Excellent Response to Very Low Dose Radiation (4Gy) For Indolent B-cell Lymphomas: Is 4Gy Suitable for Curable Patients?

Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas (iNHL), such as follicular lymphoma (FL) and marginal zone lymphoma (MZL). While the standard of care for localized iNHL remains 24Gy, de-escalation to very low dose radiotherapy (VLDRT) of 4Gy further reduces toxicities and treatment duration. Use of VLDRT outside of 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 FL and MZL treated between 2005 and 2018 (n=299 lesions; 250 patients) utilizing modern principles including PET staging and involved site radiotherapy (ISRT). Outcomes include best clinical/radiographic response between 1.5-6 months post-VLDRT, and cumulative incidence of local progression (LP) with only death as competing risk. Post-VLDRT, the overall response rate was 90% for all treated sites with 68% achieving complete response (CR). With median follow-up of 2.4 years, the 2-year cumulative incidence of LP was 25% for the entire cohort and 9% after frontline VLDRT treatment for potentially curable, localized disease. Lesion size >6cm 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 ISRT strategy where patients will be treated initially with VLDRT, reserving full dose treatment for those who fail to attain a CR.