title: Pulmonary toxicity in Stage III non-small cell lung cancer patients treated with high-dose (74 Gy) 3-dimensional conformal thoracic radiotherapy and concurrent chemotherapy following induction chemotherapy: a secondary analysis of Cancer and Leukemia Group B (CALGB) trial 30105.
abstract: OBJECTIVE
  Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity.
  
  
  METHODS
  Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity.
  
  
  RESULTS
  Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases.
  
  
  CONCLUSIONS
  Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.
authors.affiliation: Department of Radiation Oncology, Box 3085, Duke University Medical Center, Durham, NC 27710, USA. joseph.salama@duke.edu
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Salama
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Karen
authors.initials: K
authors.lastname: Morano
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bogart
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Crawford
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: A William
authors.initials: AW
authors.lastname: Blackstock
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D008168:Lung / Q000187:drug effects* / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D017239:Paclitaxel / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine