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Background: Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.Methods: We conducted a population-based, retrospective cohort study of 12,500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities.Results: Among 12 500 women (mean age = 60 years, range = 22-99 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35).Conclusions: Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety. [ABSTRACT FROM AUTHOR]

Over the years, several international guidelines have been developed by specialist organizations for the diagnosis of gestational diabetes mellitus (GDM). However, these guidelines vary and lack consensus on what level of glycemia defines GDM and worryingly, there is now evidence of over- or- under-diagnosis of women with GDM by current criteria. Towards this end, the National Priorities Research Program (NPRP) funded a program of research aimed at elucidating the problem with GDM diagnosis. It was determined, on completion of the project, that the solution required diagnosis of graded levels of dysglycemia in pregnancy and not just a diagnosis of presence or absence of GDM. A new diagnostic criterion (called the NPRP criterion) was created based on a single numerical summary of the three readings from the oral glucose tolerance test (GTT) that diagnosed women in pregnancy into four levels: normal, impaired, GDM and high risk GDM. This paper now examines existing GDM criteria vis-à-vis the NPRP criterion. It is noted that no significant change has happened over the years for existing criteria except for a gradual reduction in the threshold values of individual time-points or the number of time points, bringing us towards over-diagnosis of GDM in pregnancy. The new criterion unifies all readings from the GTT into one numerical value and, because it results in four levels of glycemia, represents a new way forwards for GDM diagnosis and can potentially reduce the rates of under diagnosis and over diagnosis of GDM., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objective: To explore the association between COVID-19-related cancer treatment cancellations and the psychological health of cancer patients in Nigeria. Methods: We analyzed data collected from 15 outpatient cancer clinics, comprising 1,097 patients between April to July 2020. Study outcome was ten psychological impacts, including feeling down, stressed, and unable to access treatment due to COVID-19 (used as continuous and categorical variable (0-3,4-7,8+ events). The independent variable was treatment cancellations due to COVID-19 categorized as 0, 1, and 2+ cancellations. Confounders included religion, ethnicity, income, cancer diagnosis/type, and treatment received. Stata/SE.v.17 was used to perform all analyses. P values of ≤0.05 were deemed statistically significant. Results: Of the 1,097 cancer patients, 65.7% were female, with a mean age (SD) of 49.4 (13.8) years. Most patients (50.3%) reported four to seven psychological health events. Cancer patients who reported two/more treatment cancellations made up only 12.8% of the study sample but accounted for a greater proportion of psychological impacts (23.5%; P <0.001). In the adjusted model, cancer patients with one treatment cancellation (Coef: 0.195, 95%CI: 0.089-0.302) and those with two/more cancellations (Coef: 0.379, 95%CI: 0.255-0.504) had a significantly higher risk of psychological health impacts than those with no treatment cancellations. Conclusion: More than half of our sample of primarily adult female cancer patients reported major psychological health effects due to COVID-19. Cancer patients who experienced at least one treatment cancellation had a higher risk of psychological health consequences than those who did not. The implications of our findings and how to mitigate the impact of COVID-19 on oncology service disruptions are discussed., Competing Interests: Disclosures: The authors have no funding related to this work and no potential conflicts of interest to disclose. The data that support the findings of this study are available from the corresponding author upon request., (Copyright © 2024 Marshfield Clinic Health System.)

Background: Cancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment., Objectives: The study's purpose was to determine whether this dose reduction is advisable for cancer-associated VTE., Methods: A randomized, double-blind trial compared apixaban 2.5 mg with 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 to 12 months of anticoagulation therapy. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding., Results: Of 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus clinically relevant nonmajor bleeding occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared with 22 of 181 patients (12.2%) in the 5 mg group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P = .39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and in 2.2% of the 5 mg group (HR, 1.26; 95% CI, 0.34-4.66; P = .73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR, 1.0; 95% CI, 0.40-2.53; P = 1.00). All-cause mortality rates were similar between groups, 13% vs 12% (HR, 1.14; 95% CI, 0.63-2.04; P = .67)., Conclusion: For secondary prevention of cancer-associated VTE, apixaban 2.5 mg compared with 5 mg twice daily did not lower combined bleeding events (EVE trial NCT03080883)., Competing Interests: Declaration of competing interests The authors declare no competing financial interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Abstract: Migration of cholecystectomy surgical clip into the common bile duct with subsequent stone formation is a rare phenomenon, one which may lead to complications including obstruction, pain, nausea, vomiting and fever. The mechanism of migration is largely unknown but may result from a combination of factors including necrosis, intra-abdominal pressure or poor surgical technique with migrated clip serving as a nidus for stone formation. We present a 55-year-old woman with clip-induced stone impacted at the distal common bile duct 12 years post-cholecystectomy and a review of the literature related to cholecystectomy clip stone formation. In addition, we reviewed relevant English language case reports and literature reviews by searching PubMed using search terms 'stone', 'clip', 'cholecystectomy' and 'biliary'. There was no limit to the date of publication. Our study found 68 unduplicated cases of clip-induced stones which had a wide range of onset and presenting systems. Further research is needed to identify risk factors, methods of prevention and benefits of early detection screening., (Copyright © 2024 Copyright: © 2024 Journal of Minimal Access Surgery.)

Background: In oncology clinical trials, there is the assumption that randomization sufficiently balances confounding covariates and therefore average treatment effects are usually reported. This paper explores the wider benefits provided by conditioning on covariates for reasons other than mitigation of confounding., Methods: We reanalyzed the data from primary randomized controlled trials listed in two meta-analyses to explore the significance of conditioning on smoking status in terms of the effect magnitude of treatment on progression free survival in non-small cell lung cancer., Results: The reanalysis revealed that conditioning on smoking status using sub-group analyses provided the closest empiric estimate of individual treatment effect based on smoking status and significantly reduced the heterogeneity of treatment effect observed across studies. In addition, smoking status was determined to be a modifier of the effect of treatment., Conclusion: Conditioning on prognostic covariates in randomized trials in oncology helps generate the closest empiric estimates of individual treatment benefit, addresses heterogeneity due to varying covariate distributions across trials and facilitates future decision making as well as evidence synthesis. Conditioning using sub-group analyses also allows examination for effect modification in meta-analysis., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Radiation therapy (RT) is an essential part of the multidisciplinary treatment of pediatric cancer. Over the past five decades, significant advances have been made in the delivery of RT, with better dose delivery to disease targets while minimizing exposure to nearby organs at risk. These advances have led to improved treatment outcomes, increased survival, and reduced treatment-related toxicities. Advanced treatment techniques, however, require significant investment in infrastructural and personnel resources. This review documents what is currently available regarding expertise and infrastructure for pediatric radiation oncology practice in Nigeria. It was performed to serve as a foundation for the creation and design of tailored solutions (initiatives and policies) to increase pediatric radiation availability, accessibility, and equity in Nigeria and ultimately improve pediatric cancer treatment outcomes in the region.

Background/Objective: No-shows have a negative effect on healthcare outcomes. It is unclear, however, whether patients' distance from the clinic is associated with higher no-show rates. To fill this knowledge gap, we examined the relationship between patients' distance from the clinic and no-shows in a rural provider network. Methods: Data from Marshfield Clinic Health System's scheduling system, including 263,464 recent patient appointments in 2021 were analyzed. The outcome was no-shows, defined as when patients missed an appointment (categorized as yes/no). The exposure was the distance to the clinic, measured in miles as a straight-line distance from the clinic in the patient's zip code to the facility where the appointment was held (classified as <5 miles, 5-10, 10-20; >20, and used as continuous). Covariates were patient demographics, appointments, providers, and insurance status. Chi-square and logistic regression were used with p-values ≤.05 considered statistically significant. Results: The no-show rate was 8.0%. Patients who lived <5 miles (8.3%) and >20 miles (8.2%) from the clinic had higher no-show rates than those who lived between 10-20 miles (8.0%) and 5-10 miles (7.6%), at P =0.001. In the adjusted model, the odds of no-show were similar between patients who did not show and those who did (OR:1.00,95%CI:1.00-1.00). No-shows were more likely among male patients compared to females (OR:1.14,95%CI:1.11-1.18), Spanish compared to English speakers (OR:1.34,95%CI:1.20-1.50), prior no-show compared to no prior no-show (OR:4.42,95%CI:4.27-4.48), >4 weeks lead time compared to <1 day (OR:5.45,95%CI:4.98-5.97), and Medicaid compared to non-Medicaid patients (OR:1.56,95%CI:1.49-1.63). Conclusion: Our analysis showed patients who lived <5 miles and >20 miles from the clinic had higher no-show rates. The odds of a no-show were comparable between patients who showed up and those who did not. Male patients, Spanish-speaking patients, patients with a history of no-shows, and Medicaid beneficiaries were more likely to miss their appointments. Understanding the impact of these variables on no-show rates can assist healthcare providers in developing strategies to improve patient access and reduce no-show rates. These findings imply that rural patients may face a variety of barriers when seeking healthcare, necessitating a comprehensive approach to addressing this issue., Competing Interests: Disclosures: The authors have disclosed no personal or financial conflicts of interest or financial support related to this work., (Copyright © 2023 Marshfield Clinic Health System.)

Purpose: The onset of the COVID-19 pandemic created major disruptions in the conduct of cancer clinical trials. In response, regulators and sponsors allowed modifications to traditional trial processes to enable clinical research and care to continue. We systematically evaluated how these mitigation strategies affected data quality and overall trial conduct., Methods: This study used surveys and live interviews. Forty-one major industry and National Cancer Institute Network groups (sponsors) overseeing anticancer treatment trials open in the United States from January 2015 to May 2022 were invited to participate. Descriptive statistics were used for survey data summaries. Key themes from interviews were identified., Results: Twenty sponsors (48.8%; 15 industry and five Network groups) completed the survey; 11/20 (55.0%) participated in interviews. Sponsors predominantly (n = 12; 60.0%) reported large (≥11 trials) portfolios of phase II and/or phase III trials. The proportion of sponsors reporting a moderate (9) or substantial (8) increase in protocol deviations in the initial pandemic wave versus the pre-pandemic period was 89.5% (17/19); the proportion reporting a substantial increased dropped from 42.1% (n = 8/19) in the initial wave to 15.8% (n = 3/19) thereafter. The most commonly adopted mitigation strategies were remote distribution of oral anticancer therapies (70.0%), remote adverse event monitoring (65.0%), and remote consenting (65.0%). Most respondents (15/18; 83.3%) reported that the pandemic had minimal (n = 14) or no impact (n = 1) on overall data integrity., Conclusion: Despite nearly all sponsors observing a temporary increase in protocol deviations, most reported the pandemic had minimal/no impact on overall data integrity. The COVID-19 pandemic accelerated an emerging trend toward greater flexibility in trial conduct, with potential benefits of reduced burden on trial participants and sites and improved patient access to research.

Background: No-show appointments pose a significant challenge for healthcare providers, particularly in rural areas. In this study, we developed an evidence-based predictive model for patient no-shows at the Marshfield Clinic Health System (MCHS) rural provider network in Wisconsin, with the aim of improving overbooking approaches in outpatient settings and reducing the negative impact of no-shows in our underserved rural patient populations., Methods: Retrospective data (2021) were obtained from the MCHS scheduling system, which included 1,260,083 total appointments from 263,464 patients, as well as their demographic, appointment, and insurance information. We used descriptive statistics to associate variables with show or no-show status, logistic regression, and random forests utilized, and eXtreme Gradient Boosting (XGBoost) was chosen to develop the final model, determine cut-offs, and evaluate performance. We also used the model to predict future no-shows for appointments from 2022 and onwards., Results: The no-show rate was 6.0% in both the train and test datasets. The train and test datasets both yielded 5.98. Appointments scheduled further in advance (> 60 days of lead time) had a higher (7.7%) no-show rate. Appointments for patients aged 21-30 had the highest no-show rate (11.8%), and those for patients over 60 years of age had the lowest (2.9%). The model predictions yielded an Area Under Curve (AUC) of 0.84 for the train set and 0.83 for the test set. With the cut-off set to 0.4, the sensitivity was 0.71 and the positive predictive value was 0.18. Model results were used to recommend 1 overbook for every 6 at-risk appointments per provider per day., Conclusions: Our findings demonstrate the feasibility of developing a predictive model based on administrative data from a predominantly rural healthcare system. Our new model distinguished between show and no-show appointments with high performance, and 1 overbook was advised for every 6 at-risk appointments. This data-driven approach to mitigating the impact of no-shows increases treatment availability in rural areas by overbooking appointment slots on days with an elevated risk of no-shows., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used., Materials and Methods: A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 -olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%., Results: A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist., Conclusion: This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy (ClinicalTrials.gov Identifier: NCT03578081)., (© The Author(s) 2023. Published by Oxford University Press.)

Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment., Significance: This study confirms the utility of the integrative IRS biomarker for predicting anti-PD-L1/PD-1 benefit. IRS significantly improved upon currently available biomarkers, including PD-L1 IHC, TMB, and MSI status. Additional utility for informing on chemotherapy, anti-PD-L1/PD-1, and anti-PD-L1/PD-1 plus chemotherapy treatments decisions is shown., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: In 2013, Marshfield Clinic Health System (MCHS) implemented the Dragon Medical One (DMO) system provided by Nuance Management Center (NMC) for Real-Time Dictation (RTD), embracing the idea of streamlined clinic workflow, reduced dictation hours, and improved documentation legibility. Since then, MCHS has observed a trend of reduced time in documentation, however, the target goal of 100% adoption of voice recognition (VR)-based RTD has not been met., Objective: To evaluate the uptake/adoption of VR technology for RTD in MCHS, between 2018-2020., Methods: DMO data for 1,373 MCHS providers from 2018-2020 were analyzed. The study outcome was VR uptake, defined as the median number of hours each provider used VR technology to dictate patient information, and classified as no/yes. Covariates included sex, age, US-trained/international medical graduates, trend, specialty, and facility. Descriptive statistics and unadjusted and adjusted logistic regression analyses were performed. Stata/SE.version.17 was used for analyses. P-values less than/equal to 0.05 were considered statistically significant., Results: Of the 1,373 MCHS providers, the mean (SD) age was 48.3 (12.4) years. VR uptake was higher than no uptake (72.0% vs. 28.0%). In both unadjusted and adjusted analyses, VR uptake was 4.3 times and 7.7 times higher in 2019-2020 compared to 2018, respectively (OR:4.30,95%CI:2.44-7.46 and AOR:7.74,95%CI:2.51-23.86). VR uptake was 0.5 and 0.6 times lower among US-trained physicians compared to internationally-trained physicians (OR:0.53,95%CI:0.37-0.76 and AOR:0.58,95%CI:0.35-0.97). Uptake was 0.2 times lower among physicians aged 60/above than physicians aged 29/less (OR:0.20,95%CI:0.10-0.59, and AOR:0.17,95%CI:0.27-1.06)., Conclusion: Since 2018, VR adoption has increased significantly across MCHS. However, it was lower among US-trained physicians than among internationally-trained physicians (although internationally physicians were in minority) and lower among more senior physicians than among younger physicians. These findings provide critical information about VR trends, physician factors, and which providers could benefit from additional training to increase VR adoption in healthcare systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Onitilo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Firearm fatalities are a major public health concern, claiming the lives of 40,000 Americans each year. While firearm fatalities have pervasive effects, it is unclear how social determinants of health (SDOH) such as residential racial segregation, income inequality, and community resilience impact firearm fatalities. This study investigates the relationships between these SDOH and the likelihood of firearm fatalities., Methods: County-level SDOH data from the Agency for Health Care Research and Quality for 2019 were analyzed, covering 72 Wisconsin counties. The dependent variable was the number of firearm fatalities in each county, used as a continuous variable. The independent variable was residential racial segregation (Dissimilarity Index), defined as the degree to which non-White and White residents were distributed across counties, ranging from 0 (complete integration) to 100 (complete segregation), and higher values indicate greater residential segregation (categorized as low, moderate, and high). Covariates were income inequality ranging from zero (perfect equality) to one (perfect inequality) categorized as low, moderate, and high, community resilience risk factors (low, moderate, and high risks), and rural-urban classifications. Descriptive/summary statistics, unadjusted and adjusted negative binomial regression adjusting for population weight, were performed using STATA/MPv.17.0; P-values ≤ 0.05 were considered statistically significant. ArcMap was used for Geographic Information System analysis., Results: In 2019, there were 802 firearm fatalities. The adjusted model demonstrates that the risk of firearm fatalities was higher in areas with high residential racial segregation compared to low-segregated areas (IRR.:1.26, 95% CI:1.04-1.52) and higher in areas with high-income inequality compared to areas with low-income inequality (IRR.:1.18, 95% CI:1.00-1.40). Compared to areas with low-risk community resilience, the risk of firearm fatalities was higher in areas with moderate (IRR.:0.61, 95% CI:0.48-0.78), and in areas with high risk (IRR.:0.53, 95% CI:0.41-0.68). GIS analysis demonstrated that areas with high racial segregation also have high rates of firearm fatalities., Conclusion: Areas with high residential racial segregation have a high rate of firearm fatalities. With high income inequality and low community resilience, the likelihood of firearm fatalities increases., (© 2023. The Author(s).)

Background: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown., Methods: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated., Results: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group., Conclusions: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.)., (Copyright © 2023 Massachusetts Medical Society.)

Purpose: To examine cancer patients' perspectives on the impact of COVID-19 on teleoncology in Nigeria., Methods: Data from a multicenter survey conducted at 15 outpatient clinics to 1,097 patients with cancer from April and July 2020 were analyzed. The study outcome was telemedicine, defined as patients who reported their routine follow-up visits were converted to virtual visits because of COVID-19 (coded yes/no). Covariates included patient age, ethnicity, marital status, income, cancer treatment, service disruption, and cancer diagnosis/type. Stata/SE.v.17 (StataCorp, College Station, TX) was used to perform chi-square and logistic regression analyses. P values ≤ .05 were considered statistically significant., Results: The majority of the 1,097 patients with cancer were female (65.7%) and age 55 years and older (35.0%). Because of COVID-19, 12.6% of patients' routine follow-ups were converted to virtual visits. More patients who canceled/postponed surgery (17.7% v 7.5%; P ≤ .001), radiotherapy (16.9% v 5.3%; P ≤ .001), and chemotherapy (22.8% v 8.5%; P ≤ .001), injection chemotherapy (20.6% v 8.7%; P ≤ .001) and those who reported being seen less by their doctor/nurse (60.3% v 11.4%; P ≤ .001) reported more follow-up conversions to virtual visits. In multivariate analyses, patients seen less by their doctors/nurses were 14.3 times more likely to have their routine follow-ups converted to virtual visits than those who did not (odds ratio, 14.33; 95% CI, 8.36 to 24.58)., Conclusion: COVID-19 caused many patients with cancer in Nigeria to convert visits to a virtual format. These conversions were more common in patients whose surgery, radiotherapy, chemotherapy, and injection chemotherapy treatments were canceled or postponed. Our findings suggest how COVID-19 affects cancer treatment services and the importance of collecting teleoncological care data in Nigeria.

Background: Anti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden (TMB) may improve benefit prediction., Methods: Using treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival (rwPFS) and overall survival (OS) prediction was validated in an independent cohort of trial patients., Results: Here, by Cox modeling, we develop IRS-which combines TMB with CD274, PDCD1, ADAM12 and TOP2A quantitative expression-to predict pembrolizumab rwPFS (648 patients; 26 tumor types; IRS-High or -Low groups). In the 248 patient validation cohort (248 patients; 24 tumor types; non-pembrolizumab PD-[L]1 monotherapy treatment), median rwPFS and OS are significantly longer in IRS-High vs. IRS-Low patients (rwPFS adjusted hazard ratio [aHR] 0.52, p = 0.003; OS aHR 0.49, p = 0.005); TMB alone does not significantly predict PD-(L)1 rwPFS nor OS. In 146 patients treated with systemic therapy prior to pembrolizumab monotherapy, pembrolizumab rwPFS is only significantly longer than immediately preceding therapy rwPFS in IRS-High patients (interaction test p = 0.001). In propensity matched lung cancer patients treated with first-line pembrolizumab monotherapy or pembrolizumab+chemotherapy, monotherapy rwPFS is significantly shorter in IRS-Low patients, but is not significantly different in IRS-High patients. Across 24,463 molecularly-evaluable trial patients, 7.6% of patients outside of monotherapy PD-(L)1 approved tumor types are IRS-High/TMB-Low., Conclusions: The validated, predictive, pan-tumor IRS model can expand PD-(L)1 monotherapy benefit outside currently approved indications., (© 2023. The Author(s).)

Purpose: To quantify the relationship between diabetes and fatigue from pre-chemotherapy to 6 months post-chemotherapy for women with breast cancer compared to women without a history of cancer (controls)., Methods: This was a secondary analysis from a nationwide prospective longitudinal study of female patients with breast cancer undergoing chemotherapy and controls. Diabetes diagnosis (yes/no) was obtained at baseline, and cancer-related fatigue was measured using the Multidimensional Fatigue Symptom Inventory (MFSI) pre-, post-, and 6 months post-chemotherapy in patients; controls were assessed at equivalent time points. Repeated measures mixed effects models estimated the association between fatigue and diabetes controlling for cancer (yes/no), body mass index, exercise and smoking habits, baseline anxiety and depressive symptoms, menopausal status, marital status, race, and education., Results: Among 439 patients and 235 controls (52.8 ± 10.5 years old), diabetes was twice as prevalent among patients as controls (11.6% vs. 6.8%). At baseline, diabetes was associated with worse fatigue (4.1 ± 1.7 points, p = 0.017). Also, diabetes was associated with clinically meaningful worse fatigue throughout the study period among all participants (5.2 ± 1.9 points, p = 0.008) and patients alone (4.5 ± 2.0, p = 0.023). For the MFSI subdomains among patients, diabetes was associated with worse general (p = 0.005) and mental fatigue (p = 0.026)., Conclusions: Diabetes was twice as prevalent in women with breast cancer compared to controls, and diabetes was associated with more severe cancer-related fatigue in patients before and after chemotherapy and at 6 months post-chemotherapy. Interventions that address diabetes management may also help address cancer-related fatigue during chemotherapy treatment., Trial Registration: ClinicalTrials.gov identifier: NCT01382082, first posted June 27, 2011., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The quality of a physician is arguably related to the depth and quality of medical education received. As cancer devastates the health and economy of developing countries like Nigeria, it becomes increasingly important for physicians in these countries to be equipped with basic knowledge and skill to adequately detect, diagnose, refer and manage common cancers. This study reviewed exposure to oncology training as a component of the medical school's curriculum in Nigeria from the trainee's perspective., Methodology: In a cross-sectional review of medical students and recent graduates of universities across Nigeria, data were collected using a predesigned tool., Results: Entries from 228 participants were recorded and analysed. The mean age of study participants was 25.4 ± 2.9 years; 53.1% were female. Respondents were primarily in government-owned medical schools. Over half (55.7%) reported none to minimal oncology exposure during their preclinical classes, 38.6% reported oncology as a distinct clinical rotation in their medical schools and only 44.3% spent time in at least one oncology unit during clinical rotations. The mean duration spent in oncology units was 3.4 weeks., Conclusion: Doubtless, Nigeria needs more oncology specialists but, it is just as important for even general practitioners to have basic oncology knowledge. This study shows slow exposure to oncology training for medical students, which has contributed to the lack of confidence in treating common cancers seen in Nigeria and low desire among medical students to specialize in oncology. As cancer incidence rises, the need for oncology knowledge in the general physician community is increasingly evident., (Copyright © 2021 Nigerian Medical Association.)

Background: Enthusiasm for precision oncology may obscure the psychosocial and ethical considerations associated with the implementation of tumor genetic sequencing., Methods: Patients with advanced cancer undergoing tumor-only genetic sequencing in the National Cancer Institute Molecular Analysis for Therapy Choice (MATCH) trial were randomized to a web-based genetic education intervention or usual care. The primary outcomes were knowledge, anxiety, depression, and cancer-specific distress collected at baseline (T0), posteducation (T1) and after results (T2). Two-sided, 2-sample t tests and univariate and multivariable generalized linear models were used., Results: Five hundred ninety-four patients (80% from NCI Community Oncology Research Program sites) were randomized to the web intervention (n = 293) or usual care (n = 301) before the receipt of results. Patients in the intervention arm had greater increases in knowledge (P for T1-T0 < .0001; P for T2-T0 = .003), but there were no significant differences in distress outcomes. In unadjusted moderator analyses, there was a decrease in cancer-specific distress among women (T0-T1) in the intervention arm but not among men. Patients with lower health literacy in the intervention arm had greater increases in cancer-specific distress and less decline in general anxiety (T0-T1) and greater increases in depression (T0-T2) in comparison with those receiving usual care., Conclusions: Web-based genetic education before tumor-only sequencing results increases patient understanding and reduces distress in women. Refinements to the intervention could benefit low-literacy groups and men., (© 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: Within the last decade, the use of ibrutinib, a first-generation, non-selective, irreversible Burton's tyrosine kinase inhibitor for the treatment of hematological malignancies has proven highly effective in improving patient outcomes. Background: Ibrutinib has been associated with an increase in atrial fibrillation (AF). The predisposing factors are thought to be pre-existing cardiovascular risk factors, but these have not been directly evaluated. Methods: We conducted a nested case-control study, recruiting consecutive ibrutinib treated subjects to evaluate cardiovascular risk factors associated with the development of AF in patients diagnosed with hematological B-cell malignancies. Results: Of the 189 patients treated with ibrutinib and without AF at baseline, 54 (29%) developed AF. Cardiovascular risk factors associated with AF development were, older age, prior hypertension (HTN), history of heart failure (HF) and congenital heart disease. A patient with HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 40%, 48%, 64%, and 71%, respectively. Patients with prior HTN without HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 5%, 10%, 23%, and 31%, respectively while on ibrutinib therapy. Conclusions: The relationship between ibrutinib, cardiovascular comorbidities, and AF is through pre-existing cardiovascular disease. An individualized, multidisciplinary approach involving cardiologists should be considered when initiating ibrutinib, particularly when there is a history of HTN, HF or congenital heart disease. In such patients, there should be close cardiovascular monitoring and prompt intervention when AF develops to improve patient outcomes., (© 2022 Marshfield Clinic Health System.)

Background: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown., Methods: This was a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and impairment on 1 or more GA domains (ClinicalTrials.gov Identifier NCT02107443; principal investigator Supriya G. Mohile). Practice sites were randomized to either the GA-intervention or usual care. Frailty was assessed with a deficit accumulation index (range, 0-1), and patients were stratified as robust (0 to <0.2), prefrail (0.2 to <0.35), or frail (≥0.35). The clinic visit after the GA-intervention was audio-recorded, transcribed, and coded to evaluate the number and quality of conversations about aging-related concerns. Linear mixed models examined differences in the number and quality of conversations within and between arms. All P values were 2-sided., Results: Patients (n = 541) were classified as robust (27%), prefrail (42%), or frail (31%). In the usual care arm, frail patients (vs robust ones) engaged in more aging-related conversations (adjusted mean difference, 1.73; 95% confidence interval [CI], 0.59-2.87), conversations of higher quality (difference, 1.12; 95% CI, 0.24-2.0), and more discussions about evidence-based recommendations (difference, 0.71; 95% CI, 0.04-1.38; all P values ≤ .01). Similarly, in the GA intervention arm, frail patients (vs robust ones) engaged in more aging-related conversations (difference, 2.49; 95% CI, 1.51-3.47), conversations of higher quality (difference, 1.31; 95% CI, 0.56-2.06), and more discussions about evidence-based recommendations (difference, 0.87; 95% CI, 0.32-1.42; all P values ≤ .01). Furthermore, the GA-intervention significantly improved the number and quality of conversations in all patients: robust, prefrail, and frail (all P values ≤ .01)., Conclusions: Patients with higher degrees of frailty and those exposed to the GA-intervention had more and higher quality conversations about aging-related concerns with oncologists., Lay Summary: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. This study conducted a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and 1 or more GA domain impairments. Patients were stratified as robust, prefrail, or frail. The number and quality of conversations about aging-related concerns that occurred during the clinic visit after the GA-intervention were determined. Patients with higher degrees of frailty and those in the GA intervention arm had more and higher quality conversations about aging-related concerns with oncologists., (© 2021 American Cancer Society.)

Purpose: Because of the global COVID-19 pandemic, health care organizations introduced guidelines for modifications to health and cancer medical care delivery to mitigate transmission and ensure quality health outcomes. To examine the extent and impact of these modifications on oncology service disruptions in Nigeria, we surveyed oncology patients across selected public and private cancer treatment centers., Materials and Methods: Participating in the study were 15 tertiary cancer treatment centers across 12 Nigerian states. We recruited adult patients with cancer (18+ years) on active treatment to complete a self-administered survey on cancer care during COVID-19. We conducted descriptive and multivariate data analysis using Stata 16.1., Results: Respondents were (n = 1,072), female (65.7%), ages 18-49 years (50.3%), and married (80.7%). The top two cancers were breast and prostate. Overall, 17.3% of respondents reported disruptions to cancer care, and more than half (51.0%) reported difficulties accessing care. Changes in chemotherapy regimens or route of administration were reported in 8.4% of respondents. Odds for any disruption were highest for older patients, western states, patients with prostate cancer, and patients with two or more flu symptoms. Odds for radiotherapy cancellation were highest for older patients, those with prostate cancer, and those with medium service perception., Conclusion: This study investigated COVID-19-influenced cancer treatment disruptions in Nigeria. Patients with cancer experienced significant disruptions to cancer care. Vulnerable patients are most likely to be negatively affected. Policies and strategies aimed at minimizing service disruptions while maintaining cancer patients' safety should be a priority for all health care institutions in the COVID-19 era., Competing Interests: Emmanuella NwachukwuHonoraria: Sanofi, PfizerConsulting or Advisory Role: Sanofi, RocheTravel, Accommodations, Expenses: ESMO Adedayo A. OnitiloConsulting or Advisory Role: Kite, a Gilead Company, Envision CommunicationsSpeakers' Bureau: GlaxoSmithKline, Puma Biotechnology, Kite/Gilead, AbbVieNo other potential conflicts of interest were reported.

Aims: Disagreement about the appropriate criteria for the diagnosis of gestational diabetes mellitus (GDM) persists. This study examines an alternative approach which combines information from all time-points on the glucose tolerance test (GTT) into a single index and expands the GDM spectrum into four categories using data from three geographically and ethnically distinct populations., Methods: A retrospective observational study design was used. Data from Wisconsin, USA (723 women) was used in derivation of the criterion and data from Doha, Qatar (1284 women) and Cape Town, South Africa (220 women) for confirmation. Pregnant women without pre-existing diabetes with a GTT done between 23 and 30 weeks gestation were included. A novel index was derived from the GTT termed the weighted average glucose (wAG). This was categorized into four pre-defined groups (henceforth National Priorities Research Program (NPRP) criterion); i) normal gestational glycemia (NGG), ii) impaired gestational glycemia (IGG), iii) GDM and iv) high risk GDM (hGDM)., Results: In the Doha cohort, compared to the NGG group, the odds of large for gestational age babies increased 1.33 fold (P = 0.432), 2.86 fold (P < 0.001) and 3.35 fold (P < 0.001) in the IGG, GDM and hGDM groups respectively. The odds of pregnancy induced hypertension increased 2.10 fold (P = 0.024) in GDM & hGDM groups compared to the IGG and NGG groups. In the Cape Town cohort, a third of women in the GDM group and two-thirds in the hGDM group progressed to T2DM at 5 years., Conclusions: The NPRP categorization identifies four distinct risk clusters of glycemia in pregnancy which may aid better decision making in routine management, avoid potential over-diagnosis of women at lower risk of complications and assist with diabetes prevention in women at high-risk after an index pregnancy with GDM., (Copyright © 2021. Published by Elsevier Ltd.)

Background: The purpose of this study was to evaluate whether a prior diagnosis of malignancy affected the assessment of parathyroid hormone (PTH) in hypercalcemic patients and whether the rate of this assessment changed over time., Methods: A retrospective cohort study was designed that included adult patients with hypercalcemia with and without a history of malignancy between January 1, 2000 and December 31, 2019 in the Marshfield Clinic Health System (MCHS). The overall and annual rates of PTH assessment in each group was determined. In patients with a PTH assessment, duration of time and number of elevated serum calcium levels between the first documentation of hypercalcemia and the assessment of PTH were recorded, as was the degree of hypercalcemia., Results: Approximately a quarter (23%) of the patients in each group had a PTH assessment. The rate of PTH assessment initially increased over time but later declined significantly. Although a more severe degree of hypercalcemia predicted a greater probability of PTH assessment, the rate of assessment declined with all degrees of hypercalcemia in the last 5 years. While most patients who had a PTH assessed did so within a few months of the first documentation of hypercalcemia, less than half (40%) had a delay of more than 2 years before a PTH level was drawn., Conclusion: This lack of appropriate and timely assessment may have significant health consequences in both groups of patients. Better education of providers about the appropriate and timely assessment of PTH in the evaluation of hypercalcemia is urgently needed., Competing Interests: Declaration Of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Context: Hypercalcemia of malignancy (HCM) has not been studied in a fashion to determine all possible mechanisms of hypercalcemia in any given patient., Objective: The 2 objectives were to assess the completeness of evaluation and to determine the distribution of etiologies of HCM in a contemporary cohort of patients., Methods: A retrospective analysis was performed of patients with cancer who developed hypercalcemia over 20 years at a single health system. Laboratory data were electronically captured from medical records to identify cases of parathyroid hormone (PTH)-independent hypercalcemia. The records were then manually reviewed to confirm the diagnosis of HCM, document the extent of evaluation, and determine underlying etiology(ies) of HCM in each patient., Results: The initial data set included 167 551 adult patients with malignancy, of which 11 589 developed hypercalcemia. Of these, only a quarter (25.4%) had assessment of PTH with a third of the latter (30.9%) indicating PTH-independent hypercalcemia. Of those with PTH-independent hypercalcemia, a third (31.6%) had assessment of PTH-related peptide (PTHrP) and/or 1,25-dihydroxy (1,25-OH) vitamin D and constituted the 153 cases of HCM examined in this study. Eighty-three of these patients had an incomplete evaluation of their HCM. The distribution of etiologies of HCM was therefore determined from the remaining 70 patients who had assessment of all 3 possible etiologies (PTHrP, 1,25-OH vitamin D, and skeletal imaging) and was as follows: PTHrP, 27%; osteolytic metastases, 50%; and 1,25-OH vitamin D, 39%, with combinations of etiologies being common (approximately 20%)., Conclusion: HCM is incompletely evaluated in many patients. The distribution of etiologies of HCM in this report differs significantly from the previous literature, warranting further study to determine whether its causes have indeed changed over time., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: Endocrine therapy resistance in advanced breast cancer remains a significant clinical problem that may be overcome with the use of histone deacetylase inhibitors such as entinostat. The ENCORE301 phase II study reported improvement in progression-free survival (PFS) and overall survival (OS) with the addition of entinostat to the steroidal aromatase inhibitor (AI) exemestane in advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer., Patients and Methods: E2112 is a multicenter, randomized, double-blind, placebo-controlled phase III study that enrolled men or women with advanced HR-positive, HER2-negative breast cancer whose disease progressed after nonsteroidal AI. Participants were randomly assigned to exemestane 25 mg by mouth once daily and entinostat (EE) or placebo (EP) 5 mg by mouth once weekly. Primary end points were PFS by central review and OS. Secondary end points included safety, objective response rate, and lysine acetylation change in peripheral blood mononuclear cells between baseline and cycle 1 day 15., Results: Six hundred eight patients were randomly assigned during March 2014-October 2018. Median age was 63 years (range 29-91), 60% had visceral disease, and 84% had progressed after nonsteroidal AI in metastatic setting. Previous treatments included chemotherapy (60%), fulvestrant (30%), and cyclin-dependent kinase inhibitor (35%). Most common grade 3 and 4 adverse events in the EE arm included neutropenia (20%), hypophosphatemia (14%), anemia (8%), leukopenia (6%), fatigue (4%), diarrhea (4%), and thrombocytopenia (3%). Median PFS was 3.3 months (EE) versus 3.1 months (EP; hazard ratio = 0.87; 95% CI, 0.67 to 1.13; P = .30). Median OS was 23.4 months (EE) versus 21.7 months (EP; hazard ratio = 0.99; 95% CI, 0.82 to 1.21; P = .94). Objective response rate was 5.8% (EE) and 5.6% (EP). Pharmacodynamic analysis confirmed target inhibition in entinostat-treated patients., Conclusion: The combination of exemestane and entinostat did not improve survival in AI-resistant advanced HR-positive, HER2-negative breast cancer., Competing Interests: Roisin M. ConnollyOther Relationship: Pfizer Kathy D. MillerConsulting or Advisory Role: Merck, Genentech/Roche, Athenex, AstraZeneca, Bristol Myers Squibb/CelgeneResearch Funding: Taiho Pharmaceutical, Novartis, Seattle Genetics, Pfizer, Astex Pharmaceuticals, British Biotech, CytomX Therapeutics, Alphamab Karen L. SmithStock and Other Ownership Interests: AbbVie, Abbott LaboratoriesHonoraria: ASiM CMEResearch Funding: Pfizer Ursa A. Brown-GlabermanConsulting or Advisory Role: Novartis, Biotheranostics, Eisai, Seattle Genetics, Taiho OncologyResearch Funding: Seattle Genetics Bryan A. FallerConsulting or Advisory Role: L.E.K. ConsultingTravel, Accommodations, Expenses: Genentech, Novartis, EB SQUIBB, Celgene, Boehringer Ingelheim, Eisai, AstraZeneca, Lilly, Amgen, Merck, TakedaOpen Payments Link: https://openpaymentsdata.cms.gov/physician/127090 Adedayo A. OnitiloConsulting or Advisory Role: Kite, a Gilead Company, Envision CommunicationsSpeakers' Bureau: GlaxoSmithKline, Puma Biotechnology, Kite/Gilead, AbbVie Mark E. BurkardConsulting or Advisory Role: Pointcare Genomics, Strata Oncology, NovartisResearch Funding: AbbVie, Strata Oncology, Puma Biotechnology, Loxo, Merck, Arcus, Apollomics, Elevation Oncology, GenentechPatents, Royalties, Other Intellectual Property: I have a patent for implantable or localized drug delivery device that can sample the tumor microenvironment and deliver drug. I have a patent for a method to detect recombination events with CRISPR-mediated editing. I have a patent for conducting expansion microscopy without specialized equipment George T. BuddHonoraria: DecipheraConsulting or Advisory Role: Deciphera, Epic SciencesSpeakers' Bureau: DecipheraResearch Funding: Genentech/Roche, TRACON Pharma, Daiichi Sankyo/Lilly, AmbrxOpen Payments Link: https://openpaymentsdata.cms.gov/physician/774695/summary Ellis G. LevineResearch Funding: Oncolytic BiotechPatents, Royalties, Other Intellectual Property: UpToDate Peter A. KaufmanStock and Other Ownership Interests: AmgenHonoraria: LillyConsulting or Advisory Role: Polyphor, Roche/Genentech, Lilly, Eisai, Macrogenics, Pfizer, Merck, AstraZenecaSpeakers' Bureau: LillyResearch Funding: Eisai, Polyphor, Roche/Genentech, Lilly, Novartis, Macrogenics, Pfizer, SanofiTravel, Accommodations, Expenses: Lilly, Polyphor, Macrogenics Alexandra ThomasStock and Other Ownership Interests: Johnson & Johnson, Gilead Sciences, Bristol Myers Squibb, PfizerConsulting or Advisory Role: BeyondSpring Pharmaceuticals, LillyResearch Funding: SanofiPatents, Royalties, Other Intellectual Property: UpToDate RoyaltiesTravel, Accommodations, Expenses: Genentech Jane B. TrepelResearch Funding: Syndax, EpicentRX, AstraZeneca Antonio C. WolffConsulting or Advisory Role: Ionis PharmaceuticalsPatents, Royalties, Other Intellectual Property: Antonio Wolff has been named as inventor on one or more issued patents or pending patent applications relating to methylation in breast cancer and has assigned his rights to JHU and participates in a royalty-sharing agreement with JHUOpen Payments Link: https://openpaymentsdata.cms.gov/physician/357301/summary Joseph A. SparanoStock and Other Ownership Interests: MetastatConsulting or Advisory Role: Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, Merrimack, Adgero Biopharmaceuticals, Cardinal Health, GlaxoSmithKline, CStone Pharmaceuticals, Epic Sciences, Daiichi Sankyo, BMSiSpeakers' Bureau: Eisai, CertaraResearch Funding: Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, Merrimack, Radius Health, Olema PharmaceuticalsTravel, Accommodations, Expenses: Menarini Silicon Biosystems, Roche/Genentech, Adgero Biopharmaceuticals, Myriad Genetics, Pfizer, AstraZeneca, Rhenium MedicalNo other potential conflicts of interest were reported.

Background: The existence of oestrogen receptor-negative (ER-)/progesterone receptor-positive (PR+) breast cancer continues to be an area of controversy amongst oncologists and pathologists., Methods: To re-evaluate breast cancers originally classified as ER-/PR+ via Oncotype DX® assay and compare molecular phenotype with Recurrence Score® (RS) result, clinicopathologic features and clinical outcomes were retrospectively obtained from electronic health records between January 1998 and June 2005. Archived formalin-fixed, paraffin-embedded (FFPE) tumour specimens were tested for the expression of ER, PR and human-epidermal-growth-factor-2. The number of positive ER-/PR+ samples confirmed by transcriptional analysis was the primary outcome of interest with event-free and overall survival as secondary outcomes. Biopsies from 26 patients underwent Oncotype DX testing and analysis., Results: Approximately 60% were middle-aged (40-50 years old) women, and 84.6% had invasive ductal carcinoma. Based on the Oncotype DX assay, approximately 65% ( N = 17) had ER+/PR+ status; 23% (N = 6) had ER-/PR- status; and 12% had a single hormone positive receptor (1 ER-/PR+, 2 ER+/PR-) status. Almost one-quarter of patients were stratified into the low-RS (<18) or intermediate-RS (18-30) results, and half of the patients had a high-RS (>30) result., Conclusion: Our findings suggest the ER-/PR+ subtype is not a reproducible entity and emphasises the value of retesting this subtype via molecular methods for appropriate treatment selection and patient outcomes. Multigene assay analysis may serve as a second-line or confirming tool for clinical determination of ER/PR phenotype in breast cancer patients for targeted therapies., Competing Interests: The authors have no personal or financial conflicts of interest to disclose., (© the authors; licensee ecancermedicalscience.)

Objective: Perioperative chemotherapy can potentially downstage esophageal cancer, reducing the risk of early systemic dissemination. One recommended neoadjuvant regimen for managing gastroesophageal junction and esophageal cancer is docetaxel, cisplatin, and 5-fluorouracil (DCF). To address the high toxicity profile of DCF, modifications in dosages and treatment intervals have been studied. We integrated a modified DCF regimen (mDCF) into a multimodal treatment approach for non-metastatic esophageal cancer (nMEC). Retrospectively, we sought to describe our community experience of administrating neoadjuvant mDCF to patients with nMEC. Design: Patients diagnosed with nMEC between August 2008 and November 2017 and prescribed mDCF were identified for retrospective review. Outcomes of interest included disease-free survival (DFS), overall survival (OS), and hematologic toxicities. Analyses were performed using SAS 9.4. Results: Thirty patients met inclusion criteria with a median age of 64.9 years; 90% were male. The 2-year and 5-year DFS was 60.8% and 41.7%, respectively, for adenocarcinoma and 71.4% and 71.4% for squamous cell carcinoma (SCC). The 2-year and 5-year OS was 64.9% and 44.5%, respectively, for adenocarcinoma and 71.4% and 71.4% for SCC. Both DFS and OS decreased with increasing disease stage, histology (adenocarcinoma versus squamous), esophageal compared to esophagogastric-junction involvement, and without surgical intervention. Frequent toxicity grades for leukopenia and thrombocytopenia were Grades I and II. Conclusion: Using an mDCF regimen in combination with chemoradiation +/- surgical resection in a community setting appears to have an acceptable toxicity profile as well as DFS and OS outcomes compared to chemotherapeutic regimens reported in other similar studies., (© 2021 Marshfield Clinic Health System.)

Background: Postcancer work limitations may affect a substantial proportion of patients and contribute to the "financial toxicity" of cancer treatment. The degree and nature of work limitations and employment outcomes are poorly understood for cancer patients, particularly in the immediate period of transition after active treatment. We prospectively examined employment, work ability, and work limitations during and after treatment., Methods: A total of 120 patients receiving curative therapy who were employed prior to their cancer diagnosis and who intended to work during or after end of treatment (EOT) completed surveys at baseline (pretreatment), EOT, and 3, 6, and 12 months after EOT. Surveys included measures of employment, work ability, and work limitations. Descriptive statistics (frequencies, percentages, means with standard deviations) were calculated., Results: A total of 111 participants completed the baseline survey. On average, participants were 48 years of age and were mostly white (95%) and female (82%) with a diagnosis of breast cancer (69%). Full-time employment decreased during therapy (from 88% to 50%) and returned to near prediagnosis levels by 12-month follow-up (78%). Work-related productivity loss due to health was high during treatment., Conclusions: This study is the first to report the effects of curative intent cancer therapy on employment, work ability, and work limitations both during and after treatment. Perceived work ability was generally high overall 12 months after EOT, although a minority reported persistent difficulty. A prospective analysis of factors (eg, job type, education, symptoms) most associated with work limitations is underway to assist in identifying at-risk patients., (© 2020 American Cancer Society.)

Background: Diagnosis and treatment of cancer rely heavily on imaging, histopathology and molecular information. Incomplete or missing tumour information can hinder the delivery of high-quality care in oncology practice, especially in resource-limited countries. To evaluate the completeness of histopathology reporting in a real-world setting and identify areas for future cancer care delivery research efforts, we retrospectively analysed reports from patients diagnosed with breast cancer who received care at a high-volume oncology department at a hospital in Lagos, Nigeria., Methods: Demographic, institutional and histopathology characteristics were retrospectively obtained from 1,001 patient records from 2007 to 2016. Completeness was defined as reporting five tumour features (tumour histology, tumour grade, laterality, oestrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)) for biopsy specimens and seven tumour features (tumour size, tumour histology, tumour grade, laterality, ER/PR, HER2 and lymph node involvement) for surgical specimens., Results: The mean age of patients was 48.6 ± 11.7 years with a predominantly female population (99.3%). A majority of pathologic reports were produced after 2011, and two-thirds of the reports originated from centres or labs within Lagos, Nigeria (67.7%). Most reports documented primary site (98.0%) and specimen type (85.0%) while other characteristics were less often recorded. This led to substantial variation in reporting between biopsy (13.4%) and surgical (6.1%) specimens for an overall low pathology report completeness <10%., Conclusion: The majority of patient records analysed lacked complete documentation of breast cancer histopathological characteristics commonly used in oncology practice. Our study highlights a need to identify and address the contributing factors for incomplete histopathological reporting in Nigeria and will guide future clinical programmatic developments., Competing Interests: There are no conflicts of interest to report on the part of any of the authors., (© the authors; licensee ecancermedicalscience.)

Hypercalcemia of malignancy develops in approximately 20-30% of patients with advanced cancer and is an ominous sign. This condition is subdivided into three categories: i) humoral hypercalcemia of malignancy (80% of cases), mediated by systemic parathyroid hormone-related protein; ii) osteolytic metastases (20% of cases), mediated by inflammatory cytokines locally released by tumor cells and/or peri-tumor macrophages; and iii) ectopic production of 1,25-dihydroxyvitamin D (<1% of cases), leading to intestinal hyperabsorption of calcium and increased osteoclastic bone resorption. Humoral hypercalcemia of malignancy is seen in a variety of solid tumors, while osteolytic metastases are most common in breast cancer and multiple myeloma. Hypercalcemia of malignancy mediated by 1,25-dihydroxyvitamin D is primarily seen in lymphomas, having only rarely been reported in solid tumors. Pharmacologic management of humoral hypercalcemia of malignancy and osteolytic metastases mainly involves inhibition of bone resorption with intravenous bisphosphonates, subcutaneous denosumab, and subcutaneous calcitonin. Glucocorticoid therapy is the mainstay for management of increased 1,25-dihydroxyvitamin D. Unfortunately, management of hypercalcemia of malignancy often requires inpatient admission in the acute setting, and loss of effectiveness of antiresorptive therapy is common. We propose oral cinacalcet may be an efficacious therapy for hypercalcemia of malignancy related to elevated 1,25-dihydroxyvitamin D, and we present supporting data from two cases involving solid tumors. Furthermore, we hypothesize that this effect is primarily mediated by cinacalcet's interaction with the calcium-sensing receptor in the intestine with lesser effects at bone and kidney. Lastly, the role of 1,25-dihydroxyvitamin D in hypercalcemia malignancy may be underappreciated in solid tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

To examine whether (a) non-minority participants differed from racial minority participants in the understanding of biospecimens collected for research purposes, (b) patients differed from comparison group in their understanding of the ways their biospecimens could be used by researchers, and (c) participants received adequate information before consenting to donate blood for research studies. We analyzed cross-sectional data from female breast cancer patients scheduled to receive chemotherapy at the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) clinical sites and a healthy comparison group. After reading a consent form related to biospecimens and consenting to participate in a clinical trial, participants' understanding of biospecimen collection was evaluated. Linear models were used to compare scores between non-minority and racial minority participants as well as cancer and non-cancer comparisons adjusting for possible confounding factors. A total of 650 participants provided evaluable data; 592 were non-minority (Caucasian) and 58 participants were a racial minority (71% Black and 29% other). There were 427 cancer patients and 223 comparisons. Non-minority participants scored higher than racial minorities on relevance-to-care items (diff. = 0.48, CI 0.13-0.80, p = 0.001). Comparison group scored higher than cancer patients on relevance-to-care items (diff. = 0.58, CI 0.37-0.78). A moderate number of the participants exhibited a poor understanding of biospecimen collection across all racial/ethnic backgrounds, but racial minority participants' scores remained lower in the relevance-to-care subscale even after adjusting for education and reading level. Differences were also noted among the patients and comparison group. Researchers should facilitate comprehension of biospecimen collection for all study participants, especially racial minority participants.

Advanced/metastatic melanoma is an aggressive cancer with a low survival rate. Traditional cytotoxic chemotherapies do not appreciably extend life and systemic cytokine/chemokine administration produces toxic side effects. By harnessing the surveillance and cytotoxic features of the immune system, immunotherapies can provide a durable response and are proved to improve disease outcomes in patients with advanced/metastatic melanoma and other cancers. Close monitoring is necessary, however, to identify and treat immune system-related adverse events before they become life-threatening. Because metastatic lesions can respond differently to immunotherapies, modified response criteria have been developed to assist physicians in tracking patient response to treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: This pilot trial aimed to assess if cooling hands and feet with crushed ice during receipt of paclitaxel helps prevent peripheral neuropathy., Methods: This prospective, randomized trial compared cryotherapy to standard care in patients initiating paclitaxel weekly x 12. For those on cryotherapy, hands and feet were cooled starting 15 min prior to and ending 15 min after each paclitaxel dose. EORTC QLQ-CIPN20 was completed at baseline, weekly x12, then monthly x6. Area under the curve (AUC) was calculated for subscale scores, adjusting for baseline, and compared between arms (Wilcoxon rank-sum test). Cross-study comparisons used data from 2 prior similarly-conducted neuropathy trials., Results: Forty-six patients were accrued. Three withdrew and one was ineligible. Of the remaining 42 (21 cryotherapy, 21 control), 39 (19 cryotherapy, 20 control) were analyzable for AUC. Cryotherapy was well tolerated, but the AUC of the CIPN20 sensory scores over 12 weeks of paclitaxel was not found to differ between the study arms (mean difference 3.45, 95% CI -3.13 to 10.02, p = 0.26). However, the control arm of the current trial experienced less neuropathy than did the placebo arms of two previous similar trials. When our cryotherapy arm was compared to the combined control arms from all three trials, the cryotherapy arm had less neuropathy (Wilcoxon Rank-Sum p = 0.01)., Conclusion: While there was no difference in CIPN20 scores identified between the 2 study arms in the current phase II trial, further investigation is needed given that the control arm experienced less neuropathy than was expected., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: A growing body of research suggests that inflammation plays a role in many chemotherapy-related toxicities such as fatigue, anxiety, and neuropathy. Regular exercise can change levels of individual cytokines (e.g., reducing IL-6, increasing IL-10); however, it is not known whether exercise during chemotherapy affects relationships between cytokines (i.e., whether cytokine concentrations change collectively vs. independently). This study assessed how 6 weeks of exercise during chemotherapy affected relationships between changes in concentrations of several cytokines., Methods: This is a secondary analysis of a randomized trial studying 6 weeks of moderate-intensity walking and resistance exercise during chemotherapy compared with chemotherapy alone. At pre- and post-intervention, patients provided blood to assess serum concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, and IFN-γ, and receptor sTNFR1. We investigated relationships between cytokines using the correlations between changes in cytokine concentrations from pre- to post-intervention., Results: We obtained complete data from 293 patients (149 randomized to exercise). Exercise strengthened the correlation between concentration changes of IL-10 and IL-6 (r = 0.44 in exercisers vs. 0.11 in controls; p = 0.001). We observed the same pattern for IL-10:IL-1β and IL-10:sTNFR1. Exercise also induced an anti-inflammatory cytokine profile, per reductions in pro-inflammatory IFN-γ (p = 0.044) and perhaps IL-1β (p = 0.099, trend-level significance)., Conclusions: Our hypothesis-generating work suggests that regular exercise during 6 weeks of chemotherapy may cause certain cytokine concentrations to change collectively (not independently). This work enhances our understanding of relationships between cytokines and complements traditional analyses of cytokines in isolation. Future work should test for replication and relationships to patient outcomes., Trial Registration: Clinical Trials.gov, # NCT00924651, http://www.clinicaltrials.gov .

Dipeptidyl peptidase 4 (DPP-4) inhibitors are increasingly used these days in management of diabetes. There has been reported in a few case reports of increasing association between DPP-4 inhibitor use and bullous pemphigoid (BP). We report a case of association between linagliptin use and BP and subsequent treatment with rituximab., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Little is known about the effects of chemotherapeutic drugs on DNA methylation status of leukocytes, which may be predictive of treatment benefits and toxicities. Based on a prospective national study, we characterize the changes in leukocyte DNA methylome from pre- to post-chemotherapy (approximately 4 months apart) in 93 patients treated for early stage breast cancer and 48 matched non-cancer controls. We further examined significant methylation changes with perceived cognitive impairment, a clinically significant problem related to cancer and chemotherapy., Results: Approximately 4.2% of the CpG sites measured using the Illumina 450K methylation array underwent significant changes after chemotherapy (p < 1e-7), in comparison to a stable DNA methylome in controls. Post-chemotherapy, the estimated relative proportions of B cells and CD4 + T cells were decreased by a median of 100% and 39%, respectively, whereas the proportion of monocytes was increased by a median of 91%. After controlling for leukocyte composition, 568 CpGs from 460 genes were still significantly altered following chemotherapy. With additional adjustment for chemotherapy regimen, cumulative infusions, growth factors, and steroids, changes in four CpGs remained significant, including cg16936953 in VMP1/MIR21, cg01252023 in CORO1B, cg11859398 in SDK1, and cg19956914 in SUMF2. The most significant CpG, cg16936953, was also associated with cognitive decline in breast cancer patients., Conclusions: Chemotherapy profoundly alters the composition and DNA methylation landscape of leukocytes in breast cancer patients. Our results shed light on the epigenetic response of circulating immune cell populations to cytotoxic chemotherapeutic drugs and provide possible epigenetic links to the degeneration of cognitive function associated with chemotherapy.

The predictive capability of combining demographic risk factors, germline genetic variants, and mammogram abnormality features for breast cancer risk prediction is poorly understood. We evaluated the predictive performance of combinations of demographic risk factors, high risk single nucleotide polymorphisms (SNPs), and mammography features for women recommended for breast biopsy in a retrospective case-control study (n = 768) with four logistic regression models. The AUC of the baseline demographic features model was 0.580. Both genetic variants and mammography abnormality features augmented the performance of the baseline model: demographics + SNP (AUC =0.668), demographics + mammography (AUC =0.702). Finally, we found that the demographics + SNP + mammography model (AUC = 0.753) had the greatest predictive power, with a significant performance improvement over the other models. The combination of demographic risk factors, genetic variants and imaging features improves breast cancer risk prediction over prior methods utilizing only a subset of these features.

A man, aged 61 years, with a history of hypogonadism and family history of cancer experienced persistent urinary difficulties with no visible prostate abnormalities. Laboratory testing and diagnostic imaging revealed a primary lesion in the prostate with lymph node involvement and multiple bone metastases. Treatment with androgen-deprivation therapy, 17,20-lyase inhibition, and bisphosphonates for 7 months was unsuccessful in preventing disease progression, but second-line chemotherapy and continued androgen-deprivation therapy improved prostate specific antigen levels. During the patient's second treatment regimen, his daughter received a diagnosis of breast cancer. The patient's daughter underwent genetic testing for oncogenic mutations, and it was discovered that she carried a mutation in RAD51C , a gene encoding a protein involved in DNA repair and genomic maintenance. Subsequent genetic testing of the patient revealed mutation in RAD51C as well. For patients with metastatic prostate cancer who are unresponsive to standard treatment and who have a positive family history of cancer, genetic testing may be warranted to develop alternative treatment regimens for the patient and guide family discussions regarding cancer risk. Targeted agents like poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors may be a consideration in prostate cancer patients with DNA repair mutations and with refractory disease., (© 2018 Marshfield Clinic.)

The incidence of differentiated thyroid cancer (DTC) has rapidly increased worldwide over the last decades. It is unknown if the increase in diagnosis has been mirrored by an increase in thyroidectomy rates with the concomitant economic impact that this would have on the health care system. DTC and thyroidectomy incidence as well as DTC-specific mortality were modeled using Poisson regression in New South Wales (NSW), Australia per year and by sex. The incidence of 2002 was the point from which the increase in rates was assessed cumulatively over the subsequent decade. The economic burden of potentially avoidable thyroidectomies due to the increase in diagnosis was estimated as the product of the additional thyroidectomy procedures during a decade attributable to rates beyond those reported for 2002 and the national average hospital cost of an uncomplicated thyroidectomy in Australia. The following results were obtained. The incidence of both DTC and thyroidectomy doubled in NSW between 2003 and 2012, while the DTC-specific mortality rate remained unchanged over the same period. Based on the 2002 incidence, the projected increase over 10 years (2003-2012) in thyroidectomy procedures was 2196. This translates to an extra cost burden of over AUD$ 18,600,000 in surgery-related health care expenditure over one decade in NSW. Our findings suggest that, if this rise is solely attributable to overdetection, then the rising expenditure serves no additional purpose. Reducing unnecessary detection and a conservative approach to managing DTC are sensible and would lead to millions of dollars in savings and reduced harms to patients., (© 2018 Society for Endocrinology.)

Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight once-weekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.

Purpose: The McGill Brisbane Symptom Score (MBSS) is a clinical score for pancreatic cancer patients upon initial presentation that takes into account four variables (weight loss, abdominal pain, jaundice, and history of smoking) to stratify them into two MBSS intensity categories. Several studies have suggested that these categories are strongly associated with eventual survival in patients with resectable (rPCa) and unresectable (uPCa) pancreatic cancer. This study aimed to validate the MBSS in a cohort of patients with pancreatic cancer from a single institution., Methods: Survival time by resection status and MBSS intensity category were analyzed among 633 patients from our institution between 2001 and 2010. Hazard ratios for death using Cox proportional hazards models, with age as the timescale, adjustment for sex and year of diagnosis, and stratified by adjuvant chemotherapy status were estimated., Results: Median survival time was the longest in patients with low-intensity MBSS and rPCa (817 days), whereas the shortest survival time was found among patients with uPCa regardless of MBSS status (144-147 days). After consideration of age and chemotherapy status, high-intensity MBSS was associated with poorer survival for both rPCa (HR 1.64; 95 % CI 1.07-2.52) and uPCa (HR 1.35; 95 % CI 1.06-1.72)., Conclusions: Preoperative MBSS intensity is a useful prognostic indicator of survival in resectable as well as unresectable pancreatic cancer.

Neurological complications related to multiple myeloma (MM) are not uncommon; however, direct involvement of the central nervous system (CNS) is extremely rare and represents a diagnostic and therapeutic challenge. Significant survival difference has been noted with the introduction of novel therapy in patients with MM, but their effect on the incidence and their use for management of leptomeningeal myeloma (LMM) is uncertain. Analysis of published data demonstrates its recent increased incidence, median time to CNS presentation, and slight improvement in median survival after diagnosis of LMM. Less common MM isotypes have been overrepresented in LMM. CNS relapse occurred mostly in patients with Durie-Salmon stage III MM. Despite treatments, standard or experimental, the survival rates of LMM remain dismal. Monitoring high risk patients closely, even after achieving complete remission, may be useful in early detection of LMM. As we gain better understanding of LMM, we recommend that future research and clinical care focus on earlier diagnosis and development of more efficient CNS-directed therapy to improve survival in this patient population., (Copyright © 2014 John Wiley & Sons, Ltd.)

Technology advances in genome-wide association studies (GWAS) has engendered optimism that we have entered a new age of precision medicine, in which the risk of breast cancer can be predicted on the basis of a person's genetic variants. The goal of this study is to evaluate the discriminatory power of common genetic variants in breast cancer risk estimation. We conducted a retrospective case-control study drawing from an existing personalized medicine data repository. We collected variables that predict breast cancer risk: 153 high-frequency/low-penetrance genetic variants, reflecting the state-of-the-art GWAS on breast cancer, mammography descriptors and BI-RADS assessment categories in the Breast Imaging Reporting and Data System (BI-RADS) lexicon. We trained and tested naïve Bayes models by using these predictive variables. We generated ROC curves and used the area under the ROC curve (AUC) to quantify predictive performance. We found that genetic variants achieved comparable predictive performance to BI-RADS assessment categories in terms of AUC (0.650 vs. 0.659, p-value = 0.742), but significantly lower predictive performance than the combination of BI-RADS assessment categories and mammography descriptors (0.650 vs. 0.751, p-value < 0.001). A better understanding of relative predictive capability of genetic variants and mammography data may benefit clinicians and patients to make appropriate decisions about breast cancer screening, prevention, and treatment in the era of precision medicine.

Rationale and Objectives: The discovery of germline genetic variants associated with breast cancer has engendered interest in risk stratification for improved, targeted detection and diagnosis. However, there has yet to be a comparison of the predictive ability of these genetic variants with mammography abnormality descriptors., Materials and Methods: Our institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study utilized a personalized medicine registry in which participants consented to provide a DNA sample and to participate in longitudinal follow-up. In our retrospective, age-matched, case-controlled study of 373 cases and 395 controls who underwent breast biopsy, we collected risk factors selected a priori based on the literature, including demographic variables based on the Gail model, common germline genetic variants, and diagnostic mammography findings according to Breast Imaging Reporting and Data System (BI-RADS). We developed predictive models using logistic regression to determine the predictive ability of (1) demographic variables, (2) 10 selected genetic variants, or (3) mammography BI-RADS features. We evaluated each model in turn by calculating a risk score for each patient using 10-fold cross-validation, used this risk estimate to construct Receiver Operator Characteristic Curve (ROC) curves, and compared the area under the ROC curve (AUC) of each using the DeLong method., Results: The performance of the regression model using demographic risk factors was not statistically different from the model using genetic variants (P = 0.9). The model using mammography features (AUC = 0.689) was superior to both the demographic model (AUC = .598; P < 0.001) and the genetic model (AUC = .601; P < 0.001)., Conclusions: BI-RADS features exceeded the ability of demographic and 10 selected germline genetic variants to predict breast cancer in women recommended for biopsy., (Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)