# Supratherapeutic PTX Buttresses Reduce Locoregional Recurrence Rates Following Surgery for Soft Tissue Sarcomas

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $749,261

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal describes an innovative surgical and bioengineering solution to the challenge of locoregional
recurrence for sarcomas. Locoregional recurrence (LRR) is the most common pattern of failure for
retroperitoneal, abdominal, and pelvic sarcomas. Despite a macroscopically complete resection, surgical
margins are frequently positive on final pathology due to large tumor size and anatomic complexity, resulting in
LRR rates of up to 40% even in leading referral centers with expertise in sarcoma. High mortality is commonly
due to locoregional disease rather than distant failure, and therefore strategies to improve survival must address
LRR. Trials evaluating perioperative and/or intraoperative external beam radiotherapy, single-dose hyperthermic
intraperitoneal chemotherapy, and systemic chemotherapy have all failed to demonstrate benefit. Our solution
is a surgically implantable buttress to locally deliver high concentrations of a chemotherapeutic drug to the
resection bed. Specifically, we describe the first example of an implantable, high-dose chemotherapeutic buttress
for biphasic extended paclitaxel (PTX) delivery post-resection. The buttress consists of a compliant
poly(caprolactone) (PCL) and poly(1,2-glycerol carbonate) (PGC) polymer blend on a mesh, where PTX is both
physically entrapped within and site-specifically conjugated to PGC enabling concentrations as high as 3.3
mg/cm2 (supraPTX-buttress). The proposed experiments will test the hypothesis that the dual release profile
combination of fast, but not burst, release of physically entrapped PTX followed by extended release of
covalently-bound PTX will: 1) reduce LRR rates and extend survival in patient-derived xenograft (PDX)
surgical models; and 2) be safe and feasible for locoregional drug delivery, achieving high local tissue
drug levels with minimal systemic delivery when implanted in a large animal along tissue planes and
vital structures commonly exposed during clinical cytoreductive sarcoma surgery. Importantly,
substantial preliminary data support the proposed studies, well-characterized materials and rigorous
experimental designs are established, and essential cross-disciplinary collaborations and expertise are in place
to address the hypotheses. supraPTX-buttresses provide an unprecedented opportunity to treat sarcomas with a
first-of-its-kind therapy. The specific aims of this five-year proposal are the following. Aim 1 characterizes the
PTX release kinetics as well as cytotoxicity and mechanism of action of supraPTX-buttresses against resected
patient-derived sarcomas in vitro. Aim 2 evaluates the efficacy of supraPTX-buttresses to prevent sarcoma
recurrence following resection in multiple PDX murine models with assessment of safety, local tissue healing,
and drug pharmacokinetics/biodistribution after film implantation. Aim 3 assesses the safety, feasibility,
perioperative morbidity, and systemic toxicity of supraPTX-buttress implantation in a...

## Key facts

- **NIH application ID:** 10500238
- **Project number:** 1R01CA272637-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Yolonda L Colson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $749,261
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10500238

## Citation

> US National Institutes of Health, RePORTER application 10500238, Supratherapeutic PTX Buttresses Reduce Locoregional Recurrence Rates Following Surgery for Soft Tissue Sarcomas (1R01CA272637-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10500238. Licensed CC0.

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