The Impact of BRAF Mutation Status on Survival Outcomes and Treatment Patterns among Metastatic Colorectal Cancer Patients in Alberta, Canada.

Colorectal cancer presents via multiple different clinical phenotypes that can arise from a variety of different genetic and molecular alterations. The aim of this study was to describe survival outcomes and treatment patterns of metastatic colorectal cancer (mCRC) patients by v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation status. The Alberta Cancer Registry was used to identify all patients >18 years old who had been diagnosed with mCRC in Alberta between 1 January 2017 and 31 December 2019 and had received at least one cycle of systemic therapy. Treatment patterns were compared between wild-type and mutant BRAF mCRC patients. Cox regression models and Kaplan-Meier curves were created to assess survival differences by both treatment pattern and BRAF status. A total of 488 patients were identified with mCRC, of which 42 (11.4%) were confirmed to have a BRAF mutation. The most common first-line treatment regimen was either capecitabine and oxaliplatin (CAPOX) or leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX). The median overall survival for mCRC patients was 20.01 months. Mutant BRAF patients had a median survival of 8.21 months compared to 20.03 months among those with wild-type BRAF. BRAF mutations among mCRC patients are associated with a considerably poor prognosis, reinforcing the need for clinical BRAF testing among newly diagnosed patients to better understand their prognosis.

Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Despite the widespread increase in the incidence of early-onset colorectal cancer (EoCRC), the reasons for this increase remain unclear. The objective of this study was to determine risk factors for the development of EoCRC. METHODS: We conducted a systematic literature review and meta-analysis of studies examining non-genetic risk factors for EoCRC, including demographic factors, comorbidities, and lifestyle factors. Random effects meta-analyses were conducted for risk factors that were examined in at least three studies. Heterogeneity was investigated using the Q-test and I2 statistic. RESULTS: From 3304 initial citations, 20 studies were included in this review. Significant risk factors for EoCRC included CRC history in a first-degree relative (RR 4.21, 95% CI 2.61-6.79), hyperlipidemia (RR 1.62, 95% CI 1.22-2.13), obesity (RR 1.54, 95% CI 1.01-2.35), and alcohol consumption (high vs. non-drinkers) (RR 1.71, 95% CI 1.62-1.80). While smoking was suggestive as a risk factor, the association was not statistically significant (RR 1.35, 95% CI 0.81-2.25). With the exception of alcohol consumption, there was considerable heterogeneity among studies (I2 > 60%). Other potential risk factors included hypertension, metabolic syndrome, ulcerative colitis, chronic kidney disease, dietary factors, sedentary behaviour, and occupational exposure to organic dusts, but these were only examined in one or two studies. CONCLUSIONS: The results of this study advance the understanding of the etiology of EoCRC. High-quality studies conducted on generalizable populations and that comprehensively examine risk factors for EoCRC are required to inform primary and secondary prevention strategies.

Development and validation of a risk prediction model for high-risk adenomas at the time of first screening colonoscopy among screening aged Canadians.

The aim of this study was to develop a risk prediction model for high risk adenomas (HRAs) detected at screening colonoscopy based on readily available participant information. The cohort consisted of 3035 participants aged 50 to 74 years with no history of cancer who underwent a primary screening colonoscopy at a centralized colon cancer screening centre between 2008 and 2016. A multivariable logistic regression model was created using CRC risk factors identified from prior research. Model covariates were collected from a baseline questionnaire and included participant demographics (age and sex), lifestyle parameters (body mass index, alcohol, smoking, and vitamin D supplement use) and medical history (family history of CRC and diabetes). Mean participant age was 58.8 years, and 54.7% were male. 249 participants with HRAs were identified (8.2%). An adjusted c-statistic of 0.67 was calculated, and a specificity and negative predictive value of 97.2% (95% CI: 96.5-97.8) and 92.5% (95% CI: 92.2-92.8) for the detection of HRAs, respectively, were achieved using 20% predicted probability as a high-risk threshold. However, only a sensitivity of 12.1% (95% CI: 8.3-16.8) was achieved. Our model has moderate predictive ability, with strengths in being able to rule out those with an absence of HRAs on screening colonoscopy. Maximizing screening efficiency through improved risk prediction can enhance resource allocation. Ultimately, this model has the potential to improve patient care by reducing unnecessary colonoscopies, limiting this invasive procedure to those most likely to have significant findings.

Association Between Endoscopist Annual Procedure Volume and Colonoscopy Quality: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: In addition to monitoring adverse events (AEs) and post-colonoscopy colorectal cancers (PCCRC), indicators for assessing colonoscopy quality include adenoma detection rate (ADR) and cecal intubation rate (CIR). It is unclear whether there is an association between annual colonoscopy volume and ADR, CIR, AEs, or PCCRC. METHODS: We searched publication databases through March 2019 for studies assessing the relationship between annual colonoscopy volume and outcomes, including ADR, CIR, AEs, or PCCRC. Pooled odds ratios (ORs) were calculated using DerSimonian and Laird random effects models. Sensitivity analyses were performed to assess for potential methodological or clinical factors associated with outcomes. RESULTS: We performed a systematic review of 9235 initial citations, generating 27 retained studies comprising 11,276,244 colonoscopies. There was no association between procedural volume and ADR (OR, 1.00; 95% CI, 0.98-1.02 per additional 100 annual procedures). CIR improved with each additional 100 annual procedures (OR, 1.17; 95% CI, 1.08-1.28). There was a non-significant trend toward decreased overall AEs per additional 100 annual procedures (OR, 0.95; 95% CI, 0.90-1.00). There was considerable heterogeneity among most analyses. CONCLUSIONS: In a systematic review and meta-analysis, we found higher annual colonoscopy volumes to correlate with higher CIR, but not with ADR or PCCRC. Trends toward fewer AEs were associated with higher annual colonoscopy volumes. There are few data available from endoscopists who perform fewer than 100 annual colonoscopies. Studies are needed on extremes in performance volumes to more clearly elucidate associations between colonoscopy volumes and outcomes.

Vitamin D supplementation reduces the occurrence of colorectal polyps in high-latitude locations.

There is suggestive evidence for the role of vitamin D in the development of colorectal cancer (CRC). Due to high latitudes in Canada, many Canadians are vitamin D deficient throughout winter. In this analysis, we examined the association between vitamin D supplement use and high-risk adenomatous polyps (HRAPs). The study population was drawn from the biorepository at the Forzani & MacPhail Colon Cancer Screening Centre (CCSC) in Calgary. Individuals enrolled between 2013 and 2016 between the age of 50 and 74 years (n = 1409) were included. When examining the association between any supplemental vitamin D use and HRAPs, a protective effect is observed with an ORadj of 0.57 (95% CI: 0.33-0.96). Similarly, meeting the recommended daily intake (RDI) of vitamin D (600 IU) is protective against HRAPs with an ORadj of 0.78 (95% CI: 0.62-0.99). This study suggests that adequate vitamin D supplementation reduces the occurrence of colorectal polyps in high-latitude locations.

National Trends in Colorectal Cancer Incidence Among Older and Younger Adults in Canada.

Importance: Recent evidence has shown that although the incidence of colorectal cancer (CRC) is decreasing among older adults, rates have increased in adults younger than 50 years. Given that younger adults are typically classified as at low risk for the disease, this epidemiologic shift is cause for concern. Objective: To analyze Canadian national cancer incidence registries to determine incidence trends for CRC among older and younger adults, updated to 2015. Design, Setting, and Participants: This cohort study determined the incidence of CRC using data from the National Cancer Incidence Reporting System (1969-1992) and the Canadian Cancer Registry (1992-2015). All Canadians diagnosed with CRC from January 1, 1969, through December 31, 2015, were included in this study. Trends among men and women were examined separately and by age category (>50 vs <50 years). Birth cohort models were fit using 5-year groups starting in 1886, with 1936 as the reference cohort. Data were analyzed from May 13, 2018 to May 16, 2018. Main Outcomes and Measures: Annualized percentage changes and incidence rate ratios of CRC. Results: From 1971 to 2015, 688 515 incident cases (52.9% women) of CRC were identified. Although the incidence of CRC has decreased in older men and women, rates among younger men and women have increased since 2006 and 2010, respectively. For women younger than 50 years, incidence has increased with a mean annual percentage change of 4.45% since 2010; for men younger than 50 years, a mean annual percentage change of 3.47% from 2006 through 2015. There was an association between CRC incidence and birth cohort, with more recent cohorts being at greater risk than those born earlier. For men, the risk of colorectal cancer in the youngest cohort is more than double that of the reference (incidence rate ratio, 2.57; 95% CI, 1.32-5.02). Incidence rate ratios were not significant for women (IRR, 2.12; 95% CI, 0.95-4.70) but increased in successively younger cohorts. Conclusions and Relevance: This study found increasing incidence of colorectal cancer diagnoses among Canadian men and women younger than 50 years of age. This increase in incidence among a low-risk population calls for additional research on possible risk factors that may be affecting these younger cohorts. It appears that primary prevention should be the highest priority to reduce the number of younger adults developing CRC in the future.