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Immunologically effective dose: a practical model for immuno-radiotherapy.

Raphaël Serre1, Fabrice Barlesi2, Xavier Muracciole3

  • 1Simulation & Modelling Adaptive Response for Therapeutics in Cancer (SMARTc), Center for Research on Cancer of Marseille, CRCM Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes, Marseille, France.

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|August 31, 2018
PubMed
Summary
This summary is machine-generated.

Radiotherapy combined with immune checkpoint blockers may improve survival by controlling metastatic spread. The new Immunologically Effective Dose (IED) model helps optimize radiotherapy schedules for better immune response and predict out-of-field effects.

Keywords:
combinationfractionationimmunotherapylinear-quadratic modelradiotherapy

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Area of Science:

  • Radiation Oncology
  • Immunology
  • Medical Physics

Background:

  • Concomitant radiotherapy and immune checkpoint blockade show synergistic potential.
  • Out-of-field radiotherapy effects may inhibit metastatic progression and improve survival.
  • Optimal radiotherapy fractionation and timing for this combination therapy remain unclear.

Purpose of the Study:

  • To introduce a novel metric, the Immunologically Effective Dose (IED), for quantifying the intrinsic immunogenicity of radiotherapy schedules.
  • To model the impact of radiotherapy dosing regimens on immune responses.
  • To provide a framework for optimizing radiotherapy in combination with immunotherapy.

Main Methods:

  • Proposed the Immunologically Effective Dose (IED) model, extending the traditional Biologically Effective Dose (BED) formula.
  • Incorporated parameters reflecting local immune effector availability within the tumor micro-environment.
  • Defined IED as the equivalent single dose at a low dose rate that elicits the same abscopal response.

Main Results:

  • The IED positively correlates with preclinical observations of out-of-field, radiotherapy-mediated immune effects.
  • Numerical simulations demonstrated the IED's applicability across various radiotherapy schedules.
  • A freely accessible web-based calculator for IED is now available.

Conclusions:

  • The IED model offers a method to predict out-of-field effects in radiotherapy combined with immune checkpoint inhibitors.
  • This model can guide the development of radiotherapy schedules with enhanced local and systemic immunogenicity.
  • The IED is independent of the specific immunotherapy used, offering broad applicability.