title: Factors Associated With Early Mortality in Patients Treated With Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.
abstract: OBJECTIVE
  Concurrent chemoradiation therapy (con-CRT) is recommended for fit patients with locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with toxicity, and observed survival continues to be limited. Identifying factors associated with early mortality could improve patient selection and identify strategies to improve prognosis.
  
  
  METHODS
  Analysis of a multi-institutional LA-NSCLC database consisting of 1245 patients treated with con-CRT in 13 institutions was performed to identify factors predictive of 180-day survival. Recursive partitioning analysis (RPA) was performed to identify prognostic groups for 180-day survival. Multivariate logistic regression analysis was used to create a clinical nomogram predicting 180-day survival based on important predictors from RPA.
  
  
  RESULTS
  Median follow-up was 43.5 months (95% confidence interval [CI]: 40.3-48.8) and 127 patients (10%) died within 180 days of treatment. Median, 180-day, and 1- to 5-year (by yearly increments) actuarial survival rates were 20.9 months, 90%, 71%, 45%, 32%, 27%, and 22% respectively. Multivariate analysis adjusted by region identified gross tumor volume (GTV) (odds ratio [OR] ≥100 cm(3): 2.61; 95% CI: 1.10-6.20; P=.029) and pulmonary function (forced expiratory volume in 1 second [FEV1], defined as the ratio of FEV1 to forced vital capacity [FVC]) (OR <80%: 2.53; 95% CI: 1.09-5.88; P=.030) as significant predictors of 180-day survival. RPA resulted in a 2-class risk stratification system: low-risk (GTV <100 cm(3) or GTV ≥100 cm(3) and FEV1 ≥80%) and high-risk (GTV ≥100 cm(3) and FEV1 <80%). The 180-day survival rates were 93% for low risk and 79% for high risk, with an OR of 4.43 (95% CI: 2.07-9.51; P<.001), adjusted by region. A clinical nomogram predictive of 180-day survival, incorporating FEV1, GTV, N stage, and maximum esophagus dose yielded favorable calibration (R(2) = 0.947).
  
  
  CONCLUSIONS
  This analysis identified several risk factors associated with early mortality and suggests that future research in the optimization of pretreatment pulmonary function and/or functional lung avoidance treatment may alter the therapeutic ratio in this patient population.
authors: Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada.
authors: Andrew
authors: A
authors: Warner
authors: Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Max
authors: M
authors: Dahele
authors: Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada.
authors: Bo
authors: B
authors: Hu
authors: Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada.
authors: David A
authors: DA
authors: Palma
authors: Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Suresh
authors: S
authors: Senan
authors: Department of Radiation Oncology, MAASTRO Clinic, Maastricht, The Netherlands.
authors: Cary
authors: C
authors: Oberije
authors: Department of Radiation Oncology, Hyogo Cancer Center, Akashi, Japan.
authors: Kayoko
authors: K
authors: Tsujino
authors: Department of Oncology, Clínica Universidad, Universidad de Navarra, Pamplona, Spain.
authors: Marta
authors: M
authors: Moreno-Jimenez
authors: Department of Radiation Oncology, National Cancer Center, Goyang-si, Gyeonggi, Korea.
authors: Tae Hyun
authors: TH
authors: Kim
authors: Department of Radiation Oncology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina.
authors: Lawrence B
authors: LB
authors: Marks
authors: Department of Radiation Oncology, University of Washington, Seattle, Washington.
authors: Ramesh
authors: R
authors: Rengan
authors: Department of Oncology and Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors: Luigi
authors: L
authors: De Petris
authors: Department of Radiation Oncology, Campus Bio-Medico University, Rome, Italy.
authors: Sara
authors: S
authors: Ramella
authors: Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
authors: Kim
authors: K
authors: De Ruyck
authors: Department of Radiation Oncology, Hospital de la Esperanza, Parc de Salut Mar, Barcelona, Spain.
authors: Núria Rodriguez
authors: NR
authors: De Dios
authors: Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.
authors: Jeffrey D
authors: JD
authors: Bradley
authors: Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada. Electronic address: George.Rodrigues@lhsc.on.ca.
authors: George
authors: G
authors: Rodrigues
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000401:mortality; D016208:Databases, Factual; D004947:Esophagus / Q000528:radiation effects; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D049451:Nomograms; D011379:Prognosis; D017564:Radiation Pneumonitis / Q000401:mortality; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D016019:Survival Analysis; D013997:Time Factors; D047368:Tumor Burden; D014797:Vital Capacity