A Phase I/II Study of Chemotherapy Concurrent with Twice-daily Radiotherapy Schedules by Intensity Modulated Radiation Therapy Using Simultaneous Integrated Boost for Limited-stage Small Cell Lung Cancer

背景与目的同步放化疗是局限期小细胞肺癌的标准治疗，但患者局部复发率和远处转移率仍较高，本研究旨在评估同步推量调强放疗治疗局限期小细胞肺癌的安全性和有效性。方法符合局限期小细胞肺癌的患者纳入研究行同步放化疗，放疗采用每日两次方案，应用经典“3+3”模式对肿瘤大体体积（gross target volume, GTV）进行同步推量剂量递增，设定为三个剂量梯度，分别为45 Gy/30 f（单次剂量1.50 Gy）、50 Gy/30 f（单次剂量1.67 Gy）和54 Gy/30 f（单次剂量1.80 Gy）。计划靶体积均为45 Gy/30 f。主要研究终点为放疗期间及结束3个月内毒性反应。次要研究终点包括1年生存率、无进展生存期、局部无进展生存期。结果研究共入组26例患者，中位年龄为52岁（30岁-68岁）。26例患者中，1例出现3级放射性食管炎，未观察到3级及以上放射性肺炎。中位随访时间11.2（3.2-36.2）个月，1年生存率、无进展生存率和局部无进展生存率分别为89.0%、51.0%和85.0%。结论局限期小细胞肺癌采用化疗联合同步推量调强放疗，将GTV由45 Gy提升至54 Gy是安全有效的。Background and objective Twice-daily radiation concurrent with chemotherapy is one of the standard methods for limited-stage small cell lung cancer. hTe study was to evaluate the feasibility of chemotherapy concurrent with dose-escalating twice-daily radiotherapy by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) approach in patients with limited-stage small cell lung cancer. Methods Patients with limited-stage small cell lung cancer were included, treated with twice-daily radiotherapy by SIB-IMRT concurrent with chemotherapy of etoposide plus cisplatin. Dose escalation was conducted by“classical”3+3 methods with three patients enrolled in each dose level. The therapeutic gross tumor volume (GTV) was treated according to three consecutive dose levels i.e., 45 Gy at 1.5 Gy twice daily, 50 Gy at 1.67 Gy twice daily and 54 Gy at 1.8 Gy twice daily. hTe planning target volume (PTV) received a dose of 45 Gy delivered in 30 fractions of 1.5 Gy. hTe primary endpoints were acute toxicities. hTe secondary endpoints included overall survival (OS), pro-gression-free survival (PFS) and loco-regional failure-free survival (LRFFS) at 1-year of follow-up. Results Twenty men and six women were included. hTe median age was 52 (30-68) months. 12 patients experienced grade 2 acute esophagitis, and 1 patient developed grade 3 acute esophagitis. Only 3 patients developed Grade 2 pneumonitis. Grade 3 or higher radiation-related pneumonia was not observed. None died of treatment-related causes. With median follow-up of 11.2 months (3.2-36.2 months), 1-year OS, PFS and LRFFS were 89.0%, 51.0%and 85.0%, respectively. Conclusion Dose escalation for twice-daily radiation concurrent with chemotherapy in LS-SCLC has been safely achieved up to 54 Gy for GTV using SIB-IMRT technique.中国科学引文数据库(CSCD)128-342