Citations

PURPOSE Women with breast cancer have a 4%-16% lifetime risk of a second primary cancer. Whether mutations in genes other than BRCA1/2 are enriched in patients with breast and another primary cancer over those with a single breast cancer (S-BC) is unknown. PATIENTS AND METHODS We identified pathogenic germline mutations in 17 cancer susceptibility genes in patients with BRCA1/2-negative breast cancer in 2 different cohorts: cohort 1, high-risk breast cancer program (multiple primary breast cancer [MP-BC], n = 551; S-BC, n = 449) and cohort 2, familial breast cancer research study (MP-BC, n = 340; S-BC, n = 1,464). Mutation rates in these 2 cohorts were compared with a control data set (Exome Aggregation Consortium [ExAC]). RESULTS Overall, pathogenic mutation rates for autosomal, dominantly inherited genes were higher in patients with MP-BC versus S-BC in both cohorts (8.5% v 4.9% [ P = .02] and 7.1% v 4.2% [ P = .03]). There were differences in individual gene mutation rates between cohorts. In both cohorts, younger age at first breast cancer was associated with higher mutation rates; the age of non–breast cancers was unrelated to mutation rate. TP53 and MSH6 mutations were significantly enriched in patients with MP-BC but not S-BC, whereas ATM and PALB2 mutations were significantly enriched in both groups compared with ExAC. CONCLUSION Mutation rates are at least 7% in all patients with BRCA1/2 mutation–negative MP-BC, regardless of age at diagnosis of breast cancer, with mutation rates up to 25% in patients with a first breast cancer diagnosed at age < 30 years. Our results suggest that all patients with breast cancer with a second primary cancer, regardless of age of onset, should undergo multigene panel testing.

Abstract Objective: Hypertensive disorders of pregnancy and menopausal symptoms, specifically vasomotor symptoms, have both been associated with cardiovascular disease risk in women. However, data are sparse on the association between these two female-specific cardiovascular risk factors. This study was conducted to investigate the association between a history of a hypertensive disorder of pregnancy and menopausal symptoms. Methods: This was a cross-sectional study of women aged 40 to 65 years seen for specialty consultation in women's health clinics at Mayo Clinic Rochester, MN and Scottsdale, AZ, between May, 2015 and September, 2019. A self-reported history of hypertensive disorders of pregnancy served as the independent variable, and menopause symptoms as assessed by the Menopause Rating Scale were the primary outcome measure. Results: Of 2,684 women included in the analysis, 180 had a self-reported history of a hypertensive disorder of pregnancy. The total menopausal symptom scores as well as somatic and psychological domain scores were higher in women with a history of a hypertensive disorder of pregnancy compared to women without a history of a hypertensive disorder of pregnancy or to women without a pregnancy. On multivariable analysis, women with a hypertensive disorder of pregnancy using hormone therapy had significantly higher total menopause symptom scores than women with no such history. Conclusions: In this large cross-sectional study, a history of hypertensive disorders of pregnancy was associated with more bothersome menopausal symptoms. Additional study is needed to determine the strength of this association, underlying mechanisms of the association, and clinical implications for cardiovascular risk prediction in women.

PURPOSE BRCA1 or BRCA2 ( BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study. METHODS We enrolled patients who progressed after one to two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious BRCA alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate. RESULTS Efficacy and safety populations included 115 patients with a BRCA alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients). CONCLUSION Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.

Telehealth has been used for decades to improve access to care for rural and underserved patients. The adoption of telehealth in orthopedic oncology is novel and expected to positively impact patient access and compliance. However, no previous evaluation has been published of this expected impact. The objective of this pilot project was to evaluate patients’ perceptions regarding orthopedic oncology telehealth services. A 13-question satisfaction survey was distributed to patients who used tele-orthopedic oncology. Fifteen respondents (a response rate of 42%) reported satisfaction with services at 9.7 of 10. Median travel distance to the nearest in-person orthopedic oncologist was greater than 150 miles (241 km). These results are consistent with the previous findings of high satisfaction with telehealth in other specialties. Health care organizations are likely to benefit from offering telehealth to orthopedic oncology patients with limited access.

Abstract Objectives: Cognitive computing has the potential to improve efficiency and accuracy of clinical trial enrollment using artificial intelligence. The cognitive computing clinical trial matching (CTM) system used for this study utilizes natural language processing to derive patient and tumor attributes from structured and unstructured electronic medical record (EMR) data. The attributes are matched to complex eligibility criteria in trial protocols. This CTM system has been implemented in our gynecologic oncology practice, for which there is lower representation of ethnic minorities, elderly, and uninsured in National Cancer Institute-sponsored trials. Methods: A clinical research coordinator (CRC) used the CTM system to screen patients for potential clinical trials one day prior to their clinic visit. Trial matches were shared with gynecologic oncology clinicians to raise awareness for study opportunities and assist in treatment decisions. Clinicians were surveyed regarding their experience with the CTM system prepared matches. The identical patients were evaluated by a clinician using the traditional manual screening method. Results: Seventeen patients with new diagnosis, recent resection, or restaging scans were screened for 41 potential gynecologic, phase I, and supportive care clinical trials. Trial screening by the CRC using the CTM system resulted in a total of 119 matched trials (mean: 7 trials/patient) compared to the clinician-generated list of 271 matched trials (mean: 16 trials/patient). The CRC using the CTM system spent an average of 18 minutes/patient (range: 7 to 40 minutes) compared to the clinician average of 22 minutes/patient (range: 7 to 37 minutes). A survey of 8 gynecologic oncology clinicians reported they were willing to spend an average of 8 minutes/patient (range: 1 to 15 minutes) to screen patients for trial eligibility. On independent review, discrepancies occurred when the clinician identified trials that the CRC excluded due to inclusion/exclusion criteria or were unknowingly closed to accrual. In addition, the CRC identified trials that were inadvertently missing from the clinician’s list of active protocols. Consistent with these observations, 100% of surveyed clinicians (8 of 8) agreed that “The CTM system has helped to include and exclude trials prior to discussion with patients.” Conclusions: Use of the CTM system by a CRC was superior to a clinician alone for the accuracy and efficiency of screening clinical trial eligibility. This process improved the identification of trials that a clinician might otherwise miss and the exclusion of trials that were not available or appropriate for patients. The CTM system can reduce the burden of clinicians and research staff to screen patients. Additional research is needed to determine if the process can improve clinical trial enrollment in gynecologic cancers. Citation Format: Thanh P. Ho, Jane M. Helgeson, Angela L. Andring, Jennifer C. Reed, Venessa L. Boyle, Nigar Sofiyeva, Konstantinos Leventakos, Tufia C. Haddad, Andrea E. Wahner Hendrickson, Saravut (John) Weroha. Implementation of cognitive computing to match clinical trials in gynecologic cancers: A single-institution experience [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 01.

Abstract Background: Sex differences in non-small cell lung cancer (NSCLC) outcomes have been described. Immune-related adverse events (IRAEs) have emerged as a serious clinical problem in the use of immune checkpoint inhibitors (ICI). Risk factors for IRAEs and their association with response to therapy remain controversial. Sex differences in innate and adaptive immune responses have been observed but the association of these differences with IRAEs remains unclear. Therefore, we studied sex differences in IRAEs and their association with response to therapy. Methods: All patients with metastatic NSCLC treated with anti-PD1 and anti-PDL1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Patients receiving treatment at an outside facility with history autoimmune disorders or radiation-induced pneumonitis were excluded. Chi-square test was used to estimate differences in categorical data. Kaplan-Meier method was used for time-to-event analysis. Results: A total of 231 patients were identified; 120 (52%) were women and 111 (48%) were men. Baseline characteristics and ICI distribution were similar among groups. Women were more likely to experience IRAEs compared to men (48% vs. 31%, p&lt;0.008). Among patients with IRAEs, women were more likely to be prescribed systemic steroids (63% vs. 41%, p&lt;0.02). On the other hand, no significant differences were observed in the administration of intravenous steroids. Women were more likely to develop pneumonitis (23% vs. 12%, p&lt;0.03) and arthralgias (17% vs. 3%, p&lt;0.04). However, dermatologic toxicities (35% vs. 9%, p&lt;0.002) were more commonly seen in men. In 17% of women the ICI was discontinued due to toxicity (men 7%). Besides sex, no other clinical characteristic was associated with increased IRAEs. Women with IRAEs were more likely to have a radiographic response compared with women without IRAEs (78% vs. 23%, p&lt;0.0001), although this was not observed in men (37% vs. 26%, p&gt;0.22). Better PFS was observed in women with IRAEs (10 months vs. 3.3 months, p&lt;0.0006) compared to women without IRAEs. Conclusions: Women with metastatic NSCLC are more likely to experience IRAEs compared to men. We also observed sex differences in the frequency of certain IRAEs. In addition, an association between IRAEs and response to therapy was observed in women. Larger studies are needed to investigate the mechanisms underlying these associations. Citation Format: Narjust Duma, Abdel-Ghani Azzouqa, Siddhartha Yadav, Kahterine Hoversten, Clay Reed, Andrea Sitek, Elizabeth Enninga, Jonas Paludo, Lisa Kottschade, Aaron Mansfield, Rami Manochakian, Roxana Dronca, Alex Adjei. Sex differences in tolerability and response to immune checkpoint inhibitors in non-small cell lung cancer patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A120.

In this Commentary, the authors seek to build on prior RIME commentaries by considering how researchers transition from worldviews, focal lengths, and research goals to research directions and methodological choices. The authors use the analogy of a hiker to illustrate how different researchers studying a similar phenomenon can choose among different research directions, which lead down different paths and offer different perspectives on a problem. Following the hiker analogy, the authors use the “Research Compass” to categorize the 15 research papers included in the 2020 Research in Medical Education supplement according to their research aim and corresponding methodological approach. The authors then discuss implications of the relative balance of these study types within this supplement and within health professions education research at large, emphasizing the critical importance of studying a topic from multiple vantage points to construct a richer and more nuanced understanding of health professions education challenges. The authors conclude by recognizing the challenges we face in the current era of COVID-19 and by calling health professions education researchers and practitioners to continue our collective efforts to improve learner education and patient care, as we together navigate the unfamiliar terrain of the present day.

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.