Recurrence and survival rates of inflammatory bowel disease-associated colorectal cancer following postoperative chemotherapy: a comparative study

Background and Aim: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC, suggesting differences in tumor behavior and response to treatment. We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD. Methods: Search of the Cleveland Clinic’s CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010. Twenty-one patients were excluded due to incomplete clinical data. Propensity score-matching based on age, surgery intent, CRC site, tumor grade, American Joint Committee on Cancer (AJCC) stage and T stage was used to match IBD and non-IBD patients (1:4). Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival, respectively. Results: Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC. Among IBD patients, 29 (66%) had ulcerative colitis, 14 (32%) had Crohn’s disease, and one (2%) had indeterminate colitis. Mean IBD diagnosis age was 28.1 ± 14.5 years, and mean IBD duration at time of CRC treatment was 21.5 ± 12.6 years. Ten (23%) IBD patients had tumor recurrence compared with 34 (19%) non-IBD patients (P = .074). There was no significant difference in disease-free survival (hazard ratio [HR] = 0.60; 95% CI: 0.35–1.05; P = 0.074) or overall survival (HR = 0.87; 95% CI: 0.54–1.4; P = 0.58) between IBD and non-IBD patients. Conclusion: Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD. Prospective studies are needed to confirm these findings and guide therapeutic decisions

Components of the anorexia-cachexia syndrome: gastrointestinal symptom correlates of cancer anorexia

Cancer-related anorexia is traditionally considered part of a complex but ill-defined anorexia-cachexia syndrome in which anorexia is intimately associated with other gastrointestinal (GI) symptoms and weight loss. We surveyed cancer patients with anorexia to learn more about the relationship between anorexia and these symptoms

Serum C-reactive protein is an important and powerful prognostic biomarker in most adult solid tumors.

INTRODUCTION:Prognostication in cancer is challenging and inaccurate. C-Reactive Protein (CRP), a cheap and sensitive marker of inflammation may help. This study investigated the relationship between CRP and prognosis in a large cohort of solid tumors with mixed cancer diagnoses and stages. METHODS:Electronic medical records of 4931 adults with solid tumors who attended the Taussig Cancer Institute from 2006-2012 were reviewed. Demographic and clinical characteristics were recorded. Maximum CRP (mCRP) was identified for each individual. CRP was analysed as a time-dependent, continuous and categorical variable for association with survival. RESULTS:Two thirds of patients had a high mCRP. This was consistently associated with shorter survival, even after correction for time from diagnosis, and when analysed as a continuous or a categorical variable. When mCRP values above 10 mg/L were subcategorized, a higher mCRP was always worse. Even among those with normal values, statistically and clinically significant shorter survival was noted at mCRP levels >5 mg/L. CONCLUSIONS:In a large representative cohort of consecutive solid tumor patients the risk of death was clinically and statistically significantly greater with a high mCRP. This was independent of other variables and regardless of statistical method from both dates of diagnosis and test. CRP appeared to be underutilized. Our results support the routine use of CRP as a universal cost-effective independent prognostic indicator in most solid tumors

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. Methods: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. Results: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1–124). The median time from pre-operative testing to surgery was 3 months (IQR: 1–4; range: 0–5), and from surgery to post-operative testing, it was 9 months (IQR: 2–22; range: 0.4–112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6–40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/−). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA−/− (n = 1, 10%), and ctDNA−/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. Conclusions: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns

Recipient and Donor Outcomes after Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases

Importance: Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic. Objective: To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs. Design, Setting, and Participants: This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021. Exposures: Living-donor liver transplant. Main Outcomes and Measures: Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients. Results: Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III). Conclusions and Relevance: This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT