# Systematic liquid biopsy to monitor residual disease and treatment efficacy in gastrointestinal cancer patients

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $271,298

## Abstract

Project Summary: Circulating tumor DNA (ctDNA) is emerging as a biomarker in oncology with several
transformative clinical applications. One application may be the ability to detect clinically undetectable minimal
residual disease (MRD) following curative intent treatment. In Stage III colorectal cancer (CRC), the primary
means of cure is surgical resection, but if any tumor cells remain post-surgery, this can lead to eventual
recurrence. In Stage III CRC, adjuvant chemotherapy also reduces recurrence risk, but 30% of patients will still
recur. ctDNA detection may predict which patients have the highest recurrence risk, but a key question is whether
an effective method to detect MRD can also identify patients who may benefit from additional therapy and
increase cure rates. In Aims 1 and 2 with a 500 patient, multi-institutional Stage III CRC trial, ACT3, funded by
Stand Up 2 Cancer, we will test the ability of ctDNA to identify patients who would recur without additional therapy
and evaluate if additional treatment allows for ctDNA “clearance.” ctDNA “clearance” will be used as a rapid
read-out for adjuvant therapy efficacy and subsequently evaluate if “clearance” correlates with improved
recurrence-free survival. With ACT3, we will also evaluate emerging technologies for MRD detection and identify
the optimal timing for MRD detection. This could create a novel approach for adjuvant clinical trials, providing a
opportunity to salvage more cures. A second potentially transformative, clinical application of ctDNA is real-time
monitoring of response to systemic therapy. While radiographic imaging remains the gold standard for measuring
treatment response and disease progression, the ability to detect early evidence of treatment response or
failure—before it is evident by standard radiographic imaging—could allow clinicians to rapidly adapt therapies
to optimize patient outcomes. A patient could be switched early on from an ineffective therapy to a potentially
effective therapy to achieve more rapid benefit, while minimizing the toxicity from continuing an ineffective
therapy. In Aim 3, we will test the hypothesis that serial ctDNA monitoring may provide a real-time, non-invasive
means to track early therapeutic response for metastatic GI cancers in a 200-patient prospective study. We will
compare ctDNA changes to changes in standard tumor markers and patient reported outcomes assessing the
ability of each modality alone or in combination to predict radiographic response. In parallel, we will evaluate
novel technologies of ctDNA for response prediction. The primary work will take place at Massachusetts General
Hospital and expands upon my established relationships with my mentorship team consisting of internationally
recognized experts in liquid biopsies and clinical trials (primary mentor: Ryan Corcoran, MD PhD and co mentors
Luis M. Diaz, MD and David B Ryan, MD). A scientific advisory committee with complementary expertise will
also provide guidan...

## Key facts

- **NIH application ID:** 10894923
- **Project number:** 5K08CA273688-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Aparna Raj Parikh
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $271,298
- **Award type:** 5
- **Project period:** 2022-09-05 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894923

## Citation

> US National Institutes of Health, RePORTER application 10894923, Systematic liquid biopsy to monitor residual disease and treatment efficacy in gastrointestinal cancer patients (5K08CA273688-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894923. Licensed CC0.

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