Abstract BACKGROUND Neo-adjuvant chemoradiation is standard of care for patients diagnosed with stage II and III rectal cancer. This treatment can cause significant toxicities and may require treatment modifications. Obesity and low muscle mass (=sarcopenia) may portend increased toxicity to chemotherapy and/or radiation and may further affect mortality in rectal patients. The present study investigates associations of pre-treatment body composition parameters with toxicity in prospectively followed rectal cancer patients. METHODS This initial analysis includes data from n=320 stage II and III rectal cancer patients from four study sites of the ColoCare Study. All patients underwent neo-adjuvant treatment. Pre-treatment CT scans were semi-automatically segmented at spinal level L3 vertebrae using SliceOmatic + ABACS software v5.0 rev13 to quantify: subcutaneous and visceral fat area (SFA/VFA, cm2) and skeletal muscle area (SMA, cm2). Information on toxicities was abstracted from medical charts and categorized into gastrointestinal, cardiovascular, and other system-specific toxicities. Median values were calculated for continuous variables (e.g., age at diagnosis, VFA, SFA, and SMA) and compared among patients who did versus did not experience toxicities. Frequencies and percentages were calculated for categorical variables. RESULTS Among n=320 rectal cancer patients, n=48 (15%) patients experienced at least one toxicity that required treatment modification (defined as dose reduction or discontinuation of therapy). Patients who experienced toxicities were older (58 years vs 56 years), more likely to be male (63% vs 59%), and more likely to be diagnosed with stage III cancer (92% vs 69%) compared to patients who did not experience toxicities. Patients who had higher VFA (166 cm2 vs 148 cm2), lower SFA (197 cm2 vs 208 cm2), and lower SMA (144 cm2 vs 147 cm2) were more likely to experience toxicities compared to patients with lower VFA, higher SFA, or higher SMA. CONCLUSIONS Body composition parameters may differ between rectal cancer patients who experience toxicities versus those who do not. Multivariate logistic regression and Cox proportional hazard analyses are underway to investigate in more detail the associations of body composition parameters (VFA, SFA, SMA), sarcopenia, and sarcopenic obesity with toxicity and survival in rectal cancer patients. Citation Format: Jennifer Ose, Jeffrey T. Yap, Daniel Jeong, Simon Ta Van, Matthew F. Covington, Biljana Gigic, Johanna Nattenmueller, Benjamin Haaland, Tengda Lin, Sheetal Hardikar, Caroline Himbert, Anita R. Peoples, Anjelica Ashworth, Juergen Boehm, Petra Schrotz-King, Jane C. Figueiredo, Adetunji T. Toriola, Erin M. Siegel, Christopher I. Li, Alexis B. Ulrich, Martin Schneider, Hans-Ulrich Kauczor, David Shibata, Cornelia M. Ulrich. Differences in body composition among rectal cancer patients with neo-adjuvant treatment-related toxicity: Results from the ColoCare Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3221.