Brooks B J, Seifter E J, Walsh T E, Lichter A S, Bunn P A, Zabell A, Johnston-Early A, Edison M, Makuch R W, Cohen M H
J Clin Oncol. 1986 Feb;4(2):200-9. doi: 10.1200/JCO.1986.4.2.200.
To assess the pulmonary toxicity of radiation therapy combined with chemotherapy v chemotherapy alone, we reviewed the clinical course of 80 patients with limited stage small-cell lung cancer treated in a randomized prospective trial. Life-threatening pulmonary toxicity, defined as bilateral pulmonary infiltrates extending beyond radiation ports with symptoms requiring hospital admission, developed in 11 patients (28%) receiving combined modality therapy and in two (5%) receiving chemotherapy alone. Eight of these 13 patients died from pulmonary complications with no clinical evidence of tumor in five. Pulmonary toxicity initially presented at a median of 63 days (range, 21 to 150 days) after the start of combined modality therapy and at a median of 217 days after chemotherapy alone. Biopsies obtained in 11 patients with severe toxicity revealed only interstitial fibrosis with no evidence of an infectious agent. Review of pretreatment parameters such as age, performance status, and radiation portal area failed to reveal any significant differences between patients with or without pulmonary complications. However, initial pulmonary function tests (PFTs) revealed a significantly lower vital capacity (P = .03) and forced expiratory volume (FEV/1.0 second) (P = .04) in patients with subsequent pulmonary complications. Pulmonary toxicity was significantly more common with combined modality therapy than with chemotherapy alone (P = .017) and worse than expected with radiotherapy alone. Six- or 12-month PFTs in completely responding patients revealed improvement within the chemotherapy alone group and no clear trend within the combined modality group. For the group treated with radiation therapy and chemotherapy, there was significantly less improvement after 6 or 12 months in the forced vital capacity (P less than .005) and FEV/1.0 second (P less than .005) than observed for the group treated with chemotherapy alone. Despite the increased incidence of pulmonary toxicity, overall survival favored the combined modality arm (P = .07). Enhanced local control and disease-free survival appeared to compensate for the initial increased pulmonary morbidity and mortality in the group with combined modality therapy.
为评估放疗联合化疗与单纯化疗相比的肺毒性，我们回顾了80例局限期小细胞肺癌患者在一项随机前瞻性试验中的临床病程。危及生命的肺毒性定义为双侧肺部浸润超出放疗野且伴有需住院治疗的症状，在接受联合治疗的11例患者（28%）和单纯接受化疗的2例患者（5%）中出现。这13例患者中有8例死于肺部并发症，其中5例无肿瘤的临床证据。肺毒性最初出现在联合治疗开始后的中位63天（范围21至150天），而在单纯化疗后中位217天出现。对11例有严重毒性的患者进行活检，仅显示间质纤维化，无感染病原体证据。回顾预处理参数如年龄、体能状态和放疗野面积，未发现有或无肺部并发症患者之间存在任何显著差异。然而，初始肺功能测试（PFTs）显示，后续有肺部并发症的患者肺活量（P = 0.03）和用力呼气量（FEV/1.0秒）（P = 0.04）显著降低。联合治疗的肺毒性明显比单纯化疗更常见（P = 0.017），且比单纯放疗预期的更严重。完全缓解患者的6个月或12个月PFTs显示，单纯化疗组有所改善，而联合治疗组无明显趋势。对于接受放疗和化疗的组，6个月或12个月后用力肺活量（P < 0.005）和FEV/1.0秒（P < 0.005）的改善明显少于单纯化疗组。尽管肺毒性发生率增加，但总体生存有利于联合治疗组（P = 0.07）。增强的局部控制和无病生存似乎弥补了联合治疗组最初增加的肺部发病率和死亡率。
