Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients?

Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas, such as follicular lymphoma and marginal zone lymphoma. Although the standard of care for localized indolent non-Hodgkin lymphomas remains 24 Gy, de-escalation to very-low-dose radiotherapy (VLDRT) of 4 Gy further reduces toxicities and duration of treatment. Use of VLDRT outside palliative indications remains controversial; however, we hypothesize that it may be sufficient for most lesions. We present the largest single-institution VLDRT experience of adult patients with follicular lymphoma or marginal zone lymphoma treated between 2005 and 2018 (299 lesions; 250 patients) using modern principles including positron emission tomography staging and involved site radiotherapy. Outcomes include best clinical or radiographic response between 1.5 and 6 months after VLDRT and cumulative incidence of local progression (LP) with death as the only competing risk. After VLDRT, the overall response rate was 90% for all treated sites, with 68% achieving complete response (CR). With a median follow-up of 2.4 years, the 2-year cumulative incidence of LP was 25% for the entire cohort and 9% after first-line treatment with VLDRT for potentially curable, localized disease. Lesion size >6 cm was associated with lower odds of attaining a CR and greater risk of LP. There was no suggestion of inferior outcomes for potentially curable lesions. Given the clinical versatility of VLDRT, we propose to implement a novel, incremental, adaptive involved site radiotherapy strategy in which patients will be treated initially with VLDRT, reserving full-dose treatment for those who are unable to attain a CR.