We noticed an increased number of patients diagnosed with colorectal cancer (CRC) in their 20s, 30s, and 40s. We analyzed all CRC patients aged < 50 at our institutions from 1972 to 2017 and found increasing trends as well as a propensity for more distal location-findings that are hypothesis generating, given the embryologic origin of these tumors. This finding may have implications for screening guidelines. Background: Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are younger than 50 years old, in most instances would not meet screening guidelines. We aimed to report the characteristics and trend of the rising proportion of young individuals being diagnosed with rectal and colon cancers at our institutions. Patients and Methods: This study included 3381 rectal and colon cancer patients from the Mayo Clinic cancer registry from 1972 to 2017 who were diagnosed with rectal or colon cancer and who were < 50 years old. Patient and cancer characteristics are described. The Cochran-Armitage trend test was used to see if the change in percentage diagnosed at age < 50 years had a significant trend over the years. A linear regression model was fit to estimate the percentage change per year when the trend was approximately linear. Results: The percentage of patients diagnosed with rectal or colon cancer in different age categories over the years showed a rising trend for individuals aged < 50. Most of these tumors were distal (rectum, left-sided colon, and rightsided colon were 49.8%, 28.8%, and 21.4%, respectively). This was more so for patients < 50 diagnosed with rectal cancer, which showed a linear increase at a rate of 0.26% per year (P < .001). Conclusion: Our study affirms the rising proportion of colorectal cancers found in young individuals, with a linear ongoing rise of rectal cancers in particular. This may have implications for the current screening recommendations for colorectal cancers, which are already being revised.

Background: The association between body mass index (BMI) and colorectal cancer is unique. There are several patient- and tumor-related factors that affect this and associations are not entirely clear. The primary aim of this study is to examine the association between BMI and survival after colorectal cancer diagnosis.Methods: Among 26,908 Mayo Clinic patients diagnosed with colorectal cancer between 1972 and 2017, 3,799 patients had information on BMI within 6 months prior to cancer diagnosis. Multivariable Cox regression models were used to assess the differences in overall survival between BMI groups in each cancer stage, controlling for age, gender, year of diagnosis, and cancer location. The impact of change of BMI at 30, 60, and 90 days on survival afterwards were also analyzed.Results: Among 3,799 patients included in the study, there were 29% normal weight, 2% underweight, 36% overweight, and 33% obese patients. With all stages combined together, the overall 5-years survival rates for underweight, normal weight, overweight, and obese patients were 33, 56, 60, and 65%, respectively (p < 0.001). The results show that, the difference in overall survival was not statistically significant when underweight, overweight, and obese patients were compared to normal weight patients in stage 1 and stage 2, although there was a trend that overweight patients had better survival than normal weight group in stage 2 cancer patients (HR = 0.8, p = 0.086). In stage 3 and 4 patients combined, underweight group demonstrated a significant disadvantage (HR = 1.96, p = 0.007) for overall survival compared to the normal weight group. Additionally, post-diagnosis BMI drop more than 10% from either a previous time (HR = 1.88, p = 0.002) or pre-diagnosis time (HR = 1.61, p < 0.001) was associated with worse overall survival after adjusting for baseline variables.Conclusions: BMI is an important consideration in patients with colorectal cancer. Outcomes are stage-dependent where in some situations obesity maybe an advantage. More importantly, being underweight is a significant negative predictor of outcome. The impact of drop in BMI or weight, on survival of CRC patients, needs to be studied further since this is potentially an actionable variable and a dynamic biomarker that may help improve outcome in these patients.

Background: Our study investigated the demographic characteristics of Mayo Clinic Colon and Rectal Cancer Registry patients and sought to associate tumor location with overall survival. Methods: Using the cohort of patients seen at Mayo Clinic (Minnesota, Arizona, Florida) from 1972 to 2017, we obtained 26,908 colorectal adenocarcinoma patient records. Overall survival of patients with colorectal cancer was analyzed by sidedness (right vs. left) and location (right vs. left vs. rectum). Kaplan–Meier method was used to analyze all demographic and cancer variables available within the dataset to trace survival over a 35-year period. Subgroups within variables were compared to each other using log-rank test and considered significantly different at P < 0.05. Cox proportional hazards regression model was used to assess impact of tumor location while controlling for age, year of diagnosis, sex, tumor stage, and tumor grade. Cox regression models were used to evaluate the independent effect of cancer location on overall survival after adjusting for age, gender, year of diagnosis, and cancer stage. To further explore the potential interaction effect of cancer location with cancer stage and year of diagnosis, similar multivariable Cox model was fit stratified by cancer stage (1–3 vs. 4) and by year of diagnosis (<1980, 1980–2000, >2000). Results: Overall survival differed significantly within all variables studied after Kaplan–Meier method analysis ( P < 0.0001). Survival was higher in the left-side group when evaluated by tumor sidedness, and rectal cancer patients had the highest median survival (101.3 months). Right-sided cancer patients had the worst prognosis in both tumor location and sidedness analyses, with a median survival of 76.6 months. However, the stratified analysis showed that, the difference in survival between left- and right-sided cancer only existed in late cancer stage (stage 4) patients but not in early cancer stage; therefore, screening for CRC to pick cancer at an early stage can influence overall survival significantly. Conclusion: These observations confirm some of the previous and recent studies on sidedness of colorectal cancer patients. Our analysis is novel in that it included patients of all stages rather than just stage IV metastatic patients. This initial study provides a platform to investigate more biologic and clinical factors associated with tumor location. Merging this dataset with other available datasets and previously conducted studies within the institution will provide a robust platform for multiple future studies and collaborations. Finally, appropriate screening can result in a decrease in incidence and mortality of CRC.

Cholangiocarcinoma is a heterogeneous and target-rich disease with differences in actionable targets. Intrahepatic and extrahepatic types of cholangiocarcinoma differ significantly in clinical presentation and underlying genetic aberrations. Research has shown that extrahepatic cholangiocarcinoma is more likely to be associated with ERBB2 (HER2) genetic aberrations. Various anti-HER2 clinical trials, case reports and other molecular studies show that HER2 is a real target in cholangiocarcinoma; however, anti-HER2 agents are still not approved for routine administration. Here, we show in a metastatic cholangiocarcinoma with ERBB2 amplification identified on liquid biopsy (circulating tumor DNA (ctDNA) testing), a dramatic response to now over 12 months of dual-anti-HER2 therapy. We also summarize the current literature on anti-HER2 therapy for cholangiocarcinoma. This would likely become another treatment option for this target-rich disease.

Introduction: Pharmacogenomics is about selecting the “right drug in the right amount for the right patient.” In metastatic colorectal cancer, germline pharmacogenomics testing presents a unique opportunity to improve outcomes, since the genes dihydropyrimidine dehydrogenase and UDP-glucuronosyltransferase metabolizing the chemotherapy drugs, 5-fluorouracil, and irinotecan are already well known. In a retrospective analysis of the landmark TRIBE clinical trial [(TRIBE - TRIplet plus BEvacizumab multicenter, phase III trial by the Italian Cooperative GONO (Gruppo Oncologico Nord Ovest) group (NCT00719797)], the proportion of patients with serious adverse events was higher in those with dihydropyrimidine dehydrogenase/UDP-glucuronosyltransferase aberrations and was dose dependent. We aimed to report on the feasibility and the results of incorporating pharmacogenomics testing into clinical practice. Methods: As a quality improvement initiative and a center of individualized medicine grant, we integrated the use of OneOme RightMed comprehensive test, which reports on 27 genes related to pharmacogenomics and over 300 medications of interest. We limited initial testing to patients with colorectal cancer. Pharmacists provided dosage recommendations based on test results in real-time. Results: At our cancer center, 155 patients underwent pharmacogenomics testing from November 2017 to January 2019. Results were available within 3 to 5 days of testing for most patients and were integrated into treatment decision-making. Of 155 sampled participants, a total of 89 (57.4%) participants had an UGT1A1 variant genotype, NM_000463.2: c.-53_-52[8] *1/*28, n = 74 (47.7%); *28/*28, n = 15 (9.7%). Additionally, 4 (2.6%) participants were heterozygous for dihydropyrimidine dehydrogenase. Two (1.3%) individuals were heterozygous for both UDP-glucuronosyltransferase and dihydropyrimidine dehydrogenase genes. All (100%) the patients had at least 1 actionable aberration related to supportive care medications ( CYP-family) of all the possible medications listed on their pharmacogenomics report. Conclusion: Preemptive comprehensive pharmacogenomics testing can be integrated into clinical practice in real-time for patients with cancer given faster turnaround and low cost. Pharmacist-driven, patient-specific medication management consults add further value given the number of genes/drugs. This sets the stage for a prospective randomized clinical trial to demonstrate the amount of benefit this can result in these patients.

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Background. Individuals after solid organ transplant may develop secondary malignancies. In our clinical practice, we noted an increasing number of individuals who developed colorectal cancers after solid organ transplantation. The primary aim of this study was to describe the characteristics and outcomes of the patients who developed colorectal cancer after solid organ transplant. Materials and Methods. Data was gathered and merged from several registries at Mayo Clinic to identify all patients who received a diagnosis of colon or rectal cancer and solid organ transplant. Continuous variables were summarized as mean (standard deviation) and median (range), while categorical variables were reported as frequency (percentage). Time to colorectal cancer after transplant and overall survival after cancer diagnosis were estimated using Kaplan-Meier method. Results. Initially, 115 colorectal cancer patients who also had a transplant were identified. The diagnosis of colorectal cancer was noted after solid organ transplant in 63 patients. The mean age at transplant was 57 years. Majority had received a kidney transplant (44.4%) followed by liver (36.5%). The median time to develop colorectal cancer was 59.3 months (range: 4.4-251.4 months). 15 (24.6%) were stage 4 at diagnosis and 13 (21.3%) had stage 3 colorectal cancer. Median overall survival was 30.8 months; 5-, 10- and 15-year survival were noted to be 42.5%, 17.9%, and 7.5%, respectively. None of the stage 4 patients were alive at 5 years; 5-year survival rate for stage 1, 2, and 3 patients was 77%, 50%, and 42%, respectively. Conclusions. Our study reports on one of the largest cohorts of patients of colorectal cancer that developed the cancer after solid organ transplant. Survival is extremely poor for advanced cases. However, long-term survivors are noted who developed the cancer at a relatively early stage. Colorectal screening recommendations may need to be revised for patients after solid organ transplant.

Background: The promising aspect of circulating tumor DNA (ctDNA) is its rapid turnaround and non-invasive nature. According to the American Society of Clinical Oncology (ASCO) and College of American Pathologists joint ctDNA review published in March 2018, there is not sufficient evidence to support the use of ctDNA in practice for GI cancers. However, there were numerous studies presented at ASCO Annual Meeting supporting its value. We aimed to summarize on its role in the management of gastrointestinal cancers based on the studies presented recently, and future directions. Methods: We limited our search to keywords “ctDNA,” “circulating tumor DNA,” “cell-free DNA (cfDNA)” and/or “liquid biopsy,” at the 2018 ASCO Annual Meeting library abstracts and presentations. Results: There were 35 studies that revolved around ctDNA as a diagnostic tool, prognostic marker and/or a measure of tumor heterogeneity in gastrointestinal cancers. Depending on the assay used, the results of several studies showed that ctDNA was able to identify relevant mutations or fusions including RAS, HER2/Neu, BRAF, MET, BRCA2, APC, TP53, ALK, ROS1, PTEN , and NF1 . The prognosis in terms of tumor mutation burden, objective response rate, metastasis and survival were also estimated by various studies based on ctDNA. The findings showed that higher baseline ctDNA levels and/or increased number of mutations detected in ctDNA were associated with poor survival and multi-site metastasis. Right-sided colon cancer was associated with higher number of mutations in ctDNA than left-sided colon and rectal cancers. Similarly, tubular adenocarcinoma subtype of gastric cancer was more likely to have higher ctDNA levels than signet-ring cell subtype. The feasibility of assessing response to therapy and residual metastatic disease by using ctDNA which was otherwise not detected on imaging was also presented. Conclusions: The studies presented at ASCO 2018 report on the many ways ctDNA is of value in patients with gastrointestinal malignancies. Experts and discussants at the meeting argued that this may well indeed be ready for prime time for certain GI malignancies including colorectal cancers, especially in the metastatic setting. These findings alongside ongoing studies showing its feasibility into practice would likely lead to revision of the current guidelines for metastatic GI cancers.