D De Ruysscher1, B Lueza2, C Le Péchoux3, D H Johnson4, M O'Brien5, N Murray6, S Spiro7, X Wang8, M Takada9, B Lebeau10, W Blackstock11, D Skarlos12, P Baas13, H Choy14, A Price15, L Seymour16, R Arriagada17, J-P Pignon18. 1. Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands Department of Oncology, Experimental Radiation Oncology, KU Leuven, Leuven, Belgium. 2. Department of Biostatistics and Epidemiology and "Ligue Nationale Contre le Cancer" meta-analysis platform, Gustave Roussy, Villejuif, France CESP, INSERM U1018, Université Paris-Sud, Université Paris-Saclay, Villejuif. 3. Department of Oncology and radiation therapy, Gustave Roussy, Villejuif Université Paris-Sud, Université Paris-Saclay, Villejuif, France. 4. UT Southwestern University School of Medicine, Dallas, USA. 5. EORTC Data Center, Brussels, Belgium. 6. British Columbia Cancer Agency, Vancouver, Canada. 7. University College London Hospitals, London, UK. 8. Alliance Data and Statistical Center, Duke University, Durham, USA. 9. Osaka Prefectural Habikino Hospital, Osaka, Japan. 10. Hôpital St Antoine, Paris, France. 11. Wake Forest University School of Medicine, Winston-Salem, USA. 12. Second Department of Medical Oncology, Metropolitan Hospital N. Faliro, Athens, Greece. 13. The Netherlands Cancer Institute, Amsterdam, The Netherlands. 14. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, USA. 15. NHS Lothian and University of Edinburgh, Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK. 16. NCIC Clinical Trials Group and Queen's University, Kingston, Canada. 17. Gustave Roussy, Villejuif, France Karolinska Institutet, Stockholm, Sweden. 18. Department of Biostatistics and Epidemiology and "Ligue Nationale Contre le Cancer" meta-analysis platform, Gustave Roussy, Villejuif, France CESP, INSERM U1018, Université Paris-Sud, Université Paris-Saclay, Villejuif jean-pierre.pignon@gustaveroussy.fr.
Abstract
BACKGROUND: Chemotherapy (CT) 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 CT. MATERIALS AND METHODS: We carried out a meta-analysis of individual patient data in randomized trials comparing earlier versus later radiotherapy, or shorter versus 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 2668 patients were eligible. Data from nine trials comprising 2305 patients were available for analysis. The median follow-up was 10 years. When all trials were analysed together, 'earlier or shorter' versus '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 CT (defined as having received 100% or more of the planned CT 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 rates of CT compliance (HR 1.19, 1.05-1.34, interaction test, P < 0.0001). The absolute gain between 'earlier or shorter' versus 'later or longer' thoracic radiotherapy in 5-year overall survival for similar and for different CT compliance trials was 7.7% (95% CI 2.6-12.8%) and -2.2% (-5.8% to 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 CT significantly improves 5-year overall survival at the expense of more acute toxicity, especially oesophagitis.
BACKGROUND: Chemotherapy (CT) 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 CT. MATERIALS AND METHODS: We carried out a meta-analysis of individual patient data in randomized trials comparing earlier versus later radiotherapy, or shorter versus 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 2668 patients were eligible. Data from nine trials comprising 2305 patients were available for analysis. The median follow-up was 10 years. When all trials were analysed together, 'earlier or shorter' versus '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 CT (defined as having received 100% or more of the planned CT 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 rates of CT compliance (HR 1.19, 1.05-1.34, interaction test, P < 0.0001). The absolute gain between 'earlier or shorter' versus 'later or longer' thoracic radiotherapy in 5-year overall survival for similar and for different CT compliance trials was 7.7% (95% CI 2.6-12.8%) and -2.2% (-5.8% to 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 CT significantly improves 5-year overall survival at the expense of more acute toxicity, especially oesophagitis.
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