194 - Simultaneous Integrated Boost vs. Conventional Radiotherapy for Patients with Limited-Stage Small Cell Lung Cancer: A Randomized, Non-Inferiority, Open-Label, Phase 3 Trial

T. Zhan¹, T. Zhang¹, L. Deng¹, W. Wang¹, X. Wang¹, J. Wang², W. Liu Jr¹, F. Qinfu¹, Y. Zhai³, Z. Xiao³, N. Bi¹, Y. X. Li³, and Z. Zhou³; ¹Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, ²Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, ³Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Purpose/Objective(s): Simultaneous integrated boost radiotherapy delivered a definitive dose to gross tumor volume and a decreased dose to clinical tumor volume and organ at risk. This study aimed to determine whether the simultaneous integrated boost is noninferior to conventional radiotherapy limited-stage small cell lung cancer (LS-SCLC). Materials/

Methods: This randomized, non-inferiority, open-label, phase 3 study was done in a single center in China. Patients aged 18–75 years who had cytologically or histologically confirmed LS-SCLC were eligible. Patients were randomly assigned (1:1) to receive conventional fractionated radiotherapy (PTV: 60Gy/2Gy/30F) or Simultaneous integrated boost radiotherapy (PGTV: 60.2Gy/2.15Gy/28F, PTV: 50.4Gy/1.8Gy/28F) with either concurrent or sequential EP/EC chemotherapy. Patients were randomly assigned (1:1), with block randomization (block sizes of 8) and stratified by the timing of TRT. The primary endpoint was progression-free survival, defined as time from randomization until death from any cause, analyzed by modified intention to- treat, and a 10% margin was used to establish non-inferiority (equivalent to a hazard ratio <1.34). This trial is registered at ClinicalTrials.gov, number NCT04500145 and is currently in follow-up.
Results: Between Feb 7, 2017, and Mar, 14, 2023, 321 patients were enrolled and randomly assigned to conventional fractionated radiotherapy group (n = 163) and simultaneous integrated boost radiotherapy (n = 158). At a median follow-up of 56 months (95%CI: 52.18-59.81), median progression-free survival was 16 months (95%CI: 11-27) in the conventional fractionated radiotherapy group versus 16 months (95%CI: 10-21) in the simultaneous integrated boost radiotherapy group (hazard ratio for progression in SIB group 1.00 [95%CI: 0.77-1.30]; P = 0.97). 2-year progression-free survival was 42.7% and 38.1% (absolute difference -1.2%, 95%CI -8.8% to 11.2%; P = 0.01 for non-inferiority). The incidence of 3-4 acute radiation pneumonitis in the groups were 7.6% and 2.5%, respectively (P = 0.030), with no significant difference in other acute toxicities. In the dose parameters, a decreased V20 (median: 22.81% vs 21.00%) and D-mean (median: 13.37Gy vs 12.06Gy) of lungs in SIB group was observed (Both P < 0.001).
Conclusion: Simultaneous integrated boost radiotherapy was non-inferior to conventional fractionated radiotherapy in treatment efficacy and results in less 3-4 acute radiation pneumonitis, which might associate with decreased lung dose. Our findings suggest that simultaneous integrated boost radiotherapy could be considered as standard of care.