title: Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA-N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy.
abstract: BACKGROUND
  This study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA-N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy.
  
  
  METHODS
  In this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life.
  
  
  RESULTS
  This trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46-0.98; P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14-0.57; P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56-1.16; P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild.
  
  
  CONCLUSIONS
  In patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.
authors.affiliation: Department of Thoracic Surgery Department of Experimental Research.
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou.
authors.forename: Z-F
authors.initials: ZF
authors.lastname: Zeng
authors.affiliation: Department of Thoracic Surgery wsysums@163.net.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery.
authors.forename: W
authors.initials: W
authors.lastname: Ou
authors.affiliation: Department of Thoracic Surgery, Guangdong General Hospital, Guangzhou.
authors.forename: X
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou.
authors.forename: X-H
authors.initials: XH
authors.lastname: He
authors.affiliation: Department of Thoracic Surgery, Henan Chest Hospital, Zhengzhou.
authors.forename: B-B
authors.initials: BB
authors.lastname: Zhang
authors.affiliation: Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Wuhan.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Henan Cancer Hospital, Zhengzhou.
authors.forename: H-B
authors.initials: HB
authors.lastname: Sun
authors.affiliation: Department of Surgical Oncology, The Central People's Hospital of Huizhou City, Huizhou.
authors.forename: Q
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Guangzhou Medical University, Guangzhou, China.
authors.forename: B-X
authors.initials: BX
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000628:therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000639:trends; D016371:Cranial Irradiation / Q000639:trends*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000639:trends; D056990:Post-Exposure Prophylaxis / Q000639:trends*; D011446:Prospective Studies; D013510:Pulmonary Surgical Procedures / Q000639:trends*; D012307:Risk Factors; D057832:Watchful Waiting / Q000639:trends*
keywords: cerebral metastases; non-small-cell lung cancer; phase III clinical trial; prophylactic cranial irradiation