Low Dose Radiotherapy Achieves Durable Control in Curable iNHL With Minimal Toxicity, Study Finds

Very low dose radiotherapy (VLDRT) is a promising approach for treating localized, indolent non-Hodgkin lymphoma (iNHL), according to Nikhil P. Mankuzhy, MD, and colleagues. Traditionally, 24 Gy has been the standard radiotherapy dose for curable patients due to its superior local control. However, VLDRT, consisting of 4 Gy in two fractions, has gained interest for its high local control potential, minimal toxicity, and favorable outcomes in specific cases, such as orbital and gastric iNHL. Researchers at a single institution implemented a response-adaptive VLDRT strategy, assessing its efficacy in curable patients with iNHL.

“At our institution, we implemented an adaptive approach for use of VLDRT in iNHL. After VLDRT, patients undergo short-interval assessment to consider additional RT. Our initial analysis reported a 9% 2-year incidence of local progression (LP) for 52 potentially curable patients with median follow up of 1.7 years,” they explained.

The study, from the 66^th ASH Annual Meeting, analyzed 157 patients treated to 165 lesions between 2010 and 2024. Eligible patients had stage I or II disease, received VLDRT as their first therapy, and underwent comprehensive treatment of all disease sites. Most patients had follicular lymphoma (45%) or marginal zone lymphoma (46%), with a median age of 62 years. Over half of the lesions were extranodal, involving sites such as the eye, gastrointestinal tract, and skin.

With a median follow-up of 27.5 months, VLDRT demonstrated a high overall response rate (95%), including a 77% complete response rate. A small subset (7 patients) required additional RT (20–30 Gy), all achieving complete response with no subsequent local progression. Local progression rates were 8% and 18% at two and five years, respectively, while progression-free survival (PFS) rates were 70% and 58%. Overall survival (OS) was exceptionally high at 99% and 92% at two and five years. Transformation to large-cell lymphoma was rare (4 patients), and systemic therapy needs were minimal.

This study highlighted VLDRT as an effective and patient-friendly treatment for curable iNHL, with low toxicity and durable local control. Progression primarily occurred outside treated areas, aligning with the indolent nature of iNHL. PFS and OS outcomes were comparable to those achieved with higher-dose radiotherapy but with fewer side effects and greater convenience.

“For potentially curable patients, VLDRT with 4 Gy in 2 fractions with a response-adapted approach offers excellent local control over 5 years with progression primarily occurring outside of the treated field,” the authors concluded. “Given a superior toxicity profile and patient convenience, we advocate for further investigation of a VLDRT-anchored approach for all potentially curable patients.”

Mankuzhy NP, Imber BS, Pammer P, et al. Very Low Dose Radiotherapy (VLDRT) with 4 Gy for Potentially-Curable Indolent Non-Hodgkin Lymphomas. Abstract 3040. Presented at ASH Annual Meeting. San Diego, CA.