title: Heart Dose Is an Independent Dosimetric Predictor of Overall Survival in Locally Advanced Non-Small Cell Lung Cancer.
abstract: In the randomized trial of standard- versus high-dose chemoradiotherapy for locally advanced (LA) NSCLC (Radiation Therapy Oncology Group 0617), overall survival (OS) was worse in the high-dose arm. Although heart dose was suggested as a contributing factor, actionable parameters have not been established. We present an analysis of clinical and dosimetric parameters affecting OS in this patient population, focusing on heart dose.
  
  
  
  Clinical data were collected on 416 patients with LA NSCLC treated at a single institution, with a subset of 333 available treatment plans recontoured using Radiation Therapy Oncology Group 0617 normal tissue guidelines. Toxicity and dosimetry data were analyzed for 322 patients; multivariate analysis was performed on 251 patients. Dosimetric parameters of radiation to tumor and organs at risk were analyzed with clinical data pertaining to OS, disease-free survival, and toxicity.
  
  
  
  Patients were treated with radiation therapy to prescribed doses of 50.0 to 84.9 Gy (median 66.0 Gy). Median follow-up was 14.5 months. Median OS was 16.8 months. The 1- and 2-year OS rates were 61.4% and 38.8%, respectively. On multivariate analysis, factors independently associated with worse OS were increasing heart V50(volume receiving ≥50 Gy), heart volume, lung V5(proportion of the lung structure [excluding the target volume]) receiving at least 5 Gy), bilateral mediastinal lymph node involvement, and lack of concurrent chemotherapy. When stratified by heart V50less than 25% versus 25% or greater, the 1-year OS rates were 70.2% versus 46.8% and the 2-year OS rates were 45.9% versus 26.7% (p < 0.0001). Median heart V50was significantly higher (20.8% versus 13.9%, p < 0.0001) for patients with cardiac toxicity with a Common Terminology Criteria for Adverse Events grade of 1 or higher.
  
  
  
  Heart dose is associated with OS and cardiac toxicity for patients with LA NSCLC treated with chemoradiotherapy.
authors.affiliation: Department of Radiation Oncology, Siteman Cancer Center, Washington University/Barnes Jewish Hospital, Saint Louis, Missouri.
authors.forename: Christina K
authors.initials: CK
authors.lastname: Speirs
authors.affiliation: Department of Radiation Oncology, Siteman Cancer Center, Washington University/Barnes Jewish Hospital, Saint Louis, Missouri.
authors.forename: Todd A
authors.initials: TA
authors.lastname: DeWees
authors.affiliation: Department of Radiation Oncology, Siteman Cancer Center, Washington University/Barnes Jewish Hospital, Saint Louis, Missouri.
authors.forename: Sana
authors.initials: S
authors.lastname: Rehman
authors.affiliation: Clinicas Oncologicas Integradas, Rio de Janeiro, Brazil.
authors.forename: Alerson
authors.initials: A
authors.lastname: Molotievschi
authors.affiliation: Department of Radiation Oncology, Siteman Cancer Center, Washington University/Barnes Jewish Hospital, Saint Louis, Missouri.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Velez
authors.affiliation: Department of Radiation Oncology, Siteman Cancer Center, Washington University/Barnes Jewish Hospital, Saint Louis, Missouri.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mullen
authors.affiliation: Department of Radiation Oncology, Siteman Cancer Center, Washington University/Barnes Jewish Hospital, Saint Louis, Missouri.
authors.forename: Sandra
authors.initials: S
authors.lastname: Fergus
authors.affiliation: Department of Radiation Oncology, Centro di Referimento Oncologico Aviano, Aviano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Trovo
authors.affiliation: Department of Radiation Oncology, Siteman Cancer Center, Washington University/Barnes Jewish Hospital, Saint Louis, Missouri.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Bradley
authors.affiliation: Department of Radiation Oncology, Siteman Cancer Center, Washington University/Barnes Jewish Hospital, Saint Louis, Missouri. Electronic address: crobinson@radonc.wustl.edu.
authors.forename: Cliff G
authors.initials: CG
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000503:physiopathology* / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D058958:Organs at Risk / Q000503:physiopathology* / Q000528:radiation effects; D011379:Prognosis; D011874:Radiometry; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D012189:Retrospective Studies; D015996:Survival Rate
keywords: Cardiac toxicity; NSCLC; Radiation dosimetry; Radiation therapy; Survival outcomes