3394 - Ultra-Low-Dose Adaptive Radiotherapy and Single-Agent Rituximab for Indolent Non-Hodgkin Lymphomas: Where Less is More in Combined Modality Therapy

K. E. Lake¹, M. Jackson¹, S. All¹, S. Brocklehurst¹, A. M. Patel¹, M. Kozak¹, X. D. Li¹, N. B. Desai¹, E. Yilmaz², H. Wolfe², F. Awan², P. Ramakrishnan Geethakumari², and K. A. Kumar Jr¹; ¹Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ²Department of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX

Purpose/Objective(s): For indolent non-Hodgkin lymphomas (iNHL), ultra-low-dose radiation therapy (ULDRT) with 4 Gy has demonstrated durable local control (70%), though distal relapses may occur. Concurrent systemic chemotherapy with RT extends PFS but is often avoided due to toxicity. We hypothesize that the combination of adaptive ULDRT, with repeat treatment as needed, and single-agent rituximab results in excellent local and systemic control with minimal toxicity. Materials/

Methods: We conducted an IRB approved retrospective review of patients with iNHL who were treated with both ULDRT and rituximab (4 weekly doses of 375 mg/m²), either concurrently, or within a short interval (median 16 days), at our institution from 2017-2024. Treatment response and disease control (local and distant) were measured by PET/CT. Overall and progression-free survival (OS and PFS) were analyzed using the Kaplan-Meier method.
Results: Baseline patient characteristics and treatment sites are shown in Table 1. The overall response rate at first follow up was 28/29 (97%), of which 17 sites (59%) achieved complete response (CR), 9 (31%) partial response (PR), and 2 (7%) stable disease (SD). Of those with PR, 7 had residual disease in-field, 1 out-of-field, and 1 both in- and out-of-field of RT.
Four patients experienced mild acute RT-related toxicities (diarrhea, dysgeusia, fatigue, and shingles), and 1 patient with Sjogren’s syndrome experienced long-term mild dry mouth. There were no major toxicities associated with rituximab. Of 18/29 initially symptomatic treatment sites, 15/18 (83%) noted resolution after treatment.
In our cohort, median time of follow up was 28 months. The 2-year PFS and OS were 70% and 90%, respectively. Two patients died of complications unrelated to their iNHL; no patient died of causes related to their iNHL or treatment. The median time to relapse was 21 months. Of the patients who relapsed, 1 relapsed in-field, 5 relapsed out-of-field, and 3 relapsed both in- and out-of-field of ULDRT. Three of these patients were retreated with ULDRT, while two underwent systemic treatment with chemotherapy.

Conclusion: For iNHL, the combination of adaptive ULDRT and single-agent rituximab demonstrates effective palliation and sustained local and distant disease control with minimal side effects. In situations where there is prohibitive toxicity concern for chemotherapy and/or higher radiation doses, this strategy presents a reasonable alternative and warrants further investigation in prospective studies. Abstract 3394 – Table 1

Disease Characteristics		N (Median (range))	%
Age (years)		72 (21-87)
ECOG PS		1 (0-2)
Gender	Male	14	58
	Female	10	42
Ethnicity	Hispanic	3	13
	Non-hispanic, white	20	83
	Asian	1	4
Stage	I	8	33
	II	7	29
	III	5	21
	IV	4	17
Histologic Subtype	Follicular	12	50
	Nodal MZL	6	25
	MALT Lymphoma	5	21
	Lymphomatoid Granulomatosis	1	4
Treatment Sites	Pelvis	5	17
	Parotid	4	14
	Abdomen	9	31
	Chest	3	10
	Head and Neck	7	24
	Other	1	3