Authors' objectives

The authors sought to evaluate therapy in metastatic Ewing's sarcoma. Specifically, whether the intensification of induction chemotherapy, either by dose escalation or the addition of drugs such as etoposide, improves response and outcome, and if consolidation of first complete response with megatherapy and haematopoietic stem cell rescue prolongs relapse-free survival.

Searching

MEDLINE and Cancerlit were searched from 1985 to 1999. The reference lists of the retrieved articles and the reviewers' personal reference lists were also examined. Only published studies were eligible for inclusion. Proceeding abstracts were excluded.

Study selection

Assessment of study quality

A standard grid was used to assess the quality of the studies. A critical appraisal was undertaken on the basis of the following: the number of patients; whether the study was prospective, retrospective, randomised or single arm; the methods of inclusion and evaluation; and the end point definition and analysis. The authors do not state how the papers were assessed for quality, or how many of the reviewers performed the quality assessment.

Data extraction

The authors do not state how the data were extracted for the review, or how many of the reviewers performed the data extraction.

Data were extracted for the categories of: study identification; sample size; age; the number of isolated lung metastases; the method used to detect metastases; chemotherapy regimen; the duration of treatment; the time of local treatment; XRT lung dose; XRT bone (yes or no); the event-free survival; and the overall survival. For patients receiving high-dose treatment, data were presented on the following: the number of participants; the stage of disease; site of metastases; the high-dose regimen; the outcome; and toxic mortality.

Methods of synthesis

Results of the review

Twelve papers examined conventional chemotherapy; these included 16 studies of 12 different chemotherapy regimens. The total number of participants was 645. The results for high-dose therapy with stem cell rescue were taken from 7 studies (123 participants out of a total of 235 high-risk patients required high-dose therapy in first complete response).

The regimens used carried certain early and late toxicities. The small numbers of participants made confidence intervals wide and comparison with previous regimens difficult. The rates of complete response at metastatic sites and local control were high when using combinations of vincristine, actinomycin, cyclophosphamide and doxorubicin, with radiation or surgery. The adverse factors, in terms of survival, were an age of greater than 15 years and combined sites. The relapse-free survival increased from 15% to 20 to 30% with more recent regimens, such as increased doses of alkylating agents and anthracyclines,

High-dose therapy with stem cell rescue, whilst tolerable to the patient group, resulted in a treatment-related mortality of 7% (17 out of 250 patients). Overall, there seemed to be little evidence of any benefit. Patients with isolated lung metastases had significantly better event-free survival at 5 years (odds ratio 2.2) than those presenting with combined sites such as bone, bone marrow and lung (odds ratio 3.9). The use of lung irradiation in children with lung metastases was associated with a reduced incidence of subsequent lung recurrence, and a consistently better, overall relapse-free survival.

Authors' conclusions

For patients with bone or bone marrow metastases, most of the treatment combinations used to date have had little beneficial effect. The timing and nature of local therapy is of importance; it is desirable to sustain dose intensity during the first few weeks of treatment. Surgery is best left until there has been a good response at local sites. In most studies, the timing of local treatment was around 10 to 15 weeks. A lot of work is needed to improve the outcomes in children with metastastic Ewing's sarcoma.

CRD commentary

The review question was clearly sated. The literature search was limited to two databases and only published studies were included. In addition, the search details were relatively sparse. It is therefore possible that some studies may have been missed and the results may be subject to publication bias. Important details of the included studies, which may be of relevance when interpreting the data, were omitted. The narrative synthesis was appropriate and the authors acknowledged the problems of small patient numbers in the studies presented. In addition, some of the publications included an overlap of participants. The quality of the studies was not formally assessed.

The authors' conclusions appear to follow from the results presented, but need to interpreted with caution given the small patient numbers involved and the limited nature of the material presented in the paper.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors state that there is a need for well-designed multicentre trials to answer specific questions, and which are likely to recruit sufficient numbers to answer these questions in a realistic period of time.

Bibliographic details

Pinkerton C R, Bataillard A, Guillo S, Oberlin O, Fervers B, Philip T. Treatment strategies for metastatic Ewing's sarcoma. European Journal of Cancer 2001; 37(11): 1338-1344. [PubMed: 11435062]

Other publications of related interest

1. Fevers, B Bonichon F, Demard, F, Heron JF, Mathoulin S, Philip T, et al. Methodology of the development of diagnostic and therapeutic standards, options and recommendations in oncology. Bull Cancer 1995;82:761-7. 2. Dosquet, P Goldberg J, Matillon Y. How to develop clinical practice guidelines. Bull Cancer 1995;82:754-60.

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Antineoplastic Agents /therapeutic use; Bone Neoplasms /pathology; Child; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation /methods; Humans; Sarcoma, Ewing /secondary /therapy; Treatment Outcome

AccessionNumber

12001004277

Database entry date

31/08/2002

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.