Factors Associated With and Characteristics of Proton Radiotherapy Use at the End of Life

Abstract

To identify the patient characteristics, treatment indications, and toxicities among patients receiving proton beam therapy (PBT) in the final year of life at a tertiary academic medical center.A retrospective review of patients who received PBT within the final 12 months of life was performed. Electronic medical records were reviewed for patient and treatment details from 2010-2019. Follow-up was calculated from start of PBT until death or last follow-up. Treatment intent was retrospectively defined as curative treatment for localized disease, for isolated local recurrence, oligometastatic disease, durable local control, or palliation of symptoms. Durable local control was defined as treatment for durable control of otherwise incurable disease whereas palliation was defined as treatment for symptom palliation only. Acute (< 3 months) and chronic (> 3 months) toxicities were graded using the CTCAE v5.0. Chi-square test was performed to evaluate factors associated with palliative treatment. Simple logistic regression was used to evaluate factors associated with any acute toxicity.During the study period, 299 patients were treated at the end of life (EOL) out of 5802 total patients treated with PBT (5.2%). Mean age was 66 years (19-94 years), with 58% male. The most common cancers were non-small cell lung cancer (27%), hepatocellular carcinoma (13%), and small cell lung cancer (6%). Eleven percent of patients were treated for symptom palliation; the remainder were treated for durable local control (57%), definitively (16%), for an isolated local recurrence (14%), or oligometastatic disease (2%). Forty-five percent received PBT for re-irradiation. Concurrent systemic therapy was delivered to 47%. Median prescribed dose was 50 Gy (15-80 Gy). Mean treatment time was 34 days (1-189 days). Seven patients received split-course proton therapy for hepatocellular carcinoma. Median time from final fraction to death was 139 days (1-363 days). On average, patients spent 24% of the remaining days of life receiving PBT. Acute toxicity of any grade was noted in 85% of patients (31% G1, 53% G2, 15% G3). Fifty-two patients (17%) experienced chronic toxicity, the most severe of which was a tracheo-esophageal fistula (G4). In the chi-square test, breast and hematologic malignancy were associated with palliative intent (χ2 (1, N = 14) = 15.9, P < 0.001; (χ2 (1, N = 14) = 15.9, P < 0.001). In the simple logistic regression model, concurrent systemic therapy was positively associated with any acute toxicity (OR: 2.0, P = 0.05).The number of patients treated with PBT at the EOL was low compared to all-comers. Many of these patients received treatment with definitive doses and concurrent systemic therapy. Nearly half received re-irradiation. Grade 3 or higher acute toxicity was moderate, and some patients spent a large portion of their remaining days on treatment. Thus, the incorporation of a prognostic indicator in clinical practice may further optimize use of PBT.