Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou; Lung Cancer Institute of Sun Yat-sen University, Guangzhou; Guangdong Association Study of Thoracic Oncology, Guangzhou.
Department of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou.
Pract Radiat Oncol. 2021 Sep-Oct;11(5):374-383. doi: 10.1016/j.prro.2021.06.004. Epub 2021 Jun 20.
We aimed to explore the efficacy and toxicity of split-course hypofractionated radiation therapy with concurrent chemotherapy (HRT-CHT) in patients with locally advanced non-small cell lung cancer (LANSCLC) in this single-arm, phase II study.
Patients with LANSCLC were considered eligible if their forced expiratory volume in 1 second/forced vital capacity (FEV/FVC%) and carbon monoxide diffusing capacity (DLCO%) were ≥40% and ≥45%, respectively. HRT-CHT using the intensity modulated radiation therapy technique was administered with 51 Gy in 17 fractions as the first course followed by a break. Patients without disease progression or persistent ≥grade 2 toxicities had an HRT-CHT of 15 to 18 Gy in 5 to 6 fractions as a boost. The primary endpoint was progression-free survival, and the secondary endpoint was overall survival (OS).
Eighty-nine patients were enrolled and analyzed. The median follow-up was 29.5 months for all patients and 35.3 months for the survivors. The objective response rate was 97.8%; the median progression-free survival and OS were 11.0 and 27.0 months, respectively. Grade 3 acute esophagitis/pneumonitis occurred in 15 (16.9%)/7 (7.9%) patients. Grade 3/5 late pneumonitis occurred in 2 (2.2%)/1 (1.1%) patients. Of the 78 (87.6%) who completed the split-course HRT-CHT per protocol, patients with better FEV/FVC% and DLCO% after the break had significantly better OS (for the FEV/FVC1% ≥ 80% vs 60%-79% vs 41%-59% groups, 2-year OS values were 57.2% vs 56.9% vs 0%, respectively, P = .024; for the DLCO% ≥ 80% vs 60%-79% vs 45%-59% groups, 2-year OS values were 70.4% vs 48.4% vs 37.5%, respectively, P = .049).
Split-course HRT-CHT achieved a promising response rate and survival with tolerable toxicity in LANSCLC. Pulmonary function tests are necessary indicators for radiation treatment planning and dose escalation.
在这项单臂、二期研究中，我们旨在探索分割疗程低分割放疗联合化疗（HRT-CHT）治疗局部晚期非小细胞肺癌（LANSCLC）的疗效和毒性。
如果患者的 1 秒用力呼气量/用力肺活量（FEV/FVC%）和一氧化碳弥散量（DLCO%）分别≥40%和≥45%，则认为其符合 LANSCLC 入组条件。采用调强放疗技术进行 HRT-CHT，第一疗程给予 51Gy，共 17 次分割，之后休息。无疾病进展或持续≥2 级毒性的患者接受 15 至 18Gy，共 5 至 6 次分割作为推量。主要终点是无进展生存期，次要终点是总生存期（OS）。
共纳入并分析了 89 例患者。所有患者的中位随访时间为 29.5 个月，幸存者的中位随访时间为 35.3 个月。客观缓解率为 97.8%；中位无进展生存期和 OS 分别为 11.0 个月和 27.0 个月。15 例（16.9%）/7 例（7.9%）患者出现 3 级急性食管炎/肺炎。2 例（2.2%）/1 例（1.1%）患者出现 3/5 级迟发性肺炎。根据方案完成分割疗程 HRT-CHT 的 78 例（87.6%）患者中，休息后 FEV/FVC%和 DLCO%更好的患者 OS 显著改善（FEV/FVC1%≥80%组 vs 60%-79%组 vs 41%-59%组，2 年 OS 值分别为 57.2% vs 56.9% vs 0%，P=0.024；DLCO%≥80%组 vs 60%-79%组 vs 45%-59%组，2 年 OS 值分别为 70.4% vs 48.4% vs 37.5%，P=0.049）。
分割疗程 HRT-CHT 治疗 LANSCLC 可获得有前景的缓解率和生存获益，且毒性可耐受。肺功能检查是放疗计划和剂量递增的必要指标。
