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LymphoDose: a lymphocyte dose estimation framework-application to brain radiotherapy.

François de Kermenguy1, Nathan Benzazon1, Pauline Maury1,2

  • 1Université Paris-Saclay, Gustave Roussy, Inserm U1030, Radiothérapie Moléculaire et Innovation Thérapeutique, F-94800, Villejuif, France.

Physics in Medicine and Biology
|April 9, 2024
PubMed
Summary

Radiation-induced lymphopenia impacts brain tumor patients. Our simulation shows lymphocyte recirculation and out-of-field doses significantly reduce lymphocyte irradiation, suggesting other factors drive lymphopenia and impacting radio-immunotherapy strategies.

Keywords:
Markov chainbrain tumorcompartments modellymphocyte-sparing radiotherapylymphocyteslymphopenia

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Area of Science:

  • Medical Physics
  • Radiation Oncology
  • Immunology

Background:

  • Severe radiation-induced lymphopenia (RIL) affects 40% of brain tumor patients, correlating with poor survival.
  • Accurate estimation of lymphocyte radiation dose is crucial for understanding RIL and optimizing cancer treatment.
  • Volumetric modulated arc therapy (VMAT) for brain tumors poses challenges in quantifying lymphocyte exposure.

Purpose of the Study:

  • To develop and validate an in-silico framework for estimating lymphocyte radiation doses during VMAT brain irradiation.
  • To investigate the impact of lymphocyte recirculation and out-of-field (OOF) doses on lymphocyte irradiation.
  • To compare different biological and physical scenarios of lymphocyte circulation and irradiation.

Main Methods:

  • Developed a simulation using two interconnected compartmental models for lymphocyte recirculation between lymphoid organs (M1) and bloodstream (M2).
  • Utilized dosimetry data from 33 glioblastoma patients undergoing chemoradiation.
  • Compared three scenarios: M2 only circulation, M1 and M2 interconnected circulation, and M1/M2 with deep-learning computed OOF head and neck doses.

Main Results:

  • The M1/M2 interconnected model (H2) significantly reduced the irradiated lymphocyte fraction (40.4%) and average dose (52.6 mGy) compared to M2 only (H1).
  • Including OOF doses to head and neck lymphoid structures (H3) increased the irradiated fraction (97.6%) and dose (265.6 mGy).
  • Recirculation limited average irradiation events to 1.58 times; estimated doses were low, suggesting other mechanisms contribute to RIL.

Conclusions:

  • The developed framework is the first to incorporate OOF doses and recirculation for lymphocyte dose assessment in brain irradiation.
  • Lymphocyte recirculation and OOF doses play a significant role in reducing direct lymphocyte irradiation.
  • Further research is needed to elucidate indirect irradiation effects on lymphopenia to enhance radio-immunotherapy and abscopal effects.