Preoperative radiotherapy for esophageal carcinoma

S J Arnott, W Duncan, M Gignoux, H S Hansen, B Launois, K Nygaard, M K B Parmar, A Rousell, G Spilopoulos, G Stewart, J F Tierney, M Wang, Z Rhugang, Oeosphageal Cancer Collaborative Group, S J Arnott, W Duncan, M Gignoux, H S Hansen, B Launois, K Nygaard, M K B Parmar, A Rousell, G Spilopoulos, G Stewart, J F Tierney, M Wang, Z Rhugang, Oeosphageal Cancer Collaborative Group

Abstract

Background: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma.

Objectives: This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy

Search strategy: MEDLINE and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. The search strategy was run again in MEDLINE, EMBASE and the Cochrane Library on 30th April 2001, two years after original publication. No new trials were found. The search strategy was re-run August 2002 and August 2003 on MEDLINE, EMBASE , CancerLit and The Cochrane Library, and July 2004 and 2005 on MEDLINE, EMBASE and the Cochrane Library. No new relevant trials were identified on any of these occasions.

Selection criteria: Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995).

Data collection and analysis: A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location.

Main results: With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent.

Authors' conclusions: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%).

Conflict of interest statement

There is no known conflict of interest.

Figures

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1
Forest plot of comparison: 1 Preoperative radiotherapy (with or without chemotherapy) versus (with or without chemotherapy) surgery, outcome: 1.1 Survival.
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2
Simple (non‐stratified) survival curves of preoperative radiotherapy (with or without chemotherapy) versus (with or without chemotherapy) surgery.
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3
Effect of preoperative radiotherapy (with or without chemotherapy) versus (with or without chemotherapy) surgery by sex, age and tumor location. Sex: interaction chisquare=3.15, df=1, p=0.08; Age: Sex: trend chisquare=0.76, df=1, p=0.38; tumor location: intercation chisquare= 1.31, df=1, p=0.25.

References

References to studies included in this review Arnott 1992 {published and unpublished data}

    1. Arnott SJ, Duncan W, Kerr GR, Walbaum PR, Cameron E, Jack WJL, et al. Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial. Radiotherapy and Oncology 1992;24:108‐13.
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Nygaard 1992 (a) {published and unpublished data}
    1. Nygaard K, Hagen S, Hansen HS, Hatlevoll R, Hultborn R, Jakobsen A, et al. Pre‐operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre‐operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. World Journal of Surgery 1992;16:1104‐10.
Nygaard 1992 (b) {published and unpublished data}
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References to studies excluded from this review de Pree 1995 {published data only}
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References to other published versions of this review OCCG 1998
    1. Arnott SJ, Duncan W, Gignoux M, Girling DJ, Hansen HS, Launois B, et al. Preoperative radiotherapy in esophageal carcinoma: a meta‐analysis using individual patient data (Oesophageal Cancer Collaborative Group). International Journal of Radiation Oncology Biology Physics 1998;41(3):579‐83.

Source: PubMed

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