Serial cytoreductive surgery and survival outcomes in recurrent adult-type ovarian granulosa cell tumors.

BACKGROUND: Few studies have evaluated the role of cytoreductive surgery in patients with recurrent adult granulosa cell tumors of the ovary. Despite a multitude of treatment modalities in the recurrent setting, the optimal management strategy is not known. Cytoreductive surgery offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of surgery compared with systemic therapy alone following the first recurrence and subsequent disease progressions. OBJECTIVE: This study aimed to determine the impact of secondary, tertiary, and quaternary cytoreductive surgery on survival outcomes in recurrent adult granulosa cell tumors of the ovary. STUDY DESIGN: This is a multicenter, retrospective cohort study evaluating patients with recurrent adult granulosa cell tumors of the ovary enrolled in the MD Anderson Rare Gynecologic Malignancy Registry from 1970 to 2022. Study inclusion criteria consisted of histology-proven recurrent disease, at least 1 documented recurrence, and treatment/treatment planning at the MD Anderson Cancer Center or Lyndon B. Johnson General Hospital. The primary exposure was cytoreductive surgery, and the outcomes of interest were progression-free survival and overall survival. Survival analyses were restricted to eligible patients with resectable disease without medical barriers to surgery at each progression episode. Demographic and clinicopathologic characteristics were summarized using descriptive statistics. Progression-free survival (after first, second, and third progression) and overall survival were estimated with methods of Kaplan and Meier, and were modeled via Cox proportional hazards regression. Multivariable analyses were performed for progression-free survival after first progression and overall survival. RESULTS: Among the 369 patients with adult granulosa cell tumors of the ovary in the registry, 149 patients met the study inclusion criteria. Secondary cytoreductive surgery was associated with a significant improvement in progression-free survival on univariable (hazard ratio, 0.37; 95% confidence interval, 0.17-0.81, P=.01) and multivariable analyses (hazard ratio, 0.42; 95% confidence interval, 0.19-0.92; P=.03). Those who underwent secondary cytoreductive surgery had a significantly improved median overall survival compared with those who did not undergo cytoreductive surgery (181.92 vs 61.56 months, respectively; P=.002). Overall survival benefit remained statistically significant on multivariable analysis (hazard ratio, 0.28; 95% confidence interval, 0.11-0.67; P=.004). Tertiary cytoreductive surgery was similarly associated with a significant improvement in progression-free survival (hazard ratio, 0.43; 95% confidence interval, 0.26-0.70; P=.001). Despite a similar trend, quaternary cytoreductive surgery was not associated with a significant improvement in progression-free survival (hazard ratio, 0.74; 95% confidence interval, 0.42-1.26; P=.27). CONCLUSION: Among those with resectable disease and no medical contraindications to surgery, cytoreductive surgery may have a beneficial impact on progression-free survival and overall survival in patients with recurrent adult granulosa cell tumors of the ovary.

Improving genetic testing following abnormal mismatch repair immunohistochemistry results in endometrial cancer.

OBJECTIVES: Although universal mismatch repair (MMR) immunohistochemistry (IHC) in endometrial cancer began at our institution in July 2015, not all eligible patients were referred for genetic testing (GT). In April 2017, genetic counselors obtained IHC data and contacted physicians to approve genetic counseling referrals (GCRs) for Lynch Syndrome (LS) in eligible patients. We assessed if this protocol increased frequency of GCRs and GT in patients with abnormal MMR IHC. METHODS: We retrospectively (7/2015-5/2022) identified patients with abnormal MMR IHC at a large urban hospital. GCRs and GT were compared between cases from 7/2015-4/2017 (pre-protocol) and 5/2017-5/2022 (post-protocol) with chi-square and Fisher's exact tests. RESULTS: Of 794 patients with IHC testing, 177 (22.3%) had abnormal MMR results with 46 (26.0%) meeting criteria for LS screening with GT. Of 46 patients, 16 (34.8%) were identified prior to and 30 (65.2%) after the protocol initiation. GCRs significantly increased from 11/16 (68.8%) to 29/30 (96.7%) in the pre-protocol versus post-protocol groups, p = 0.02. There was no statistically significant difference in GT between groups (10/16, 62.5% vs 26/30, 86.7%, p = 0.07). Of 36 patients who underwent GT, 16 (44.4%) had LS: MSH6, 9; MSH2, 4; PMS2, 2; MLH1, 1. CONCLUSIONS: Increased frequency of GCRs was observed following the change in protocol, which is important as LS screening has clinical implications for patients and their families. Despite this additional effort, approximately 15% who met criteria did not undergo GT; further efforts such as universal germline testing in patients with endometrial cancer should be considered.

Syndrome of inappropriate antidiuretic hormone secretion associated with an ovarian immature teratoma: A case report and review of the literature.

•SIADH can be associated with an ovarian immature teratoma.•Medical management of SIADH improved but did not resolve the hyponatremia.•Complete resolution of the hyponatremia was only obtained after surgical debulking.

Persistent trophoblastic atypia on endocervical curettage found to be an epithelioid trophoblastic Tumor: A case report and review of the literature.

We present an unusual case of a 28-year-old female who had atypical trophoblastic proliferation on her endocervical curettage (ECC) performed at the time of a colposcopy. The indication for colposcopy was a Pap smear notable for atypical squamous cells of unknown significance, positive HPV. Initially conservative management was pursued, but given persistent atypia the patient ultimately decided to proceed with definitive management via hysterectomy. Final histologic assessment demonstrated an epithelioid trophoblastic tumor (ETT). This case highlights the unusual scenario of ETT presenting as atypical trophoblastic cells on endocervical curettage and the possible evolution of an atypical placental site nodule into an ETT.

Medical marijuana utilization in gynecologic cancer patients.

BACKGROUND: Medical marijuana (MM) use is common among cancer patients, but relatively little is known about the usage patterns and efficacy of MM used by gynecologic cancer patients. METHODS: Demographic and clinical data were collected for gynecologic cancer patients prescribed MM between May 2016 and February 2019. The electronic medical record was used to query formulation prescribed, usage patterns, length of use, symptom relief, and side effect profile. Descriptive statistics were calculated. RESULTS: Of 45 gynecologic cancer patients prescribed MM, 89% were receiving chemotherapy; 56% were undergoing primary treatment. MM was used for a median of 5.2 months (range 0.6-25.4). Over 70% of patients reported improvement in nausea/vomiting, compared to 36% of patients using MM for pain relief (p = 0.02). Of 41 patients with follow-up information, 71% found MM improved at least one symptom. CONCLUSIONS: Among a small sample of gynecologic cancer patients prescribed MM for symptom management, self-reported follow-up indicated symptom relief for the majority of patients and minimal therapy-related side effects. This data can prove useful for counseling gynecologic cancer patients on the efficacy and side effects of MM.

Trends and geographic variation in women's representation as principal investigators (PI) in phase 3 gynecologic oncology clinical trials.

OBJECTIVE: To investigate the representation of women as principal investigators (PI) in phase 3, gynecologic oncology clinical trials. METHODS: ClinicalTrials.gov was queried for all phase 3 clinical trials with start dates between January 1, 2010 and December 31, 2020 using the search terms: "ovarian cancer", "endometrial cancer", and "cervical cancer". Trial characteristics were abstracted from the website. Gender of the PI was assessed by name, image on institutional website or by querying the trial coordinator. Trials were considered to have women's representation if women were the sole PI or among multiple co-PIs. Chi-square tests and relative risks were used to compare proportions across groups. Linear regression was used to assess trends over time. RESULTS: 200 unique clinical trials were included in this analysis, of which women were represented as PI in 76 (38%). Women were more likely to be a PI of trials funded by multiple sites than a single entity (RR = 1.80, 95% confidence interval (CI) 1.25, 2.61, p = 0.01), registered outside of Asia than those in Asia (RR = 1.78, 95% CI 1.11, 2.88, p = 0.02), and trials with multiple co-PIs than with one PI (RR = 1.78 (95% CI 1.18, 2.67), p = 0.01). Overall, women's representation as a PI increased by 3% annually (by year of registration, R2 = 0.61, p = 0.01). This increase was most evident in trials registered in multiple continents and Europe (both 4% annually). CONCLUSIONS: Women's representation as PIs in clinical trials has increased in the last decade. Trials funded by multiple sources outside of Asia have the highest proportion of PIs who are women. These trends may represent ongoing leadership and mentorship opportunities for women gynecologic oncologists.

Optimizing Robotic Hysterectomy for the Patient Who Is Morbidly Obese with a Surgical Safety Pathway.

STUDY OBJECTIVE: Obesity is a growing worldwide epidemic, and patients classified as obese undergoing gynecologic robotic surgery are at increased risk for surgical complications. This study aimed to evaluate the feasibility and outcomes of a surgical safety protocol known as the High BMI [Body Mass Index] Pathway (HBP) for patients with BMI ≥40 kg/m2 undergoing planned robotic hysterectomy. Our primary outcome was the rate of all-cause perioperative complications in patients undergoing surgery with the use of the HBP. DESIGN: A retrospective cohort study. SETTING: An academic teaching hospital. PATIENTS: A total of 138 patients classified as morbidly obese (BMI ≥40 kg/m2) undergoing robotic hysterectomy. INTERVENTIONS: The HBP was developed by a multidisciplinary team and was instituted on January 1, 2016, as a quality improvement project. Patients classified as morbidly obese undergoing robotic hysterectomy after this date were compared with consecutive historical controls. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients underwent robotic hysterectomies on the HBP and were compared with 66 controls. There were no differences in age, BMI, blood loss, number of comorbidities, or cancer diagnosis. Since the implementation of the HBP, there has been a decrease in anesthesia time (-57.0 minutes; p = .001) and total operating room time (-47.0 min; p = .020), as well as lower estimated blood loss (median 150 mL [interquartile range 100-200] vs 200 mL [interquartile range 100-300]; p = .002) and reduction in overnight hospital admissions (33.3% vs 63.6%; p <.001). In the HBP group, there were fewer all-cause complications (19.4% vs 37.9%; p = .023) and infectious complications (8.3% vs 33.3%; p = .001), and there was no increase in the readmission rates (p = .400). In multivariable analysis, the HBP reduced all-cause complications (odds ratio 0.353; p = .010) after controlling for the covariate (total time in the operating room). CONCLUSION: The HBP is a feasible method of optimizing the outcome for patients classified as morbidly obese undergoing major gynecologic surgery. Initiation of the HBP can lead to decreased anesthesia and operating times, all-cause complications, and overnight hospital admissions without increasing readmission rates.

Phase I and pharmacokinetic study of veliparib, a PARP inhibitor, and pegylated liposomal doxorubicin (PLD) in recurrent gynecologic cancer and triple negative breast cancer with long-term follow-up.

OBJECTIVE: Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. METHODS: Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1-14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. RESULTS: 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. CONCLUSIONS: The RP2D is 200 mg veliparib BID on days 1-14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.

Missed opportunities: Genetic counseling and testing among an ethnically diverse cohort of women with endometrial cancer.

OBJECTIVES: Lynch syndrome (LS) accounts for the majority of inherited endometrial cancers (EC), and the identification of probands presents a unique opportunity to treat and prevent multiple cancers. The diagnosis of EC can provide the indication for women with specific risk factors to undergo genetic testing (GT). We sought to evaluate genetic counseling referrals (GCR) and subsequent GT rates in an ethnically diverse group of high-risk women. METHODS: All women diagnosed with EC between 2011 and 2016 were identified. Risk factors for LS including age, family and personal histories of Lynch-related cancers and loss of tumor mismatch repair (MMR) protein expression were identified from laboratory and medical records. Standard two-sided statistical tests were used. RESULTS: Of 583 women diagnosed with EC, 184 (31.6%) were found to have at least one high-risk characteristic for LS. Among these high-risk women, 58% were given GCR and resulting in only 35% undergoing GT. Ten of the 65 high-risk women who had GT (15.4%) were diagnosed with Lynch syndrome, and all ten met high-risk criteria. Two women of Asian race had tumors exhibiting retained MMR protein expression despite germline testing demonstrating Lynch syndrome. CONCLUSIONS: Many high-risk women do not receive GCR despite a high rate of germline mutations among these women. Improving GCR among high-risk women will lead to more subsequent GT to identify more Lynch syndrome families and prevent additional cancers. Among our ethnically diverse cohort, two women diagnosed with LS had retained MMR protein expression. GCR should be offered to women who possess high-risk characteristics despite normal MMR protein expression.