# Bio-Physical Modeling of Immuno-Radiotherapy Combinations based on Patient Data

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $182,700

## Abstract

The immuno-modulatory effects of radiotherapy (RT) associated with anti-tumor immunity
have recently become a focus of investigations in a range of indications. Meanwhile, the
radiation dose, fractionation and timing on clinical trials has been highly variable. A
concerted approach to determine the radiation regimen needed to stimulate the immune
system in humans is needed.
Animal experiments have confirmed the existence a synergy between immunotherapy and
radiation, but it is unclear how these results translate to patients in terms of dose,
sequencing, timing and fractionation.
The objective of this proposal is to develop a novel bio-physical approach to derive the
synergism of radiotherapy with immunotherapy directly, i.e. without using parameters
derived from animal experiments, from clinical patient and outcome data. The model is
based on observable patient information, such as tumor load and circulating lymphocyte
counts, and will be validated using clinical trial data from our institution.
In SA1 we will first develop the tumor-immune-radiation model, enabling us to predict the
lymphocyte depleting effect of radiation and the tumor-lymphocyte interaction, validated by
clinical data of hepatocellular carcinoma (HCC) patients treated with radiotherapy. Most
importantly, we will be able to simulate the effect of different fractionation regimen on the
circulating lymphocyte count. In SA2 we will include the effect of immunotherapy based on
HCC patient data and validate the combined approach by predicting the results of an
innovative Immuno-RT trial currently conducted at our institution. We will subsequently
apply the model to investigate optimal dose & fractionation regimen and their dependence
upon patient characteristics in the treatment of locally advanced and metastatic HCC.

## Key facts

- **NIH application ID:** 9949683
- **Project number:** 5R21CA241918-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Clemens Grassberger
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $182,700
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949683

## Citation

> US National Institutes of Health, RePORTER application 9949683, Bio-Physical Modeling of Immuno-Radiotherapy Combinations based on Patient Data (5R21CA241918-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9949683. Licensed CC0.

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