Simultaneous integrated boost vs. routine IMRT in limited-stage small-cell lung cancer:an open-label,non-inferiority,randomized, phase 3 trial
Zhan Tianyou, Zhang Tao, Zhou Zongmei, Yan Wenbin, Zhai Yirui, Deng Lei, Wang Wenqing, Bi Nan, Wang Jianyang, Wang Xin, Liu Wenyang, Xiao Zefen, Feng Qinfu, Chen Dongfu, Lyu Jima, Hui Zhouguang, Liang Jun, Wang Lyuhua
Department 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 100021, China
Abstract：Objective Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy. Methods Patients diagnosed with treatment-naiveand confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1:1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2Gy/2.15Gy/28F,PTV 50.4Gy/1.8Gy/28F) or conventional fractionated radiotherapy (PTV 60Gy/2Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity. Results Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95%CI:35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%(HR=1.22,95%CI:0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%(HR=1.35,95%CI:0.90-2.04,P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%(HR=0.98,95%CI:0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups (HR=1.69,95%CI:1.18-2.41,P=0.003;HR=1.72,95%CI:1.09-2.70,P=0.018;HR=1.66,95%CI:1.01-2.73,P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64,95%CI:1.15-11.57,P=0.028). The most common grade 3–4 adverse events were myelosuppression (21.7% vs. 15.4%,P=0.83),radiation pneumonitis (4.7% vs. 2.7%,P=0.44) and radiation esophagitis (3.8% vs. 1.8%,P=0.51). Conclusions Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.
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