IIIA-N2期非小细胞肺癌诱导化疗后手术切除与放射治疗的随机对照试验

Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer.

作者信息

van Meerbeeck Jan P, Kramer Gijs W P M, Van Schil Paul E Y, Legrand Catherine, Smit Egbert F, Schramel Franz, Tjan-Heijnen Vivianne C, Biesma Bonne, Debruyne Channa, van Zandwijk Nico, Splinter Ted A W, Giaccone Giuseppe

机构信息

Department of Respiratory Medicine, 7K12IE, University Hospital Ghent, De Pintelaan 185, 9000 Gent, Belgium.

出版信息

J Natl Cancer Inst. 2007 Mar 21;99(6):442-50. doi: 10.1093/jnci/djk093.

DOI:10.1093/jnci/djk093

PMID:17374834

Abstract

BACKGROUND

Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy.

METHODS

Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. Responding patients were subsequently randomly assigned to surgical resection or radiotherapy. Survival curves were estimated using Kaplan-Meier analyses from time of randomization.

RESULTS

Induction chemotherapy resulted in a response rate of 61% (95% confidence interval [CI] = 57% to 65%) among the 579 eligible patients. A total of 167 patients were allocated to resection and 165 to radiotherapy. Of the 154 (92%) patients who underwent surgery, 14% had an exploratory thoracotomy, 50% a radical resection, 42% a pathologic downstaging, and 5% a pathologic complete response; 4% died after surgery. Postoperative radiotherapy was administered to 62 (40%) of patients in the surgery arm. Among the 154 (93%) irradiated patients, overall compliance to the radiotherapy prescription was 55%, and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7%; one patient died of radiation pneumonitis. Median and 5-year overall survival for patients randomly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (hazard ratio = 1.06, 95% CI = 0.84 to 1.35). Rates of progression-free survival were also similar in both groups.

CONCLUSION

In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy, surgical resection did not improve overall or progression-free survival compared with radiotherapy. In view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these patients.

摘要

背景

对于ⅢA-N2期非小细胞肺癌（NSCLC）患者，手术切除前进行诱导化疗相比单纯手术切除可提高生存率。我们假设，在诱导化疗有效后，手术切除作为局部区域治疗将优于胸部放疗。

方法

选择经组织学或细胞学证实为ⅢA-N2期NSCLC的患者，给予三个周期的铂类诱导化疗。随后，将有反应的患者随机分配至手术切除组或放疗组。从随机分组时间开始，使用Kaplan-Meier分析估计生存曲线。

结果

在579例符合条件的患者中，诱导化疗的缓解率为61%（95%置信区间[CI]=57%至65%）。共有167例患者被分配至手术切除组，165例被分配至放疗组。在接受手术的154例（92%）患者中，14%进行了 exploratory thoracotomy（探查性开胸手术），50%进行了根治性切除，42%实现了病理降期，5%达到了病理完全缓解；4%在术后死亡。手术组中有62例（40%）患者接受了术后放疗。在154例（93%）接受放疗的患者中，放疗处方的总体依从率为55%，3/4级急性和晚期食管及肺部毒性反应的发生率分别为4%和7%；1例患者死于放射性肺炎。随机分配至手术切除组与放疗组的患者的中位总生存期和5年总生存率分别为16.4个月对17.5个月和15.7%对14%（风险比=1.06，95%CI=0.84至1.35）。两组的无进展生存率也相似。