Pulmonary Function Testing (PFT) after Photon and Proton Radiotherapy for Stage II-III Breast Cancer

Abstract

<h3>Purpose/Objective(s)</h3> The Breast Cancer Lung Late Effects (BELLE) study prospectively enrolled patients with breast cancer who received adjuvant photon (XRT) or proton (PT) radiotherapy (RT) to evaluate potential early markers of induced lung injury, including pulmonary function tests (PFTs). <h3>Materials/Methods</h3> Patients ≥18 years with AJCC 8^th edition anatomic stage II-III or greater breast cancer were enrolled into the BELLE study between May 27, 2016 and May 26, 2020. All patients underwent clinical evaluation, computed tomography imaging, PFTs, and QoL questionnaires at baseline, 6 months, and 12 months relative to RT start. Fisher's exact tests and Kruskal-Wallis rank sum tests were used to compare the XRT and PT groups. <h3>Results</h3> A total of 37 patients were included in the final analysis (XRT, n=21; PT, n=16). Median age at diagnosis was 51 years (range, 31-76); 26 patients identified as white (70.3%), 8 as Black (21.6%), and 3 other (7.1%). Most patients did not have pre-existing respiratory disease (83.8%) or prior smoking history (62.2%), while 35.1% were former smokers and 1 was a current smoker (2.7%). The median BMI was 29.4 (range, 18.9-44.2). Most patients received chemotherapy (75.7%) and regional nodal irradiation (RNI; 78.4%). Median lung V20 was 25.3% (range, 5.6-39.7) and median lung V5 was 59.6% (range, 29.7-86.4). XRT patients had more pre-existing respiratory disease and were less likely to receive RNI (p=0.027 and p=0.006, respectively). There was no statistically significant difference between the XRT and PT cohorts for median lung V20 or V5. The median FEV1/FVC ratio at baseline, 6 months, and 12 months were not significantly different between the XRT and PT cohorts (80.2 % vs 81.5%, p=0.81; 79.3% vs 81.3%, p=0.95; and 80.6% vs 79.4% p>0.99, respectively). Similarly, the median FVC values at baseline, 6 months, and 12 months were not significantly different between the XRT and PT cohorts (3.4 L vs 3.1 L, p=0.76; 3.2 L vs 3.0 L, p=0.38; and 3.5 L vs 3.0 L, p=0.23, respectively). While the median DLCO at baseline was significantly worse for the PT cohort (91% vs 76%, p=0.005), there was no difference between cohorts at 6 and 12 months (79.0% vs 78.0%, p=0.38; 89.0% vs 84.0%, p=0.80, respectively). Four patients developed radiation pneumonitis (RP) within a year of RT including 3 with transient grade 1 (n=1 PT; n=2 XRT) and 1 with grade 3 (XRT). <h3>Conclusion</h3> Despite high variability among patients across all PFT parameters, the median FEV1/FVC ratio and FVC were stable over time and did not cross the threshold for concern of restrictive lung disease in either cohort. Although DLCO decreased at 6 months in the XRT cohort, both cohorts showed improvement at one year without diagnosis of restrictive lung disease. Utilizing PFTs as an early marker of RT-induced lung injury, neither patients treated with XRT nor PT exhibited sustained PFT abnormalities with 1 year of follow-up.