Abstract Introduction We sought to evaluate the associations of post-diagnostic consumption of flavonoids and flavonoid-rich foods with survival among patients with stage III colon cancer enrolled in a clinical trial. Methods We conducted a prospective observational study of 1625 patients with stage III colon cancer enrolled in the CALGB/SWOG 80702 (Alliance) randomized adjuvant chemotherapy trial who completed a self-reported food frequency questionnaire within 6 weeks of and again 14-16 months post-randomization. Intakes of flavonoids overall and by subclasses (anthocyanidins, flavanones, flavan-3-ols, flavones, flavonols, isoflavones) were computed by multiplying the consumption frequency of each dietary item by the nutrient content of its respective specified portions. Multivariable analyses for the primary (disease-free survival [DFS]) and secondary (overall survival [OS]) endpoints were adjusted for sociodemographic, clinical, dietary, and lifestyle factors. Bonferroni corrections were applied for analyses of flavonoid subclasses and flavonoid-rich foods. Results Over median follow-up of 5.9 years, flavonoid consumption either overall or by subclasses was not significantly associated with survival outcomes, with a hazard ratio (HR) (95% confidence interval [CI]) of 1.01 (0.75-1.37) for DFS among those in the highest relative to lowest consumption quintiles of total flavonoids. Exploratory analyses of flavonoid-rich foods intake did not demonstrate significant associations with DFS or OS after Bonferroni correction. Conclusion Among resected stage III colon cancer patients who received standardized treatment and follow-up within a nationwide randomized clinical trial, consumption of flavonoids was not associated with survival outcomes. ClinicalTrials.gov identifier: NCT01150045
Abstract PURPOSE To examine whether Medicare’s 2018 National Coverage Determination (NCD) for next-generation sequencing (NGS) was associated with changes in the use of targeted oral anticancer therapies among older adults with lung cancer. METHODS Retrospective cohort study. Multivariable logistic regression was used to estimate the probability of initiating an oral targeted therapy within 12 months of diagnosis. Key exposures were (1) diagnosis before versus after the NCD and (2) residence in a region with versus without pre-NCD NGS. Data were drawn from the SEER–Medicare linked data with Part D claims, including diagnosis years 2016–2019 with follow-up through 2020. The analytic sample included Medicare fee-for-service Part D beneficiaries aged 65 years or older with newly diagnosed lung cancer. RESULTS Among 30,855 Medicare fee-for-service Part D beneficiaries with lung cancer, 7.1% used targeted oral anticancer therapies. The NCD was not associated with a significant overall change in targeted therapy use (0.4 Percentage Point; 95% CI, −1.6 to 2.4; p = 0.71). Before NCD implementation, targeted therapy use was 1.0 PP higher in regions with pre-NCD NGS coverage than in regions without such coverage (95% CI, 0.2–1.9; p = 0.015). In stage-stratified analyses, the additional post-NCD change was significant among patients with distant-stage disease (3.2 PPs; 95% CI, 2.6–4.0; p < 0.001) but not among those with regional-stage disease (p = 0.29). CONCLUSIONS Medicare's NCD for NGS was not associated with a significant overall increase in targeted oral anticancer therapy use but was associated with increased use among patients with distant-stage disease. Targeted therapy use remained higher in regions with preexisting NGS coverage.
Abstract Comprehensive genomic profiling has expanded the ability to identify potentially actionable molecular alterations across cancers, but identification of an actionable finding does not ensure that a patient will receive a genomically matched therapy. Studies of precision-oncology programs and molecular tumor boards consistently demonstrate substantial attrition between treatment recommendation and treatment initiation. The reasons extend beyond molecular interpretation and include the timing of genomic profiling, clinical deterioration, geographic availability of biomarker-selected trials, insurance and financial barriers, and disparities in access to specialty cancer care. Importantly, these barriers arise after a potentially useful molecular finding has already been identified, creating a distinction between molecular actionability and practical treatment access. This commentary argues that the next implementation challenge for precision oncology is to make clinically meaningful genomic findings realistically actionable. Comprehensive genomic profiling should occur early enough to inform treatment planning; molecular tumor board recommendations should be linked to realistic treatment and trial opportunities; financial and insurance barriers should be anticipated when recommendations are made; and equity should be evaluated beyond access to testing to include receipt of genomically informed treatment. As genomic profiling becomes increasingly integrated into routine cancer care, precision oncology should be judged not only by its ability to identify therapeutic opportunities but also by whether patients can reach those opportunities while they remain clinically relevant.
Abstract Background The incidence of gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) has increased, alongside novel therapies and care models. Whether these advances translated into improved survival is unclear. Methods Population-based retrospective cohort study of GEP-NENs between 2000–2019. Overall survival (OS) was analyzed using time-to-event methods. Restricted cubic splines assessed non-linear associations between diagnosis year and hazards of death; multivariable Cox regression adjusted for age, sex, primary site, and metastatic status. Results Among 9,420 patients, 5-year OS was 75.8% overall, 88.8% for non-metastatic disease, and 57.0% for metastatic disease. Mortality risk declined in more recent years, with diagnoses in 2013–2019 associated with lower hazards of death (adjusted HR 0.91, 95%CI 0.83–0.99). Improvements were confined to non-metastatic disease and to pancreas, stomach, and rectal primaries. Conclusion OS has modestly improved over two decades, largely reflecting stage migration rather than clear therapeutic gains. Advances that meaningfully improve survival in advanced GEP-NENs are needed.
Abstract COVID-19 has been associated with an increased thrombotic risk, potentially exacerbated in patients with active cancer. We conducted a retrospective cohort study including 119 cancer patients with COVID-19 and 214 matched pre-pandemic controls. Patients with COVID-19 had poorer performance status and were more frequently treated with palliative intent. After a median follow-up of 32.7 months, overall thrombotic event rates did not differ between groups. However, after adjustment for clinically relevant covariates and accounting for death as a competing event, COVID-19 status and palliative treatment intent remained independently associated with a higher cumulative incidence of thrombotic events. In conclusion, COVID-19 may increase thrombotic risk in patients with cancer and occurs more frequently in patients with poorer clinical status. These findings are exploratory and require confirmation in larger prospective studies.
