Wahner Hendrickson, Andrea

Objectives: This trial served as a proof-of-concept for whether inhibition of protein kinase C iota (PKCι) with auranofin and sirolimus provide antineoplastic effects in patients with recurrent high-grade serous ovarian cancer. Methods: This drug combination was administered to patients with recurrent high-grade serous ovarian cancer. Dosing was based on unpublished phase 1 data and consisted of auranofin 6 mg and sirolimus 5 mg both orally per day of a 28-day cycle. The primary endpoint was tumor response. Available tumor tissue was assessed for PKCι protein expression by immunohistochemistry (IHC) and PRKCI copy number by fluorescence in-situ hybridization (FISH) after the start of cancer therapy. Results: Twenty-two patients were enrolled, and 21 were evaluable for all clinical trial endpoints. One patient was unevaluable because she did not receive a full chemotherapy cycle. No tumor responses were seen in the first 21 patients, resulting in early trial termination per a priori trial design. The median progression-free survival was 2.1 months (95% CI: 1.8-3.7). The median overall survival was 4.4 months (95% CI: 2.6-12.5). Fourteen (67%) patients had at least one grade 3 or worse adverse event. Nineteen of 21 evaluable patients had available tumor tissue, which showed the median PKCι copy number averaged per cell of 3 (range: 2 to 7), and PKCι expression (at least 1+) in all. Conclusions: As prescribed here, auranofin and sirolimus manifested no antineoplastic activity in patients with recurrent high-grade serous ovarian cancer that expressed PKCι.

Background: Parenthood during medical training is common and impacts trainee well-being. However, current graduate medical education parental health policies are often limited in scope. We explored current fellowship trainees’ knowledge of/satisfaction with current policies as well as interest in potential changes/additions to existing policies. Methods: Fellowship program directors/coordinators at a three-site academic institution were surveyed and information was collected from 2015 to 2019 regarding fellow demographics and parental health policies. We distributed an electronic survey to fellows containing Likert-type-scale questions rating knowledge/level of satisfaction with current parental health policies and interest in potential additions/modifications to current policies. Results: Thirty-five of 47 (74%) fellowship programs responded. An average of 11% of female fellows and 15% of male fellows took parental leave during the study period. Three (9%) of the programs had at least one additional parental health policy beyond institutional graduate medical education policies. In the fellow survey, 175 of 609 fellows responded (28.7%), of which 84 (48.6%) were female. Although 89.1% agreed/strongly agreed that parental health is an important part of health and well-being for fellows, only 32% were satisfied/very satisfied with current policies (no significant sex-related differences). Fellows reported the following potential interventions as important/very important: 79.2% increased (paid) maternity leave (72.7% male, 86.7% female, p = 0.02), 78% increased (paid) paternity leave (76.4% male, 81.9% female, p = 0.37), 72.3% part-time return to work (60.2% male, 84.3% female, p = 0.0005), 63% coverage for workup/management of infertility (52.3% male, 74.7% female, p = 0.002), and 79.9% on-site day care (70.7% male, 89.2% female, p = 0.003). Conclusions: Parental health includes multiple domains, not all of which are covered by current policies. Fellows feel that parental health is an important part of overall health and well-being, but most are not satisfied with current policies. Expanded access to parental leave and new policies (part-time return to work, infertility management, and on-site day care) are opportunities for innovation.