Clinical and Dosimetric Predictors of Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation Therapy

Abstract

Purpose: Radiation pneumonitis (RP) is a common and potentially life-threatening toxicity from lung cancer radiation therapy. Data sets reporting RP rates after postoperative radiation therapy (PORT) have historically been small and with predominantly outdated field designs and radiation techniques. We examined a large cohort of patients in this context to assess the incidence and causes of RP in the modern era.

Methods and materials: We reviewed 285 patients with non-small cell lung cancer treated with PORT at our institution from May 2004 to January 2017. Complete dosimetric data and clinical records were reviewed and analyzed with grade 2 or higher RP as the endpoint (RP2+) (Common Terminology Criteria for Adverse Events v4.0). Patients were a median of 67 years old (range, 28-87), and most had pathologic stage III non-small cell lung cancer (91%) and received trimodality therapy (90%). Systematic dosimetric analyses using Dx increments of 5% and Vx increments of 2 Gy were performed to robustly evaluate dosimetric variables. Lung V₅ was also evaluated.

Results: The incidence of RP2+ after PORT was 12.6%. Dosimetric factors most associated with RP2+ were total lungV₄ (hazard ratio [HR] 1.04, P < .001) and heart V₁₆ (HR 1.03, P = .001). On univariate analysis, the clinical factors of age (HR 1.05, P = .006) and carboplatin chemotherapy (HR 2.32, P = .012) were correlated with RP2+. On step-up multivariate analysis, only bivariate models remained significant, including lungV₅ (HR 1.037, P < .001) and age (HR 1.052, P = .011).

Conclusions: The incidence of RP after PORT is consistent with the literature. Factors correlated with RP include lung and heart doses, age, and carboplatin chemotherapy. These data also suggest that elderly patients may be more susceptible to lower doses of radiation to the lung. Based on these data, dose constraints to limit the risk of RP2+ to <5% in the setting of PORT include lungV₅ ≤65% in patients <65 years old and lungV₅ ≤36% in patients 65 years or older.