# A Computational Method to Calculate the Radiation Dose to Circulating Lymphocytes

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $246,460

## Abstract

There is growing enthusiasm in response to emerging data that combining immunotherapy
with radiation therapy (RT) can increase response rates. However, persistent
immunosuppression caused by radiation itself appears to limit this synergy.
The effects of the exact RT delivery parameters (radiation modality, fractionation scheme,
daily radiation exposure time and radiation dose rate) on the patient’s lymphocytes remain
unknown, and there are currently no methods to calculate the radiation dose to circulating
lymphocytes.
The objective of this proposal is to develop a computational model to simulate the radiation
dose to the lymphocyte population during intracranial irradiation based on vascular
segmentation (SA1). The blood flow in the rest of the body will be modeled by a simplified
Markov chain formalism. This will be combined with the patient-specific, time-dependent
dose delivery information to simulate the dose to the circulating lymphocytes using a
generalized Monte-Carlo approach. Furthermore we will validate our computational
framework in patients treated with (conventional) photon and proton therapy. Due to the
different dose distributions and time courses between proton and photon patients, we will
be able to correlate the measured depletion in vivo to the patient-specific lymphocyte dose
calculation to validate our computational model (SA2).
Quantifying the dose delivered to the lymphocytes has great clinical potential and
actionable significance because of the ease to modify radiation delivery parameters.
Accurate knowledge of this effect would be transformative for the implementation of
immunotherapy trials that are augmented with RT (>100 trials currently recruiting patients).
Accurate dosimetry for circulating lymphocytes can control for variability among patients
and will be key for the correct interpretation of trial results.

## Key facts

- **NIH application ID:** 9950246
- **Project number:** 1R21CA248118-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Clemens Grassberger
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $246,460
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-11-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9950246

## Citation

> US National Institutes of Health, RePORTER application 9950246, A Computational Method to Calculate the Radiation Dose to Circulating Lymphocytes (1R21CA248118-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9950246. Licensed CC0.

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