A qualitative approach to understanding the drivers of unequal receipt of definitive therapy for Black men with prostate cancer in Massachusetts.

BACKGROUND: Despite mandated insurance coverage since 2006 and robust health infrastructure in urban settings with high concentrations of minority patients, race-based disparities in prostate cancer (PCa) treatment persist in Massachusetts. In this qualitative study, the authors sought to identify factors driving inequities in PCa treatment in Massachusetts. METHODS: Four hospitals offering PCa treatment in Massachusetts were selected using a case-mix approach. Purposive sampling was used to conduct semistructured interviews with hospital stakeholders. Additional interviews were conducted with representatives from grassroots organizations providing PCa education. Two study staff coded the interviews to identify major themes and recurrent patterns. RESULTS: Of the 35 informants invited, 25 participated in the study. Although national disparities in PCa outcomes were readily discussed, one half of the informants were unaware that PCa disparities existed in Massachusetts. Informants and grassroots organization representatives acknowledged that patients with PCa are willing to face transportation barriers to receive treatment from trusted and accommodating institutions. Except for chief equity officers, most health care providers lacked knowledge on accessing or using metrics regarding racial disparities in cancer outcomes. Although community outreach was recognized as a potential strategy to reduce treatment disparities and engender trust, informants were often unable to provide a clear implementation plan. CONCLUSIONS: This statewide qualitative study builds on existing quantitative data on the nature and extent of disparities. It highlights knowledge gaps in recognizing and addressing racial disparities in PCa treatment in Massachusetts. Improved provider awareness, the use of disparity metrics, and strategic community engagement may ensure equitable access to PCa treatment. PLAIN LANGUAGE SUMMARY: Despite mandated insurance and urban health care access, racial disparities in prostate cancer treatment persist in Massachusetts. This qualitative study revealed that, although national disparities were acknowledged, awareness about local disparities are lacking. Stakeholders highlighted the importance of ancillary services, including translators, rideshares, and navigators, in the delivery of care. In addition, whereas hospital stakeholders were aware of collected equity outcomes, they were unsure whether and who is monitoring equity metrics. Furthermore, stakeholders agreed that community outreach showed promise in ensuring equitable access to prostate cancer treatment. Nevertheless, most interviewed stakeholders lacked clear implementation plans.

A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO.

INTRODUCTION: Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO) and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility. METHODS: We expanded the existing framework for PANCPRO and BRCAPRO to jointly model risk of pancreatic, breast, and ovarian cancer and validated this new model, BRCAPANCPRO on three data sets each reflecting the common target populations. RESULTS: BRCAPANCPRO outperformed the prior BRCAPRO and PANCPRO models and yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUCs 0.79, 95% CI: 0.73-0.84 and 0.70, 95% CI: 0.60-0.80) in families seen in high-risk clinics and pancreatic cancer family registries, respectively. In addition, BRCAPANCPRO was reasonably well calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.81 [0.69, 0.94]). DISCUSSION: The BRCAPANCPRO model provides improved risk assessment over our previous risk models, particularly for pedigrees with a co-occurrence of pancreatic cancer and breast and/or ovarian cancer.

Examination of ATM, BRCA1, and BRCA2 promoter methylation in patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer is a lethal disease with a poor 5-year survival rate. Pathogenic germline variants in the coding regions of ATM, BRCA1, and BRCA2 are found in up to 4.8% of pancreatic cancer patients. Germline promoter methylation and gene silencing arising from a germline variant or through other mechanisms have been described as a cause of tumor suppressor gene inactivation. METHODS: We measured the level of promoter methylation of the ATM, BRCA1, and BRCA2 genes in peripheral blood lymphocytes from 655 patients with pancreatic cancer using real-time PCR. RESULTS: No evidence of germline promoter methylation of any of these genes was found. Promoter methylation levels were minimal with no patient having promoter methylation greater than 3.4%, 3.3%, and 7.6% for ATM, BRCA1 and BRCA2, respectively, well below levels found in patients who have inherited promoter methylation (∼50%). CONCLUSIONS: We found no evidence of germline promoter methylation for the pancreatic susceptibility genes ATM, BRCA1 and BRCA2 in patients with pancreatic cancer. This study reveals that constitutive germline methylation of promoter CpG islands is rare in pancreatic cancer.

Progestin and breast cancer risk: a systematic review.

This systematic review summarizes research on the use of progestin and breast cancer risk. Although mainly used for contraception, progestin can help treat menstrual disorders, and benign breast, uterine, and ovarian diseases. Breast cancer is the leading site of new, non-skin, cancers in females in the United States, and possible factors that may modulate breast cancer risk need to be identified. ProQuest (Ann Arbor, MI) and PubMed-Medline (US National Library of Medicine, Bethesda MD, USA) databases were used to search for epidemiologic studies from 2000 to 2015 that examined the association between progestin and breast cancer. Search terms included epidemiologic studies + progesterone or progestin or progestogen or contraceptive or contraceptive agents + breast cancer or breast neoplasms. A total of six studies were included in the review. Five of the six studies reported no association between progestin-only formulations (including norethindrone oral contraceptives, depot medroxyprogesterone acetate, injectable, levonorgestrel system users, implantable and intrauterine devices) and breast cancer risk. Duration of use was examined in a few studies with heterogeneous results. Unlike studies of other oral contraceptives, studies indicate that progestin-only formulations do not increase the risk of breast cancer, although the literature is hampered by small sample sizes. Future research is needed to corroborate these findings, as further understanding of synthetic progesterone may initiate new prescription practices or guidelines for women's health.

Diabetes Status and Being Up-to-Date on Colorectal Cancer Screening, 2012 Behavioral Risk Factor Surveillance System.

INTRODUCTION: Although screening rates for colorectal cancer are increasing, 22 million Americans are not up-to-date with recommendations. People with diabetes are an important and rapidly growing group at increased risk for colorectal cancer. Screening status and predictors of being up-to-date on screening are largely unknown in this population. METHODS: This study used logistic regression modeling and data from the 2012 Behavioral Risk Factor Surveillance System to examine the association between diabetes and colorectal cancer screening predictors with being up-to-date on colorectal cancer screening according to criteria of the US Preventive Services Task Force for adults aged 50 or older. State prevalence rates of up-to-date colorectal cancer screening were also calculated and mapped. RESULTS: The prevalence of being up-to-date with colorectal cancer screening for all respondents aged 50 or older was 65.6%; for respondents with diabetes, the rate was 69.2%. Respondents with diabetes were 22% more likely to be up-to-date on colorectal cancer screening than those without diabetes. Among those with diabetes, having a routine checkup within the previous year significantly increased the odds of being up-to-date on colorectal cancer screening (odds ratio, 1.90). Other factors such as age, income, education, race/ethnicity, insurance status, and history of cancer were also associated with up-to-date status. CONCLUSION: Regardless of diabetes status, people who had a routine checkup within the past year were more likely to be up-to-date than people who had not. Among people with diabetes, the duration between routine checkups may be of greater importance than the frequency of diabetes-related doctor visits. Continued efforts should be made to ensure that routine care visits occur regularly to address the preventive health needs of patients with and patients without diabetes.

Disparities in Breast Cancer Incidence, Mortality, and Quality of Care among African American and European American Women in South Carolina.

OBJECTIVES: Breast cancer is the most frequently diagnosed cancer among women and the second-leading cause of female cancer deaths in the United States. African Americans and other minorities in the United States experience lower survival rates and have a worse prognosis than European Americans despite European Americans having a much higher incidence of the disease. Adherence to breast cancer treatment-quality measures is limited, particularly when the data are stratified by race/ethnicity. METHODS: We aimed to examine breast cancer incidence and mortality trends in South Carolina by race and explore possible racial disparities in the quality of breast cancer treatment received in South Carolina. RESULTS: African Americans have high rates of mammography and clinical breast examination screenings yet suffer lower survival compared with European Americans. For most treatment-quality metrics, South Carolina fairs well in comparison to the United States as a whole; however, South Carolina hospitals overall lag behind South Carolina Commission on Cancer-accredited hospitals for all measured quality indicators, including needle biopsy utilization, breast-conserving surgeries, and timely use of radiation therapy. Accreditation may a play a major role in increasing the standard of care related to breast cancer diagnosis and treatment. CONCLUSIONS: These descriptive findings may provide significant insight for future interventions and policies aimed at eliminating racial/ethnic disparities in health outcomes. Further risk-reduction approaches are necessary to reduce minority group mortality rates, especially among African American women.

Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens.

Uncontrolled delayed nausea and vomiting remains a problem after high-dose preparative regimens used for autologous and allogeneic hematopoietic stem cell transplants. Recently, aprepitant was approved for highly and moderately emetogenic chemotherapy, and, in particular, is effective for decreasing delayed emesis. To evaluate its safety and efficacy in the transplantation setting, we performed a randomized, placebo-controlled, phase 3 trial of aprepitant in combination with ondansetron and dexamethasone in patients treated with ablative preparative regimens. Patients were randomized to receive oral aprepitant or placebo daily with oral ondansetron and dexamethasone during and for 3 days after the completion of the preparative regimen in this prospective randomized, double-blind study. The primary objective was complete response (CR) rate, defined as no emesis with no or mild nausea. Other endpoints included number of emetic episodes, nausea severity assessed using a 100-mm visual analog scale (VAS), the need for rescue antiemetics, and transplantation outcome, including regimen-related toxicity. One hundred eighty-one patients were randomized and 179 patients were eligible for analysis. Overall, CR rates were 81.9% for the aprepitant and 65.8% for the placebo arms (P < .001). Percentages of patients with no emesis all days were 73.3% for aprepitant and 22.5% placebo (P < .001). Mean VAS scores were 16.6 mm aprepitant and 16.9 mm placebo (NS), and there were no differences in the amount of rescue antiemetics used, regimen related toxicity, engraftment, or transplantation outcome. Aprepitant in combination with dexamethasone and ondansetron significantly decreased emesis and significant nausea, whereas not increasing RRT or affecting short-term survival but had no significant impact on the use of PRN antiemetics, or overall VAS nausea scores.

Risk of Pancreatic Cancer in the Long-Term Prospective Follow-Up of Familial Pancreatic Cancer Kindreds.

BACKGROUND: A family history of pancreatic cancer is associated with increased pancreatic cancer risk. However, risk estimates for individuals in kindreds with an aggregation of pancreatic cancer (>1 relative) are imprecise because of small samples sizes or potentially impacted by biases inherent in retrospective data. OBJECTIVE: The objective of this study is to determine the age-specific pancreatic cancer risk as a function of family history using prospective data. METHODS: We compared pancreatic cancer incidence (n = 167) in 21 141 individuals from 4433 families enrolled in the National Familial Pancreatic Cancer Registry with that expected based on Surveillance Epidemiology and End Results data and estimated the cumulative probability of pancreatic cancer using competing risk regression. RESULTS: Familial pancreatic kindred members (kindreds with pancreatic cancer in 2 first-degree relatives [FDRs] or a pathogenic variant) had a standardized incidence ratio of 4.86 (95% confidence interval [CI] = 4.01 to 5.90), and sporadic kindred members (kindreds not meeting familial criteria) had a standardized incidence ratio of 2.55 (95% CI = 1.95 to 3.34). Risk in familial pancreatic cancer kindreds increased with an increasing number of FDRs with pancreatic cancer, with a standardized incidence ratio of 3.46 (95% CI = 2.52 to 4.76), 5.44 (95% CI = 4.07 to 7.26), and 10.78 (95% CI = 6.87 to 16.89) for 1, 2, and 3 or more FDRs with pancreatic cancer, respectively. Risk was also higher among individuals with a family history of young-onset (aged younger than 50 years) pancreatic cancer. CONCLUSION: Pancreatic cancer risk is strongly dependent on family history, including both the degree of relationship(s) and age of onset of pancreatic cancer in relatives. These risk estimates will help inform the design of early detection studies and the risk and benefit analysis of screening trials.

Risk of Pancreatic Cancer Among Individuals With Pathogenic Variants in the ATM Gene.

IMPORTANCE: Pathogenic germline variants in the ATM gene have been associated with pancreatic cancer risk. Although genetic testing identifies these variants in approximately 1% to 3% of unselected patients with pancreatic cancer, the lifetime risk of pancreatic cancer among individuals with pathogenic ATM variants has not been well estimated. OBJECTIVE: To estimate age-specific penetrance of pancreatic cancer in individuals with a pathogenic variant in the ATM gene. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter cohort study of pancreatic cancer family registries in the US and Canada using pedigree data from 130 pancreatic cancer kindreds with a pathogenic germline ATM variant. Data analyses were performed from January 2020 to February 2021. MAIN OUTCOMES AND MEASURES: Observational age-specific risk of pancreatic cancer. Penetrance was estimated using modified segregation analysis. RESULTS: The study population of 130 families (123 [95%] White families) comprised 2227 family members (mean age [SD], 58 [22] years; 1096 [49%] women) with complete records (ie, including familial relationships, pancreatic cancer diagnosis, ATM status, proband status, and age), of which 155 individuals had positive results for an ATM pathogenic variant, 16 had a negative result, and the remainder did not have a test result. In these 130 families, 217 individuals had pancreatic cancer: 78 families had 1 such member; 34 families had 2 such members; and 18 families had 3 or more members with pancreatic cancer. The average (range) age at diagnosis was 64 (31-98) years. The cumulative risk of pancreatic cancer among individuals with a germline pathogenic ATM variant was estimated to be 1.1% (95% CI, 0.8%-1.3%) by age 50 years; 6.3% (95% CI, 3.9%-8.7%) by age 70 years; and 9.5% (95% CI, 5.0%-14.0%) by age 80 years. Overall, the relative risk of pancreatic cancer was 6.5 (95% CI, 4.5-9.5) in ATM variant carriers compared with noncarriers. CONCLUSIONS AND RELEVANCE: This multicenter cohort study found that individuals with a germline pathogenic ATM variant were at an increased lifetime risk of pancreatic cancer. These risk estimates can help guide decision-making when evaluating the risks and benefits of enhanced early detection surveillance.

Planning and Implementation of Low-Dose Computed Tomography Lung Cancer Screening Programs in the United States.

BACKGROUND: One of the largest, most expensive randomized, controlled trials, the National Lung Screening Trial, found that annual low-dose computed tomography (LDCT) scans led to a 20% reduction in lung cancer deaths. OBJECTIVES: This study describes the characteristics and program implementation barriers experienced by LDCT screening programs in the United States. METHODS: Using a mixed-methods approach, Lung Cancer Alliance Screening Centers of Excellence were surveyed and interviewed in 2013. Representatives from 65 centers completed an electronic questionnaire, followed by in-depth interviews with 13 physicians and nurse navigators regarding their institution's screening programs. FINDINGS: Participants cited low patient demand and few physician referrals as barriers, but few centers reported needing additional staff or equipment. Those interviewed discussed the importance of a multidisciplinary team and overcoming barriers related to insurance reimbursement, costs, and physician knowledge to improve program implementation.

Mobile mammography: An evaluation of organizational, process, and information systems challenges.

The purpose of this case study was to evaluate the information systems, personnel, and processes involved in mobile mammography settings, and offer recommendations to improve efficiency and satisfaction among patients and staff. Data includes on-site observations, interviews, and an electronic medical record review of a hospital who offers both mobile and fixed facility mammography services to their community. The optimal expectations for the process of mobile mammography from multiple perspectives were defined as (1) patient receives mammogram the day of their visit, (2) patient has efficient intake process with little wait time, (3) follow-up is completed and timely, (4) site contact and van staff are satisfied with van visit and choose to schedule future visits, and (5) the MMU is able to assess its performance and set goals for improvement. Challenges that prevent the realization of those expectations include a low patient pre-registration rate, difficulty obtaining required physician orders, frequent information system downtime/Internet connectivity issues, ill-defined organizational communication/roles, insufficient site host/patient education, and disparate organizational and information systems. Our recommendations include employing a dedicated mobile mammography team for end-to-end oversight, mitigating for system connectivity issues, allowing for patient self-referrals, integrating scheduling and registration processes, and a focused approach to educating site hosts and respective patients about expectations for the day of the visit. The MMU is an important community resource; we recommend simple process improvements and information flow improvements to further enable the MMU׳s goals.