Faculty Bibliography

Introduction/UNASSIGNED:Elective surgical procedures were suspended during the coronavirus disease pandemic (COVID-19) in New York City (NYC) between March 16 and June 15, 2020. This study characterizes the impact of the ban on surgical delays for patients scheduled for surgery during this first wave of the COVID-19 outbreak. Methods/UNASSIGNED:Patients who were scheduled for surgical treatment of malignant or pre-invasive disease by gynecologic oncologists at three NYC hospitals during NYC's ban on elective surgery were included. Outcomes of interest were the percentage of patients experiencing surgical delay and the nature of delays. Kruskal-Wallis, chi-square, and logistic regression tests were performed with significance set at p < 0.05. Results/UNASSIGNED:Of the 145 patients with malignant or pre-invasive diseases scheduled for surgery during the ban on elective surgery, 40% of patients experienced one or more surgical delays, 10% experienced two or more and 1% experienced three surgical delays. Of patients experiencing an initial delay, 77% were hospital-initiated and 11% were due to known or suspected personal COVID-19. Overall, 81% of patients completed their planned treatment, and 93% of patients underwent their initially planned surgery. Among patients for whom adjuvant therapy was recommended, 67% completed their planned treatment, and the most common reasons for not completing treatment were medically indicated followed by concerns regarding COVID-19. Conclusion/UNASSIGNED:During the ban on elective surgery in NYC during the first outbreak of the COVID-19 pandemic, many patients experienced minor surgical delays, but most patients obtained appropriate, timely care with either surgery or alternative treatment.

BACKGROUND:In women with BRCA mutations, risk-reducing bilateral salpingo-oophorectomy (RRSO) has been shown to decrease gynecologic cancer-specific and overall mortality. The National Comprehensive Cancer Network (NCCN) recommends that patients with BRCA mutations undergo RRSO between the ages of 35-40 years for BRCA1 mutation carriers and between the ages of 40-45 years for BRCA2 mutation carriers, or after childbearing is complete. Currently, uptake and timing of RRSO and reasons for delays in RRSO are not well understood. OBJECTIVE:We sought to evaluate uptake and timing of RRSO among women with BRCA1/2 mutations in relation to NCCN guidelines, and reasons for delays in RRSO. STUDY DESIGN/METHODS:In this retrospective chart review, we identified women with BRCA1/2 mutations who discussed RRSO with a provider between 2012 and 2021. Uptake of RRSO was documented, and patients were classified as having timely or delay in RRSO based on NCCN guidelines. For those with delay in RRSO, reasons cited for delay were collected. Comparative statistical analyses were performed to evaluate characteristics of those with timely vs delayed RRSO. A multivariable logistic regression model was used to evaluate the associations between factors related to timing of RRSO. RESULTS:We identified 638 BRCA1/2 mutation carriers seen between 2012 and 2021. Of these patients, 306 (48.0%) had undergone RRSO and 332 (52.0%) had not. When evaluating timing of RRSO, 136 (21.3%) underwent timely RRSO, 239 (37.5%) had delay in RRSO, and 263 (41.2%) had not undergone RRSO but were younger than NCCN age guidelines so were neither timely nor delayed. Patients with delay in RRSO were significantly older at the time of genetic testing compared to those with timely RRSO (mean 49.8 vs 36.3 years; p < 0.001). Of the 306 patients who underwent RRSO, those with delayed RRSO had a significantly shorter interval between BRCA identification and RRSO compared to those with timely RRSO (median 8.7 vs 17.6 months; p < 0.001). Patients with delay in RRSO were more likely to have a personal history of cancer than those with timely RRSO (49.8% vs 37.5%; p=0.028). Of the 239 women with delay in RRSO, reasons included: 188 (78.7%) for delayed BRCA mutation identification; 29 (12.1%) for menopausal concerns; 17 (7.1%) for ongoing cancer treatment; 12 (5.0%) for coordination with breast surgery; 20 (8.4%) for miscellaneous reasons; and 19 (7.9%) with no reasons documented. In the multivariate model, older age at BRCA diagnosis (OR 0.73; 95%CI [0.68-0.78]; p<0.001) was significantly associated with delayed RRSO timing; those with BRCA2 mutation type were 7.54 times as likely to have timely RRSO compared to BRCA1 mutation carriers (OR 7.54; 95%CI [3.70-16.42]; p<0.001). CONCLUSION/CONCLUSIONS:Nearly 38% of BRCA1/2 mutation carriers undergo or have yet to undergo RRSO beyond the NCCN recommended age. The most common reason for delay in RRSO was delayed identification of BRCA mutation, noted in 79% of patients with delayed RRSO. Timely genetic testing for eligible patients can increase appropriately timed RRSO for prevention of ovarian cancer and reduction of mortality in BRCA mutation carriers.

OBJECTIVES/OBJECTIVE:We evaluated the incidence of breast cancer and overall survival in a multi-center cohort of ovarian cancer patients carrying BRCA1/2 mutations in order to assess risks and formulate optimal preventive interventions and/or surveillance. METHODS:Medical records of 502 BRCA1/2 mutation carriers diagnosed with ovarian cancer between 2000 and 2018 at 7 medical centers in Israel and one in New York were retrospectively analyzed for breast cancer diagnosis. Data included demographics, type of BRCA mutations, surveillance methods, timing of breast cancer diagnosis, and family history of cancer. RESULTS:The median age at diagnosis of ovarian cancer was 55.8 years (range, 23.9-90.1). A third (31.5%) had a family history of breast cancer and 17.1% of ovarian cancer. Most patients (67.3%) were Ashkenazi Jews, 72.9% were BRCA1 carriers. Breast cancer preceded ovarian cancer in 17.5% and was diagnosed after ovarian cancer in 6.2%; an additional 2.2% had a synchronous presentation. Median time to breast cancer diagnosis after ovarian cancer was 46.0 months (range, 11-168). Of those diagnosed with both breast cancer and ovarian cancer (n = 31), 83.9% and 16.1% harbored BRCA1 and BRCA2 mutations, respectively. No deaths from breast cancer were recorded. Overall survival did not differ statistically between patients with an ovarian cancer diagnosis only and those diagnosed with breast cancer after ovarian cancer. CONCLUSION/CONCLUSIONS:The low incidence of breast cancer after ovarian cancer in women carrying BRCA1/2 mutations suggests that routine breast surveillance, rather than risk-reducing surgical interventions, may be sufficient in ovarian cancer survivors.

Objectives: To characterize the effect that a ban on elective surgery had for patients who were scheduled for surgery with a gynecologic oncologist during the first coronavirus disease 19 (COVID-19) outbreak in New York City.
Method(s): Patients who were scheduled to undergo surgery by a gynecologic oncologist at one of three campuses of a New York City based academic hospital during the ban on elective surgery between March 16, 2020 and June 15, 2020 were included. Patients with benign disease were excluded. Data on patient demographics, perioperative characteristics, nature of surgical delay, and post-operative treatment were abstracted from patient charts. Standard of care was considered met if surgical procedures occurred for suspected malignant and pre-invasive disease, or if an appropriate treatment plan and follow up was documented for malignant cases. Kruskal-Wallis and chi-square test of independence were performed with significance set at p<0.05.
Result(s): A total of 196 patients were scheduled to undergo a surgical procedure during the ban on elective surgery, of which 146 were for malignant, suspected malignant or pre-invasive disease. The majority of cases (42.4%) occurred in patients with known malignancy, followed by suspected malignancy (37.7%) and pre-invasive disease (19.9%). Forty percent of patients experienced one or more surgical delay, 9.6% experienced 2 or more surgical delays and 1.4% experienced three or more surgical delays. Of patients who experienced surgical delays, 75.9% experienced hospital-initiated delays and 24.1% experienced patient-initiated delays. There were no differences between hospital versus patient initiated delays by White vs non-White race (p=0.167). Eight percent of delays were due to a patient with known or suspected COVID-19. The median time from surgical consultation to proposed date of surgery was 20 days for both known malignancy and suspected malignancy, and 34.5 days for pre-invasive disease (p=0.005). Similarly, the median time from surgical consultation to actual date surgery was 23 days for patients with known or suspected malignancy compared to 64 days for preinvasive disease (p=0.011). Of eight patients undergoing treatment for ovarian cancer, 50% underwent primary debulking and 50% underwent neoadjuvant chemotherapy. Among all scheduled cases, the standard of care was met in 89.7% of cases. Standard of care treatment was achieved with a documented alternative plan in 6.1% of cases and with a non-surgical plan in 3% of cases. [Formula presented]
Conclusion(s): During the ban on elective surgery in New York City during the first outbreak of the COVID-19 pandemic, many patients experienced minor surgical delays, but the majority of patients with known or suspected malignancies obtained appropriate, timely care. Ten percent of patients did not receive standard of care.
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Objective: We sought to prospectively evaluate the feasibility of obtaining genetic testing for at least 1 first- or second-degree family member of a proband known to have actionable germline mutation associated with endometrial and/or ovarian cancer through a coordinated referral system. We also identified barriers to genetic assessment in family members. Here we report initial probands screened and their reasons for declining cascade testing.
Method(s): Patients with a diagnosed pathogenic or suspected pathogenic mutation associated with ovarian and/or endometrial cancer were identified from the gynecologic oncology and genetics clinics. If patients did not consent to the study, their reasons for declining participation were documented. Patients who provided consent were asked to contact their first- and/or second-degree relatives to disclose their genetic testing results and advise them to contact our center for a referral to a genetic counselor. The number of relatives per proband who contacted us for a genetic counseling referral was recorded. In addition to providing the referral, we followed up with relatives to determine whether they attended their genetic counseling appointment, received genetic testing, or took any cancer risk-reducing measures based on their results.
Result(s): This study opened in March 2019. To date, we have screened 71 patients and enrolled 26 (37%). Among the 45 patients who were screened but not enrolled, 48.9% (n = 22) reported that their reason for declining participation in the study was that their family members had already received genetic testing. Other common reasons for declining participation were family members refusing testing (17.8%, n = 8) or no eligible family members (17.8%, n = 8) (Table 1).
Conclusion(s): The majority of probands declined participation in this facilitated cascade testing protocol. The most common reason for lack of participation was family members already having genetic testing or not having eligible family members. Patients who declined participation because family members refused testing could benefit from counseling on how to best to communicate with their relatives. Genetic testing for both patients and their relatives is critical to provision of appropriate cancer screening and prevention services. Knowledge of these barriers is important to further improve cascade testing among family members.
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BACKGROUND:Timely genetic testing at ovarian cancer diagnosis is essential as results impact front line treatment decisions. Our objective was to determine rates of genetic counseling and testing with an expedited genetics referral pathway wherein women with newly-diagnosed ovarian cancer are contacted by a genetics navigator to facilitate genetic counseling. METHODS:Patients were referred for genetic counseling by their gynecologic oncologist, contacted by a genetics navigator and offered appointments for genetic counseling. Patients completed quality of life (QoL) surveys immediately pre- and post-genetic assessment and 6 months later. The primary outcome was feasibility of this pathway defined by presentation for genetic counseling. RESULTS:From 2015 to 2018, 100 patients were enrolled. Seventy-eight had genetic counseling and 73 testing. Median time from diagnosis to genetic counseling was 34 days (range 10-189). Among patients who underwent testing, 12 (16%) had pathogenic germline mutations (BRCA1-7, BRCA2-4, MSH2-1). Sixty-five patients completed QoL assessments demonstrating stress and anxiety at time of testing, however, scores improved at 6 months. Despite the pathway leveling financial and logistical barriers, patients receiving care at a public hospital were less likely to present for genetic counseling compared to private hospital patients (56% versus 84%, P = 0.021). CONCLUSIONS:Facilitated referral to genetic counselors at time of ovarian cancer diagnosis is effective, resulting in high uptake of genetic counseling and testing, and does not demonstrate a long term psychologic toll. Concern about causing additional emotional distress should not deter clinicians from early genetics referral as genetic testing can yield important prognostic and therapeutic information.

Objectives To identify referral patterns and uptake of risk reducing surgery (RRS) in patients with non-BRCA genes associated with an increased risk of epithelial ovarian cancer. Methods A chart review of patients with mutations in MLH1, MSH2, EPCAM, MSH6, PMS2, RAD51C/D, BRIP1 was conducted from 2015-2018. Patients with BRCA1/2 and variants of uncertain significance were excluded; MSH6 and PMS2 were included (though recent change to insufficient evidence). Primary outcomes of interest were referral to a gynecologic oncologist and the uptake of RRS. Results Of 78 patients, 18 had undergone surgical management for treatment of cancer prior to genetic testing and were excluded. The majority of the patients (41 of 60, 68%) with non-BRCA actionable mutations were associated with Lynch Syndrome (LS). Of these patients, 23 of 60 (56%) were seen by gynecologic oncologists. Twenty of 41 (49%) underwent RRS. Excluding the MSH6 and PMS2 patients, 9 of 21 (43%) of patients with LS underwent RRS. Among patients with the non-BRCA and non-LS associated genes (RAD51C, RAD51D, BRIP1) the most common reason for testing was family history of cancer (10 of 19). Fifteen of 19 were referred to a gynecologic oncologist; all patients with BRIP1 mutation were referred, while 70% of those with RAD51/D were referred. Among this subset of patients, 9/19 (47%) patients underwent RRS; the remaining patients were screened with surveillance ultrasounds and/or CA-125. Conclusions Two-thirds of patients with non-BRCA genes associated with increased risk of ovarian cancer were referred to gynecologic oncologists, with a 48% of uptake or RRS

Objective: Enhanced Recovery Protocols (ERPs) minimize the stress response associated with surgery, decrease postoperative opioid consumption, and reduce length of stay (LOS). However, several of the medications on standard ERPs are expensive, which may limit their availability in low-resource settings. Our gynecologic oncology service takes care of patients at both an academic tertiary care center and a safety net hospital. We sought to examine whether a modified ERP at the safety net hospital led to comparable patient outcomes when compared to a standard protocol.
Method(s): From January 2016 to June 2017, patients undergoing scheduled laparotomy by 1 team of gynecologic oncologists who cover 2 hospital networks were placed on a perioperative ERP. Hospital A is an academic medical center; hospital B is a safety net public hospital. ERP was modified at hospital B because of the high cost of several medications (Figure 1). Demographics and perioperative outcomes including LOS, complication, and readmission rates were compared.
Result(s): One hundred and four patients at hospital A and 45 patients at hospital B were included. Patients at hospital B were younger on average (49.0 +/- 13.2 years vs 55.7 +/- 14.4 years, P < 0.001), more likely to be nonwhite (93.3% vs 40.4%, P < 0.001), utilize public insurance (48.9% vs 26.0%, P < 0.001), and be unmarried (55.7% vs 33.7%, P < 0.001). There were no statistically significant differences in LOS, postoperative complications, final pathology, estimated blood loss, 30-day readmission, or 30-day complication rates. Compared to patients at hospital A, patients at hospital B were less likely to receive intraoperative transfusions (0% vs 11.5%, P = 0.018) and had fewer inpatient complications (6.7% vs 21.2%, P = 0.032)
Conclusion(s): Despite the lack of several medications, patients on a modified ERP had similar outcomes to patients on a standard ERP protocol. A lower cost ERP is feasible, effective, and may represent an opportunity for cost reduction. [Figure presented]
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Objective: Ovarian cancer patients with germline BRCA1/2 mutations (gBRCAmut) often have improved survival compared to patients without mutations. We characterized the molecular features of tumors from gBRCAmut patients with short-term compared to longer term survival.
Method(s): DNA was extracted from FFPE tumor and normal samples collected at the time of surgery for gBRCAmut high-grade serous ovarian cancer (HGSOC) patients from a single institution. Short-term survivors (STS) were defined as those having a PFS <18 months and compared with longer term survivors (LTS) who had a PFS >36 months. gBRCAmut were confirmed using Sanger sequencing and targeted next-generation sequencing (NGS) of a panel of over 500 cancer-relevant genes. Fragment analysis was performed to identify loss of heterozygosity (LOH) for patients with frameshift mutations. Molecular data were correlated with clinicopathologic characteristics.
Result(s): Of the 16 patients with sufficient tumor available for this study, 9 were STS and 7 LTS, with median PFS of 16 (range 10-18) and 57 (range 43-92) months, respectively. There were no differences in age at diagnosis, stage, rates of neoadjuvant chemotherapy, and optimal cytoreduction between STS and LTS. Somatic TP53 mutations were identified in all 15 patients who underwent targeted NGS. Of 11 patients with evaluable LOH data, LOH was present in 6/7 (86%) STS and 4/4 (100%) LTS. Among STS, additional mutations were detected in the RB (2), HRD (4), and PI3K/RAS (4) pathways more frequently than LTS (RB, 1; HRD, 1; and PI3K/RAS, 1). The 1 tumor without LOH was from a BRCA2 gmut patient who developed recurrent disease 11 months after diagnosis.
Conclusion(s): Among a small cohort of gBRCAmut patients with HGSOC, no differences in rates of TP53 mut, LOH, or other somatic mutations were found to account for short-term compared to longer term survival. LOH was absent in 1 patient with poor STS, and larger sample sizes may help to determine the contribution of LOH to tumor behavior in HGSOC patients with gBRCAmut.
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