title: High mutagen sensitivity in peripheral blood lymphocytes predicts poor overall and disease-specific survival in patients with stage III non-small cell lung cancer treated with radiotherapy and chemotherapy.
abstract: OBJECTIVE
  To investigate whether the bleomycin sensitivity assay, an in vitro peripheral blood lymphocyte assay, can predict outcome in patients with inoperable stage III non-small-cell lung cancer (NSCLC) treated with definitive radiotherapy and chemotherapy.
  
  
  METHODS
  We identified 102 patients with inoperable stage III NSCLC cell lung cancer treated with definitive radiotherapy and chemotherapy. The patients' pretreatment peripheral blood lymphocyte cultures were treated with the radiomimetic mutagen bleomycin. An index of bleomycin sensitivity was determined by counting the number of chromatid breaks in 50 metaphases. The correlation between bleomycin sensitivity (expressed as mean breaks per cell) and clinical outcome was analyzed.
  
  
  RESULTS
  High bleomycin sensitivity (defined as a mean of >1.02 chromatid breaks/cell, representing the third quartile of bleomycin sensitivity) predicted poor disease-specific survival and overall survival. The 6-year disease-specific survival was 27% in patients with high bleomycin sensitivity compared with 46% in patients without such sensitivity (P = 0.0094). The association remained statistically significant when adjusted for smoking status, age, and radiation dose. The 6-year overall survival was 19% for patients with high bleomycin sensitivity and 29% for those without (P = 0.0193). There was a trend toward worse local regional control and worse disease-free survival among patients with high bleomycin sensitivity. There was no difference between the two groups in distant metastasis-free survival or radiation treatment-related complications.
  
  
  CONCLUSIONS
  High bleomycin sensitivity correlated with poor overall survival and disease-specific survival in these patients with stage III NSCLC treated with radiotherapy and chemotherapy. Bleomycin sensitivity may function as a biomarker for poor clinical outcome for this group of patients.
authors.affiliation: Department of Radiation Oncology, Epidemiology, and Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. jychang@mdanderson.org
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: Ryohei
authors.initials: R
authors.lastname: Sasaki
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Craig W
authors.initials: CW
authors.lastname: Stevens
authors.forename: Charles
authors.initials: C
authors.lastname: Lu
authors.forename: Frank V
authors.initials: FV
authors.lastname: Fossella
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Allen
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D002869:Chromosome Aberrations / Q000187:drug effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000494:pharmacology; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D009153:Mutagens; D001761:Bleomycin