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Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis

Abstract : Background Chemotherapy combined with radiotherapy is the standard treatment of “limited-stage” small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and chemotherapy. Material and methods We performed a meta-analysis of individual patient data in randomised trials comparing earlier versus later radiotherapy, or shorter vs. longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival. Results Twelve trials with 2,668 patients were eligible. Data from nine trials comprising 2,305 patients were available for analysis. The median follow-up was 10 years. When all trials were analysed together, “earlier or shorter” vs. “later or longer” thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of “earlier or shorter” radiotherapy among trials with a similar proportion of patients who were compliant with chemotherapy (defined as having received 100% or more of the planned chemotherapy cycles) in both arms (HR 0.79, 95% CI 0.69–0.91) and in favour of “later or longer” radiotherapy among trials with different chemotherapy compliance (HR 1.19, 1.05–1.34, interaction test p<0.0001). The absolute gain between “earlier or shorter” vs. “later or longer” thoracic radiotherapy in 5-year overall survival for similar and for different chemotherapy compliance trials was 7.7% (95% CI 2.6–12.8 %) and -2.2% (-5.8–1.4 %), respectively. However, “earlier or shorter” thoracic radiotherapy was associated with a higher incidence of severe acute oesophagitis than “later or longer” radiotherapy. Conclusion “Earlier or shorter” delivery of thoracic radiotherapy with planned chemotherapy significantly improves 5-year overall survival at the expense of more acute toxicity, especially oesophagitis.
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https://www.hal.inserm.fr/inserm-01441456
Contributor : Béranger Lueza <>
Submitted on : Thursday, January 19, 2017 - 5:25:35 PM
Last modification on : Wednesday, September 16, 2020 - 5:12:09 PM

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D. de Ruysscher, B. Lueza, C. Le Péchoux, H. Johnson, M. O'Brien, et al.. Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis. Annals of Oncology, Elsevier, 2016, 27 (10), pp.1818 - 1828. ⟨10.1093/annonc/mdw263⟩. ⟨inserm-01441456⟩

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