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Influence of Fractionation and Beam Sequencing on Absorbed Dose to Circulating Lymphocytes During Ultra-High Dose
François de Kermenguy1,2, Camilla Satragno1, Mohammed El-Aichi1
1Inserm U1030 Radiothérapie Moléculaire et Innovation Thérapeutique, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
JCO Clinical Cancer Informatics
|July 17, 2026
Summary
Ultra-high dose rate (UHDR) radiotherapy may not spare circulating lymphocytes as predicted. Fractionation and beam sequencing significantly impact lymphocyte dose, suggesting UHDR treatment strategies are crucial for clinical success.
Area of Science:
- Radiation Oncology
- Medical Physics
- Immunology
Background:
- In silico models suggested ultra-high dose rate (UHDR) radiotherapy spares circulating lymphocytes.
- Preclinical studies contradicted these findings, showing no reduction in radiation-induced lymphopenia with UHDR compared to conventional (CONV) dose rates.
Purpose of the Study:
- To investigate the influence of fractionation and beam sequencing on absorbed dose to circulating lymphocytes during CONV and UHDR irradiations.
- To compare lymphocyte dose patterns between CONV and UHDR radiotherapy.
Main Methods:
- Applied the LymphoDose framework to 162 brain tumor patients treated with 3D conformal radiotherapy.
- Compared four UHDR scenarios: single fraction simultaneous beams (S1), single fraction sequential beams (S2), three fractions simultaneous beams (S3), and three fractions sequential beams (S4).
Main Results:
- UHDR fractionation and beam sequencing significantly impacted irradiated blood volume and lymphocyte pool dose.
- UHDR scenarios primarily irradiated lymphocytes via head-and-neck lymph node exposure, not circulating blood.
- Distinct temporal dose patterns emerged: CONV showed numerous low-dose fractions, while UHDR presented few high-dose pulses.
Conclusions:
- Doses to lymphoid organs constitute a significant portion of the total lymphocyte pool dose, with limited differences between UHDR and CONV.
- Fractionation strategy for UHDR irradiation beams is critical for successful clinical translation.
