Seminal work from Lowry et al.1 and Hoskin et al.2 have established the efficacy of differential dose thresholds in the management of indolent and aggressive non-Hodgkin lymphomas. More recently, prospective data demonstrate the efficacy of even lower doses of radiotherapy long thought to be reserved for palliation in the management of indolent orbital3 and gastric lymphomas,4 as well as cutaneous T-cell lymphomas.5
In this vein, Nikhil Mankuzhy, MD, et al. retrospectively examined outcomes of the routine application of a response-adapted very low dose radiation therapy (VLDRT) to 4 Gy in either one or two fractions in a single institution over nearly 20 years. Over a thousand lesions were treated in 813 patients, with a mix of indolent histologies and 63% extranodal locations, leading to an impressive 91% overall response rate at 12 weeks (65% complete responses). A quarter of lesions progressed over five years, copacetic with results from the FoRT trial2, but interestingly, patients with treatment naïve, limited stage disease treated comprehensively with this approach experienced superior control rates with a 5-year local progression rate of only 16%.
In contrast, VLDRT may not be enough for the optimal management of primary cutaneous B-cell lymphoma. A single institutional retrospective review by Gabrielle Gard et al. noted a statistically significantly inferior one- and two-year freedom from treatment failure utilizing 4 Gy compared to 8-12 Gy. While 25% of lesions required retreatment in the first two years after 4 Gy, 0% did after 8-12 Gy. Of note, CR rates were only approximately 60% in both cohorts at three months, emphasizing the virtue of patience in response assessments prior to pursing retreatment.
Notwithstanding the demonstrated success of ultra low dose radiation therapy in the indolent setting, 30 Gy has been the dogmatic standard for consolidation for aggressive B cell lymphomas since Lowry et al.1 However, a long-awaited prospective multi-institutional Phase II trial from the International Lymphoma Radiation Oncology Group (ILROG) by Andrea Ng, MD, MPH, FASTRO, et al. , presented on Sunday at the Clinical Trials Sessions by Christopher Kelsey, MD, FASTRO, adopted a PET response-adapted approach, testing if a dose of 19.5-20 Gy of RT in 1.5-2 Gy/fractions would maintain a five-year freedom from local recurrence ≥95%. Between 2019-2023, 243 patients were enrolled across three continents and represented an intermediate risk cohort with only 9% harboring double hit genetics, 34% having Stage III-IV disease, 32% bulky disease (≥7.5 cm) and 51% IPI >1. Of special note, 70% of patients received ≥5 cycles of induction chemoimmunotherapy (ChI) rather than the 3-4 cycles that would be standard for low-risk Stage I-II patients.
After a median follow-up of 2.1 years, an impressive 94% of patients remained disease free with only four experiencing local recurrences in the entire cohort, resulting in a three-year freedom from local recurrence, progression free survival, and overall survival of 98.6%, 91.4%, and 95.7%, respectively. Although early, these initial data may serve to redirect the standard of care for aggressive B cell lymphomas. Despite representing a much more heterogeneous risk profile than patients treated on SWOG S1001(ChI x4, no RT)6 and FLYER (ChI x4 + rituximab x2 versus ChI x6),7 contextualizing those results raises the question of how best to dial in cycles of ChI vis-à-vis RT dose.
Taken together, these studies provide some touchstones to refine the principle of “less is more” in the management of non-Hodgkin lymphomas across the spectrum of histologies. Recapitulating some results of prior studies, response-adaptation should be at the forefront non-Hodgkin lymphoma radiation paradigms to truly personalize care and reduce toxicity in this patient population with excellent treatment responses to radiotherapy and expected long term survival.
Abstract 1097, Response Rate and Local Control of Response-Adapted Very Low Dose Radiotherapy (RA-VLDRT) with 4 Gy for Indolent Non-Hodgkin Lymphoma, was presented during the QP 17 - Hem 3: Radiating Precision: Tailoring Therapy for Lymphoma, Leukemia, and Myeloma session of the 67th ASTRO Annual Meeting.
Abstract 1098, Optimizing Palliative Radiation Therapy for Primary Cutaneous B-Cell Lymphoma: Is Ultra-Low Dose (4 Gy) Enough?, was presented during the QP 17 - Hem 3: Radiating Precision: Tailoring Therapy for Lymphoma, Leukemia, and Myeloma session of the 67th ASTRO Annual Meeting.
Abstract 4, Decreasing the Dose of Consolidation Radiation Therapy in DLBCL/HGBL: A Phase II Trial by the International Lymphoma Radiation Oncology Group, was presented during the Clinical Trials session of the 67th ASTRO Annual Meeting.
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