title: Prophylactic cranial irradiation in locally advanced non-small-cell lung cancer after multimodality treatment: long-term follow-up and investigations of late neuropsychologic effects.
abstract: OBJECTIVE
  Relapse pattern and late toxicities in long-term survivors were analyzed after the introduction of prophylactic cranial irradiation (PCI) into a phase II trial on trimodality treatment of locally advanced (LAD) non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Seventy-five patients with stage IIIA(N2)/IIIB NSCLC were treated with induction chemotherapy, preoperative radiochemotherapy, and surgery. PCI was routinely offered during the second period of study accrual. Patients were given a total radiation dose of 30 Gy (2 Gy per daily fraction) over a 3-week period starting 1 day after the last chemotherapy cycle.
  
  
  RESULTS
  Introduction of PCI reduced the rate of brain metastases as first site of relapse from 30% to 8% at 4 years (P =.005) and that of overall brain relapse from 54% to 13% (P <.0001). The effect of PCI was also observed in the good-prognosis subgroup of 47 patients who had a partial response or complete response to induction chemotherapy, with a reduction of brain relapse as first failure from 23% to 0% at 4 years (P =.01). Neuropsychologic testing revealed impairments in attention and visual memory in long-term survivors who received PCI as well as in those who did not receive PCI. T2-weighted magnetic resonance imaging revealed white matter abnormalities of higher grades in patients who received PCI than in those who did not.
  
  
  CONCLUSIONS
  PCI at a moderate dose reduced brain metastases in LAD-NSCLC to a clinically significant extent, comparable to that in limited-disease small-cell lung cancer. Late toxicity to normal brain was acceptable. This study supports the use of PCI within intense protocols for LAD-NSCLC, particularly in patients with favorable prognostic factors.
authors.affiliation: Departments of Radiotherapy, Internal Medicine (Cancer Research), Radiology, and Neurology, University of Essen Medical School, and Department of Pneumology and Thoracic Surgery, Ruhrlandklinik, Essen-Heidhausen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stuschke
authors.forename: W
authors.initials: W
authors.lastname: Eberhardt
authors.forename: C
authors.initials: C
authors.lastname: Pöttgen
authors.forename: G
authors.initials: G
authors.lastname: Stamatis
authors.forename: H
authors.initials: H
authors.lastname: Wilke
authors.forename: G
authors.initials: G
authors.lastname: Stüben
authors.forename: F
authors.initials: F
authors.lastname: Stöblen
authors.forename: H H
authors.initials: HH
authors.lastname: Wilhelm
authors.forename: H
authors.initials: H
authors.lastname: Menker
authors.forename: H
authors.initials: H
authors.lastname: Teschler
authors.forename: R D
authors.initials: RD
authors.lastname: Müller
authors.forename: V
authors.initials: V
authors.lastname: Budach
authors.forename: S
authors.initials: S
authors.lastname: Seeber
authors.forename: H
authors.initials: H
authors.lastname: Sack
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000517:prevention & control* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000517:prevention & control* / Q000556:secondary / Q000628:therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017567:Karnofsky Performance Status; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009483:Neuropsychological Tests; D012074:Remission Induction; D016019:Survival Analysis; D017741:Survivors; D017211:Treatment Failure