Adherence to National Comprehensive Cancer Network ALK Testing Guidelines for Patients with Advanced Non-Small Cell Lung Cancer in U.S. Community Medical Centers.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend biomarker testing as the first step in the management of patients with advanced non-small cell lung cancer (aNSCLC). We assessed anaplastic lymphoma kinase (ALK) testing rates and factors related to underuse in community medical systems between 2012 and 2019 to understand guideline adoption. METHODS: A retrospective observational study using a nationwide electronic health record (EHR)-derived deidentified database was conducted. Patients with aNSCLC diagnosed in community medical centers from January 2012 to May 2019 were included to describe the ALK testing trend. This cohort was further restricted to patients diagnosed after 2015 to understand factors associated with testing underuse using mixed-effects multivariable logistic regression models. RESULTS: Trends for increased ALK testing rates by year were observed in both NCCN guideline-eligible patients (59.5% in 2012 to 84.1% in 2019) and -ineligible patients (15.6% to 50.8%) in a cohort of 41,728 patients. Histology type and smoking status had the greatest impact on test use. Compared with patients with nonsquamous histology and no smoking history, patients with squamous histology and no smoking history (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 5.6-10.4), NSCLC histology not otherwise specified (NOS) with smoking history (aOR, 3.4; 95% CI, 2.8-4.2); NSCLC NOS/nonsmoker (aOR, 1.8; 95% CI, 1.1-3.2), and nonsquamous/smoker (aOR, 1.5; 95% CI, 1.3-1.7) were less likely to be tested. Factors related to underuse also included Eastern Cooperative Oncology Group performance status, stage at initial diagnosis, and demographics. CONCLUSION: This analysis of real-world data shows increasing test use by year; however, one fifth of patients eligible for ALK testing still remain untested and potentially missing therapeutic options. IMPLICATIONS FOR PRACTICE: Advancement in treatment of lung cancer is accompanied by an increasing number of tests that should be run to determine potential therapy options for each patient. This study assessed adoption of testing recommendations for anaplastic lymphoma kinase rearrangements in a national database. Although test use increased over the time period studied (2012-2019), there is still room for improvement. Efforts are needed to increase test use in undertested groups, thus enabling eligible patients to benefit from novel lung cancer therapies.

Clinical Impact of Adherence to NCCN Guidelines for Biomarker Testing and First-Line Treatment in Advanced Non-Small Cell Lung Cancer (aNSCLC) Using Real-World Electronic Health Record Data.

INTRODUCTION: Although clinical guidelines are broadly available, the relationship between adherence and outcomes is not well studied. This study aimed to assess the association between adherence to National Comprehensive Cancer Network (NCCN) guidelines and clinical outcomes for adult patients with advanced non-small-cell lung cancer (aNSCLC). METHODS: This was a retrospective cohort study of adult patients with aNSCLC (stages IIIB, IIIC, and IV) from a de-identified real-world database. The objective was accomplished in a two-step analysis process. We first assessed adherence to NCCN recommendations for biomarker testing and overall survival (OS). Next, we assessed adherence to NCCN-recommended first-line therapy and time to treatment discontinuation (TTD). Multivariable Cox regression analyses were conducted to evaluate the association between guideline adherence and patient outcomes. Kaplan-Meier analyses were used to assess median OS and TTD. RESULTS: A total of 28,784 patients with a diagnosis for aNSCLC between January 1, 2011 and July 31, 2019 met the inclusion criteria for the analysis of NCCN-recommended biomarker testing adherence. Two-thirds of these patients (n = 19,787) had evidence of biomarker testing (adherent). Multivariable Cox models found that testing-adherent patients had a significantly lower risk of mortality [hazard ratio (HR) = 0.89, 95% confidence interval (CI) 0.86, 0.92; p < 0.01]. Median OS was modestly longer in the testing-adherent group compared to the testing-non-adherent group (15.4 vs. 14.2 months; p < 0.01). For the first-line therapy analysis, 15,898 patients met the inclusion criteria, of which 69.9% had evidence of appropriate first-line therapy (first-line-adherent). The multivariable Cox model found that adherent patients had significantly lower risk of treatment discontinuation versus non-adherent patients (HR = 0.60, 95% CI 0.57, 0.62; p < 0.01). First-line-adherent patients had a modest, yet significantly longer median TTD compared to first-line-non-adherent patients (3.45 vs. 2.40 months; p < 0.01). CONCLUSIONS: Improved clinical outcomes were observed in patients who were adherent to NCCN-recommended biomarker testing and first-line therapy. This study demonstrated the value of following NCCN guideline recommendations and the need to prioritize timely access to biomarker testing and individualized treatment.

Garlic consumption and colorectal cancer risk in the CPS-II Nutrition Cohort.

PURPOSE: The World Cancer Research Fund/American Institute for Cancer Research identified a probable role for garlic in colorectal cancer prevention based on preclinical evidence and epidemiologic studies, but prospective data are limited. The purpose of this paper was to contribute additional evidence on this topic for men and women in a large prospective cohort study. METHODS: In 1999, 42,824 men and 56,876 women in the Cancer Prevention Study II Nutrition Cohort completed a questionnaire with information on dietary garlic consumption. Garlic supplement use was assessed in 2001. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard rate ratios (HRs) and 95 % confidence intervals (CIs). RESULTS: During 7 years of follow-up, 579 men and 551 women were diagnosed with colorectal cancer. Among men, daily garlic consumption was associated with a non-significant higher colorectal cancer risk (HR = 1.04, 95 % CI 0.99-1.08 for each additional clove or "4 shakes" of garlic per week), whereas the association was borderline inverse in women (HR = 0.95, 95 % CI 0.91-1.00, p heterogeneity by sex = 0.03). Garlic supplement use was not related to a lower risk of colorectal cancer, and in men, former use was associated with a higher risk of colorectal cancer (HR = 1.85, 95 % CI 1.13-3.03). CONCLUSIONS: These results provide weak support for a role of dietary garlic consumption in colorectal cancer prevention in women, but a possible increased risk in men. Further research is needed to confirm different associations by sex.

Caffeine and risk of Parkinson's disease in a large cohort of men and women.

Caffeine consumption has been associated with a reduced risk of Parkinson's disease (PD). The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy (HRT). We sought to confirm these findings using data on PD incidence in the Cancer Prevention Study II Nutrition Cohort (CPS II-Nutrition), a large, prospective study of men and women. We conducted a prospective study of caffeine intake and risk of PD within the CPS II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RRs) were estimated using proportional hazards models, adjusting for age, smoking, and alcohol consumption. After adjustment for age, smoking, and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The RR comparing the 5th to the 1st quintile of caffeine intake was 0.43 (95% confidence interval [CI]: 0.26, 0.71; P trend = <0.002) in men, and 0.61 (95% CI: 0.34, 1.09; P trend = 0.05) in women. Among women, this association was stronger among never users of HRT (RR = 0.32) than among ever users (RR = 0.81; P interaction = 0.15). Consumption of decaffeinated coffee was not associated with PD risk. Findings from this large, prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of HRT in women. © 2012 Movement Disorder Society.

Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults.

BACKGROUND: Flavonoids are plant-based phytochemicals with cardiovascular protective properties. Few studies have comprehensively examined flavonoid classes in relation to cardiovascular disease mortality. OBJECTIVE: We examined the association between flavonoid intake and cardiovascular disease (CVD) mortality among participants in a large, prospective US cohort. DESIGN: In 1999, a total of 38,180 men and 60,289 women in the Cancer Prevention Study II Nutrition Cohort with a mean age of 70 and 69 y, respectively, completed questionnaires on medical history and lifestyle behaviors, including a 152-item food-frequency questionnaire. Cox proportional hazards modeling was used to calculate multivariate-adjusted hazard RRs and 95% CIs for associations between total flavonoids, 7 flavonoid classes, and CVD mortality. RESULTS: During 7 y of follow-up, 1589 CVD deaths in men and 1182 CVD deaths in women occurred. Men and women with total flavonoid intakes in the top (compared with the bottom) quintile had a lower risk of fatal CVD (RR: 0.82; 95% CI: 0.73, 0.92; P-trend = 0.01). Five flavonoid classes-anthocyanidins, flavan-3-ols, flavones, flavonols, and proanthocyanidins-were individually associated with lower risk of fatal CVD (all P-trend < 0.05). In men, total flavonoid intakes were more strongly associated with stroke mortality (RR: 0.63; 95% CI: 0.44, 0.89; P-trend = 0.04) than with ischemic heart disease (RR: 0.90; 95% CI: 0.72, 1.13). Many associations appeared to be nonlinear, with lower risk at intakes above the referent category. CONCLUSIONS: Flavonoid consumption was associated with lower risk of death from CVD. Most inverse associations appeared with intermediate intakes, suggesting that even relatively small amounts of flavonoid-rich foods may be beneficial.