Radiation therapy (RT) is the single most effective treatment modality for achieving local control in most types of lymphomas. RT causes DNA damage, which can be modulated very accurately in space and time. Modern advanced imaging (PET, MRI, image fusion) and treatment techniques (3-dimensional conformal RT, intensity modulated therapy [IMRT], volumetric arc therapy [VMAT], proton therapy, breathing adaptation, MR-accelerators) have changed lymphoma RT dramatically. The prescribed radiation dose is now delivered very precisely to the macroscopic lymphoma volume, and no more than that (1). This makes RT eminently suited for combination with systemic treatments, either as consolidation using spatial cooperation with cytotoxic systemic treatments, or as immune stimulators in combination with immunomodulatory treatments, the so-called abscopal effect. RT in the curative setting has always been given in many small fractions to protect the critical normal tissues from serious long-term effects. However, with modern conformal RT and very steep dose gradients around targets, the surrounding normal tissues get a much lower dose than before. Hence, even if large fractions to the tumor tissue are employed (so-called hypofractionation) the fraction size for the normal tissues will be in the desired low-dose range. During the recent COVID-19 pandemic RT resources became scarce, and the International Lymphoma Radiation Oncology Group (ILROG) published emergency guidelines for hypofractionation for lymphomas in order to reduce the pressure on RT departments (2). Preliminary experience has been encouraging. Delivering RT to lymphomas in a few large fractions may make it even more convenient for combination with systemic treatments. We and others have shown that the lymphocyte count decreases during a course of RT, most pronounced when many fractions are given, and that it does not reach its former level even a year after treatment (3). A low lymphocyte count increases the risk of infections and may also lead to an increased risk of long-term side effects. Hypofractionation may therefore prove not more but less toxic, challenging the radiobiologic paradigm that has hitherto formed the basis of RT in the curative setting. In conclusion, technological progress and innovative implementation of RT open new possibilities for combinations with systemic treatments to benefit patients with malignant lymphoma.

References: 1. Specht L. Radiotherapy for Hodgkin lymphoma: Reducing toxicity while maintaining efficacy. Cancer J 2018;24:237-43. 2. Yahalom J, Dabaja BS, Ricardi U, et al. ILROG emergency guidelines for radiation therapy of hematological malignancies during the COVID-19 pandemic pandemic. Blood (in press). 3. Terrones-Campos C, Ledergerber B, Vogelius IR, et al. Lymphocyte count kinetics, factors associated with the end-of-radiation-therapy lymphocyte count, and risk of infection in patients with solid malignant tumors treated with curative-intent radiation therapy. IJROBP 2019;105:812-23.

Citation Format: Lena Specht. Rethinking radiation therapy in the modern era of advanced systemic treatments of malignant lymphoma [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-61.