G. Rajeev-Kumar1, M. R. McKeever2, M. Koshy3, A. R. McCall4, F. Arif5, S. M. Smith6, J. Kline7, P. Riedell7, and Y. Hasan8; 1University of Chicago, Chicago, IL, 2University of Chicago, Department of Radiation and Cellular Oncology, Chicago, IL, 3Department of Radiation and Cellular Oncology, The University of Chicago Medicine, Chicago, IL, 4Department of Radiation and Cellular Oncology, University of Illinois at Chicago, Chicago, IL, 5Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, 6The University of Chicago, Chicago, IL, 7Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL, 8Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, IL
Purpose/Objective(s): While radiation therapy (RT) can significantly improve progression free survival (PFS) for relapsed/refractory Hodgkin/non-Hodgkin lymphoma (RRL), many patients do not receive RT. With the goal of increasing access to RT and improving outcomes, this phase I trial aims to determine the safety of hypofractionated RT in RRL, where the biologically equivalent dose is kept constant between dose levels (DLs). We hypothesized that hypofractionated RT in RRL is safe and tolerable. Materials/
Methods: In this single-institution i3+3 phase I trial, patients with RRL (ECOG =2 with =5 lesions) are enrolled. The first 3 patients are enrolled on DL 1 (D1, 42 Gy/10 fractions[fx]). Subsequent DLs include D2, 39.2 Gy/7 fx; D3, 34 Gy/5 fx; D4, 30 Gy/3 fx. Dose-limiting toxicity (DLT) was defined as any grade (Gr) 3 or 4 toxicities within 1 week of end of RT. If there are difficulties meeting normal tissue constraints, a minimum dose is prescribed to the tumor per DL: D1, 32 Gy/10 fx; D2, 29.4 Gy/7 fx; D3, 27 Gy/5 fx; D4, 23.4 Gy/3 fx. The primary endpoint is DLT; secondary endpoints include local control (LC), PFS, and overall survival (OS). We report median [interquartile range] for baseline characteristics. Results: The dose escalation phase was completed with 12 patients; an expansion cohort is ongoing. The 17 patients evaluated (52.9% male, median age 75 [37, 84], 58.8% ECOG 0) received a median of 2 [1, 7] lines of systemic therapy prior to RT. The most common histology included DLBCL (52.9%), B cell lymphoma and follicular lymphoma (17.6% each). The most commonly treated site was mediastinum (41.2%) followed by bone and abdomen (23.5% each). There was no acute DLT; each DL was completed with 3 patients. One Gr 3 abdominal pain adverse event (AE) at D2 was initially attributed to pre-existing and ongoing multifactorial pain due to possible disease progression and CMV gastritis, though was ultimately attributed to chronic radiation gastritis. After this, all subsequent patients treated on the protocol received the minimum dose as outlined in the methods section above. Most often, AE were Gr 2 (56%) followed by Gr 1 (41%) and commonly included nausea, fatigue, odynophagia, and pain. At a median follow-up of 14 months [3, 19], 11/17 patients (64.7%) are alive, 8 with no locoregional or distant progression. The 1-year OS is 85.2%, PFS 92.9%, and LC 100%. There were 6 deaths, 3 from disease progression (1 in-field 18 months post-RT, 2 out of field), 1 from pancreatic cancer, 1 from COVID-19, and the other was unknown. Conclusion: In this first prospective trial investigating hypofractionation in RRL, a dose of 23.4 Gy in 3 fx demonstrated acceptable safety. Favorable LC and OS are seen at a median follow up of 14 months. Incorporation of shorter treatment regimens may increase access to RT as a treatment modality for patients with RRL and improve outcomes.
