CRD summary

This review concluded that there was evidence in favour of adding hypoxic modification to radiotherapy for the treatment of squamous cell carcinomas of the head and neck. It is difficult to judge the reliability of these conclusions given the lack of details on trial quality and lack of transparency in the review process and methods.

Authors' objectives

To assess the efficacy of hypoxic modification of radiotherapy for the treatment of squamous cell carcinoma of the head and neck.

Searching

MEDLINE and SCOPUS were searched. Search terms were reported, but search dates were not. The author did not report whether language restrictions were applied to the search. Abstracts from a number of relevant conferences were searched for unpublished studies. Study authors, experts in the field and pharmaceutical companies were contacted for any additional studies.

Study selection

Randomised controlled trials (RCTs) that compared curative intended primary radiotherapy alone versus the addition of hypoxic modification of radiotherapy (being known only to influence hypoxic radioresistance and have no other cytotoxic effect) in patients with squamous cell carcinoma of the head and neck were eligible for inclusion. Trials that involved chemoradiotherapy either as baseline treatment or as an intended hypoxic modifier or hyperthermia were excluded, as were trials of patients with metastatic disease. Trials with haemoglobin modification by transfusion or the use of erythropoietin were excluded.

The outcomes of interest were loco-regional failure, disease-specific survival, overall survival, occurrence of distant metastases and radiation-related complications.

In the included trials, hypoxic modification involved oxygen breathing under normobaric/hyperbaric pressure or the use of nitroimidazoles. The fractionation schedules varied between included trials. The mean age of included patients was not reported. The included trials were published from 1962 to 2010.

The author did not state how many reviewers assessed studies for inclusion.

Assessment of study quality

The authors did not state that they assessed study quality.

Data extraction

Data were extracted on event rates to calculate of odds ratios (ORs) with 95% confidence intervals (CIs).

The author did not state how many reviewers performed data extraction.

Methods of synthesis

The trials were combined in a meta-analysis. Pooled odds ratios with 95% confidence intervals were calculated, but it was unclear which method (fixed-effect or random-effects model) was used. The numbers needed to treat (NNT) were calculated. Statistical heterogeneity was assessed, but it was unclear which test was employed.

Results of the review

Thirty-two RCTs were included in the review (4,805 patients). The number of patients per trial ranged from 17 to 622. The duration of follow-up ranged from over three months to over five years.

Compared with curative intended primary radiotherapy alone, the addition of hypoxic modifications to radiotherapy in head and neck cancer was associated with a significant reduction in loco-regional failure (OR 0.71, 95% CI 0.63 to 0.80; NNT=13; 32 RCTs), disease-specific death (OR 0.73, 95% CI 0.64 to 0.82; NNT=14; 30 RCTs) and overall death (OR 0.87, 95% CI 0.77 to 0.98; NNT=31; 29 RCTs).

There were no significant differences in the rate of occurrence of distant metastases and radiation-related complications between the two groups.

No significant heterogeneity was observed.

Authors' conclusions

There was evidence in favour of adding hypoxic modification to radiotherapy for the treatment of squamous cell carcinomas of the head and neck.

CRD commentary

The inclusion criteria of the review were clear. Relevant databases were searched. Attempts were made to find both published and unpublished studies, which reduced the potential for publication bias. It was unclear whether language restrictions were applied to the search, which made difficult to assess the risk of language bias. It was unclear whether sufficient attempts were made to minimise errors and biases in any of the review process. A formal quality assessment of included trials was not performed. Statistical heterogeneity was assessed, but it was unclear which methods were used to pool the results.

Without further details on trial quality, and given a number of limitations outlined above, it is difficult to judge the reliability of the authors' conclusions.

Implications of the review for practice and research

Practice: The author stated that, unless a lack of hypoxic radioresistance could be shown in tumours, hypoxic modification should be part of the optimal radiotherapeutic treatment strategy for patients with squamous cell carcinoma of the head and neck.

Research: The author did not state any implications for further research.

Funding

Danish Cancer Society; Danish Research Council; Lundbeck Foundation Center for Interventional Research in Radiation Oncology (CIRRO), Denmark.

Bibliographic details

Overgaard J. Hypoxic modification of radiotherapy in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis. Radiotherapy and Oncology 2011; 100(1): 22-32. [PubMed: 21511351]

Original Paper URL

http://www.thegreenjournal.com/article/S0167-8140(11)00125-3/abstract

Indexing Status

Subject indexing assigned by NLM

MeSH

Anoxia /metabolism; Carcinoma, Squamous Cell /mortality /pathology /radiotherapy; Head and Neck Neoplasms /mortality /pathology /radiotherapy; Humans; Neoplasm Metastasis; Radiotherapy /adverse effects; Radiotherapy Dosage

AccessionNumber

12011005398

Database entry date

21/05/2012

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.