Brian Egleston

An eHealth Delivery Alternative for Cancer Genetic Testing for Hereditary Predisposition in Patients With Metastatic Cancers: Protocol for a Randomized Trial

Background Germline BRCA1 and BRCA2 testing is a standard evidence-based practice, with established risk reduction and cancer screening guidelines for genetic carriers. With Food and Drug Administration approval for poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors in patients with metastatic breast, ovarian, pancreatic, and prostate cancer, there is an additional therapeutic rationale for testing all patients with these cancers for germline BRCA1 and BRCA2 mutations. However, many at-risk patients do not have access to genetic services, leaving many genetic carriers unidentified. Objective The eREACH (A Randomized Study of an eHealth Delivery Alternative for Cancer Genetic Testing for Hereditary Predisposition in Metastatic Breast, Ovarian, Prostate, and Pancreatic Cancer Patients) study evaluates the effectiveness of a theoretically and stakeholder-informed eHealth (eg, digital) delivery alternative to traditional genetic counseling for patients with metastatic breast or prostate cancer or advanced or metastatic ovarian or pancreatic cancer referred for genetic testing to determine whether they are candidates for a PARP inhibitor. Methods The eREACH study is a randomized noninferiority study using a 2 × 2 design to test a self-directed digital intervention to deliver clinical genetic testing for patients with metastatic cancers. The traditional standard-of-care pretest (visit 1) and posttest (visit 2—disclosure) counseling delivered by a genetic counselor is replaced with our patient-informed digital intervention. The four arms were as follows: arm A, genetic counselor for visits 1 and 2; arm B, genetic counselor for visit 1 and digital intervention for visit 2; arm C, digital intervention for visit 1 and genetic counselor for visit 2; and arm D, digital intervention for both visits. Participants were adults with advanced or metastatic breast, ovarian, pancreatic, and prostate cancer. The primary outcomes of this study were change in genetic knowledge and anxiety from baseline to postdisclosure assessment. We will test whether the digital intervention is noninferior to standard-of-care counseling with a genetic counselor using a modified noninferiority ANOVA of the posttest disclosure minus baseline change scores. In secondary analyses, we will test pairwise differences among the 4 groups. Results As of January 2025, we have completed enrollment of 229 participants. Data analysis is ongoing, and we expect the results to be published in 2025. Conclusions Increasing indications for BRCA1 and BRCA2 testing create a pressing need to evaluate alternative delivery models to increase access and uptake of these tests while maintaining adequate patient cognitive, affective, and behavioral outcomes. The eREACH study evaluates the effectiveness of an interactive, patient-centered digital intervention to deliver clinical genetic testing to patients with metastatic cancers. We expect that this work will inform evidence-based guidelines and the standard of care for delivery of genetic testing, and it is designed to be broadly applicable and easily adaptable for other populations and settings even beyond oncology. Trial Registration ClinicalTrials.gov NCT04353973; https://clinicaltrials.gov/study/NCT04353973 International Registered Report Identifier (IRRID) DERR1-10.2196/72515

Changes in Risk Tolerance for Ovarian Cancer Prevention Strategies during the COVID-19 Pandemic: Results of a Discrete Choice Experiment

Background Prior to COVID-19, little was known about how risks associated with such a pandemic would compete with and influence patient decision making regarding cancer risk reducing medical decision making. We investigated how the pandemic affected preferences for medical risk-reducing strategies among women at elevated risk of breast or ovarian cancer. Methods We conducted a discrete choice experiment. Women about to undergo genetic testing and counseling at 2 medical centers participated. Enrollment occurred between 2019 and 2022, allowing us to investigate changes in preferences from before the pandemic to after the pandemic. Women chose from permuted scenarios that specified type of surgery, age of menopause, quality of menopausal symptoms, and risk of ovarian cancer, heart disease, or osteoporosis. Results A total of 355 women, with a median age of 36 y, participated. In 2019, women were less likely to choose prevention scenarios with higher ovarian cancer risk (odds ratio [OR] = 0.42 per 10-point increase in risk, 95% confidence interval [CI] 0.22–0.61). In June 2020, the effect of higher ovarian cancer risk scenarios on choice was attenuated (OR = 0.86, 95% CI 0.68–1.04), with the effect becoming more salient again by July 2021 (OR = 0.59, 95% CI 0.52–0.67) ( P = 0.039 for test of temporal interaction). No other attribute demonstrated a temporal trend. Conclusion The risks associated with the COVID-19 pandemic may have attenuated the impact of risk of ovarian cancer on choice of risk-reducing prevention strategies for ovarian cancer. The maximum attenuation occurred at the beginning of the pandemic when access to risk-reducing surgery was most restricted. Our findings highlight how individuals evaluate competing health risks and adjust their uptake of cancer prevention strategies when faced with a future pandemic or similar global crisis. Highlights In this discrete choice experiment, women were much less likely to choose prevention scenarios that had higher ovarian cancer risk prior to the COVID-19 pandemic than after the pandemic. The attenuation of preferences may have persisted through 2022. COVID-19 may have altered the relative importance of factors that motivate women to undergo risk-reducing surgeries.

National Cancer Database analysis of radiation therapy consolidation modality and dose for inoperable endometrial cancer.

We utilized the National Cancer Database (NCDB) to evaluate trends and assess outcomes in radiation therapy (RT) boost modality and total dose among medically inoperable endometrial cancer (EC) patients with locoregional disease. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I - IIIC2 inoperable EC treated with RT ± chemotherapy were analyzed. Practice patterns compared external beam RT (EBRT) versus high-dose-rate brachytherapy (BT) boost and total RT dose (palliative: ≤3000 cGy, definitive low dose [DLD]: 4500 - 6249 cGy, definitive high dose [DHD]: ≥6250 cGy) over time. Kaplan-Meier method evaluated overall survival (OS) and Cox proportional hazard modeling assessed variables associated with OS. NCDB included 1755 total cases, of which 1209 received a radiotherapy boost. From 2004 to 2019, boost modality rates differed with increasing utilization of BT consolidation and a decreasing rate of palliation. Predictors of a palliative dose were stage III disease, Black race, N2 disease, and poorly or undifferentiated grade. Multivariable analysis found BT boost was associated with lower mortality compared to EBRT (HR: 0.81, CI: 0.68-0.97; p = 0.019). Mortality rates were higher for palliation versus DHD. Additional factors associated with inferior survival were increasing age, worse Charlson-Deyo score, higher T stage, higher N stage, and moderately, poorly, or undifferentiated grade. Utilization of BT boost for locoregionally confined, medically inoperable EC has increased since 2004. Brachytherapy consolidation remains an effective RT modality for medically inoperable EC, associated with lower mortality compared to EBRT consolidation.