ICML 2025 | Local control with response-adapted very low-dose radiotherapy of 4 Gy for indolent NHL

So at MSK we are currently offering very low dose radiation for indolent non-Hodgkin lymphomas because these lymphomas are very sensitive to radiation therapy. The standard treatment dose is 24 gray but 4 gray has shown in randomized data to have excellent local control of 70%. We wanted to evaluate our experience retrospectively and we updated our prior publication looking at 1025 lesions treated with very low dose radiation therapy. We offer this therapy in a response-adapted approach where patients get the 4 gray and then get a scan eight to 12 weeks later and based off that response additional radiation is recommended or just further observation. 

In these 1025 lesions we found that at two years the incidence of local progression was only 16% and then at five years only 26%. When comparing what factors might correlate with increased local progression, we found that patients that were treated with curative intent had improved local progression at just 15% at five years. We also found that patients that had larger tumors of greater than six centimeters, stage three disease, or had prior exposure to systemic therapy, that they would also have an increased local progression rate. Finally, we found that the response rate was 91% in the entire cohort and given that this treatment is very easy for patients of just two fractions with still excellent local control that we think this is very versatile treatment that can be offered for patients and benefit their disease control but also palliation of symptoms as well. 

So this approach seems appropriate for patients that have a need for palliation and advanced stage disease, but the challenge remains, is this lower dose of radiation appropriate for patients that are treated with curative intent? The current standard of care treatment for indolent non-Hodgkin lymphoma when it’s localized is 24 gray of radiation. We discussed this in another presentation at this meeting and showed that the freedom from progression at five years of doing this approach in patients for potential cure is 64%. And as we mentioned, the local control is better in these patients. So the next step to make this go out into the community and change the standard of care is a prospective trial. My mentors at MSK Radiation Oncology have designed and now recently opened a trial called FORTRESS, which will be randomizing patients that have indolent non-Hodgkin lymphoma treated with curative intent to being treated with 4 gray with our response-adapted approach to 24 gray with the primary endpoint of progression-free survival. We hope this way we can evaluate this approach in a rigorous manner and ultimately influence standard of care.

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