title: Positive Interaction between Prophylactic Cranial Irradiation and Maintenance Sunitinib for Untreated Extensive-Stage Small Cell Lung Cancer Patients After Standard Chemotherapy: A Secondary Analysis of CALGB 30504 (ALLIANCE).
abstract: BACKGROUND
  Prophylactic cranial irradiation (PCI) has become a standard option for patients with extensive-stage small cell lung cancer (ES-SCLC). The Cancer and Leukemia Group B 30504 trial was a randomized phase II study of the effect of sunitinib versus placebo in ES-SCLC patients responding to platinum-based systemic therapy. The study required preenrollment brain imaging. PCI was provided at the discretion of treating physicians. We performed a secondary analysis of the Cancer and Leukemia Group B trial to determine the impact of PCI on patients with ES-SCLC.
  
  
  METHODS
  Fisher's exact test and the Wilcoxon rank-sum test were conducted to identify the differences between patients receiving PCI and patients not receiving PCI. Kaplan-Meier analyses described progression-free survival (PFS) and overall survival (OS) for patients in the PCI and non-PCI groups.
  
  
  RESULTS
  A total of 85 patients received maintenance therapy (41 received placebo and 44 received sunitinib). Patient characteristics were balanced between the PCI and non-PCI groups. The patients receiving PCI plus sunitinib had a nonsignificant 2.7-month improvement in PFS (5.0 months versus 2.3 months, p = 0.14, hazard risk [HR] = 0.62, 95% confidence interval [CI]: 0.33-1.18) trending toward improved OS (8.9 months versus 5.4 months, p = 0.053, HR = 0.47, 95% CI: 0.22-1.03). PCI was associated with a trend toward improved median PFS (2.9 months versus 2.2 months, p = 0.096, HR = 0.69, 95% CI: 0.45-1.07) but not median OS (8.3 months in the PCI group versus 8.7 months in the non-PCI group, p = 0.76, HR = 1.07, 95% CI: 0.67-1.71). The patients receiving placebo had no improvement in PFS or OS with PCI.
  
  
  CONCLUSIONS
  Trends toward improved PFS and OS were seen in patients receiving PCI and sunitinib, thus supporting the need for further prospective research evaluating the integration of maintenance systemic therapy and PCI for patients with ES-SCLC. Improved outcomes for patients with ES-SCLC after induction chemotherapy may require PCI, thoracic radiotherapy, and maintenance systemic therapy to achieve control of both intracranial and extracranial disease.
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, NC, USA. Electronic address: joseph.salama@duke.edu.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Salama
authors.affiliation: Alliance Statistics and Data Center, Duke University, Durham, NC, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.affiliation: Alliance Statistics and Data Center, Duke University, Durham, NC, USA.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Alliance Statistics and Data Center, Duke University, Durham, NC, USA; School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong SAR, People's Republic of China.
authors.forename: Herbert H
authors.initials: HH
authors.lastname: Pang
authors.affiliation: Department of Radiation Oncology, SUNY Upstate Medical Center, Syracuse, NY, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bogart
authors.affiliation: Section of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crawford
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schild
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.affiliation: Section of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA.
authors.forename: Neal E
authors.initials: NE
authors.lastname: Ready
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D016371:Cranial Irradiation / Q000379:methods*; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D000077210:Sunitinib
chemical_list: D007211:Indoles; D010919:Placebos; D011758:Pyrroles; D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin; D000077210:Sunitinib
keywords: Extensive-stage small cell lung cancer; Maintenance chemotherapy; Prophylactic cranial irradiation; Sunitinib; Survival