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

Award Number: R01CA244975
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $646,356 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	5	5/1/2024	NON-COMPETING CONTINUATION	$34,019
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	5	11/20/2023	NON-COMPETING CONTINUATION	$612,337
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	002	5	9/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $646,356

Issue Date FY: 2023 ( Subtotal = $666,767 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	4	3/29/2023	NON-COMPETING CONTINUATION	$54,430
2023	2023	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	4	12/23/2022	NON-COMPETING CONTINUATION	$612,337
														Subtotal = $666,767

Issue Date FY: 2022 ( Subtotal = $666,767 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	002	3	6/13/2022	NON-COMPETING CONTINUATION	$54,430
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	3	12/17/2021	NON-COMPETING CONTINUATION	$612,337
2022	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	2	10/21/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $666,767

Issue Date FY: 2021 ( Subtotal = $694,319 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	2	11/10/2020	NON-COMPETING CONTINUATION	$659,602
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	2	1/21/2021	NON-COMPETING CONTINUATION	$34,717
														Subtotal = $694,319

Issue Date FY: 2020 ( Subtotal = $711,319 )
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	1	2/5/2020	NEW	$16,731
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	1	12/13/2019	NEW	$694,588
														Subtotal = $711,319

Grand Total All Awards = $3,385,528

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

Award Number: R01CA244975

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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