Prospective Evaluation of Implementation of Esophageal Dose-Volume Constraints in Patients with Breast Cancer Undergoing Regional Nodal Irradiation

Abstract

<h3>Purpose/Objective(s)</h3> We have previously reported that esophageal mean dose, V10 Gy, and/or V20 Gy were independently associated with increased rates of symptomatic (grade 2) radiation esophagitis (G2E) in a cohort of 531 patients treated with regional nodal irradiation (RNI) using conventional fractionation (CF, 2 Gy/day). We subsequently implemented these esophageal organ-at-risk (E-OAR) constraints in treatment planning and prospectively collected acute toxicities, including G2E, in the electronic medical record (EMR) using a standardized flowsheet. Here, we present the impact of E-OAR constraints for RNI on subsequent rates of G2E. <h3>Materials/Methods</h3> Patients treated with curative intent RNI from 07/2019-12/2021 using CF and hypofractionation (HF, 2.66 Gy/day) were studied. The esophagus from cricoid to tracheal bifurcation was prospectively contoured as E-OAR on all cases with a mean dose<1100 cGy (<880 cGy if HF), V10 Gy (V8 Gy if HF) <30%, and V20 Gy (V16 Gy if HF) <15% used as constraints. Mean dose, V20 Gy (V16 Gy if HF), and V10 Gy (V8 Gy if HF) and presence or absence of prospectively collected G2E were noted. We used the t-test to compare E-OAR doses in this current cohort compared to our previously published cohort and the chi-square test to compare the rates of G2E (p<0.05 considered statistically significant). <h3>Results</h3> We identified 397 patients (303 CF; 94 HF) that met inclusion criteria with median age 54 y (IQR, 45-62 y); 63% were hormone receptor (HR)+/HER2-, 23% HER2+, 14% triple negative; 79% had chemotherapy; 34% underwent lumpectomy; 62% had axillary node dissection; 54% had left-sided breast cancer. Radiation was 3DCRT for 66%, IMRT for 34%. After implementation of E-OAR constraints, significantly lower esophageal doses were found in the current cohort: mean dose: 8.6 Gy (SD 4.4) vs 10.5 Gy (SD 6.1) previously, p<0.0001; V10 (or V8): 29.9% (SD 21.9) vs. 35.1%, (SD 16.8), p=0.0002; and V20 Gy (or V16 Gy): 10.0% (SD 11.3) vs. 16.3% (SD 16.3), p<0.0001. The rate of G2E was not significantly different in the current cohort at 17.9% vs. 16.2% in the prior (p=0.50). On further analyses of the current cohort (N=397), 56.2% met all 3 esophageal constraints, 12.3% met 2 constraints, 10.6% met 1 constraint, and 20.9% met 0; corresponding to G2E rates of 7.6% (17/223), 20.4% (10/49), 23.8% (10/42), and 41.0% (34/83), respectively (p<0.0001). Patients that did not meet any E-OAR constraint were significantly more likely to receive IMRT compared to those that met all 3 constraints (62% vs. 12%, p<0.0001). There was a trend towards lower G2E rates in patients treated with HF vs. CF: 11.7% vs. 19.8%, p=0.07. <h3>Conclusion</h3> Implementation of E-OAR constraints resulted in significantly reduced esophageal mean dose, V10/V8 Gy and V20/V16 Gy across the current cohort. In order to significantly reduce G2E, all 3 esophageal constraints need to be met. Practically, these results help practitioners stratify patients into G2E low-risk (<10%) and high-risk (>20%) groups based on number of constraints met.