MTE 04.01 Role of Radiotherapy in Multimodality Treatment for SCLC

Abstract

Major advances in SCLC include improvements in RT techniques, the use of prophylactic cranial irradiation (PCI) for all stages of SCLC and the improved combination of chemotherapy and RT (Califano). The role of thoracic radiotherapy is well established in the management of stage I-III SCLC (Pignon). There is increasing evidence in the literature in favor of early concurrent chemo-radiotherapy, and a standard of care for patients with a good performance status is twice-daily thoracic radiotherapy (45 Gy in 3 weeks) with concurrent cisplatin and etoposide (Turrisi). Although current clinical trials are exploring the efficacy of new chemotherapeutic strategies, essential questions related to the optimization of thoracic radiotherapy and the benefit of chemo-radiotherapy in sub-groups of patients remain unanswered, e.g. the elderly (Blackhall). The CONVERT trial (twice-daily (BD) versus once daily (OD) radiotherapy given concurrently with chemotherapy in stage I-III SCLC) was reported at ASCO 2016 (Faivre-Finn). OD RT did not result in a superior survival or worse toxicity than BD RT (two-year survival was 56% (95% CI 50-61) vs 51% (95% CI 45-57), p= 0.14). The survival for both regimens was higher than previously reported and using modern RT techniques radiation toxicities were lower than expected. In the stage IV setting the CREST trial as shown that the addition on thoracic RT to chemotherapy and PCI leads to a significant reduction in intrathoracic recurrence and, despite the lack of a significant benefit in overall survival at 1 year, there were significant improvements in overall survival at 2 years (Slotman). It is crucial that patients with SCLC are given the opportunity to participate in clinical research in order to continue to improve the survival of this disease. Molecular studies are ongoing aiming to gain improved insight into the molecular biology of SCLC, discover and/or validate candidate biomarkers for response, resistance to or toxicity of systemic treatment and radiation. It is expected that this understanding will lead to the development of targeted therapies that will not only prove efficacious but also less toxic than more conventional chemotherapy treatments. In combination with advanced RT techniques and better imaging, it is hoped that the rates of long term survivors will increase significantly in the future. We will address the following controversial questions: 1) Should BDRT be considered standard of care in stage I-III SCLC? 2) Role of CTRT in stage I-II SCLC 3) Role of CTRT in elderly patients with LS-SCLC 4) Should thoracic RT be given to all patients with stage IV SCLC? 1. Califano R, et al. Management of small cell lung cancer: recent developments for optimal care. Drugs. 2012 5;72(4):471-90. 2. Pignon JP, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992; 327:1618-1622. 3. Turrisi AT, et al. Twice daily compared to once-daily thoracic radiotherapy in limited-stage small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999; 340: 265-271. 4. Auperin A, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341(7):476-84. 5. Blanchard P, et al. Prophylactic cranial irradiation in lung cancer. Curr Opin Oncol. 2010; 22(2):94-101. 6. Blackhall F et al. Treatment of limited small cell lung cancer: an old or new challenge? Curr Opin Oncol. 2011; 23(2):158-62. 7. Faivre-Finn C, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017;18(8):1116-1125. 8. Slotman BJ, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015 3;385(9962):36-42. 9. Slotman BJ, et al. Which patients with ES-SCLC are most likely to benefit from more aggressive radiotherapy: A secondary analysis of the Phase III CREST trial. Lung Cancer. 2017; 108:150-153. small-cell, radiotherapy, thoracic