title: Impaired diffusion capacity predicts for decreased treatment tolerance and survival in limited stage small cell lung cancer patients treated with concurrent chemoradiation.
abstract: OBJECTIVE
  To determine if stratification of limited stage small cell lung cancer (LSCLC) patients by pre-treatment pulmonary function test (PFT) prognostic indicators predicts for treatment-related toxicity risks and survival following concurrent chemoradiation.
  
  
  METHODS
  From 1989 to 1999, 215 LSCLC patients received six cycles of alternating cyclophosphamide/doxorubicin/vincristine and etoposide/cisplatin (EP). Thoracic radiation (RT) was initiated only with EP and at cycle 2 or 3. RT dose was: 40 Gy/15 fractions/3 weeks or 50 Gy/25 fractions/5 weeks. RT fields encompassed gross and suspected microscopic disease with a 2 cm margin. Pre-treatment PFT values analyzed included forced expiratory volume in 1s (FEV1) (in liter and as % predicted) and diffusion capacity for carbon monoxide (DLCO) (as % predicted). The "marker" for toxicity during concurrent chemoradiation was the duration of any RT breaks initiated for severe hematologic or locoregional symptomatology. Patient outcomes were analyzed for associations between recognized PFT cut-offs (FEV1 <2l, > or =2l; FEV1 <60%, > or =60% predicted; DLCO <60%, > or =60% predicted), toxicity rates, and survival.
  
  
  RESULTS
  For the whole study cohort, median, 2- and 5-year overall survivals were: 14.7 months, 22.7 and 7.2%, respectively. Fifty-six patients (26%) required treatment breaks due to toxicity. FEV1 and DLCO results were available for 96 (45%) and 86 (40%) patients, respectively. Two thirds of FEV1s measured were <2l. On statistical analysis, the incidence of toxicity-related interruptions was significant for DLCO<60% (P=0.043), suggestive for FEV1<2l (P=0.1) and non-significant for FEV1<60%. Patients with simultaneous DLCO<60% and FEV1<2l showed a trend toward increase toxicity risk (P=0.1). For selected PFT measures, median overall survivals were: 12.7 months versus 14.8 months for DLCO<60% versus > or =60%; 13.4 months versus 17.7 months for FEV1<2l versus > or =2l; 15.4 months versus 19.9 months for DLCO<60% + FEV1<2l versus DLCO> or =60% + FEV1> or =2l. Although absolute differences favored all patients with PFT values above the prognostic cut-offs, differences were not statistically significant on this analysis. Patients with both a treatment break and a DLCO<60% had the poorest median survival of all patient subsets, at 11.4 months (P=0.09).
  
  
  CONCLUSIONS
  Impaired DLCO (i.e. <60%) is a novel predictor of increased treatment-related toxicity leading to interruptions. The present study suggests a probable role for DLCO and FEV1 (in l) as prognostic factors for predicting survival but larger patient samples are required for confirmation. Patients with impaired DLCOs experiencing treatment interruptions have the poorest survival. Assessment of pre-treatment PFTs contributes to determining optimal management strategies for LSCLC patients receiving definitive chemoradiation.
authors.affiliation: Department of Radiation Oncology/T28, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. videtig@ccf.org
authors.forename: Gregory M M
authors.initials: GM
authors.lastname: Videtic
authors.forename: Larry W
authors.initials: LW
authors.lastname: Stitt
authors.forename: Robert B
authors.initials: RB
authors.lastname: Ash
authors.forename: Pauline T
authors.initials: PT
authors.lastname: Truong
authors.forename: A Rashid
authors.initials: AR
authors.lastname: Dar
authors.forename: Edward W
authors.initials: EW
authors.lastname: Yu
authors.forename: Frances
authors.initials: F
authors.lastname: Whiston
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011832:Radiation Injuries / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D013147:Spirometry; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin