Cardiac Toxicity after Definitive Standard Fractionated Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)

Abstract

Cardiac toxicity after radiotherapy (RT) for LA-NSCLC is not well understood. Published data suggest heart dose impacts overall survival (OS). Direct retrieval of cardiac diagnosis codes via the electronic medical record (EMR), pre- and post-RT, can objectively evaluate putative RT-induced cardiac toxicity (RICT). As part of an IRB approved project, the EMR was queried using billing codes with accompanying dates for cardiac related diagnoses (CRD) before and after the specified RT start date for individual patients receiving thoracic RT between 2009-2017. Patients with LA-NSCLC, stage IIA-IIIB, treated with a single curative course of RT +/- chemotherapy were included. Dose-volume histogram (DVH), patient characteristics, and clinical outcomes data were retrieved from the EMR and departmental database. Analysis was completed including descriptive statistics (Pearson Chi Square), ROC analysis for heart dosimetry to determine optimal cut-points, univariate analysis (UVA, Kaplan-Meier), and multivariate analysis (MVA, cox proportional hazards). 147/521 patients met inclusion criteria. Patient characteristics, UVA and MVA are in the accompanied table. Median follow-up was 18.5 mos. For the entire cohort, the median MHD was 10.5 Gy, V5 44%, V10 32%, and V20 17%. Median overall survival (OS) was 21mos; median freedom from cardiac toxicity (fCT) was 22.6mos; and median time to develop cardiac toxicity was 6 mos. On MVA only heart V5>80% (HR 2.5 [1.04-5.9]) and age 70+ (HR 1.7 [1.1-2.7]) predicted worse OS. 2y OS for heart V5>80% vs ≤ 80% was 35 vs 50% (p = 0.04). However, V50 > 25% predicted cardiac toxicity on both UVA and MVA (HR 7 [2-25]), while MHD >20Gy trended towards worse toxicity (HR 1.6 [0.95-2.7]). 2y fCT for heart V50 > 25% vs <= 25% was 0 vs 54%, p<0.0001. Direct EMR query of cardiac diagnosis codes before and after RT is an objective way to score cardiac toxicity and allowed for robust retrieval of CRDs for scoring potential RICT. OS was significantly related to multiple heart dose parameters, however only heart V5 > 80% independently predicted for worse OS. MHD (> 20 Gy) independently correlated with worse fCT on UVA; however, only heart V50 > 25% remained significant on MVA. These findings further contribute to the increasing body of literature addressing RICD after RT for LA-NSCLC, and emphasize the need for prospective trials directly incorporating multi-disciplinary cardio-oncologic care.Abstract 3192; Table 1OS UVA HROS MVA HRfCT UVA HRfCT MVA HRPt Char.MHD ≥20Gy1.6 (1-2.4)NS1.8 (1.1-2.9)NSAgeMed. (IQR)72 (12)V5 > 80%1.9 (1.2-2.8)2.5 (1.04-5.9)1.5 (0.9-2.5)RaceWhite122 (83%)V10 > 65%1.6 (1.2-3.1)NS1.4 (0.9-2.2)Black14 (9.5%)V20 > 50%1.9 (1.2-3.1)NS1.3 (0.7-2.5)Other11 (7.5%)V50 > 25%2.6 (0.8-8.3)9.7 (2.8-33)7 (2-25)GenderM89 (60.5%)Age ≥ 701.6 (1.1-2.4)1.7 (1.1-2.7)1.2 (0.8-2)F58 (39.5%)Dose >70 Gy1.1 (0.7-1.7)1.1 (0.6-1.8)StageII29 (19.7%)Stage II v III1.0 (0.6-1.7)1.5 (0.8-2.9)III118 (80.3%)DoseMed. (IQR)66 Gy (10) Open table in a new tab