Effect of neighborhood and individual-level socioeconomic factors on breast cancer screening adherence in a multi-ethnic study.

BACKGROUND: Although mammography can significantly reduce breast cancer mortality, many women do not receive their annual breast cancer screening. Differences in screening adherence exist by race/ethnicity, socioeconomic status (SES), and insurance status. However, more detailed investigations into the impact of neighborhood disadvantage and access to resources on screening adherence are lacking. METHODS: We comprehensively examined the effect of individual social, economic, and demographic factors (n = 34 variables), as well as neighborhood level SES (nSES) indicators (n = 10 variables) on breast cancer screening adherence across a multi-ethnic population (n = 472). In this cross-sectional study, participants were surveyed from 2017 to 2018. The data was analyzed using univariate regression and LASSO for variable reduction. Significant predictors were carried forward into final multivariable mixed-effect logistic regression models where odds ratios (OR), 95% confidence intervals and p-values were reported. RESULTS: Nineteen percent of participants were non-adherent to breast screening guidelines. Race/ethnicity was not associated with adherence; however, increasing age (OR = 0.97, 95%CI = 0.95-0.99, p = 0.01), renting a home (OR = 0.53, 95%CI = 0.30-0.94, p = 0.04), food insecurity (OR 0.46, 95%CI = 0.22-0.94, p = 0.01), and overcrowding (OR = 0.58, 95% CI = 0.32-0.94, p = 0.01) were significantly associated with lower breast cancer screening adherence. CONCLUSION: Socioeconomic indicators at the individual and neighborhood levels impact low breast cancer screening adherence and may help to inform future screening interventions.

Systemic Therapies Following Progression on First-line CDK4/6-inhibitor Treatment: Analysis of Real-world Data.

BACKGROUND: Metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor-2 negative (Her2-) breast cancer remains a significant cause of cancer-related mortality. First-line treatment with endocrine therapy (ET) with a cyclin-dependent kinases 4 and 6 inhibitor (CDK4/6i) has largely become the standard systemic therapy. Following progression, no prospective randomized data exist to help guide second-line treatment. MATERIALS AND METHODS: This study used a nationwide electronic health record (EHR)-derived de-identified database, specifically analyzing 1210 patients with HR+/Her2- metastatic breast cancer (MBC) who were treated in the first-line setting with a CDK4/6i from the years 2015-2020. The aim of this study was to assess what therapies were given after first-line progression on CDK4/6i and to observe treatment patterns over time. Determination of second-line treatment efficacy, specifically assessing real-world progression-free survival (rwPFS) and overall survival (OS) was performed. RESULTS: A total of 839 patients received a documented second-line therapy after progression on first-line CDK4/6i treatment. Chemotherapy was chosen for 29.7% of patients, and the use of chemotherapy decreased over time. Three hundred two (36.0%) of patients continued a CDK4/6i. Data were adjusted for age, race, Eastern Cooperative Oncology Group (ECOG) performance status, stage at breast cancer diagnosis, and insurance payer type. Continuation of the CDK4/6i was associated with improved rwPFS (HR 0.48, 95% CI 0.43-0.53, P < .0001) and OS (HR 0.30, 95% CI 0.26-0.35, P < .0001) compared to chemotherapy. A majority of these patients continued the same CDK4/6i in the second-line setting, as was given in the first-line setting. CONCLUSION: While prospective data are needed, analysis of real-world data suggests a survival benefit for continuation of a CDK4/6i beyond frontline progression for patients with HR+/Her2- MBC.

Prospective Comparison of Geriatric Assessment and Provider's Assessment of Older Adults With Metastatic Breast Cancer in the Community.

BACKGROUND: Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP). METHODS: Self-administered GA was compared to provider's assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar's test was used to detect differences between PA and GA. RESULTS: One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of 356 abnormalities in 96 patients; of which, 223 required interventions. African American and widowed/single patients were more likely to have abnormalities identified by GA. On average, across 100 patients, PA did not detect 25.5% of GA-detected abnormalities, mostly in functional status, social support, nutrition, and cognition. These differences were less pronounced among providers with more clinical experience. Patients with abnormal Timed Up and Go tests more likely had additional abnormalities in other domains, and more abnormalities that were not identified by PA. Providers were "surprised" by GA results in 33% of cases, mainly with cognitive or social support findings, and reported plans for management change for 39% of patients based on GA findings. CONCLUSIONS: Including a GA in the care of OA-MBC in CP is beneficial for the detection of multiple abnormalities not detected by routine PA.

The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Real-World Multi-Institutional Analysis.

PURPOSE: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) was challenged by the results of the CARMENA trial. Here we evaluate the role of CN in mRCC patients, including those receiving modern therapies. MATERIALS AND METHODS: We included patients with synchronous mRCC between 2011-2020 from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic therapy alone, CN followed by systemic therapy (up-front CN [uCN]) and systemic therapy followed by CN (deferred CN [dCN]). The primary outcome was median overall survival (mOS) in patients receiving systemic therapy alone vs uCN. Secondary outcome was overall survival in patients receiving uCN vs dCN. First-treatment, landmark and time-varying covariate analyses were conducted to overcome immortal time bias. Weighted Kaplan-Meier curves, log-rank tests and Cox proportional hazards regressions were used to assess the effect of therapy on survival. RESULTS: Of 1,910 patients with mRCC, 972 (57%) received systemic therapy, 605 (32%) received uCN, 142 (8%) dCN and 191 (10%) CN alone; 433 (23%) patients received immunotherapy-based therapy. The adjusted mOS was significantly improved in first-treatment, landmark and time-varying covariate analysis (mOS 26.6 vs 14.6 months, 36.3 vs 21.1 months and 26.1 vs 12.2 months, respectively) in patients undergoing CN. Among patients receiving CN and systemic therapy, the timing of systemic therapy relative to CN was not significantly related to overall survival (HR=1.0, 95% CI 0.76-1.32, p=0.99). CONCLUSIONS: Our findings support an oncologic role for CN in select mRCC patients. In patients receiving both CN and systemic therapy, the survival benefit compared to systemic alone was similar for up-front and deferred CN.

Demographic and Psychosocial Characteristics Associated With Use of a Prostate Cancer Survivorship Website: Implications From a Multisite Randomized Controlled Trial.

BACKGROUND: Many prostate cancer (PC) survivors experience disease and treatment-related symptomatology in both the physical and psychosocial domains. Although the benefits and barriers to using web-based resources for cancer patients are well-documented, less research has focused on the personal characteristics important for efficient tailoring and targeting of information that are associated with usage. OBJECTIVE: We used the Cognitive-Social Health Information Processing (C-SHIP) framework to guide our exploration of personal characteristics associated with use of PROGRESS, an informational PC survivorship website that addresses physical, emotional, interpersonal, and practical concerns relevant for PC survivors. METHODS: PC survivors (N=217) were randomized to the intervention arm (PROGRESS) of a randomized controlled trial. Of those randomized to the intervention arm, 84 used PROGRESS, and 133 did not use PROGRESS. Multivariable analyses evaluated demographic and psychosocial characteristics (eg, style of coping, health literacy, self-efficacy, affective states of depression, anxiety, and fatigue) associated with website use. RESULTS: A larger proportion of non-Hispanic White (68/160, 42.5%), compared with non-Hispanic Black (9/40, 23%), participants used PROGRESS (P<.001). Further, PROGRESS users were older in age (P<.001), had a monitoring style of coping (P=.01), and were less depressed (P=.004), anxious (P=.02), and fatigued (P<.001) than nonusers. Education, income, health literacy, blunting style of coping, self-efficacy, and treatment type (radiation therapy or surgery) were not significantly related to use. On multivariable analyses, race (OR 0.28, P<.001), age (OR 1.05, P<.001), monitoring style of coping (OR 1.27, P=.02), and overall mood (OR 0.98, P<.001) remained significant. CONCLUSIONS: A combination of monitoring and low levels of negative affect were associated with website use. Additionally, users were older, non-Hispanic White survivors. To ensure that important survivorship-relevant information reaches users, future efforts need to focus on enhancing patient engagement. TRIAL REGISTRATION: ClinicalTrials.gov NCT02224482; https://clinicaltrials.gov/ct2/show/NCT02224482.

Analysis of survival data with nonproportional hazards: A comparison of propensity-score-weighted methods.

One of the most common ways researchers compare cancer survival outcomes across treatments from observational data is using Cox regression. This model depends on its underlying assumption of proportional hazards, but in some real-world cases, such as when comparing different classes of cancer therapies, substantial violations may occur. In this situation, researchers have several alternative methods to choose from, including Cox models with time-varying hazard ratios; parametric accelerated failure time models; Kaplan-Meier curves; and pseudo-observations. It is unclear which of these models are likely to perform best in practice. To fill this gap in the literature, we perform a neutral comparison study of candidate approaches. We examine clinically meaningful outcome measures that can be computed and directly compared across each method, namely, survival probability at time T, median survival, and restricted mean survival. To adjust for differences between treatment groups, we use inverse probability of treatment weighting based on the propensity score. We conduct simulation studies under a range of scenarios, and determine the biases, coverages, and standard errors of the average treatment effects for each method. We then demonstrate the use of these approaches using two published observational studies of survival after cancer treatment. The first examines chemotherapy in sarcoma, which has a late treatment effect (i.e., similar survival initially, but after 2 years the chemotherapy group shows a benefit). The other study is a comparison of surgical techniques for kidney cancer, where survival differences are attenuated over time.

Use of empiric methods to inform prostate cancer health disparities: Comparison of neighborhood-wide association study "hits" in black and white men.

BACKGROUND: Black men are more likely to die of prostate cancer (PCa) compared with white men. Factors ranging from genetics to neighborhood environment contribute to these disparities. However, unlike genetics, agnostic investigations that identify candidate variables from large-scale data, and that allow for empiric investigations into differential associations between neighborhood and PCa by race/ethnicity, to the authors' knowledge have not been well explored. Thus, herein, the authors built on their previously developed, empiric neighborhood-wide association study (NWAS) in white men and conducted a NWAS in black men to determine whether findings differed by race. METHODS: Pennsylvania Cancer Registry data were linked to US Census data. For the NWAS in non-Hispanic black men, the authors evaluated the association between 14,663 neighborhood census variables and advanced PCa (11 high-stage and/or high-grade cases and 8632 low-stage and/or low-grade cases), adjusting for age, diagnosis year, spatial correlation, and multiple testing. Odds ratios and 95% credible intervals were reported. Replication of NWAS findings across black and white races was assessed using Bayesian mixed effects models. RESULTS: Five variables related to housing (3 variables), education (1 variable), and employment and/or transportation (1 variable) were found to be significantly associated with advanced PCa in black men compared with 17 socioeconomic variables (mostly related to poverty and/or income) in white men. The top hit in black men was related to crowding in renter-occupied housing (odds ratio, 1.10; 95% credible interval, 1.001-1.12). Nine of 22 NWAS hits (4 of 5 hits in black men) were replicated across racial/ethnic groups. CONCLUSIONS: Different neighborhood variables, or "candidates," were identified across race-specific NWASs. These findings and empiric approaches warrant additional study and may inform PCa racial disparities, particularly future gene-environment studies aimed at identifying patients and/or communities at risk of advanced PCa.

Time to Surgery and the Impact of Delay in the Non-Neoadjuvant Setting on Triple-Negative Breast Cancers and Other Phenotypes.

BACKGROUND: Characterization of breast cancer phenotypes has improved our ability to predict breast cancer behavior. Triple-negative (TN) breast cancers have higher and earlier rates of distant events. It has been suggested that this behavior necessitates treating TNs faster than others, including use of neoadjuvant chemotherapy (NACT) if time to surgery is not rapid. METHODS: A review of women diagnosed with non-inflammatory, invasive breast cancer was conducted using the National Cancer Database for patients not having NACT, diagnosed between 2010 and 2014. Changes in overall survival due to delay were measured by phenotype. RESULTS: Overall, 351,087 patients met the inclusion criteria, including 36,505 (10.4%) TNs, 77.9% hormone receptor-positive (HR+) and 11.7% human epidermal growth factor receptor 2 (HER2)-enriched (HER2+). Phenotype, among other factors, was predictive of treatment delays. Adjusted median days from diagnosis to surgery and chemotherapy were 29.9, 31.6 and 31.5 (p< 0.001), and 72.7, 78.0 and 74.4 (p< 0.001) for TNs, HR+ and HER2+ cancers, respectively. After diagnosis, OS declined for all patients per month of preoperative delay (hazard ratio 1.104; p< 0.001). In models separating or combining surgery and chemotherapy, this survival decline did not vary by breast cancer phenotype (p > 0.3). CONCLUSIONS: Delays cause small but measurable effects overall, but the effect on survival does not differ among breast cancer phenotypes. Our data suggest that urgency between diagnosis and surgery or chemotherapy is similar for breast cancers of different subtypes. Although NACT is sometimes advocated solely to avoid treatment delays, this study does not suggest a greater surgical urgency for TNs compared with other breast cancer phenotypes.

Association of Skin Cancer Risk and Protective Behaviors with Health Literacy Among Young Adults in the USA.

BACKGROUND: The goal of this study was to investigate the association of health literacy with skin cancer risk and protective behaviors among young adults at moderate to high risk of skin cancer, the most common cancer. METHOD: A US national sample of 958 adults, 18-25 years old, at moderate to high risk of developing skin cancer, completed a survey online. Behavioral outcomes were ultraviolet (UV) radiation exposure (e.g., indoor and outdoor tanning, sunburn) and protective (e.g., sunscreen use, sunless tanning) behaviors. Multivariable regression analyses were conducted to determine whether health literacy (a four-item self-report measure assessing health-related reading, understanding, and writing) was associated with behavioral outcomes while controlling for demographic factors. RESULTS: Higher health literacy was independently associated with less sunbathing, odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.60-0.98; less indoor tanning, OR = 0.38, CI = 0.31-0.48; and less use of tanning oils, OR = 0.54, CI = 0.43-0.69. However, health literacy was also associated with a lower likelihood of wearing long pants, OR = 0.76, CI = 0.58-0.99, or a hat, OR = 0.68, CI = 0.53-0.87, when outdoors. On the other hand, higher health literacy was associated with higher incidental UV exposure, OR = 1.69, CI = 1.34-2.14, and a greater likelihood of ever having engaged in sunless tanning, OR = 1.50, CI = 1.17-1.92. CONCLUSION: Interestingly, higher health literacy was associated with lower levels of intentional tanning yet also higher incidental UV exposure and lower skin protection among US young adults. These findings suggest that interventions may be needed for young adults at varying levels of health literacy as well as populations (e.g., outdoor workers, outdoor athletes/exercisers) who may be receiving large amounts of unprotected incidental UV.

Partial nephrectomy is not associated with an overall survival advantage over radical nephrectomy in elderly patients with stage Ib-II renal masses: An analysis of the national cancer data base.

BACKGROUND: Partial nephrectomy (PN) is recommended for localized T1a (≤4 cm) renal masses and is preferred over radical nephrectomy (RN) for amenable T1b/T2 (>4 cm) tumors. The objective of the current study was to assess overall survival (OS) differences between PN and RN in patients with T1 and T2 renal cell carcinoma (RCC). METHODS: The National Cancer Data Base was queried for patients with T1 and T2 RCC who underwent PN or RN from 2004 to 2014. Trends in surgery were evaluated using Cochran-Armitage tests. Differences in OS were assessed using adjusted Kaplan-Meier methods. The effects of procedure on OS were analyzed using propensity score-based, weighted Cox proportional hazards models. RESULTS: In total, 212,016 patients with T1 and T2 RCC who underwent either RN (59.7%) or PN (40.3%) were included. The use of PN rose from 2004 to 2014 (T1a: from 40.6% to 71.4%; T1b/T2: from 8.4% to 26.5%; P < .01). Adjusted 5-year OS was longer for patients who underwent PN in both subsets, although effect magnitude was reduced in the T1b/T2 cohort (T1a: 89.6% vs 85.1%; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.70-0.75; P < .01; T1b/T2: 82.5% vs 80.8%; HR, 0.88; 95% CI, 0.83-0.94; P = .01). The benefit of PN on OS diminished as age and time from diagnosis increased; no OS improvement was observed in patients age ≥75 years who had T1b/T2 tumors (HR, 0.89; 95% CI, 0.76-1.06). CONCLUSIONS: Receipt of PN is associated with improved OS in patients with T1a RCC. No procedure-related differences in OS were observed for patients age ≥75 years who had tumors measuring >4 cm. Decisions to undergo PN for T1b/T2 tumors should be based on individualized risk assessment.

Omission of radiotherapy after breast conservation surgery in the postneoadjuvant setting.

BACKGROUND: Breast conservation therapy (BCT) consists of breast conservation surgery (BCS) and radiotherapy (RT). Neoadjuvant chemotherapy (NACT) can downstage tumors, broadening BCS eligibility in patients requiring mastectomy. However, tumor downstaging does not obviate need for RT. This study evaluated factors that predict RT omission after NACT and BCS. METHODS: The National Cancer Database was queried for women with unilateral, clinical stage II-III breast cancer, treated with NACT and BCS between 2008 and 2012. Patients not receiving RT after NACT and BCS were identified. A subgroup analysis was performed eliminating patients for whom RT was recommended but not received. RESULTS: Among 10,220 patients meeting study eligibility, 974 (9.53%) did not receive RT after BCS. Predictors of RT omission included older age, insurance status, facility type, facility region, more recent year of diagnosis, receptor status unknown, human epidermal growth factor receptor 2 status positive or unknown, and positive margins. Factors increasing the likelihood of RT receipt included cN3 disease, receptor positivity, and primary downstaging. Race, Hispanicity, education, income, comorbidities, rural versus urban setting, histology, grade, and nodal stage change were not associated with RT omission. When excluding the 314 patients for whom RT was recommended but not received, age, Medicaid insurance, facility type, facility region, receptor status unknown, human epidermal growth factor receptor 2 status unknown, and positive margins were predictors of RT omission. CONCLUSIONS: Race, comorbidities, and socioeconomic status were not predictors of RT omission. It remains unclear whether omission of RT in some cases is due to lack of physician knowledge. Further efforts are needed to ensure that physicians and patients recognize that RT is a vital and required part of BCT, even after NACT.

Addressing multilevel barriers to cervical cancer screening in Korean American women: A randomized trial of a community-based intervention.

BACKGROUND: Korean American women have among the lowest rates of cervical cancer screening in the United States. The authors evaluated a multicomponent intervention combining community education with navigation services to reduce access barriers and increase screening rates in this underserved population. It was hypothesized that cervical cancer screening rates would be higher among women who received the intervention program compared with those in the control program. METHODS: Korean American women (N = 705) were recruited from 22 churches. In this matched-pair, group-randomized design, 347 women received the intervention, which consisted of a culturally relevant cancer education program combined with provision of navigation services. The control group (N = 358) received general health education, including information about cervical cancer risk and screening and where to obtain low-cost or no-cost screening. Screening behavior was assessed 12 months after the program. RESULTS: Screening behavior data were obtained from 588 women 12 months after the program. In both site-level and participant-level analyses, the intervention program contributed to significantly higher screening rates compared with the control program (odds ratio [OR], 25.9; 95% confidence interval [CI], 10.1-66.1; P < .001). In sensitivity analysis, the treatment effect remained highly significant (OR, 16.7; 95% CI, 8.1-34.4; P < .001). CONCLUSIONS: A multicomponent intervention combining community cancer education with navigation services yielded significant increases in cervical cancer screening rates among underscreened Korean American women. Community-accessible programs that incorporate cancer education with the delivery of key navigation services can be highly effective in increasing cervical cancer screening rates in this underserved population. Cancer 2017;123:1018-26. © 2016 American Cancer Society.

Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder-preservation therapy for muscle-invasive bladder cancer.

BACKGROUND: The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of the bladder. METHODS: The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan-Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria. RESULTS: A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR, 1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406 [95% CI, 1.235-1.601]) analyses. CONCLUSIONS: In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337-45. © 2017 American Cancer Society.

Emotional approach coping and depressive symptoms in colorectal cancer patients: The role of the intimate relationship.

This study examined whether emotional approach coping was associated with lower depressive symptoms, and whether intimacy moderated this association, in 121 married/partnered colorectal cancer (CRC) outpatients. Prospective analyses of survey data on emotional approach coping, depressive symptoms, and intimacy measured at baseline and 6-month follow-up showed that depressive symptoms were inversely related to processing, expression, and intimacy. At baseline, the association between processing and depressive symptoms was moderated by intimacy: greater processing was associated with lower depressive symptoms only for those in relatively high-intimacy relationships. Enhancing emotional approach coping efforts and relationship quality may benefit CRC patients' adjustment.

Genetic Variants That Predispose to DNA Double-Strand Breaks in Lymphocytes From a Subset of Patients With Familial Colorectal Carcinomas.

BACKGROUND & AIMS: DNA structural lesions are prevalent in sporadic colorectal cancer. Therefore, we proposed that gene variants that predispose to DNA double-strand breaks (DSBs) would be found in patients with familial colorectal carcinomas of an undefined genetic basis (UFCRC). METHODS: We collected primary T cells from 25 patients with UFCRC and matched patients without colorectal cancer (controls) and assayed for DSBs. We performed exome sequence analyses of germline DNA from 20 patients with UFCRC and 5 undiagnosed patients with polyposis. The prevalence of identified variants in genes linked to DNA integrity was compared with that of individuals without a family history of cancer. The effects of representative variants found to be associated with UFCRC was confirmed in functional assays with HCT116 cells. RESULTS: Primary T cells from most patients with UFCRC had increased levels of the DSB marker γ(phosphorylated)histone2AX (γH2AX) after treatment with DNA damaging agents, compared with T cells from controls (P < .001). Exome sequence analysis identified a mean 1.4 rare variants per patient that were predicted to disrupt functions of genes relevant to DSBs. Controls (from public databases) had a much lower frequency of variants in the same genes (P < .001). Knockdown of representative variant genes in HCT116 CRC cells increased γH2AX. A detailed analysis of immortalized patient-derived B cells that contained variants in the Werner syndrome, RecQ helicase-like gene (WRN, encoding T705I), and excision repair cross-complementation group 6 (ERCC6, encoding N180Y) showed reduced levels of these proteins and increased DSBs, compared with B cells from controls. This phenotype was rescued by exogenous expression of WRN or ERCC6. Direct analysis of the recombinant variant proteins confirmed defective enzymatic activities. CONCLUSIONS: These results provide evidence that defects in suppression of DSBs underlie some cases of UFCRC; these can be identified by assays of circulating lymphocytes. We specifically associated UFCRC with variants in WRN and ERCC6 that reduce the capacity for repair of DNA DSBs. These observations could lead to a simple screening strategy for UFCRC, and provide insight into the pathogenic mechanisms of colorectal carcinogenesis.

DEVELOPMENT AND VALIDATION OF A NOVEL TOOL TO PREDICT HOSPITAL READMISSION RISK AMONG PATIENTS WITH DIABETES.

OBJECTIVE: To develop and validate a tool to predict the risk of all-cause readmission within 30 days (30-d readmission) among hospitalized patients with diabetes. METHODS: A cohort of 44,203 discharges was retrospectively selected from the electronic records of adult patients with diabetes hospitalized at an urban academic medical center. Discharges of 60% of the patients (n = 26,402) were randomly selected as a training sample to develop the index. The remaining 40% (n = 17,801) were selected as a validation sample. Multivariable logistic regression with generalized estimating equations was used to develop the Diabetes Early Readmission Risk Indicator (DERRI™). RESULTS: Ten statistically significant predictors were identified: employment status; living within 5 miles of the hospital; preadmission insulin use; burden of macrovascular diabetes complications; admission serum hematocrit, creatinine, and sodium; having a hospital discharge within 90 days before admission; most recent discharge status up to 1 year before admission; and a diagnosis of anemia. Discrimination of the model was acceptable (C statistic 0.70), and calibration was good. Characteristics of the validation and training samples were similar. Performance of the DERRI™ in the validation sample was essentially unchanged (C statistic 0.69). Mean predicted 30-d readmission risks were also similar between the training and validation samples (39.3% and 38.7% in the highest quintiles). CONCLUSION: The DERRI™ was found to be a valid tool to predict all-cause 30-d readmission risk of individual patients with diabetes. The identification of high-risk patients may encourage the use of interventions targeting those at greatest risk, potentially leading to better outcomes and lower healthcare costs. ABBREVIATIONS: DERRI™ = Diabetes Early Readmission Risk Indicator ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification GEE = generalized estimating equations ROC = receiver operating characteristic.

Increasing time to treatment initiation for head and neck cancer: an analysis of the National Cancer Database.

BACKGROUND: The objective of this study was to identify trends and predictors of the time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The National Cancer Database (NCDB) was reviewed for the following head and neck cancer sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was defined as the number of days from diagnosis to the initiation of definitive treatment and was measured according to covariates. Significant differences in the median TTI across each covariate were measured using the Kruskal-Wallis test, and the Spearman test was used to measure trends within covariates. For multivariate analysis, a zero-inflated, negative, binomial regression model was used to estimate the expected TTI, which was expressed in the predicted number of days; and the Vuong test was used to identify the predictors of TTI. RESULTS: In total, 274,630 patients were included. Between 1998 and 2011, the median TTI for all patients was 26 days, and it increased from 19 days to 30 days (P < .0001). Treatment with chemoradiation (CRT) (P < .0001), treatment at academic facilities (P < .0001), and stage IV disease (P < .0001) were associated with increased TTI. TTI significantly increased for each disease stage (P < .0001), treatment modality (P < .0001), and facility type (P < .0001) over time. In addition, patients became more likely to transition care between facilities after diagnosis for treatment initiation (P < .0001) over time. On multivariate analysis, treatment at academic facilities (33 days), transitioning care (37 days), and receipt of CRT (39 days) predicted for a longer TTI. CONCLUSIONS: TTI is rising for patients with HNSCC. Those who have advanced-stage disease, receive treatment with CRT, are treated at academic facilities, and who have a transition in care realized the greatest increases in TTI.

Postmastectomy radiation therapy for T3N0: a SEER analysis.

BACKGROUND: There is conflicting evidence regarding the benefit of postmastectomy radiation therapy (PMRT) for pathologic stage T3N0M0 breast cancers. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database to investigate the benefit of PMRT in this patient population. METHODS: We queried the SEER database for T3N0M0 breast cancer patients diagnosed from 2000 to 2010 who underwent modified radical mastectomy. We excluded males, patients with unknown radiation timing/type, other primary tumors, and survival <6 months. A total of 2525 patients were included in the analysis. We performed univariate and multivariate statistical analysis using chi-square tests, log-rank tests, and Cox proportional hazards regression. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). RESULTS: Of the 2525 patients identified, 1063 received PMRT. The median follow-up was 56 months (range, 6-131 months). On univariate analysis, PMRT improved OS (76.5% vs 61.8%, P<.01) and CSS (85.0% vs 82.4%, P<.01) at 8 years. The use of PMRT remained significant on multivariate analysis: PMRT improved OS (hazard ratio 0.63, P<.001) and CSS (hazard ratio 0.77, P = .045). Low tumor grade (P<.01) and marital status of "married" (P = .01) also was a predictor of improved CSS on multivariate analysis. CONCLUSIONS: PMRT was associated with significant improvements in both CSS and OS in patients with T3N0M0 breast cancers treated with modified radical mastectomy from 2000 to 2010. PMRT should be strongly considered in T3N0M0 patients. Postmastectomy radiation therapy is associated with significant improvements in overall and cause-specific survival in patients with T3N0M0 breast cancers treated with modified radical mastectomy from 2000 to 2010 in the SEER database. Postmastectomy radiation therapy should be strongly considered for patients who have T3N0M0 tumors.

The rise and fall of prostate brachytherapy: use of brachytherapy for the treatment of localized prostate cancer in the National Cancer Data Base.

BACKGROUND: Brachytherapy has been shown to be an efficacious and cost-effective treatment among patients with localized prostate cancer. In this study, the authors examined trends in brachytherapy use for localized prostate cancer using a large national cancer registry. METHODS: In the National Cancer Data Base (NCDB), a total of 1,547,941 patients with localized prostate cancer were identified from 1998 through 2010. Excluding patients with lymph node-positive or metastatic disease, the authors examined primary treatment trends focusing on the use of brachytherapy over time. Patients with available data (2004-2009) were stratified by National Comprehensive Cancer Network risk criteria. Controlling for year of diagnosis and demographic, clinical, and pathologic characteristics, multivariate analyses were performed examining the association between patient characteristics and receipt of brachytherapy. RESULTS: In the study cohort, brachytherapy use reached a peak of 16.7% in 2002, and then steadily declined to a low of 8% in 2010. Of the 719,789 patients with available data for risk stratification, 41.1%, 35.3%, and 23.6%, respectively, met low, intermediate, and high National Comprehensive Cancer Network risk criteria. After adjustment, patients of increasing age and those with Medicare insurance were more likely to receive brachytherapy. In contrast, patients with intermediate-risk or high-risk disease, Medicaid insurance, increasing comorbidity count, and increasing year of diagnosis were less likely to receive brachytherapy. CONCLUSIONS: For patients with localized prostate cancer who are treated at National Cancer Data Base institutions, there has been a steady decline in brachytherapy use since 2003. For low-risk patients, the declining use of brachytherapy monotherapy compared with more costly emerging therapies has significant health policy implications.

Direct-to-patient disclosure of results of mismatch repair screening for Lynch syndrome via electronic personal health record: a feasibility study.

PURPOSE: The adoption of universal mismatch repair screening of colorectal and endometrial cancers has the potential to improve detection of Lynch syndrome, as well as to improve health outcomes among cancer patients and their family members. Electronic patient health records represent an innovative, resource-efficient route of delivering results directly to patients that could be enhanced by multimedia interventions to improve critical downstream outcomes. The current study examines the feasibility and acceptability of this approach. METHODS: Patients hospitalized for resection of colorectal or endometrial cancer were recruited to receive their mismatch repair result via institutional electronic patient health record. Baseline and follow-up assessments were conducted. RESULTS: In all, 74% (49/66) of eligible patients consented, and 81% (29/36) of participants who had a result posted to their electronic patient health record completed follow-up, surpassing feasibility thresholds, with 14% (5/36) receiving an abnormal result. Ratings of the study approach surpassed the acceptability threshold--97% had a mean score of ≥ 4 on a 7-point scale--and were high, regardless of whether the results were normal or abnormal. Ineligibility was more common among non-white patients (P = 0.009) and patients ≥ 65 of age (P = 0.035) due to either low Internet use or access to the Internet. CONCLUSION: Electronic patient health record-based result disclosure for mismatch repair screening is feasible to study and is acceptable to patients, but minority and elderly patients may experience greater barriers to participation.Genet Med 16 11, 854-861.