ABSTRACT
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
proposed Cross Training Core, a novel structure to form future leaders in radiation oncology and biology, a task
each of the three P.I.s consider crucial to the future of our discipline.