Clinicopathologic Characteristics of a Single-institution Cohort of Ovarian Adult Granulosa Cell Tumors, With Biomarker and Therapeutic Implications Utilizing the Detection of Androgen, Estrogen, and Progesterone Hormone Receptor Expression by Immunohistochemistry.

Adult granulosa cell tumors (AGCTs) are rare ovarian tumors with generally good prognosis after surgical resection; however, they do have recurrence potential. Therapeutic and management options for recurrences are currently limited, and the need for expanded adjuvant therapies is increasingly recognized. Anti-hormonal therapy is being explored as an option, which relies on the detection and assessment of hormone receptor expression (androgen, estrogen, and progesterone receptors) as a biomarker and therapeutic target. Our study identifies several clinicopathologic characteristics with significant associations for recurrence of AGCT, which were younger age, higher stage, and larger tumor size. Our study also demonstrates that androgen receptor (AR) expression may be utilized as a potential biomarker for hormonal therapy and that detection of AR expression in AGCT by immunohistochemistry (IHC) varies depending on the antibody clone used for testing. AR was detected in 95% of samples tested with antibodies derived from clone AR27. This detection rate is much higher than previously reported.

Syndromes of Concurrent Hypertension, Diastolic Dysfunction, and Pulmonary or Peripheral Edema in Cardio-Oncology: Case Studies, Literature Review, and New Classification System.

OPINION STATEMENT: Individuals who have ever been diagnosed with cancer are at increased risk for cardiovascular conditions during and after cancer treatment. Especially during cancer treatment, cardiovascular conditions can manifest in many ways, including peripheral or pulmonary edema. Edema can indicate volume overload affecting the heart even without other unequivocal evidence of apparent diastolic or systolic left ventricular dysfunction, particularly at rest. We propose a novel algorithm to streamline the diagnostic evaluation and cardiovascular classification for cancer patients with edema. We initially advise prompt evaluation with a chest X-ray and echocardiogram. We then suggest classification into one of five categories based on the timing of presentation of edema relative to cancer treatment, as well as echocardiography results and the presence or absence of hypertension or lymphatic causes of edema. This classification tool can then be utilized to guide further cardiovascular management suggestions. These concurrent syndromes presenting as edema may indicate the development or aggravation of undiagnosed diastolic dysfunction with or without hypertension, even if transiently present only while on cancer treatment.

Survival differences by race and surgical approach in early-stage operable cervical Cancer.

OBJECTIVE: To evaluate if the higher rate of open radical hysterectomy in Black patients, prior to the widespread return to open surgical techniques, mitigated survival disparities and to identify other actionable factors to target for systemic change. METHODS: This is a retrospective cohort study including patients from the National Cancer Database with cervical cancer who underwent radical hysterectomy from 2010 to 2018. Patient demographics, clinical characteristics and survival were compared by race and surgical route. Kaplan-Meier plots were constructed. Cox proportional hazards modeling was used to adjust for covariates. RESULTS: 7201 patients were eligible for inclusion, 687 (9.5%) Black and 4870 (68%) White. We found that 51% of Black patients and 39% of White patients underwent open surgery. Black patients were 10% less likely to receive Guideline Concordant Care (GCC). Those with publicly-funded insurance had a 40% higher hazard of death compared to private insurance (CI 1.19-1.73 p < 0.001). Black patients who had open surgery had similar 5-year survival compared to White patients who had MIS surgery (0.90 vs 0.91, NS). After adjusting for potential confounders including age, insurance, nodal status, and lymphovascular space invasion, Black patients who had surgery had a 40% higher hazard for death (HR 1.40 95% CI 1.10-1.79, p = 0.007) compared to White patients. CONCLUSIONS: A lower 5 and 10-year survival was seen in Black patients, regardless of surgical approach. Adjustment for significant covariates did not resolve this disparity, confirming that these factors do not fully account racial disparities.

Pathologic, immunologic, and clinical analysis of the microsatellite instability phenotype in endometrial carcinoma.

The objective of this study was to determine if quantifying the microsatellite instability (MSI) phenotype could serve as a biomarker for clinical and immunologic features of deficient mismatch repair (dMMR) endometrial cancer (EC). Patients with EC undergoing hysterectomy whose tumors demonstrated dMMR were included. Immunohistochemistry (IHC) of mismatch repair proteins and polymerase chain reaction analysis of NR27, BAT25, BAT26, NR24, and NR21 microsatellite loci were performed on each case. The MSI phenotype was quantified by subtracting the number of nucleotides of each microsatellite in tumor tissue from the corresponding microsatellite in paired normal tissue and summing the absolute differences. This was termed marker sum (MS) and is a novel quantification. Tumor-infiltrating lymphocytes (TILs) were identified by IHC for CD3, CD4, and CD8 and quantified with digital image analysis. Tumor infiltration of lymphocytes and clinical characteristics were stratified by MS. Four hundred fifty-nine consecutive patients with dMMR EC were analyzed. MS ranged from 1 to 32. Post hoc, 2 cohorts were defined using receiver operating characteristic curves (MS less than 13 and MS greater than 12). With the exception of tumor grade, all clinical and pathologic features, all tumor characteristics, and the numbers of TILs were similar between cohorts. The MSI phenotype is highly variable in dMMR EC, and no correlation between the immune profile and the severity of the MSI phenotype was observed.

A case series of triplet anti-hormonal therapy in androgen receptor-positive recurrent adult ovarian granulosa cell tumor.

Therapeutic options for recurrent adult granulosa cell tumors (AGCT) are limited. After examining the hormonal pathways involved in FOXL2-mutated granulosa cell tumor development, a novel treatment regimen was utilized for recurrent AGCT: a combination of an androgen receptor antagonist, a gonadotropin-releasing hormone receptor agonist, and an aromatase inhibitor for hormonal blockade. In this case series, seven patients at our institution were treated with bicalutamide 50 mg orally once daily, Leuprolide acetate 7.5 mg intramuscular (IM) injection every 4 weeks, and a daily oral aromatase inhibitor. These patients had recurrent AGCT with androgen receptor positive tumors and had failed prior aromatase inhibitor therapy. All patients had undergone multiple surgical resections and many cycles of chemotherapy. Patients were monitored for toxicities and for response to treatment. Of the seven patients receiving the triple therapy, six saw clinical benefit. Two patients demonstrated a partial response and four patients had stable disease. One patient had progressive disease on the regimen. For the two patients who had a partial response to the triple therapy, there was strong expression of the androgen receptor (AR) noted on tumor immunohistochemistry. This drug combination was well-tolerated except for severe hot flashes in one patient. In conclusion, the triple therapy combination of an androgen receptor antagonist, aromatase inhibitor, and GnRH agonist demonstrated measurable responses in patients with recurrent AGCTs after multiple previous treatments. A prospective clinical trial is planned to further investigate these findings.

Ovarian cancer resistance to PARPi and platinum-containing chemotherapy.

Epithelial ovarian cancer remains the most lethal female malignancy despite options for systemic therapy and the emergence of targeted therapies. Although initial response to therapy is observed, recurrence and ultimately chemoresistance result in overall therapeutic failure. This pattern has been evident with platinum therapy since the 1980s. Significant excitement surrounded the approval of poly (ADP-ribose) polymerase inhibition (PARPi) as a novel therapeutic option, especially with the advent of personalized medicine, but resistance has similarly developed to these treatments. Novel agents are constantly being sought, but if the obstacle of chemoresistance remains, the durability of responses will remain tenuous. Unraveling the multifactorial mechanisms of platinum and PARPi resistance is increasingly important as a therapeutic failure with current strategies is almost assured. Focusing greater efforts on expanding the current understanding of the complex nature of platinum and PARPi chemoresistance has tremendous potential to improve clinical outcomes.

Postoperative Risks for Hispanic Patients Undergoing Hysterectomy for Benign Indications.

BACKGROUND: Hispanic patients have previously been shown to have relatively lower odds of complication following hysterectomy compared with non-Hispanic white patients, but little is known about specific risks for this group. Our primary objective was to identify differences in proportions of specific complications experienced by Hispanic patients following hysterectomy for benign indications as compared with non-Hispanic white patients. DESIGN: Retrospective cohort study examining differences in complication rates following benign hysterectomy between Hispanic and non-Hispanic white patients in NSQIP-participating hospitals from 2012 to 2016. MEASUREMENTS AND MAIN RESULTS: A total of 102,051 women were included. A total of 15.0% were Hispanic and 85.0% were non-Hispanic white. Hispanic patients were more likely to have class 1 or 2 obesity (59.7 vs 49.8%), diabetes (10.9 vs 6.7%), and anemia (hematocrit < 33: 14.1 vs 6.5%); p < 0.01 for all. Hispanic patients were more likely to undergo abdominal hysterectomy (30.0 vs 19.1%, p < 0.01) and to remain inpatient for 2-6 days (38.8 vs 24.0%, p < 0.01). After adjustment for possible confounders including anemia, an increased odds of requiring blood transfusion persisted only in the laparoscopic and vaginal groups. Hispanic patients had a decreased or equal odds for all other examined complications. CONCLUSIONS: Compared with non-Hispanic white patients, Hispanic women had a higher odds of requiring blood transfusion even when undergoing minimally invasive laparoscopic and vaginal approaches to hysterectomy. Despite a higher proportion of open surgery, Hispanic patients had a decreased or equal odds of postoperative complications.

Iterative approach to journal club.

To identify, evaluate and refine a journal club (JC) format that increases faculty and resident engagement. An initial needs assessment followed by a trial of three JC formats: traditional single presenter, debate style and facilitated small group discussion was piloted over 6 months. Anonymous feedback was collected. The facilitated small group format was chosen. Narrative and quantitative feedback were collected from residents and faculty at 6-month intervals for the next 24 months. Changes to the format were made using feedback. Fourteen residents (n=20, 70%) and 10 faculty (n=20, 50%) completed baseline surveys. We initially observed low resident (8/14, 57%) interest in JCs. Additionally, 9/14 (64%) of residents and 1/15 (7%) of faculty reported low confidence presenting articles publicly. After implementation of the new JC format, resident reported enjoyment, on a scale of 1-5, improved from 3.6 to 4.4 (p<0.01). We observed improvement in resident confidence in the ability to critique a paper (2.7 to 4.1, p<0.01) and in confidence speaking in front of both peers (3.8 to 4.6, p<0.01) and faculty (3.0 to 3.8, p=0.04). Faculty confidence with literature critique decreased (from 4.2 to 3.8), but enjoyment remained stable (4.3 to 4.2). A facilitated small group JC format was preferred in our programme. We observed measurable improvements in both resident interest and confidence, as well as sustained faculty interest in JCs. We fostered an environment of inquiry and identified areas of continued professional development.