# Validation and implementation of ctDNA as a clinically informative biomarkerin AYAs with sarcomas.

> **NIH NIH K08** · DANA-FARBER CANCER INST · 2024 · $253,273

## Abstract

PROJECT SUMMARY/ABSTRACT
Advances in our understanding of disease biology and development of new technologies have made
individualized treatment a reality for many patients with cancer. Such improvements have been elusive for
adolescents and young adults (AYAs) with sarcomas. Treatments for these diverse sarcomas often include
intensive multiagent chemotherapy, surgery and radiation, yet many patients still suffer relapse and die of
disease. Survivors are left with debilitating late effects including infertility, heart disease, and secondary cancers.
Outcomes in other cancers have been vastly improved using biomarkers to delineate disease sub-groups,
evaluate response to therapy, and detect relapse, maximizing chance of cure and minimizing late effects. In
contrast, there are no validated biomarkers in AYA sarcomas to facilitate testing of risk-stratified therapy. This
scientific gap presents a major barrier to improving outcomes.
My long-term objective is to improve outcomes for AYAs with sarcomas through biomarker-informed clinical
trials. Circulating tumor DNA (ctDNA) is an exciting candidate biomarker for this purpose and holds the potential
for broad application across the majority of AYAs with sarcomas. I have demonstrated that elevated ctDNA
burden at diagnosis is associated with an increased risk of disease relapse and death for patients with the two
most common bone sarcomas affecting this population: Ewing sarcoma (EWS) and osteosarcoma. Broadly, all
high-grade sarcomas can be divided into fusion-positive sarcomas like EWS or fusion-negative sarcomas with a
high level of aneuploidy like osteosarcoma. ctDNA holds the potential to be paradigm shifting for the treatment
of AYA sarcomas by leveraging these genomic characteristics to inform risk-stratification. We have assembled
large patient cohorts (n>700) of two fusion-positive sarcomas (EWS and synovial sarcoma) and two fusion-
negative sarcomas [osteosarcoma and undifferentiated pleomorphic sarcoma (UPS)] to perform validation
studies to establish ctDNA prognostic thresholds at diagnosis and following initial therapy. To assess the clinical
impact of return of results on clinicians, I have launched a pilot study using commercial liquid biopsy testing for
fusion detection during disease surveillance for patients with EWS.
I will evaluate the central hypothesis that ctDNA burden is clinically informative in sarcomas affecting AYAs and
can inform trials of risk-adapted therapy in the near future by addressing the following aims: (1) Determine
ctDNA-based prognostic thresholds for risk of relapse in fusion-negative sarcomas at baseline; (2)
Determine ctDNA-based prognostic thresholds for risk of relapse in fusion-positive sarcomas at baseline
and following initial treatment; and (3) Evaluate the clinical impact of ctDNA testing for disease
surveillance in EWS. At the conclusion of this project, we will have validated ctDNA as a prognostic biomarker
in multiple clinical settings and position...

## Key facts

- **NIH application ID:** 10865581
- **Project number:** 1K08CA290061-01
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** David Shulman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $253,273
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10865581

## Citation

> US National Institutes of Health, RePORTER application 10865581, Validation and implementation of ctDNA as a clinically informative biomarkerin AYAs with sarcomas. (1K08CA290061-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10865581. Licensed CC0.

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