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Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (&lt, 50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III–IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82–3.83) and 2.00 (1.43–2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21–1.98) and 0.56 (0.41–0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.

PURPOSE: The ColoCare Study is an international cohort of men and women (>18 years age) newly diagnosed with stage I-IV colorectal cancer from seven centers in the United States and Germany. Study enrollment is currently ongoing. Here, we describe the clinical and demographic characteristics of this large cohort of prospectively followed colorectal cancer patients and describe differences in demographic, lifestyle, and clinical characteristics by age of onset and tumor site. METHODS: Data on demographics (sex, age, race, ethnicity) and lifestyle factors (smoking, body mass index) collected at baseline are included in this analysis, in addition to information on tumor characteristics (tumor stage and site), treatment (neoadjuvant and adjuvant therapy), and clinical outcomes (vital status, recurrence). Patients were categorized into early- ( RESULTS: Data on 1,933 stage I-IV colorectal cancer cases were included in this study, 19% of which were deceased at the time of this analysis. On average, patients were 60 years old, had a BMI of 29 kg/m2, and were predominantly diagnosed with stage II (25%) and stage III (33%) colorectal cancer. Fifty three percent of cases were diagnosed with colon cancer, while 47% were rectal cancer cases. Twenty percent (n=364) of patients were diagnosed before age 50 (i.e. early-onset cases). The early-onset group presented with a higher percentage of rectal cancer (52%) and more advanced disease (64% stage III-IV cancer) compared to late-onset cases (46% and 48%, respectively). Percentages of ever smokers were higher among late-onset compared to early-onset patients (51% vs. 38%), independent of tumor site. Early-onset cancers were more likely to originate in the rectum compared to colon, particularly among women (61% vs. 51%). Early-onset rectal cancer cases were more likely to be female as compared to late-onset rectal cancer cases (61% vs. 36%). Corresponding with national trends, early-onset cases received more aggressive adjuvant therapy after surgical resection compared to late-onset patients (54% vs. 40%). DISCUSSION: Within this large international multi-center cohort, patients with early-onset colorectal cancer were more likely to be diagnosed with rectal cancer and advanced stage disease. The majority of early-onset cases in the ColoCare Study were non-smokers. As expected, more aggressive treatment modalities were used in patients with early-onset disease. Citation Format: Caroline Himbert, Jane Figueiredo, Lyen Huang, Biljana Gigic, Courtney L. Scaife, Bartley Pickron, Laura Lambert, Jessica Cohan, Mary Bronner, Jolanta Jedrzkiewicz, Esther Herpel, Matthias Kloor, Johanna Nattenmueller, Hans-Ulrich Kauczor, Alexis Ulrich, Seth Felder, Julian Sanchez, Sophie Dessureault, Nathan Hinkle, Justin Monroe, Matthew Mutch, Cory Bernadt, Deyali Chatterjee, Mika Sinanan, Stacey Cohen, Ulrik Wallin, Deepti Reddi, Mukta Krane, Afshin E. Gabayan, David M. Hoffman, Yosef Y. Nasseri, Robert W. Decker, Karen Zaghiyan, Zuri A. Murrell, Andrew E. Hendifar, Jun Gong, Eiman Firoozmand, Alexandra Gangi, Beth A. Moore, Kyle G. Cologne, Maryliza El-Masry, William Grady, Martin Schneider, Stephanie L. Schmit, Erin Siegel, David Shibata, Adetunji Toriola, Christopher Li, Cornelia Ulrich, Sheetal Hardikar. Clinical characteristics and outcomes of colorectal cancer in the ColoCare Study: Differences by age of onset [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2364.

While obesity is considered a prognostic factor in colorectal cancer (CRC), there is increasing evidence that not simply body mass index (BMI) alone but specifically abdominal fat distribution is what matters. As part of the ColoCare study, this study measured the distribution of adipose tissue compartments in CRC patients and aimed to identify the body metric that best correlates with these measurements as a useful proxy for adipose tissue distribution. In 120 newly-diagnosed CRC patients who underwent multidetector computed tomography (CT), densitometric quantification of total (TFA), visceral (VFA), intraperitoneal (IFA), retroperitoneal (RFA), and subcutaneous fat area (SFA), as well as the M. erector spinae and psoas was performed to test the association with gender, age, tumor stage, metabolic equivalents, BMI, waist-to-height (WHtR) and waist–to-hip ratio (WHR). VFA was 28.8 % higher in men (pVFA

BACKGROUND Obesity is associated with colorectal cancer (CRC) risk and prognosis. We investigated associations between plasma metabolites and multiple dimensions of body fatness in early- and late-stage CRC patients enrolled in the ColoCare Study, a multicenter international cohort. METHODS Pre-operatively collected plasma samples of newly diagnosed CRC patients [n=212; (stage I-IV)] from the ColoCare Study were utilized to perform targeted metabolomics by mass spectrometry using the AbsoluteIDQ p180 Kit assay (Biocrates; intra-plate CVs RESULTS A total of 127 metabolites from 5 different compound classes (i.e., amino acids, biogenic amines, glycerophospholipids, sphingomyelins, acylcarnitines) were included for statistical analysis. Overall obesity (BMI) and VAT were not associated with any metabolites in early-stage or late-stage tumors. SAT (L3/L4 and L4/L5) was inversely associated with 3 glycerophospholipids in analyses restricted to late-stage, but not early-stage tumors: PC-ae-C34_0 (pFDR=0.02), PC-ae-C36_0 (pFDR=0.03), PC-ae-C36_1 (pFDR=0.03). A doubling of concentration in selected glycerophospholipids was associated with a significant increase in risk for death in late-stage (III and IV) CRC. CONCLUSIONS We observed a negative association between subcutaneous abdominal adiposity and glycerophospholipids in late-stage CRC. Glycerophospholipids are major components of cellular membranes and are pertinent to cancer cells that undergo progression and metastasis. Our results suggest that a metabolic shift in glycerophospholipid metabolism in late-stage tumors may take place and have potential impact on survival. Note: This abstract was not presented at the meeting. Citation Format: Jennifer Ose, Tengda Lin, Nina Habermann, David Achaintre, Pekka Keski-Rahkonen, Augustin Scalbert, Juergen Boehm, Biljana Gigic, Dominique Scherer, Johanna Nattenmueller, Mariam Salou, Lin Zielske, Alexis Ulrich, Jewel Samadder, Hanno Glimm, Stephen Hursting, Hans-Ulrich Kauczor, Cornelia M. Ulrich. Associations between adipose tissue compartments and the plasma metabolome in colorectal cancer patients: Results from the ColoCare Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5325. doi:10.1158/1538-7445.AM2017-5325

Background Branched-chain amino acids (BCAA; e.g., valine, leucine and isoleucine) have been previously linked with survival in colorectal cancer patients. It is unclear whether BCAAs are prognostic biomarkers or a surrogate endpoint for factors related to muscle mass. Thus, we investigated the correlation between BCAAs and muscle mass, physical activity and body mass index (BMI) at multiple time points during the course of disease in a prospective cohort of patients. Methods Patients with newly diagnosed colorectal cancer [n = 197; (stage I - IV)] from the ColoCare study in Heidelberg, Germany with baseline and follow-up data, and measurements of urinary BCAAs were eligible. Skeletal muscle mass of the dorsal muscle was quantified based on abdominal computed tomography (CT)-scans (vertebral body L3/4 and L4/5). BMI (kg/m2) and physical activity [metabolic equivalent (MET) hours/week] were reported by questionnaire. In addition, minutes of moderate and vigorous physical activity/week were measured by accelerometry. We prospectively monitored the urinary metabolome of these patients at multiple time points after surgery [baseline (n = 197), 6-month follow-up (n = 107) and 12 month follow-up (n = 75)]. BCAAs (valine, leucine and isoleucine) were identified using gas chromatography mass spectrometry (GC/MS). Metabolites were normalized based on the sum intensity of all annotated metabolites for statistical analyses. Pearson and partial correlation coefficients with parameters of energy balance/muscle mass were computed for each time point, adjusted for gender and age at diagnosis. Results As expected, urinary valine, leucine and isoleucine were highly correlated, independent of time point (r>0.95, P Conclusion The present data suggests that urinary levels of BCAA in colorectal cancer patients do not reflect parameters of energy balance and muscle mass. Thus, they warrant further investigation as potential prognostic biomarkers. Citation Format: Jennifer Ose, David B. Liesenfeld, Juergen Boehm, Nina Habermann, Robert W. Owen, Biljana Gigic, Stefanie Skender, Johanna Nattenmueller, Hans-Ulrich Kauczor, Cornelia Ulrich. Branched-chain amino acids in the urinary metabolic profile of colorectal cancer patients and associations with muscle mass, BMI, and physical activity in the ColoCare Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4282.