Influence of Fractionation and Beam Sequencing on Absorbed Dose to Circulating Lymphocytes During Ultra-High Dose Rate and Conventional Radiotherapy: An In Silico Study.

Abstract

Several in silico models concluded that ultra-high dose rate (UHDR) radiotherapy could spare large quantities of circulating lymphocytes. However, preclinical studies failed to show a reduction in radiation-induced lymphopenia after UHDR irradiation compared with conventional dose rates (CONV). This study aims to investigate the influence of fractionation and beam sequencing on absorbed dose to circulating lymphocytes during CONV and UHDR irradiations. The LymphoDose framework was applied to a cohort of 162 patients treated for brain tumors with 3D conformal radiotherapy. Four scenarios of UHDR treatment were compared: (S1) one fraction with all beams delivered simultaneously, (S2) one fraction with sequentially delivered beams, (S3) three fractions with all beams delivered simultaneously, and (S4) three fractions with sequentially delivered beams. UHDR fractionation and the beam delivery scheme had a significant impact on irradiated blood volume (1.3% ± 0.1% for S1 <i>v</i> 13% ± 3.2% for S4) and lymphocyte pool (12.5% ± 0.1% for S1 <i>v</i> 32.8% ± 0.2% for S4). UHDR scenarios primarily irradiate lymphocytes through exposure of head-and-neck lymph node rather than circulating blood. CONV and UHDR result in distinct temporal dose patterns for lymphocytes, characterized by either numerous low-dose fractions or a few high-dose pulses. The doses delivered to lymphoid organs account for a substantial portion of the total dose received by the lymphocyte pool, showing only a limited difference between UHDR and CONV in terms of lymphocyte exposure. The fractionation strategy of UHDR irradiation beams could play an important role in successfully translating UHDR treatments into clinical practice.