Circulating Tumor DNA (ctDNA) and Its Role in Gynecologic Malignancies.

OPINION STATEMENT: Circulating tumor DNA (ctDNA) refers to small fragments of DNA released into the bloodstream by cancer cells. It is obtained through "liquid biopsy;" which most commonly refers to plasma or blood samples, but can be obtained from a number of bodily fluids including ascitic fluid, saliva, and even urine and stool. ctDNA is detected via polymerase chain reaction (PCR) or next-generation sequencing (NGS). The DNA from these samples is analyzed for the detection of point mutations, copy-number alterations, gene fusion, and DNA methylation. These results have the potential for use in cancer diagnosis, determining prognosis, targeting gene-specific therapies, and monitoring for/predicting disease recurrence and response to treatment. ctDNA offers an alternative to tissue biopsy; it is less invasive and can be monitored serially over time without multiple procedures. Moreover it may have the ability to detect disease recurrence or predict behavior in a way that solid tissue biopsies, tumor marker surveillance, and imaging cannot. Recent explosion in interest in ctDNA shows promising developments for widespread adoption of these techniques in cancer care. However, the use of ctDNA in diagnosis and treatment of gynecologic malignancies is currently limited, compared to adoption in other solid-organ tumors such as breast and colorectal cancers. Compared to other cancer types, there appear to be fewer comprehensive studies and clinical validations specifically focusing on the use of ctDNA in gynecologic cancers. More research is needed in this area to advance the potential for use of ctDNA in ovarian, endometrial, and cervical cancers before this can be routinely adopted to improve care for patients with gynecologic malignancies.

Perspectives of gynecologic oncology fellowship training and preparedness for practice.

We aimed to examine the preparedness of recent gynecologic oncology fellowship graduates for independent practice.We conducted a web-based survey study using REDCap targeting Society of Gynecologic Oncology (SGO) members who graduated gynecologic oncology fellowship within the last six years. The survey included 52 items assessing fellowship training experiences, level of comfort in performing core gynecologic oncology surgical procedures and administering cancer-directed therapies. Questions also addressed factors driving participants' selection of fellowship programs, educational experience, research and preparedness for independent practice. A total of 296 participants were invited to complete the survey. Response rate was 42% with n = 124 completed surveys included for analysis. The highest ranked factor for fellowship selection was fit with program 36% (n = 45). Upon completing fellowship, most were uncomfortable performing ureteral conduit formation 84% (n = 103), ureteroneocystostomy 77% (n = 94), exenteration 68% (n = 83), splenectomy 67% (n = 83) and lower anterior resection 41% (n = 51). Most were comfortable managing intraoperative complications 85% (n = 104) and standard cancer staging procedures (range: 61%-99%). Majority were comfortable providing cancer directed therapies with chemotherapy 99% (n = 123), immunotherapy 84% (n = 104), and poly ADP-ribose polymerase (PARP) inhibitors 97% (n = 120). Upon completing fellowship, 77% (n = 95) report having mentorship that met their expectations during fellowship and 94% (n = 116) felt they were ready for independent practice. Majority of fellowship graduates were prepared for independent practice and felt comfortable performing routine surgical procedures and cancer directed treatment. However, most are not comfortable with ultra-radical gynecologic oncology procedures. Maximizing surgical opportunities during fellowship training and acquiring early career mentorship may help.

Primary clear cell carcinoma of the vulva: A case report.

Clear cell carcinoma (CCC) of the vulva is extremely rare. We report a case of a 54-year-old woman who presented with a 5 cm mass of the mons pubis. She underwent needle biopsy demonstrating CCC. She then underwent radical vulvectomy with bilateral inguinofemoral lymph node dissection. Surgical pathology revealed CCC of the vulva with lymphovascular space invasion (LVSI) and metastatic carcinoma in 1/7 inguinal lymph nodes. The patient has a history of endometriosis, raising suspicion that her CCC could have arisen from endometriosis in the mons. She completed adjuvant treatment with cisplatin and concurrent external beam radiation therapy with radiographic evidence of complete response. However, short-interval imaging demonstrated multi-focal recurrence, which was confirmed with supraclavicular lymph node biopsy. She then completed 8 cycles carboplatin, paclitaxel, and biosimilar bevacizumab-bvzr with favorable response on imaging. She was continued on bevacizumab maintenance. She was later started on pembroluzimab for disease progression based on new mediastinal adenopathy and worsening retroperitoneal lymphadenopathy. She received eight cycles of pembrolizumab with ongoing disease progression before enrolling in hospice and discontinuing cancer-directed treatment. As described in the related literature which we summarize here, the majority of reported cases of vulvar CCC arise from endometriosis implants at the site of prior episiotomy or from the Bartholin's gland. This patient had clinical history of endometriosis; prior tissue sampling was not performed to support the diagnosis. Given the absence of data regarding this rare type of primary vulvar cancer, treatment of this patient's disease was based on existing data specific to squamous cell carcinoma of the vulva and extrapolated from treatment guidelines for CCC of the ovary and endometrium. Continued research is needed on this rare form of vulvar carcinoma to determine the risk factors, prognostic factors, and treatment recommendations specific to this disease.

Complex Family Planning fellowship graduates' intended practice plans and barriers to practicing in areas of unmet need.

OBJECTIVES: To describe practice patterns and challenges encountered by Complex Family Planning (CFP) fellowship graduates. STUDY DESIGN: We invited all 110 obstetrics and gynecology physicians who graduated from the CFP fellowship from 2017-2020 via email to complete an anonymous online survey. We inquired about demographics, intended and obtained postfellowship positions, and successes and challenges in obtaining jobs. We used Fisher's exact test to assess if the proportion of graduates who grew up, attended residency, and completed fellowship in a US region (Northeast, Midwest, South, and West) and practiced in that same region differed. RESULTS: Ninety-nine (90.0%) graduates completed the survey. When entering fellowship, most (n = 92 [92.9%]) expected to practice in an academic environment. About half (n = 49 [49.5%]) pursued fellowship with the intent to practice in a location with an unmet need for abortion providers, of which 22 (44.9%) did so. Forty-nine (49.5%) respondents did not practice after fellowship where they initially intended, citing common challenges of job availability, family-related concerns, safety concerns, and relationship status changes. We found associations between regions where graduates completed residency and currently practice (p = 0.004), driven primarily by higher associations in the South (76.9%) and West (70.6%) and a lower association in the Midwest (22.7%). We found no association between current practice region and where graduates grew up (p = 0.15) or completed fellowship (p = 0.23). CONCLUSIONS: CFP fellowship graduates from 2017-2020 primarily intended to practice in academic environments with half planning to practice in underserved locations. However, more than half of those who entered fellowship hoping to fill an unmet need for abortion providers did not do so. IMPLICATIONS: About half of CFP fellowship graduates from 2017-2020 intended to obtain positions in areas they defined as having an unmet need for abortion provision. Personal life and job barriers prevented many from serving in such positions after fellowship. Practice location intentions and outcomes may be different in a post-Dobbs environment.

A Problem-Based Learning Session on Pregnancy Options, Counseling, and Abortion Care.

Introduction: Before their clinical rotations, medical students have limited exposure to women's health issues, particularly abortion. Methods: We piloted a problem-based learning (PBL) module to introduce second-year medical students at the University of Louisville School of Medicine to counseling patients about pregnancy options. Students were divided into groups of 10 and met for two 2-hour sessions. In the first session, learners were presented with a case about a woman diagnosed with Zika virus who was considering pregnancy termination. Students discussed the case and developed learning objectives to research. One week later, students reconvened and shared what they had learned individually. Students were asked to complete pre- and post-PBL surveys. PBL facilitators also completed a survey evaluating the module. Results: Fifty-eight percent of students felt informed or very informed about abortion after the PBL, compared to 30% before (p < .001). Students' mean quiz score increased from 29% on the pretest to 40% on the posttest (p < .001). Ninety-three percent of facilitators believed this PBL provided students with tools to better counsel about abortion, but only 56% of faculty felt adequately trained to facilitate this discussion. Discussion: Students appreciated this PBL as an opportunity to discuss pregnancy options counseling and to clarify their own values surrounding abortion provision. Despite their positive response to the module, students identified barriers that would prevent them from implementing knowledge learned from this module in practice.

Abortion training in US obstetrics and gynecology residency programs.

BACKGROUND: Nearly 15 years ago, 51% of US obstetrics and gynecology residency training program directors reported that abortion training was routine, 39% reported training was optional, and 10% did not have training. The status of abortion training now is unknown. OBJECTIVE: We sought to determine the current status of abortion training in obstetrics and gynecology residency programs. STUDY DESIGN: Through surveying program directors of US obstetrics and gynecology residency training programs, we conducted a cross-sectional study on the availability and characteristics of abortion training. Training was defined as routine if included in residents' schedules with individuals permitted to opt out, optional as not in the residents' schedules but available for individuals to arrange, and not available. Findings were compared between types of programs using bivariate analyses. RESULTS: In all, 190 residency program directors (79%) responded. A total of 64% reported routine training with dedicated time, 31% optional, and 5% not available. Routine, scheduled training was correlated with higher median numbers of uterine evacuation procedures. While the majority believed their graduates to be competent in first-trimester aspiration (71%), medication abortion (66%), and induction termination (67%), only 22% thought graduates were competent in dilation and evacuation. Abortion procedures varied by clinical indication, with some programs limiting cases to pregnancy complication, fetal anomaly, or demise. CONCLUSION: Abortion training in obstetrics and gynecology residency training programs has increased since 2004, yet many programs graduate residents without sufficient training to provide abortions for any indication, as well as dilation and evacuation. Professional training standards and support for family planning training have coincided with improved training, but there are still barriers to understand and overcome.