Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.
目的： 分析局限期小细胞肺癌(SCLC)接受常规分割与大分割调强放疗(IMRT)的不良反应差异，探讨大分割放疗相关不良反应风险因素。 方法： 研究为回顾性研究，选取2016年3月至2022年4月于中国医学科学院肿瘤医院接受根治性IMRT同步化疗的局限期SCLC患者，根据放疗分割模式将患者分为常规分割组与大分割组。采用不良事件通用术语标准5.0版对放射性食管损伤和肺损伤进行分级。影响因素分析采用logistic回归分析。 结果： 211例患者中，常规分割组108例，大分割组103例。常规分割组和大分割组患者中≥2级急性食管炎累积发生率分别为38.9%(42/108)和35.0%(36/103)，≥3级急性食管炎累积发生率分别为1.9%(2/108)和5.8%(6/103)，差异均无统计学意义(均P>0.05)，每组各有1例患者发生≥2级晚期食管损伤。常规分割组和大分割组患者中≥2级急性肺炎累积发生率分别为12.0%(13/108)和5.8%(6/103)，≥2级晚期肺损伤累积发生率分别为5.6%(6/108)和10.7%(11/103)，差异均无统计学意义(均P>0.05)。两组患者均无≥3级肺损伤发生。大分割组中，食管平均剂量(D(mean))≥13 Gy(OR＝3.33，95% CI：1.23~9.01)、计划靶体积(PTV)与食管重叠体积≥8 cm(3)(OR＝3.99，95% CI：1.24~12.79)是发生2级及以上急性食管炎的独立危险因素(均P<0.05)，是否患有慢性阻塞性肺疾病(OR＝7.08，95% CI：1.28~39.19)与≥2级急性肺炎的发生有关(P＝0.025)；肿瘤部位(OR＝4.31，95% CI：1.10~16.94)与发生≥2级晚期肺损伤有关(P＝0.036)。 结论： 局限期SCLC接受大分割IMRT不良反应可控，食管D(mean)、PTV与食管重叠体积是≥2级急性食管炎的独立影响因素，慢性阻塞性肺疾病及肿瘤部位与放射性肺损伤的发生有关。.
Keywords: Lung neoplasms; Radiation dose hypofractionation; Radiation-induced esophagus injuries; Radiation-induced lung injuries; Radiotherapy, intensity-modulated; Small cell carcinoma.