Renewed interest for low-dose radiation therapy in follicular lymphomas: From biology to clinical applications

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoproliferative disorders. Treatment strategies for FL may include several therapeutic choices, ranging from a "watchful waiting" approach to stem cell transplantation, mostly depending on staging, age, risk factors, and disease burden at diagnosis. The high radiosensitivity of FL compared with other solid tumors has been known since the beginning of radiotherapy treatment in lymphoma patients. Doses of 24 to 40 Gy were considered appropriate in first line curative treatment for localized disease (stages I-II), but several publications investigating low-dose radiotherapy (LDRT) of 4Gy (2 × 2Gy) reported an overall response rate surprisingly high. Due to its high local efficacy and negligible toxicity, LDRT might be offered to both early and advanced stage FL patients in combination with new agents, at diagnosis or after several lines of systemic therapy. The aim of this review is to summarize and discuss the current knowledge on LDRT for FL and its potential application in a curative setting in combination with new drugs for both early and advanced disease.