromatosis: Response to targeted therapy with imatinib. Am J Med Genet A 179 (9): 1895-1897, 2019. [PubMed: 31291054]
222. Wenger TL, Bly RA, Wu N, et al.: Activating variants in PDGFRB result in a spectrum of disorders responsive to imatinib monotherapy. Am J Med Genet A 182 (7): 1576-1591, 2020. [PubMed: 32500973]
223. Mudry P, Slaby O, Neradil J, et al.: Case report: rapid and durable response to PDGFR targeted therapy in a child with refractory multiple infantile myofibromatosis and a heterozygous germline mutation of the PDGFRB gene. BMC Cancer 17 (1): 119, 2017. [PMC free article: PMC5301362] [PubMed: 28183292]
224. Pond D, Arts FA, Mendelsohn NJ, et al.: A patient with germ-line gain-of-function PDGFRB p.N666H mutation and marked clinical response to imatinib. Genet Med 20 (1): 142-150, 2018. [PubMed: 28726812]
225. Wilkes D, Charitakis K, Basson CT: Inherited disposition to cardiac myxoma development. Nat Rev Cancer 6 (2): 157-65, 2006. [PubMed: 16491075]
226. Carney JA, Young WF: Primary pigmented nodular adrenocortical disease and its associated conditions. Endocrinologist 2: 6-21, 1992.
227. Ryan MW, Cunningham S, Xiao SY: Maxillary sinus melanoma as the presenting feature of Carney complex. Int J Pediatr Otorhinolaryngol 72 (3): 405-8, 2008. [PubMed: 18082273]
228. Sultan I, Rodriguez-Galindo C, Saab R, et al.: Comparing children and adults with synovial sarcoma in the Surveillance, Epidemiology, and End Results program, 1983 to 2005: an analysis of 1268 patients. Cancer 115 (15): 3537-47, 2009. [PubMed: 19514087]
229. Spunt SL, Million L, Chi YY, et al.: A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol 21 (1): 145-161, 2020. [PMC free article: PMC6946838] [PubMed: 31786124]
230. Wang JG, Li NN: Primary cardiac synovial sarcoma. Ann Thorac Surg 95 (6): 2202-9, 2013. [PubMed: 23647858]
231. Chirmade PC, Parikh S, Anand A, et al.: Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation. Adv Respir Med 85 (4): 206-210, 2017. [PubMed: 28871588]
232. Frazier AA, Franks TJ, Pugatch RD, et al.: From the archives of the AFIP: Pleuropulmonary synovial sarcoma. Radiographics 26 (3): 923-40, 2006 May-Jun. [PubMed: 16702463]
233. Essary LR, Vargas SO, Fletcher CD: Primary pleuropulmonary synovial sarcoma: reappraisal of a recently described anatomic subset. Cancer 94 (2): 459-69, 2002. [PubMed: 11905413]
234. Scheer M, Blank B, Bauer S, et al.: Synovial sarcoma disease characteristics and primary tumor sites differ between patient age groups: a report of the Cooperative Weichteilsarkom Studiengruppe (CWS). J Cancer Res Clin Oncol 146 (4): 953-960, 2020. [PubMed: 31932909]
235. Pappo AS, Fontanesi J, Luo X, et al.: Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience. J Clin Oncol 12 (11): 2360-6, 1994. [PubMed: 7964951]
236. Ferrari A, De Salvo GL, Oberlin O, et al.: Synovial sarcoma in children and adolescents: a critical reappraisal of staging investigations in relation to the rate of metastatic involvement at diagnosis. Eur J Cancer 48 (9): 1370-5, 2012. [PubMed: 22322070]
237. van de Rijn M, Barr FG, Collins MH, et al.: Absence of SYT-SSX fusion products in soft tissue tumors other than synovial sarcoma. Am J Clin Pathol 112 (1): 43-9, 1999. [PubMed: 10396284]
238. Krsková L, Sumerauer D, Stejskalová E, et al.: A novel variant of SYT-SSX1 fusion gene in a case of spindle cell synovial sarcoma. Diagn Mol Pathol 16 (3): 179-83, 2007. [PubMed: 17721327]
239. Su L, Sampaio AV, Jones KB, et al.: Deconstruction of the SS18-SSX fusion oncoprotein complex: insights into disease etiology and therapeutics. Cancer Cell 21 (3): 333-47, 2012. [PMC free article: PMC3734954] [PubMed: 22439931]
240. Arnold MA, Arnold CA, Li G, et al.: A unique pattern of INI1 immunohistochemistry distinguishes synovial sarcoma from its histologic mimics. Hum Pathol 44 (5): 881-7, 2013. [PubMed: 23245672]
241. Vlenterie M, Ho VK, Kaal SE, et al.: Age as an independent prognostic factor for survival of localised synovial sarcoma patients. Br J Cancer 113 (11): 1602-6, 2015. [PMC free article: PMC4705887] [PubMed: 26554650]
242. Smolle MA, Parry M, Jeys L, et al.: Synovial sarcoma: Do children do better? Eur J Surg Oncol 45 (2): 254-260, 2019. [PubMed: 30077520]
243. Okcu MF, Munsell M, Treuner J, et al.: Synovial sarcoma of childhood and adolescence: a multicenter, multivariate analysis of outcome. J Clin Oncol 21 (8): 1602-11, 2003. [PubMed: 12697886]
244. Brecht IB, Ferrari A, Int-Veen C, et al.: Grossly-resected synovial sarcoma treated by the German and Italian Pediatric Soft Tissue Sarcoma Cooperative Groups: discussion on the role of adjuvant therapies. Pediatr Blood Cancer 46 (1): 11-7, 2006. [PubMed: 16292743]
245. Stanelle EJ, Christison-Lagay ER, Healey JH, et al.: Pediatric and adolescent synovial sarcoma: multivariate analysis of prognostic factors and survival outcomes. Ann Surg Oncol 20 (1): 73-9, 2013. [PubMed: 22878620]
246. Trassard M, Le Doussal V, Hacène K, et al.: Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients. J Clin Oncol 19 (2): 525-34, 2001. [PubMed: 11208847]
247. Guillou L, Benhattar J, Bonichon F, et al.: Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis. J Clin Oncol 22 (20): 4040-50, 2004. [PubMed: 15364967]
248. Ferrari A, Gronchi A, Casanova M, et al.: Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer 101 (3): 627-34, 2004. [PubMed: 15274077]
249. Lagarde P, Przybyl J, Brulard C, et al.: Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas. J Clin Oncol 31 (5): 608-15, 2013. [PubMed: 23319690]
250. Stegmaier S, Leuschner I, Poremba C, et al.: The prognostic impact of SYT-SSX fusion type and histological grade in pediatric patients with synovial sarcoma treated according to the CWS (Cooperative Weichteilsarkom Studie) trials. Pediatr Blood Cancer 64 (1): 89-95, 2017. [PubMed: 27621063]
251. Scheer M, Dantonello T, Hallmen E, et al.: Primary Metastatic Synovial Sarcoma: Experience of the CWS Study Group. Pediatr Blood Cancer 63 (7): 1198-206, 2016. [PubMed: 27003095]
252. Orbach D, Mosseri V, Pissaloux D, et al.: Genomic complexity in pediatric synovial sarcomas (Synobio study): the European pediatric soft tissue sarcoma group (EpSSG) experience. Cancer Med 7 (4): 1384-1393, 2018. [PMC free article: PMC5911585] [PubMed: 29533008]
253. Ferrari A, Chi YY, De Salvo GL, et al.: Surgery alone is sufficient therapy for children and adolescents with low-risk synovial sarcoma: A joint analysis from the European paediatric soft tissue sarcoma Study Group and the Children's Oncology Group. Eur J Cancer 78: 1-6, 2017. [PMC free article: PMC5567853] [PubMed: 28391003]
254. McGrory JE, Pritchard DJ, Arndt CA, et al.: Nonrhabdomyosarcoma soft tissue sarcomas in children. The Mayo Clinic experience. Clin Orthop (374): 247-58, 2000. [PubMed: 10818984]
255. Van Glabbeke M, van Oosterom AT, Oosterhuis JW, et al.: Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol 17 (1): 150-7, 1999. [PubMed: 10458228]
256. Koscielniak E, Harms D, Henze G, et al.: Results of treatment for soft tissue sarcoma in childhood and adolescence: a final report of the German Cooperative Soft Tissue Sarcoma Study CWS-86. J Clin Oncol 17 (12): 3706-19, 1999. [PubMed: 10577842]
257. Pappo AS, Devidas M, Jenkins J, et al.: Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study. J Clin Oncol 23 (18): 4031-8, 2005. [PubMed: 15767644]
258. Pappo AS, Rao BN, Jenkins JJ, et al.: Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience. Med Pediatr Oncol 33 (2): 76-82, 1999. [PubMed: 10398180]
259. Brennan B, Stevens M, Kelsey A, et al.: Synovial sarcoma in childhood and adolescence: a retrospective series of 77 patients registered by the Children's Cancer and Leukaemia Group between 1991 and 2006. Pediatr Blood Cancer 55 (1): 85-90, 2010. [PubMed: 20213848]
260. Ferrari A, Miceli R, Rey A, et al.: Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups. Eur J Cancer 47 (5): 724-31, 2011. [PMC free article: PMC3539303] [PubMed: 21145727]
261. Raney RB: Synovial sarcoma in young people: background, prognostic factors, and therapeutic questions. J Pediatr Hematol Oncol 27 (4): 207-11, 2005. [PubMed: 15838392]
262. Orbach D, Mc Dowell H, Rey A, et al.: Sparing strategy does not compromise prognosis in pediatric localized synovial sarcoma: experience of the International Society of Pediatric Oncology, Malignant Mesenchymal Tumors (SIOP-MMT) Working Group. Pediatr Blood Cancer 57 (7): 1130-6, 2011. [PubMed: 21495161]
263. Ladenstein R, Treuner J, Koscielniak E, et al.: Synovial sarcoma of childhood and adolescence. Report of the German CWS-81 study. Cancer 71 (11): 3647-55, 1993. [PubMed: 8387883]
264. Venkatramani R, Xue W, Randall RL, et al.: Synovial Sarcoma in Children, Adolescents, and Young Adults: A Report From the Children's Oncology Group ARST0332 Study. J Clin Oncol 39 (35): 3927-3937, 2021. [PMC free article: PMC8660012] [PubMed: 34623899]
265. Ferrari A, De Salvo GL, Brennan B, et al.: Synovial sarcoma in children and adolescents: the European Pediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005). Ann Oncol 26 (3): 567-72, 2015. [PubMed: 25488687]
266. Ferrari A, De Salvo GL, Dall'Igna P, et al.: Salvage rates and prognostic factors after relapse in children and adolescents with initially localised synovial sarcoma. Eur J Cancer 48 (18): 3448-55, 2012. [PubMed: 22835783]
267. Scheer M, Dantonello T, Hallmen E, et al.: Synovial Sarcoma Recurrence in Children and Young Adults. Ann Surg Oncol 23 (Suppl 5): 618-626, 2016. [PubMed: 27638676]
268. Dhakal S, Corbin KS, Milano MT, et al.: Stereotactic body radiotherapy for pulmonary metastases from soft-tissue sarcomas: excellent local lesion control and improved patient survival. Int J Radiat Oncol Biol Phys 82 (2): 940-5, 2012. [PubMed: 21277105]
269. Lai JP, Robbins PF, Raffeld M, et al.: NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis. Mod Pathol 25 (6): 854-8, 2012. [PMC free article: PMC6309776] [PubMed: 22388761]
270. Robbins PF, Kassim SH, Tran TL, et al.: A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response. Clin Cancer Res 21 (5): 1019-27, 2015. [PMC free article: PMC4361810] [PubMed: 25538264]
271. D'Angelo SP, Melchiori L, Merchant MS, et al.: Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1 c259T Cells in Synovial Sarcoma. Cancer Discov 8 (8): 944-957, 2018. [PMC free article: PMC8092079] [PubMed: 29891538]
272. Chbani L, Guillou L, Terrier P, et al.: Epithelioid sarcoma: a clinicopathologic and immunohistochemical analysis of 106 cases from the French sarcoma group. Am J Clin Pathol 131 (2): 222-7, 2009. [PubMed: 19141382]
273. Hornick JL, Dal Cin P, Fletcher CD: Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol 33 (4): 542-50, 2009. [PubMed: 19033866]
274. Knutson SK, Warholic NM, Wigle TJ, et al.: Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc Natl Acad Sci U S A 110 (19): 7922-7, 2013. [PMC free article: PMC3651445] [PubMed: 23620515]
275. Guzzetta AA, Montgomery EA, Lyu H, et al.: Epithelioid sarcoma: one institution's experience with a rare sarcoma. J Surg Res 177 (1): 116-22, 2012. [PMC free article: PMC3715113] [PubMed: 22575361]
276. Hawkins DS, Spunt SL, Skapek SX, et al.: Children's Oncology Group's 2013 blueprint for research: Soft tissue sarcomas. Pediatr Blood Cancer 60 (6): 1001-8, 2013. [PMC free article: PMC3777409] [PubMed: 23255356]
277. Casanova M, Ferrari A, Collini P, et al.: Epithelioid sarcoma in children and adolescents: a report from the Italian Soft Tissue Sarcoma Committee. Cancer 106 (3): 708-17, 2006. [PubMed: 16353216]
278. Sparber-Sauer M, Koscielniak E, Vokuhl C, et al.: Epithelioid sarcoma in children, adolescents, and young adults: Localized, primary metastatic and relapsed disease. Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry. Pediatr Blood Cancer 66 (9): e27879, 2019. [PubMed: 31215116]
279. Spunt SL, Francotte N, De Salvo GL, et al.: Clinical features and outcomes of young patients with epithelioid sarcoma: an analysis from the Children's Oncology Group and the European paediatric soft tissue Sarcoma Study Group prospective clinical trials. Eur J Cancer 112: 98-106, 2019. [PMC free article: PMC6944741] [PubMed: 30954717]
280. Gounder M, Schöffski P, Jones RL, et al.: Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol 21 (11): 1423-1432, 2020. [PubMed: 33035459]
281. Orbach D, Brennan B, Casanova M, et al.: Paediatric and adolescent alveolar soft part sarcoma: A joint series from European cooperative groups. Pediatr Blood Cancer 60 (11): 1826-32, 2013. [PubMed: 23857870]
282. Ferrari A, Sultan I, Huang TT, et al.: Soft tissue sarcoma across the age spectrum: a population-based study from the Surveillance Epidemiology and End Results database. Pediatr Blood Cancer 57 (6): 943-9, 2011. [PMC free article: PMC4261144] [PubMed: 21793180]
283. Wang HW, Qin XJ, Yang WJ, et al.: Alveolar soft part sarcoma of the oral and maxillofacial region: clinical analysis in a series of 18 patients. Oral Surg Oral Med Oral Pathol Oral Radiol 119 (4): 396-401, 2015. [PubMed: 25660276]
284. Kayton ML, Meyers P, Wexler LH, et al.: Clinical presentation, treatment, and outcome of alveolar soft part sarcoma in children, adolescents, and young adults. J Pediatr Surg 41 (1): 187-93, 2006. [PubMed: 16410131]
285. Sparber-Sauer M, Seitz G, von Kalle T, et al.: Alveolar soft-part sarcoma: Primary metastatic disease and metastatic relapse occurring during long-term follow-up: Treatment results of four Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry. Pediatr Blood Cancer 65 (12): e27405, 2018. [PubMed: 30124238]
286. Flores RJ, Harrison DJ, Federman NC, et al.: Alveolar soft part sarcoma in children and young adults: A report of 69 cases. Pediatr Blood Cancer 65 (5): e26953, 2018. [PubMed: 29350467]
287. Ladanyi M, Lui MY, Antonescu CR, et al.: The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 20 (1): 48-57, 2001. [PubMed: 11244503]
288. Williams A, Bartle G, Sumathi VP, et al.: Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: useful diagnostic tools in cases with unusual histological features. Virchows Arch 458 (3): 291-300, 2011. [PubMed: 21279521]
289. Lieberman PH, Brennan MF, Kimmel M, et al.: Alveolar soft-part sarcoma. A clinico-pathologic study of half a century. Cancer 63 (1): 1-13, 1989. [PubMed: 2642727]
290. Casanova M, Ferrari A, Bisogno G, et al.: Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group. Ann Oncol 11 (11): 1445-9, 2000. [PubMed: 11142485]
291. Pennacchioli E, Fiore M, Collini P, et al.: Alveolar soft part sarcoma: clinical presentation, treatment, and outcome in a series of 33 patients at a single institution. Ann Surg Oncol 17 (12): 3229-33, 2010. [PubMed: 20593242]
292. Wilky BA, Trucco MM, Subhawong TK, et al.: Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Lancet Oncol 20 (6): 837-848, 2019. [PubMed: 31078463]
293. Roozendaal KJ, de Valk B, ten Velden JJ, et al.: Alveolar soft-part sarcoma responding to interferon alpha-2b. Br J Cancer 89 (2): 243-5, 2003. [PMC free article: PMC2394261] [PubMed: 12865909]
294. Conde N, Cruz O, Albert A, et al.: Antiangiogenic treatment as a pre-operative management of alveolar soft-part sarcoma. Pediatr Blood Cancer 57 (6): 1071-3, 2011. [PubMed: 21744483]
295. Stacchiotti S, Negri T, Zaffaroni N, et al.: Sunitinib in advanced alveolar soft part sarcoma: evidence of a direct antitumor effect. Ann Oncol 22 (7): 1682-90, 2011. [PubMed: 21242589]
296. Jagodzińska-Mucha P, Świtaj T, Kozak K, et al.: Long-term results of therapy with sunitinib in metastatic alveolar soft part sarcoma. Tumori 103 (3): 231-235, 2017. [PubMed: 28291905]
297. Kummar S, Allen D, Monks A, et al.: Cediranib for metastatic alveolar soft part sarcoma. J Clin Oncol 31 (18): 2296-302, 2013. [PMC free article: PMC3677840] [PubMed: 23630200]
298. Cohen JW, Widemann BC, Derdak J, et al.: Cediranib phase-II study in children with metastatic alveolar soft-part sarcoma (ASPS). Pediatr Blood Cancer 66 (12): e27987, 2019. [PMC free article: PMC6803032] [PubMed: 31502400]
299. Judson I, Morden JP, Kilburn L, et al.: Cediranib in patients with alveolar soft-part sarcoma (CASPS): a double-blind, placebo-controlled, randomised, phase 2 trial. Lancet Oncol 20 (7): 1023-1034, 2019. [PMC free article: PMC6602919] [PubMed: 31160249]
300. Kim M, Kim TM, Keam B, et al.: A Phase II Trial of Pazopanib in Patients with Metastatic Alveolar Soft Part Sarcoma. Oncologist 24 (1): 20-e29, 2019. [PMC free article: PMC6324645] [PubMed: 30254189]
301. Stacchiotti S, Mir O, Le Cesne A, et al.: Activity of Pazopanib and Trabectedin in Advanced Alveolar Soft Part Sarcoma. Oncologist 23 (1): 62-70, 2018. [PMC free article: PMC5759809] [PubMed: 28754721]
302. Coindre JM, Hostein I, Terrier P, et al.: Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues: clinicopathologic and molecular analysis of 44 patients from the French sarcoma group. Cancer 107 (5): 1055-64, 2006. [PubMed: 16878328]
303. Meis-Kindblom JM: Clear cell sarcoma of tendons and aponeuroses: a historical perspective and tribute to the man behind the entity. Adv Anat Pathol 13 (6): 286-92, 2006. [PubMed: 17075294]
304. Dim DC, Cooley LD, Miranda RN: Clear cell sarcoma of tendons and aponeuroses: a review. Arch Pathol Lab Med 131 (1): 152-6, 2007. [PubMed: 17227118]
305. Blazer DG, Lazar AJ, Xing Y, et al.: Clinical outcomes of molecularly confirmed clear cell sarcoma from a single institution and in comparison with data from the Surveillance, Epidemiology, and End Results registry. Cancer 115 (13): 2971-9, 2009. [PubMed: 19402173]
306. Fujimura Y, Siddique H, Lee L, et al.: EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function. Oncogene 20 (46): 6653-9, 2001. [PubMed: 11709699]
307. Hisaoka M, Ishida T, Kuo TT, et al.: Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. Am J Surg Pathol 32 (3): 452-60, 2008. [PubMed: 18300804]
308. Ferrari A, Casanova M, Bisogno G, et al.: Clear cell sarcoma of tendons and aponeuroses in pediatric patients: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Cancer 94 (12): 3269-76, 2002. [PubMed: 12115360]
309. Karita M, Tsuchiya H, Yamamoto N, et al.: Caffeine-potentiated chemotherapy for clear cell sarcoma: a report of five cases. Int J Clin Oncol 18 (1): 33-7, 2013. [PubMed: 22041928]
310. Schöffski P, Wozniak A, Stacchiotti S, et al.: Activity and safety of crizotinib in patients with advanced clear-cell sarcoma with MET alterations: European Organization for Research and Treatment of Cancer phase II trial 90101 'CREATE'. Ann Oncol 28 (12): 3000-3008, 2017. [PMC free article: PMC5834120] [PubMed: 28950372]
311. Tsuneyoshi M, Enjoji M, Iwasaki H, et al.: Extraskeletal myxoid chondrosarcoma--a clinicopathologic and electron microscopic study. Acta Pathol Jpn 31 (3): 439-47, 1981. [PubMed: 7270148]
312. Hachitanda Y, Tsuneyoshi M, Daimaru Y, et al.: Extraskeletal myxoid chondrosarcoma in young children. Cancer 61 (12): 2521-6, 1988. [PubMed: 2835146]
313. Hisaoka M, Ishida T, Imamura T, et al.: TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma. Genes Chromosomes Cancer 40 (4): 325-8, 2004. [PubMed: 15188455]
314. Enzinger FM, Shiraki M: Extraskeletal myxoid chondrosarcoma. An analysis of 34 cases. Hum Pathol 3 (3): 421-35, 1972. [PubMed: 4261659]
315. McGrory JE, Rock MG, Nascimento AG, et al.: Extraskeletal myxoid chondrosarcoma. Clin Orthop Relat Res (382): 185-90, 2001. [PubMed: 11153986]
316. Drilon AD, Popat S, Bhuchar G, et al.: Extraskeletal myxoid chondrosarcoma: a retrospective review from 2 referral centers emphasizing long-term outcomes with surgery and chemotherapy. Cancer 113 (12): 3364-71, 2008. [PMC free article: PMC2779719] [PubMed: 18951519]
317. Stacchiotti S, Pantaleo MA, Astolfi A, et al.: Activity of sunitinib in extraskeletal myxoid chondrosarcoma. Eur J Cancer 50 (9): 1657-64, 2014. [PubMed: 24703573]
318. Leuschner I, Radig K, Harms D: Desmoplastic small round cell tumor. Semin Diagn Pathol 13 (3): 204-12, 1996. [PubMed: 8875710]
319. Kushner BH, LaQuaglia MP, Wollner N, et al.: Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy. J Clin Oncol 14 (5): 1526-31, 1996. [PubMed: 8622067]
320. Saab R, Khoury JD, Krasin M, et al.: Desmoplastic small round cell tumor in childhood: the St. Jude Children's Research Hospital experience. Pediatr Blood Cancer 49 (3): 274-9, 2007. [PubMed: 16685737]
321. Wang LL, Perlman EJ, Vujanic GM, et al.: Desmoplastic small round cell tumor of the kidney in childhood. Am J Surg Pathol 31 (4): 576-84, 2007. [PubMed: 17414105]
322. Hayes-Jordan A, LaQuaglia MP, Modak S: Management of desmoplastic small round cell tumor. Semin Pediatr Surg 25 (5): 299-304, 2016. [PMC free article: PMC5614508] [PubMed: 27955733]
323. Arora VC, Price AP, Fleming S, et al.: Characteristic imaging features of desmoplastic small round cell tumour. Pediatr Radiol 43 (1): 93-102, 2013. [PubMed: 23179482]
324. Gerald WL, Ladanyi M, de Alava E, et al.: Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol 16 (9): 3028-36, 1998. [PubMed: 9738572]
325. Slotkin EK, Bowman AS, Levine MF, et al.: Comprehensive Molecular Profiling of Desmoplastic Small Round Cell Tumor. Mol Cancer Res 19 (7): 1146-1155, 2021. [PMC free article: PMC8293793] [PubMed: 33753552]
326. Chow WA, Yee JK, Tsark W, et al.: Recurrent secondary genomic alterations in desmoplastic small round cell tumors. BMC Med Genet 21 (1): 101, 2020. [PMC free article: PMC7216377] [PubMed: 32393201]
327. Lal DR, Su WT, Wolden SL, et al.: Results of multimodal treatment for desmoplastic small round cell tumors. J Pediatr Surg 40 (1): 251-5, 2005. [PubMed: 15868593]
328. Philippe-Chomette P, Kabbara N, Andre N, et al.: Desmoplastic small round cell tumors with EWS-WT1 fusion transcript in children and young adults. Pediatr Blood Cancer 58 (6): 891-7, 2012. [PubMed: 22162435]
329. Sedig L, Geiger J, Mody R, et al.: Paratesticular desmoplastic small round cell tumors: A case report and review of the literature. Pediatr Blood Cancer 64 (12): , 2017. [PubMed: 28509382]
330. Subbiah V, Lamhamedi-Cherradi SE, Cuglievan B, et al.: Multimodality Treatment of Desmoplastic Small Round Cell Tumor: Chemotherapy and Complete Cytoreductive Surgery Improve Patient Survival. Clin Cancer Res 24 (19): 4865-4873, 2018. [PMC free article: PMC6168359] [PubMed: 29871905]
331. Schwarz RE, Gerald WL, Kushner BH, et al.: Desmoplastic small round cell tumors: prognostic indicators and results of surgical management. Ann Surg Oncol 5 (5): 416-22, 1998 Jul-Aug. [PubMed: 9718171]
332. Goodman KA, Wolden SL, La Quaglia MP, et al.: Whole abdominopelvic radiotherapy for desmoplastic small round-cell tumor. Int J Radiat Oncol Biol Phys 54 (1): 170-6, 2002. [PubMed: 12182988]
333. Osborne EM, Briere TM, Hayes-Jordan A, et al.: Survival and toxicity following sequential multimodality treatment including whole abdominopelvic radiotherapy for patients with desmoplastic small round cell tumor. Radiother Oncol 119 (1): 40-4, 2016. [PubMed: 26527430]
334. Atallah V, Honore C, Orbach D, et al.: Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors. Int J Radiat Oncol Biol Phys 95 (4): 1244-53, 2016. [PubMed: 27354131]
335. Hayes-Jordan AA, Coakley BA, Green HL, et al.: Desmoplastic Small Round Cell Tumor Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Results of a Phase 2 Trial. Ann Surg Oncol 25 (4): 872-877, 2018. [PMC free article: PMC5842144] [PubMed: 29383611]
336. Scalabre A, Philippe-Chomette P, Passot G, et al.: Cytoreductive surgery and hyperthermic intraperitoneal perfusion with chemotherapy in children with peritoneal tumor spread: A French nationwide study over 14 years. Pediatr Blood Cancer 65 (4): , 2018. [PubMed: 29286576]
337. Honoré C, Atallah V, Mir O, et al.: Abdominal desmoplastic small round cell tumor without extraperitoneal metastases: Is there a benefit for HIPEC after macroscopically complete cytoreductive surgery? PLoS One 12 (2): e0171639, 2017. [PMC free article: PMC5325210] [PubMed: 28234908]
338. Stiles ZE, Murphy AJ, Anghelescu DL, et al.: Desmoplastic Small Round Cell Tumor: Long-Term Complications After Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol 27 (1): 171-178, 2020. [PMC free article: PMC7424843] [PubMed: 30963398]
339. Cook RJ, Wang Z, Arora M, et al.: Clinical outcomes of patients with desmoplastic small round cell tumor of the peritoneum undergoing autologous HCT: a CIBMTR retrospective analysis. Bone Marrow Transplant 47 (11): 1455-8, 2012. [PMC free article: PMC3951901] [PubMed: 22465977]
340. Tarek N, Hayes-Jordan A, Salvador L, et al.: Recurrent desmoplastic small round cell tumor responding to an mTOR inhibitor containing regimen. Pediatr Blood Cancer 65 (1): , 2018. [PubMed: 28941151]
341. Kodet R, Newton WA, Sachs N, et al.: Rhabdoid tumors of soft tissues: a clinicopathologic study of 26 cases enrolled on the Intergroup Rhabdomyosarcoma Study. Hum Pathol 22 (7): 674-84, 1991. [PubMed: 1712749]
342. Biegel JA, Zhou JY, Rorke LB, et al.: Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 59 (1): 74-9, 1999. [PubMed: 9892189]
343. Eaton KW, Tooke LS, Wainwright LM, et al.: Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatr Blood Cancer 56 (1): 7-15, 2011. [PMC free article: PMC3086793] [PubMed: 21108436]
344. Lee RS, Stewart C, Carter SL, et al.: A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers. J Clin Invest 122 (8): 2983-8, 2012. [PMC free article: PMC3408754] [PubMed: 22797305]
345. Morgan KM, Siow VS, Strotmeyer S, et al.: Characteristics and Outcomes in Pediatric Non-Central Nervous System Malignant Rhabdoid Tumors: A Report from the National Cancer Database. Ann Surg Oncol 29 (1): 671-678, 2022. [PubMed: 34251553]
346. Sultan I, Qaddoumi I, Rodríguez-Galindo C, et al.: Age, stage, and radiotherapy, but not primary tumor site, affects the outcome of patients with malignant rhabdoid tumors. Pediatr Blood Cancer 54 (1): 35-40, 2010. [PubMed: 19798737]
347. Nemes K, Bens S, Kachanov D, et al.: Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK). Eur J Cancer 142: 112-122, 2021. [PubMed: 33249395]
348. Puri DR, Meyers PA, Kraus DH, et al.: Radiotherapy in the multimodal treatment of extrarenal extracranial malignant rhabdoid tumors. Pediatr Blood Cancer 50 (1): 167-9, 2008. [PubMed: 16856154]
349. Madigan CE, Armenian SH, Malogolowkin MH, et al.: Extracranial malignant rhabdoid tumors in childhood: the Childrens Hospital Los Angeles experience. Cancer 110 (9): 2061-6, 2007. [PubMed: 17828773]
350. Bourdeaut F, Fréneaux P, Thuille B, et al.: Extra-renal non-cerebral rhabdoid tumours. Pediatr Blood Cancer 51 (3): 363-8, 2008. [PubMed: 18506766]
351. Wetmore C, Boyett J, Li S, et al.: Alisertib is active as single agent in recurrent atypical teratoid rhabdoid tumors in 4 children. Neuro Oncol 17 (6): 882-8, 2015. [PMC free article: PMC4483126] [PubMed: 25688119]
352. Martignoni G, Pea M, Reghellin D, et al.: Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors. Arch Pathol Lab Med 134 (1): 33-40, 2010. [PubMed: 20073603]
353. Bissler JJ, McCormack FX, Young LR, et al.: Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 358 (2): 140-51, 2008. [PMC free article: PMC3398441] [PubMed: 18184959]
354. Davies DM, Johnson SR, Tattersfield AE, et al.: Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med 358 (2): 200-3, 2008. [PubMed: 18184971]
355. Agaram NP, Sung YS, Zhang L, et al.: Dichotomy of Genetic Abnormalities in PEComas With Therapeutic Implications. Am J Surg Pathol 39 (6): 813-25, 2015. [PMC free article: PMC4431898] [PubMed: 25651471]
356. Folpe A, Inwards C, eds.: Bone and Soft Tissue Pathology: A Volume in the Foundations in Diagnostic Pathology. WB Saunders Co, 2010.
357. Armah HB, Parwani AV: Perivascular epithelioid cell tumor. Arch Pathol Lab Med 133 (4): 648-54, 2009. [PubMed: 19391667]
358. Alaggio R, Cecchetto G, Martignoni G, et al.: Malignant perivascular epithelioid cell tumor in children: description of a case and review of the literature. J Pediatr Surg 47 (6): e31-40, 2012. [PubMed: 22703822]
359. Wagner AJ, Malinowska-Kolodziej I, Morgan JA, et al.: Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol 28 (5): 835-40, 2010. [PMC free article: PMC4810029] [PubMed: 20048174]
360. Wagner AJ, Ravi V, Riedel RF, et al.: nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors. J Clin Oncol 39 (33): 3660-3670, 2021. [PMC free article: PMC8601264] [PubMed: 34637337]
361. Laetsch TW, Roy A, Xu L, et al.: Undifferentiated Sarcomas in Children Harbor Clinically Relevant Oncogenic Fusions and Gene Copy-Number Alterations: A Report from the Children's Oncology Group. Clin Cancer Res 24 (16): 3888-3897, 2018. [PMC free article: PMC6335968] [PubMed: 29691299]
362. Randall RL, Albritton KH, Ferney BJ, et al.: Malignant fibrous histiocytoma of soft tissue: an abandoned diagnosis. Am J Orthop 33 (12): 602-8, 2004. [PubMed: 15641745]
363. Alaggio R, Collini P, Randall RL, et al.: Undifferentiated high-grade pleomorphic sarcomas in children: a clinicopathologic study of 10 cases and review of literature. Pediatr Dev Pathol 13 (3): 209-17, 2010 May-Jun. [PubMed: 20055602]
364. Le Guellec S, Chibon F, Ouali M, et al.: Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas? Am J Surg Pathol 38 (3): 293-304, 2014. [PubMed: 24525499]
365. Bjerkehagen B, Smeland S, Walberg L, et al.: Radiation-induced sarcoma: 25-year experience from the Norwegian Radium Hospital. Acta Oncol 47 (8): 1475-82, 2008. [PubMed: 18607853]
366. Daw NC, Billups CA, Pappo AS, et al.: Malignant fibrous histiocytoma and other fibrohistiocytic tumors in pediatric patients: the St. Jude Children's Research Hospital experience. Cancer 97 (11): 2839-47, 2003. [PubMed: 12767098]
367. Tawbi HA, Burgess M, Bolejack V, et al.: Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 18 (11): 1493-1501, 2017. [PMC free article: PMC7939029] [PubMed: 28988646]
368. Coffin CM, Dehner LP: Vascular tumors in children and adolescents: a clinicopathologic study of 228 tumors in 222 patients. Pathol Annu 28 Pt 1: 97-120, 1993. [PubMed: 8416140]
369. Mehrabi A, Kashfi A, Fonouni H, et al.: Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive review of the literature with emphasis on the surgical therapy. Cancer 107 (9): 2108-21, 2006. [PubMed: 17019735]
370. Haro A, Saitoh G, Tamiya S, et al.: Four-year natural clinical course of pulmonary epithelioid hemangioendothelioma without therapy. Thorac Cancer 6 (4): 544-7, 2015. [PMC free article: PMC4511336] [PubMed: 26273413]
371. Sardaro A, Bardoscia L, Petruzzelli MF, et al.: Epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. Oncol Rev 8 (2): 259, 2014. [PMC free article: PMC4419652] [PubMed: 25992243]
372. Dong K, Wang XX, Feng JL, et al.: Pathological characteristics of liver biopsies in eight patients with hepatic epithelioid hemangioendothelioma. Int J Clin Exp Pathol 8 (9): 11015-23, 2015. [PMC free article: PMC4637634] [PubMed: 26617819]
373. Adams DM, Hammill A: Other vascular tumors. Semin Pediatr Surg 23 (4): 173-7, 2014. [PubMed: 25241094]
374. Xiao Y, Wang C, Song Y, et al.: Primary epithelioid hemangioendothelioma of the kidney: the first case report in a child and literature review. Urology 82 (4): 925-7, 2013. [PubMed: 23726166]
375. Reich S, Ringe H, Uhlenberg B, et al.: Epithelioid hemangioendothelioma of the lung presenting with pneumonia and heart rhythm disturbances in a teenage girl. J Pediatr Hematol Oncol 32 (4): 274-6, 2010. [PubMed: 20445417]
376. Cournoyer E, Al-Ibraheemi A, Engel E, et al.: Clinical characterization and long-term outcomes in pediatric epithelioid hemangioendothelioma. Pediatr Blood Cancer 67 (2): e28045, 2020. [PubMed: 31724797]
377. Daller JA, Bueno J, Gutierrez J, et al.: Hepatic hemangioendothelioma: clinical experience and management strategy. J Pediatr Surg 34 (1): 98-105; discussion 105-6, 1999. [PubMed: 10022152]
378. Ackermann O, Fabre M, Franchi S, et al.: Widening spectrum of liver angiosarcoma in children. J Pediatr Gastroenterol Nutr 53 (6): 615-9, 2011. [PubMed: 21832953]
379. Raheja A, Suri A, Singh S, et al.: Multimodality management of a giant skull base hemangioendothelioma of the sphenopetroclival region. J Clin Neurosci 22 (9): 1495-8, 2015. [PubMed: 25986183]
380. Ahmad N, Adams DM, Wang J, et al.: Hepatic epithelioid hemangioendothelioma in a patient with hemochromatosis. J Natl Compr Canc Netw 12 (9): 1203-7, 2014. [PubMed: 25190690]
381. Otte JB, Zimmerman A: The role of liver transplantation for pediatric epithelioid hemangioendothelioma. Pediatr Transplant 14 (3): 295-7, 2010. [PubMed: 20331517]
382. Stacchiotti S, Provenzano S, Dagrada G, et al.: Sirolimus in Advanced Epithelioid Hemangioendothelioma: A Retrospective Case-Series Analysis from the Italian Rare Cancer Network Database. Ann Surg Oncol 23 (9): 2735-44, 2016. [PubMed: 27334221]
383. Semenisty V, Naroditsky I, Keidar Z, et al.: Pazopanib for metastatic pulmonary epithelioid hemangioendothelioma-a suitable treatment option: case report and review of anti-angiogenic treatment options. BMC Cancer 15: 402, 2015. [PMC free article: PMC4437555] [PubMed: 25967676]
384. Engel ER, Cournoyer E, Adams DM, et al.: A Retrospective Review of the Use of Sirolimus for Pediatric Patients With Epithelioid Hemangioendothelioma. J Pediatr Hematol Oncol 42 (8): e826-e829, 2020. [PubMed: 31714437]
385. Cioffi A, Reichert S, Antonescu CR, et al.: Angiosarcomas and other sarcomas of endothelial origin. Hematol Oncol Clin North Am 27 (5): 975-88, 2013. [PubMed: 24093171]
386. Jeng MR, Fuh B, Blatt J, et al.: Malignant transformation of infantile hemangioma to angiosarcoma: response to chemotherapy with bevacizumab. Pediatr Blood Cancer 61 (11): 2115-7, 2014. [PubMed: 24740626]
387. Dehner LP, Ishak KG: Vascular tumors of the liver in infants and children. A study of 30 cases and review of the literature. Arch Pathol 92 (2): 101-11, 1971. [PubMed: 5559952]
388. Ferrari A, Casanova M, Bisogno G, et al.: Malignant vascular tumors in children and adolescents: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Med Pediatr Oncol 39 (2): 109-14, 2002. [PubMed: 12116058]
389. Deyrup AT, Miettinen M, North PE, et al.: Pediatric cutaneous angiosarcomas: a clinicopathologic study of 10 cases. Am J Surg Pathol 35 (1): 70-5, 2011. [PubMed: 21164289]
390. Elliott P, Kleinschmidt I: Angiosarcoma of the liver in Great Britain in proximity to vinyl chloride sites. Occup Environ Med 54 (1): 14-8, 1997. [PMC free article: PMC1128629] [PubMed: 9072028]
391. Lezama-del Valle P, Gerald WL, Tsai J, et al.: Malignant vascular tumors in young patients. Cancer 83 (8): 1634-9, 1998. [PubMed: 9781959]
392. Fata F, O'Reilly E, Ilson D, et al.: Paclitaxel in the treatment of patients with angiosarcoma of the scalp or face. Cancer 86 (10): 2034-7, 1999. [PubMed: 10570428]
393. Lahat G, Dhuka AR, Hallevi H, et al.: Angiosarcoma: clinical and molecular insights. Ann Surg 251 (6): 1098-106, 2010. [PubMed: 20485141]
394. Orlando G, Adam R, Mirza D, et al.: Hepatic hemangiosarcoma: an absolute contraindication to liver transplantation--the European Liver Transplant Registry experience. Transplantation 95 (6): 872-7, 2013. [PubMed: 23354302]
395. Aldén J, Baecklund F, Psaros Einberg A, et al.: Is primary hepatic angiosarcoma in children an indication for liver transplantation?-A single-centre experience and review of the literature. Pediatr Transplant 25 (8): e14095, 2021. [PubMed: 34288297]
396. Sanada T, Nakayama H, Irisawa R, et al.: Clinical outcome and dose volume evaluation in patients who undergo brachytherapy for angiosarcoma of the scalp and face. Mol Clin Oncol 6 (3): 334-340, 2017. [PMC free article: PMC5403362] [PubMed: 28451409]
397. Dickson MA, D'Adamo DR, Keohan ML, et al.: Phase II Trial of Gemcitabine and Docetaxel with Bevacizumab in Soft Tissue Sarcoma. Sarcoma 2015: 532478, 2015. [PMC free article: PMC4446476] [PubMed: 26074722]
398. Scott MT, Portnow LH, Morris CG, et al.: Radiation therapy for angiosarcoma: the 35-year University of Florida experience. Am J Clin Oncol 36 (2): 174-80, 2013. [PubMed: 22314000]
399. North PE, Waner M, Mizeracki A, et al.: A unique microvascular phenotype shared by juvenile hemangiomas and human placenta. Arch Dermatol 137 (5): 559-70, 2001. [PubMed: 11346333]
400. Boye E, Yu Y, Paranya G, et al.: Clonality and altered behavior of endothelial cells from hemangiomas. J Clin Invest 107 (6): 745-52, 2001. [PMC free article: PMC208946] [PubMed: 11254674]
401. Ravi V, Patel S: Vascular sarcomas. Curr Oncol Rep 15 (4): 347-55, 2013. [PubMed: 23852636]
402. Grassia KL, Peterman CM, Iacobas I, et al.: Clinical case series of pediatric hepatic angiosarcoma. Pediatr Blood Cancer 64 (11): , 2017. [PubMed: 28521077]
403. Koo J, Knight-Perry J, Galambos C, et al.: Pediatric Metastatic Cardiac Angiosarcoma Successfully Treated With Multimodal Therapy: Case Report and Review of Literature. J Pediatr Hematol Oncol 43 (2): e203-e206, 2021. [PubMed: 31725539]

Pulmonary Metastases

Generally, a surgical procedure, with resection of all gross disease, should be considered for children with isolated pulmonary metastases.[10] For patients with multiple or recurrent pulmonary metastases, additional surgical procedures can be performed if the morbidity is deemed acceptable. In a retrospective review, patients with synovial sarcoma and pulmonary metastases who underwent complete resection of all metastatic lung lesions had better survival than did patients who did not undergo complete resections.[10][Level of evidence C1] Formal segmentectomy, lobectomy, and mediastinal lymph node dissection are unnecessary.[11]

An alternative approach is focused radiation therapy (fractionated stereotactic radiation therapy), which has been successfully used in adults to control lesions. The estimated 5-year survival rate after thoracotomy for pulmonary metastasectomy has ranged from 10% to 58% in adult studies.[12]

References

1. Demetri GD, Elias AD: Results of single-agent and combination chemotherapy for advanced soft tissue sarcomas. Implications for decision making in the clinic. Hematol Oncol Clin North Am 9 (4): 765-85, 1995. [PubMed: 7490240]
2. Elias A, Ryan L, Sulkes A, et al.: Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol 7 (9): 1208-16, 1989. [PubMed: 2504890]
3. Edmonson JH, Ryan LM, Blum RH, et al.: Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 11 (7): 1269-75, 1993. [PubMed: 8315424]
4. Rao BN: Nonrhabdomyosarcoma in children: prognostic factors influencing survival. Semin Surg Oncol 9 (6): 524-31, 1993 Nov-Dec. [PubMed: 8284572]
5. deCou JM, Rao BN, Parham DM, et al.: Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience. Ann Surg Oncol 2 (6): 524-9, 1995. [PubMed: 8591083]
6. Pappo AS, Rao BN, Jenkins JJ, et al.: Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience. Med Pediatr Oncol 33 (2): 76-82, 1999. [PubMed: 10398180]
7. Pratt CB, Pappo AS, Gieser P, et al.: Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study. J Clin Oncol 17 (4): 1219, 1999. [PubMed: 10561182]
8. Pratt CB, Maurer HM, Gieser P, et al.: Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study. Med Pediatr Oncol 30 (4): 201-9, 1998. [PubMed: 9473754]
9. Ferrari A, Merks JHM, Chisholm JC, et al.: Outcomes of metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated within the BERNIE study: a randomised, phase II study evaluating the addition of bevacizumab to chemotherapy. Eur J Cancer 130: 72-80, 2020. [PubMed: 32179448]
10. Stanelle EJ, Christison-Lagay ER, Wolden SL, et al.: Pulmonary metastasectomy in pediatric/adolescent patients with synovial sarcoma: an institutional review. J Pediatr Surg 48 (4): 757-63, 2013. [PubMed: 23583130]
11. Putnam JB, Roth JA: Surgical treatment for pulmonary metastases from sarcoma. Hematol Oncol Clin North Am 9 (4): 869-87, 1995. [PubMed: 7490246]
12. Dhakal S, Corbin KS, Milano MT, et al.: Stereotactic body radiotherapy for pulmonary metastases from soft-tissue sarcomas: excellent local lesion control and improved patient survival. Int J Radiat Oncol Biol Phys 82 (2): 940-5, 2012. [PubMed: 21277105]

Treatment Options Under Clinical Evaluation

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

The following is an example of a national and/or institutional clinical trial that is currently being conducted:

• APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified in a patient's tumor (refractory or recurrent). Children and adolescents aged 1 to 21 years are eligible for the trial.
  Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Bergamaschi L, Bisogno G, Manzitti C, et al.: Salvage rates and prognostic factors after relapse in children and adolescents with malignant peripheral nerve sheath tumors. Pediatr Blood Cancer 65 (2): , 2018. [PubMed: 28926683]
2. Belal A, Salah E, Hajjar W, et al.: Pulmonary metastatectomy for soft tissue sarcomas: is it valuable? J Cardiovasc Surg (Torino) 42 (6): 835-40, 2001. [PubMed: 11698958]
3. Zagars GK, Ballo MT, Pisters PW, et al.: Prognostic factors for disease-specific survival after first relapse of soft-tissue sarcoma: analysis of 402 patients with disease relapse after initial conservative surgery and radiotherapy. Int J Radiat Oncol Biol Phys 57 (3): 739-47, 2003. [PubMed: 14529779]
4. Stanelle EJ, Christison-Lagay ER, Wolden SL, et al.: Pulmonary metastasectomy in pediatric/adolescent patients with synovial sarcoma: an institutional review. J Pediatr Surg 48 (4): 757-63, 2013. [PubMed: 23583130]
5. Maki RG, Wathen JK, Patel SR, et al.: Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected]. J Clin Oncol 25 (19): 2755-63, 2007. [PubMed: 17602081]
6. Le Cesne A, Cresta S, Maki RG, et al.: A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas. Eur J Cancer 48 (16): 3036-44, 2012. [PubMed: 22749255]
7. Garcia-Carbonero R, Supko JG, Maki RG, et al.: Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol 23 (24): 5484-92, 2005. [PubMed: 16110008]
8. Garcia-Carbonero R, Supko JG, Manola J, et al.: Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol 22 (8): 1480-90, 2004. [PubMed: 15084621]
9. Glade Bender JL, Lee A, Reid JM, et al.: Phase I pharmacokinetic and pharmacodynamic study of pazopanib in children with soft tissue sarcoma and other refractory solid tumors: a children's oncology group phase I consortium report. J Clin Oncol 31 (24): 3034-43, 2013. [PMC free article: PMC3739862] [PubMed: 23857966]
10. van der Graaf WT, Blay JY, Chawla SP, et al.: Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 379 (9829): 1879-86, 2012. [PubMed: 22595799]
11. Casanova M, Basso E, Magni C, et al.: Response to pazopanib in two pediatric patients with pretreated relapsing synovial sarcoma. Tumori 103 (1): e1-e3, 2017. [PubMed: 27647230]
12. Tawbi HA, Burgess M, Bolejack V, et al.: Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 18 (11): 1493-1501, 2017. [PMC free article: PMC7939029] [PubMed: 28988646]
13. Dhakal S, Corbin KS, Milano MT, et al.: Stereotactic body radiotherapy for pulmonary metastases from soft-tissue sarcomas: excellent local lesion control and improved patient survival. Int J Radiat Oncol Biol Phys 82 (2): 940-5, 2012. [PubMed: 21277105]
14. Howard TP, Boyle PJ, Marcus KJ, et al.: Clinical outcomes for pediatric patients receiving radiotherapy for solid tumor central nervous system metastases. Pediatr Blood Cancer 68 (12): e29331, 2021. [PubMed: 34569132]
15. Cameron AL, Elze MC, Casanova M, et al.: The Impact of Radiation Therapy in Children and Adolescents With Metastatic Rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 111 (4): 968-978, 2021. [PubMed: 34217789]
16. Ferrari A, De Salvo GL, Dall'Igna P, et al.: Salvage rates and prognostic factors after relapse in children and adolescents with initially localised synovial sarcoma. Eur J Cancer 48 (18): 3448-55, 2012. [PubMed: 22835783]
17. Soole F, Maupain C, Defachelles AS, et al.: Synovial sarcoma relapses in children and adolescents: prognostic factors, treatment, and outcome. Pediatr Blood Cancer 61 (8): 1387-93, 2014. [PubMed: 24664883]

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood soft tissue sarcoma. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Childhood Soft Tissue Sarcoma Treatment are:

• Denise Adams, MD (Children's Hospital Boston)
• Louis S. Constine, MD (James P. Wilmot Cancer Center at University of Rochester Medical Center)
• Holcombe Edwin Grier, MD
• Andrea A. Hayes-Jordan, MD, FACS, FAAP (Howard University)
• William H. Meyer, MD (University of Oklahoma Health Sciences Center)
• Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
• Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
• Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
• Stephen J. Shochat, MD (St. Jude Children's Research Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Soft Tissue Sarcoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/soft-tissue-sarcoma/hp/child-soft-tissue-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389361]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website’s Email Us.