# Using MRI and circulating tumor DNA to improve the interpretation of response to immunotherapy and targeted therapy in CNS metastases

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $646,356

## Abstract

Project Summary/Abstract
 There is increasing interest in using immunotherapy or targeted therapy to treat brain metastases,
including leptomeningeal disease from cancer. However, it can be challenging to interpret response to
treatment or to understand patterns of response or resistance to treatment since serial tissue samples are
difficult to obtain from the brain. Thus, there is a critical need to identify noninvasive makers of response or
resistance to new therapies being evaluated in this understudied patient population.
 In this proposal, Aim 1 will combine circulating tumor DNA with sophisticated MRI scans to improve our
ability to interpret response of brain metastases patients treated with pembrolizumab, a PD-1 inhibitor. With
pembrolizumab, increase in contrast enhancement on MRI can be tumor progression or inflammation from
successful re-activation of the immune system with treatment. We hypothesize that by combining a quantitative
measure of tumor burden, specifically circulating tumor DNA, with MRI scans, we will be able to disambiguate
true progression from pseudoprogression and, moreover, to understand mechanisms of response/resistance.
Aim 2 will use circulating tumor DNA to shed light on the clonal evolution of brain metastases in response to
targeted therapy, allowing for noninvasive means to understand response and resistance patterns. Aim 3 will
address the clinical challenge of accurately determining radiographic response in patients with leptomeningeal
disease from cancer. Similar to our hypothesis for parenchymal brain metastases, we expect that adding
ctDNA to MRI will improve our ability to more reliably measure LMD response to treatment.

## Key facts

- **NIH application ID:** 10757395
- **Project number:** 5R01CA244975-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Priscilla Kaliopi Brastianos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $646,356
- **Award type:** 5
- **Project period:** 2019-12-15 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757395

## Citation

> US National Institutes of Health, RePORTER application 10757395, Using MRI and circulating tumor DNA to improve the interpretation of response to immunotherapy and targeted therapy in CNS metastases (5R01CA244975-05). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10757395. Licensed CC0.

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