Outcomes of Proton Therapy for Patients with Infradiaphragmatic Lymphoma.

Abstract

While the role of proton radiation (PT) in treating supradiaphragmatic targets in lymphoma patients is becoming increasingly well-established, outcomes of PT for infradiaphragmatic locations have not been reported. We report on the radiation planning details, doses achieved to key organs at risk (OARs), and clinical outcomes for a cohort of lymphoma patients treated with PT to infradiaphragmatic locations. This is a single institution retrospective study of patients with biopsy-proven lymphoma who received PT to an infradiaphragmatic target between 2011-2022. Patient, disease, and radiation details were collected. Comparison photon plans were generated for a subset of patients. Toxicity was reported using CTCAE version 5.0. Dosimetric and clinical factors associated with toxicity and oncologic outcomes were assessed via linear regression, Wilcoxon rank sum test, Fisher's exact test, and/or independent t-test while the paired t-test or Wilcoxon signed rank test was used for dosimetric analyses. 38 patients comprising 40 PT courses were included. Median age was 63 years and median follow-up was 48 months. The most common diagnoses were DLBCL (58%) and Hodgkin lymphoma (18%). 28% of PT courses had direct overlap with a prior radiation field and 20% were palliative. Median dose was 30.6 GyE over 17 fractions to the retroperitoneum (30%), spine/paraspinal region (30%), pelvis (18%), inguinals (8%), spleen (3%), or other (8%). Top G1 toxicities were fatigue (65%), dermatitis (28%), and nausea (23%). 10% of PT courses led to a G2 toxicity and there were no G3+ toxicities. Higher number of fractions was associated with increased incidence of dermatitis (mean 16 vs. 19, p = 0.008), but no OAR parameters were associated with CTCAE toxicities. Among patients treated with curative intent, 44% experienced progression of disease (PD) at a median time of 3 months after PT; of these progressions, 60% were distant only, 20% were marginal only, 10% was marginal and distant, and 10% was in-field and distant. Higher number of systemic therapy lines received prior to PT was associated with increased likelihood of PD (mean 1.4 vs. 4.1, p = 0.01), and PD increased the risk of death (OR 15.3, 95% CI 2.5-95.2). 5/39 patients were diagnosed with a second malignancy after PT, two of which were hematologic. Among the 10 patients with photon comparison plans, PT provided a significant decrease in kidney doses (mean and V5), small bowel V5 Gy, large bowel V5 Gy, bowel bag V15 Gy, and mean liver (all p = 0.045 or less). However, average spinal cord/cauda Dmax was slightly higher with PT (24 vs. 25 Gy, p = 0.0156). PT is a well-tolerated treatment for infradiaphragmatic lymphoma that leads to excellent outcomes with minimal high-grade toxicities. Compared to photon therapy, PT can significantly reduce doses to key abdominopelvic OARs.