Faculty Bibliography

BACKGROUND: Low-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24-50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant. METHODS: We performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n = 625) versus no nodules (n = 557), and lung cancer patients (n = 30) versus benign nodules (n = 128). RESULTS: The NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas. CONCLUSIONS: NCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases.

Summary Exact unconditional tests have been widely applied to test the difference between two probabilities for 2 x 2 matched-pairs binary data with small sample size. In this context, Lloyd (2008, Biometrics 64, 716-723) proposed an E + M p-value, that showed better performance than the existing M p-value and C p-value. However, the analytical calculation of the E + M p-value requires that the Barnard convexity condition be satisfied; this can be challenging to prove theoretically. In this article, by a simple reformulation, we show that a weaker condition, conditional monotonicity, is sufficient to calculate all three p-values (M, C, and E + M) and their corresponding exact sizes. Moreover, this conditional monotonicity condition is applicable to noninferiority tests

BACKGROUND: Prostate-specific antigen (PSA) is the only independent predictor of biochemical recurrence (BCR) following radical prostatectomy (RP) subject to change over time. OBJECTIVE: To determine whether an ultrasensitive PSA measured at 3 yr following RP is a predictor of subsequent BCR. DESIGN, SETTING, AND PARTICIPANTS: There were 1197 consecutive men with clinically localized prostate cancer who underwent an open radical retropubic prostatectomy (ORRP) at a tertiary referral academic medical center. Exclusions included 107 men (8.9%) who developed a PSA level >/=0.2 ng/ml or underwent hormone therapy or radiation therapy (RT) within the first 3 r after surgery, 191 men (16%) who did not undergo a 3-yr ultrasensitive PSA assay, and 98 men (8.2%) who had PSA levels >/=0.1 and <0.2 at 3 yr. The remaining 801 men were stratified into two groups based on their ultrasensitive PSA level at 3 yr postoperatively: group 1, which consisted of patients whose PSA was </=0.04 (n=765), and group 2, which consisted of patients whose PSA was >0.04 and <0.10 (n=36). MEASUREMENTS: Delayed BCR was the primary end point and represented those men in this cohort who developed a PSA level >/=0.2 or underwent salvage RT for a persistently rising PSA level after 3 yr of follow-up. RESULTS AND LIMITATIONS: The 7-yr cumulative BCR-free survival rate for groups 1 and 2 was 0.957 (95% confidence interval [CI], 0.920-0.978) and 0.654 (95% CI, 0.318-0.855), respectively. In multivariable Cox proportional hazards models, ultrasensitive PSA level at 3 yr remained the only significant predictor of delayed BCR (likelihood ratio chi(2) for full model: 27.03; df=1; p < 0.001). A limitation of the study is that no uniform PSA assay was obtained. CONCLUSIONS: Our findings provide compelling evidence that an ultrasensitive PSA at 3 yr following RP provides useful insights into delayed BCR and is a source of reassurance for the overwhelming majority of men being followed for delayed recurrences

Minority melanoma patients have worse survival. In this study, we evaluated the impact of socioeconomic and demographic factors on minority melanoma patients presenting to two different New York City hospitals (one public and one private) managed by the same multidisciplinary team. Sociodemographic and clinicopathologic characteristics were retrieved for melanoma patients presenting to Bellevue Hospital Center (BHC), a public hospital, and the New York University Cancer Institute (NYUCI), a private cancer center. Socioeconomic data was obtained from the United States Census Bureau database. The Kruskal-Wallis and chi-square tests were used to evaluate the associations between race/ethnicity and continuous and categorical variables (e.g. income, stage at presentation), respectively. Minorities comprised 2% (27/1296) of melanoma patients at the NYUCI compared to 42% (50/119) at BHC. Those presenting to the NYUCI were more likely to have a higher median household income (P = 0.05), a higher educational level (P = 0.04), and an earlier stage at presentation (P = 0.02) than those at BHC. NYUCI patients were predominantly covered by commercial insurance (70%), whereas Medicaid (62%) was common among BHC patients. Only 19% of Hispanic patients at BHC chose English as their preferred language. Our data demonstrate that language and health care system factors affect melanoma presentation in minorities

Introduction The NYU Lung Cancer Biomarker Center recruited 1054 smokers (<=20 pack-years) between 03/2000 and 06/2010 and screened them with CT-scans and respiratory questionnaires. Questionnaires contained demographic characteristics, occupational exposures, lifestyle information including smoking history and alcohol use, personal and family medical history, and pulmonary symptoms. CT-scans showed the disease status and emphysema. We hypothesized that information collected in the questionnaires would be associated with the subject's disease status. Methods The 1054 Subjects were classified into 4 groups based on the results of enrollment CT-scans. This categorization showed 331 subjects with solid nodule(s) only, 95 with ground glass opacity (GGO) only, 126 with both solid nodule(s) and GGO(s), and the remaining 502 subjects with no nodules. Chi-squared tests were used to assess the relationship between disease category and each single predictor. Polytomous logistic regression was used to assess the association between disease category and multiple predictors. Forward/backward stepwise regression was used in model selection. Results Univariate analysis showed that gender (CMH =8.7092, p-value=0.0032), age (CMH=29.2219, p-value<0.0001), marijuana smoking (CMH=10.9024, p-value=0.0010), emphysema (CMH=9.0929, p-value=0.0026) and years of smoking (CMH=15.4712, p-value<0.0001) were significantly associated with disease categories. Further tests showed that years of smoking was highly associated with age, and did not contribute to prediction of disease category when age was included in the model, as shown by our multivariate analysis. In multivariate analysis, increasing age, gender (male) and history of emphysema were significant predictors of worsening disease class. Moreover, when we stratified by gender, the analysis indicated that in males, older men were more likely to develop solid nodules (OR=1.275, 95% CI [1.0063, 1.0490]) and more likely to have mixed nodules (OR= 1.0664, 95% CI= [1.0331, 1.1008]) than younger men. Males with emphysema were far more likely to have solid nodules compared with those without emphysema (OR= 1.9678, 95% CI= [1.3128, 2.9495]). Our analysis also revealed that in females, age was the only significant risk factor: older women were more likely to have mixed nodules than younger women (OR= 1.0593, 95% CI= [1.0274, 1.0922]). It is notable that all smoking related variables were not significantly associated with nodule class in our multivariable analysis. Conclusion Our analysis suggests that age, gender and emphysema play a critical role in the development of disease (solid nodule or GGO). Also, our analysis has shown that smoking is not likely to play a major role in the development of the disease in this high risk cohort