Spectrum of Advanced Colorectal Neoplasia and Anticipated Yield of Average-Risk Screening in Veterans Under Age 50.

The incidence of early onset colorectal cancer, or colorectal cancer (CRC) diagnosed before age 50, is increasing.1 In response, multiple societal guidelines in the United States now recommend initiating CRC screening at age 45 in average-risk individuals (ie, those without high-risk clinical characteristics, such as bleeding, or iron deficiency anemia), inflammatory bowel disease, or family history of colorectal neoplasia.2 The Veterans Health Administration (VHA) is the largest integrated health system in the United States and is contending with how best to expand CRC screening access to this younger population in the setting of limited colonoscopy resources. Understanding the rate and anatomic location of colorectal neoplasia in Veterans younger than age 50 can inform the expected yield of different screening modalities. Prior work has shown that individuals undergoing colonoscopy for low-risk diagnostic indications have equivalent risk of colorectal neoplasia as those undergoing average-risk screening.3 This study and a recent meta-analysis4 reported that 3.6% (95% confidence interval, 1.9%-6.7%) to 3.7% (95% confidence interval, 3.0%-4.7%) of average-risk individuals age 45-49 have advanced colorectal neoplasia (ACN), defined as an advanced polyp or carcinoma; however, data specific to the VHA population are lacking.

Impact of Relative Dose Intensity of FOLFOX Adjuvant Chemotherapy on Risk of Death Among Stage III Colon Cancer Patients.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines have recommended tailored chemotherapy for stage III high-risk (T4 and/or N2) and low-risk (T1-T3 and N1) colon cancer since 2018. Studies have investigated the effect of relative dose intensity (RDI) of FOLFOX on stage III colon cancer survival, however, none has performed a stratified analysis by risk profiles. This study aims to identify the FOLFOX optimal RDI for high-risk and low-risk stage III colon cancer patients. METHODS: Data on 407 eligible patients, diagnosed with stage III colon cancer in 2011 who received FOLFOX, were collected by 8 population-based cancer registries. Multivariable Cox model and Fine-Gray competing risks model were employed to explore Optimal RDI defined as the lowest RDI administered without significant differences in either overall or cause-specific death. RESULTS: Among the 168 high-risk patients, the optimal RDI cut-off was 70% (HR = 1.59 with 95% CI: 0.69-3.66 in overall mortality; HR = 1.24 with 95% CI: 0.42-3.64 in cause-specific mortality when RDI < 70% vs. RDI ≥ 70%). Among the 239 low-risk patients, none of the evaluated cut-offs were associated with significant differences in risk of death between comparison groups. The lowest assessed RDI was 45%, HR = 0.80; 95% CI: 0.24 to 2.73 for overall mortality and HR = 0.53; 95% CI: 0.06 to 4.95 for cause-specific mortality, when RDI <45% versus RDI ≥45%. CONCLUSIONS: There is no significant harm on the risk of death when reducing RDI by <30% for high-risk patients. For the low-risk patients, we found that RDI as low as 45% did not significantly affect the risk of death.

KRAS testing and first-line treatment among patients diagnosed with metastatic colorectal cancer using population data from ten National Program of Cancer Registries in the United States.

BACKGROUND: In 2011, the National Comprehensive Cancer Network (NCCN) recommended KRAS testing for metastatic colorectal cancer (mCRC) patients. Our study assessed KRAS testing prevalence and its association with socio-demographic and clinical factors and examined first-line treatment. METHODS: Ten state population-based registries supported by Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) collected detailed cancer information on mCRC cases diagnosed in 2011, including KRAS biomarker testing and first-line treatment from ten central cancer registries. Data were analyzed with Chi-square tests and multivariate logistic regression. RESULTS: Of the 3,608 mCRC cases, 27% (n = 992) had a documented KRAS test. Increased age at diagnosis (p < 0.0001), racial/ethnic minorities (p = 0.0155), public insurance (p = 0.0018), and lower census tract education (p = 0.0023) were associated with less KRAS testing. Significant geographic variation in KRAS testing (p < 0.0001) ranged from 46% in New Hampshire to 18% in California. After adjusting for all covariates, age and residence at diagnosis (both p < 0.0001) remained predictors of KRAS testing. Non-Hispanic Blacks had less KRAS testing than non-Hispanic Whites (OR = 0.77, 95% CI = 0.61-0.97). Among those tested and found to have normal (wild-type) KRAS, 7% received anti-EGFR treatment; none received such treatment among those with KRAS mutated gene. CONCLUSIONS: Despite NCCN guideline recommendations, 73% of mCRC cases diagnosed in 2011 had no documented KRAS test. Disparities in KRAS testing existed based on age, race, and residence at diagnosis. IMPACT: These findings show the capacity of monitoring KRAS testing in the US using cancer registry data and suggest the need to understand the low uptake of KRAS testing, and associated treatment choices during the first year since diagnosis.

Population-Based Lynch Syndrome Screening by Microsatellite Instability in Patients ≤50: Prevalence, Testing Determinants, and Result Availability Prior to Colon Surgery.

OBJECTIVES: As there are no US population-based studies examining Lynch syndrome (LS) screening frequency by microsatellite instability (MSI) and immunohistochemistry (IHC), we seek to quantitate statewide rates in patients aged ≤50 years using data from a Centers for Disease Control and Prevention-funded Comparative Effectiveness Research (CER) project and identify factors associated with testing. Screening rates in this young, high-risk population may provide a best-case scenario as older patients, potentially deemed lower risk, may undergo testing less frequently. We also seek to determine how frequently MSI/IHC results are available preoperatively, as this may assist with decisions regarding colonic resection extent. METHODS: Data from all Louisiana colorectal cancer (CRC) patients aged ≤50 years diagnosed in 2011 were obtained from the Louisiana Tumor Registry CER project. Registry researchers and physicians analyzed data, including pathology and MSI/IHC. RESULTS: Of the 2,427 statewide all-age CRC patients, there were 274 patients aged ≤50 years, representing health care at 61 distinct facilities. MSI and/or IHC were performed in 23.0% of patients. Testing-associated factors included CRC family history (P<0.0045), urban location (P<0.0370), and care at comprehensive cancer centers (P<0.0020) but not synchronous/metachronous CRC or MSI-like histology. Public hospital screening was disproportionately low (P<0.0217). Of those tested, MSI and/or IHC was abnormal in 21.7%. Of those with abnormal IHC, staining patterns were consistent with LS in 87.5%. MSI/IHC results were available preoperatively in 16.9% of cases. CONCLUSIONS: Despite frequently abnormal MSI/IHC results, LS screening in young, high-risk patients is low. Provider education and disparities in access to specialized services, particularly in underserved populations, are possible contributors. MSI/IHC results are infrequently available preoperatively.