# A Digital Twin for rectal cancer to guide adaptive radiotherapy

> **NIH NIH U54** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $246,001

## Abstract

This application is being submitted in response to the Notice of Special Interest (NOSI) identified as
NOT-CA-24-015. Despite the recognition of the contribution of the immune system to cancer response to
ionizing radiation, successful translation to the clinic is lagging. We are proposing to adapt the ROBIN
mechanisms of research to enable a deep dive into the field of radiation (RT) and immunity. Representatives
from seven international academic centers already engaged in RT and immunity research have converged to
participate in a small prospective clinical trial (accrual: 25 patients in US and 25 patients in Europe), to
synergize and accelerate discovery. The setting of preoperative short course radiotherapy (SCRT) in rectal
cancer, has emerged as ideal for the scientific questions posed. SCRT is a standard treatment, preceded and
followed by colonoscopies to respectively assess tumor baseline extent and response (at the end of RT):
during each colonoscopy consenting patients can donate a tumor biopsy, as well as stool and blood (PBMC)
samples. The same set of specimens can be harvested, six weeks later at surgery, where research sampling
of lymph nodes will also be possible, within and outside the RT field. These sequential sets of tissues will
enable us to conduct cutting edge multiple “omics” approaches to study irradiated normal and cancer tissue
and the microbiome in the RT field. The PBMC analysis will allow correlation at a single cell level between RT-
induced oxidative stress, changes in immunophenotype and PBMC biology. Similarly, the ability to analyze
lymph nodes harvested inside and outside the radiation field will allow to pinpoint at the single cell level the RT
effects on each immune subpopulation. The longitudinal analysis on cancer biopsy, collected before and after
RT and at surgery, will give a snapshot on the RT-induced “omics” changes. An orthogonal radiomic study will
analyze MR images obtained before SCRT and before surgery (also standard imaging procedures in rectal
cancer) together with images obtained at CT simulation. Compliance with international regulations for data
sharing, standardization of procedures and data acquisition and harmonization of uploaded data will be
essential to this effort. Advanced bioinformatics tools will be applied through a dedicated Data Sharing and
Integrative Analysis Core, capable to deconvolute and interpret complex biological and imaging data, sorted by
utilizing NCI FireCloud workspaces. By converging experienced clinical investigators, bio-scientists and bio-
informaticians to address fundamental radiation biology questions, this ROBIN will rapidly enable
unprecedented discovery that will be shared with the ROBIN network and the scientific community at large.
Finally, since inception, ROBIN has revealed an optimal environment for cross-training and cross-fertilization of
the scientists and clinicians involved in the grant preparation and has created a robust foundation for the
propo...

## Key facts

- **NIH application ID:** 11059810
- **Project number:** 3U54CA274291-03S1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Joseph O Deasy
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,001
- **Award type:** 3
- **Project period:** 2022-09-21 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11059810

## Citation

> US National Institutes of Health, RePORTER application 11059810, A Digital Twin for rectal cancer to guide adaptive radiotherapy (3U54CA274291-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11059810. Licensed CC0.

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