NCCN Guidelines® Insights: Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer, Version 3.2024.

The NCCN Guidelines for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer provide multidisciplinary diagnostic workup, staging, and treatment recommendations for this disease. These NCCN Guidelines Insights detail how the evolution of the use of PARP inhibitors as maintenance and single-agent regimens for the treatment of ovarian cancer informed panel recommendations in the guidelines.

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

Development of Delivery Systems for Local Administration of Cytokines/Cytokine Gene-Directed Therapeutics: Modern Oncologic Implications.

PURPOSE OF REVIEW: In this review, we discuss modern cytokine delivery systems in oncologic care, focusing on modalities being developed in the clinical trials or currently in use. These include pegylation, immune-cytokine drug conjugates, cytokine-expressing plasmid nanoparticles, nonviral cytokine nanoparticles, viral systems, and AcTakines. RECENT FINDINGS: Cytokine therapy has the potential to contribute to cancer treatment options by modulating the immune system towards an improved antitumor response and has shown promise both independently and in combination with other immunotherapy agents. Despite promising preliminary studies, systemic toxicities and challenges with administration have limited the impact of unmodified cytokine therapy. In the last decade, novel delivery systems have been developed to address these challenges and facilitate cytokine-based oncologic treatments. Novel delivery systems provide potential solutions to decrease dose-limiting side effects, facilitate administration, and increase the therapeutic activity of cytokine treatments in oncology care. The expanding clinical and translational research in these systems provides an opportunity to augment the armamentarium of immune oncology and may represent the next frontier of cytokine-based immuno-oncology.

Adherence to treatment guidelines as a major determinant of survival disparities between black and white patients with ovarian cancer.

OBJECTIVE: To evaluate whether non-adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines and other factors related to treatment access contribute to racial disparities in ovarian cancer survival. METHODS: This large cohort study included patients from the National Cancer Database who were diagnosed with ovarian cancer between 2004 and 2014, with follow-up data up to 2017. The multivariable Cox regression was used to assess the effect of study variables on five-year overall survival. The proportion contributions of prognostic factors to the survival disparities were estimated using individual and sequential adjustment of these factors based on the Cox proportional hazards models. RESULTS: Of the 120,712 patients eligible for this study, 110,032 (91.1%) were whites and 10,680 (8.9%) were blacks. Black patients, compared with their white counterparts, had a lower adherence to NCCN guidelines (60.8% vs. 70.4%, respectively, P < 0.001), and a higher five-year mortality after cancer diagnosis (age- and tumor characteristics- adjusted hazard ratio: 1.22, 95% confidence interval: 1.19-1.25). Non-adherence to NCCN treatment guidelines was the most significant contributor to racial disparity in ovarian cancer survival, followed by access to care and comorbidity, each explaining 36.4%, 22.7%, and 18.2% of the racial differences in five-year overall survival, respectively. These factors combined explain 59.1% of racial survival disparities. Risk factors identified for non-adherence to treatment guidelines among blacks include insurance status, treatment facility type, educational attainment, age, and comorbidity. CONCLUSIONS: Adherence status to NCCN treatment guidelines is the most important contributor to the survival disparities between black and white patients with ovarian cancer. Our findings call for measures to promote equitable access to guideline-adherence care to improve the survival of black women with ovarian cancer.

Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

Microhematuria: AUA/SUFU Guideline.

PURPOSE: Patients presenting with microhematuria represent a heterogeneous population with a broad spectrum of risk for genitourinary malignancy. Recognizing that patient-specific characteristics modify the risk of underlying malignant etiologies, this guideline sought to provide a personalized diagnostic testing strategy. MATERIALS AND METHODS: The systematic review incorporated evidence published from January 2010 through February 2019, with an updated literature search to include studies published up to December 2019. Evidence-based statements were developed by the expert Panel, with statement type linked to evidence strength, level of certainty, and the Panel's judgment regarding the balance between benefits and risks/burdens. RESULTS: Microhematuria should be defined as ≥ 3 red blood cells per high power field on microscopic evaluation of a single specimen. In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. The Panel created a risk classification system for patients with microhematuria, stratified as low-, intermediate-, or high-risk for genitourinary malignancy. Risk groups were based on factors including age, sex, smoking and other urothelial cancer risk factors, degree and persistence of microhematuria, as well as prior gross hematuria. Diagnostic evaluation with cystoscopy and upper tract imaging was recommended according to patient risk and involving shared decision-making. Statements also inform follow-up after a negative microhematuria evaluation. CONCLUSIONS: Patients with microhematuria should be classified based on their risk of genitourinary malignancy and evaluated with a risk-based strategy. Future high-quality studies are required to improve the care of these patients.

Survival outcomes for robotic-assisted laparoscopy versus traditional laparoscopy in clinical stage I epithelial ovarian cancer.

BACKGROUND: The US Food and Drug Administration recently called for studies addressing long-term survival after robotic-assisted laparoscopy in oncologic settings. Long-term clinical outcomes of robotic-assisted laparoscopy among ovarian cancer patients are understudied. OBJECTIVE(S): To investigate the long-term mortality of robotic-assisted laparoscopy compared to traditional laparoscopy for clinical stage I epithelial ovarian cancer. MATERIALS AND METHODS: Using data from the National Cancer Database, we identified a total of 1901 patients who received minimally invasive surgery (ie, robotic-assisted laparoscopy or traditional laparoscopy) for clinical stage I epithelial ovarian cancer between 2010 and 2014. Multivariable logistic or linear regression analyses were conducted to evaluate the short-term outcomes, including conversion-to-open surgery, number of lymph nodes examined, length of hospitalization, unplanned 30-day readmission, and 30- and 90-day mortality. Multivariable Cox proportional hazards models were used to derive adjusted hazard ratios and 95% confidence intervals for 1-, 3-, and 5-year total mortality associated with surgical approaches. Covariates adjusted for included age, tumor size and upstaging, number of lymph nodes evaluated, time from diagnosis to surgery, length of hospitalization, histologic subtype, insurance status, region, distance to care, surgical procedure type, and hospital experience with these procedures. RESULTS: Compared to traditional laparoscopy, robotic-assisted laparoscopy was less likely to result in conversion-to-open surgery (conversion rate: 7.2% versus 17.9%, P < .001; adjusted odds ratio, 0.49; 95% confidence interval, 0.33-0.73). In multivariable analyses, there were no significant differences in survival between robotic-assisted laparoscopy- and traditional laparoscopy-treated patients. Compared with traditional laparoscopy, the adjusted hazard ratios for 1-, 3-, and 5-year mortality were 0.97 (95% confidence interval, 0.43-2.18), 0.68 (95% confidence interval, 0.43-1.08), and 0.78 (95% confidence interval, 0.53-1.16), respectively. CONCLUSION(S): Robotic-assisted laparoscopy had comparable overall mortality in comparison to traditional laparoscopy when treating clinical stage I epithelial ovarian cancer.

Reengineering academic departments of obstetrics and gynecology to operate in a pandemic world and beyond: a joint American Gynecological and Obstetrical Society and Council of University Chairs of Obstetrics and Gynecology statement.

The coronavirus disease 2019 pandemic has significantly disrupted operations in academic departments of obstetrics and gynecology throughout the United States and will continue to affect them in the foreseeable future. It has also created an environment conducive to innovation and the accelerated implementation of new ideas. These departments will need to adapt their operations to accommodate coronavirus disease 2019 and to continue to meet their tripartite mission of clinical excellence, medical education, and women's health research. This "Call to Action" paper from the leaders of American Gynecological and Obstetrical Society and Council of University Chairs of Obstetrics and Gynecology provides a framework to help the leaders of departments of obstetrics and gynecology reimagine and reengineer their operations in light of the current coronavirus disease 2019 crisis and future pandemics.

The American Gynecological and Obstetrical Society-reinvigorating for the 21st century.

The American Gynecological and Obstetrical Society (AGOS) has the potential to serve as a unifying organization to advocate for women's reproductive health care, education, and research. This report reviews a strategic plan designed to reinvigorate AGOS to address, together with our partner organizations, the ever more pressing issues and challenges in women's reproductive health.

NCCN Guidelines Insights: Ovarian Cancer, Version 1.2019.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.

A Ketogenic Diet Reduces Central Obesity and Serum Insulin in Women with Ovarian or Endometrial Cancer.

Background: The glycolytic nature of cancer cells presents a potential treatment target that may be addressed by a ketogenic diet (KD). Objective: We hypothesized that a KD would improve body composition and lower serum insulin and insulin-like growth factor-I (IGF-I) in women with ovarian or endometrial cancer. Methods: In this randomized controlled trial, women with ovarian or endometrial cancer [age: ≥19 y; body mass index (kg/m2): ≥18.5] were randomly assigned to a KD (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer Society diet (ACS; high-fiber, low-fat). Body composition (DXA) and fasting serum insulin, IGF-I, and ß-hydroxybutyrate were obtained at baseline and at 12 wk; urinary ketones were also measured throughout the intervention. We assessed differences between the diets with ANCOVA and independent t tests. We used correlation analyses to estimate associations between changes in serum analytes and body composition. Results: After 12 wk, the KD (compared with ACS) group had lower adjusted total (35.3 compared with 38.0 kg, P < 0.05) and android (3.0 compared with 3.3 kg, P < 0.05) fat mass. Percentage of change in visceral fat was greater in the KD group (compared with the ACS group; -21.2% compared with -4.6%, P < 0.05). Adjusted total lean mass did not differ between the groups. The KD (compared with ACS) group had lower adjusted fasting serum insulin (7.6 compared with 11.2 µU/mL, P < 0.01). There was a significant inverse association between the changes in serum ß-hydroxybutyrate and IGF-I concentrations (r = -0.57; P < 0.0001). Conclusions: In women with ovarian or endometrial cancer, a KD results in selective loss of fat mass and retention of lean mass. Visceral fat mass and fasting serum insulin also are reduced by the KD, perhaps owing to enhanced insulin sensitivity. Elevated serum ß-hydroxybutyrate may reflect a metabolic environment inhospitable to cancer proliferation. This trial was registered at www.clinicaltrials.gov as NCT03171506.

Characteristics of African American women at high-risk for ovarian cancer in the southeast: Results from a Gynecologic Cancer Risk Assessment Clinic.

OBJECTIVES: Describe patient characteristics in African American (AA) women seen for gynecologic cancer related genetic counseling at a large southeastern comprehensive cancer center. METHODS: We reviewed an IRB approved, prospective observational cohort of patients from a Gynecologic Cancer Risk Assessment Clinic. Data evaluated included personal cancer history, family history, frequency of genetic testing, frequency/type of genetic mutations, and frequency of surgical intervention. Standard statistical statistics were utilized. RESULTS: 1227 patients were evaluated from 2003 to 2015, of which 95 (7.7%) were AA. Sixteen patients had a personal history of ovarian cancer. 21 women (22%) underwent genetic counseling only; subsequent genetic testing was not recommended based on absence of risk factors. Of the seventy-four AA patients in whom genetic testing was recommended, sixty-six (69.5%) completed testing. Of women tested, 37 (56%) had abnormal results. Eight and 14 patients had pathogenic variants in BRCA1 and BRCA2, respectively. Two were found to have pathogenic PALB2 variants; one had a pathogenic ATM variant and one constitutional MLH1 epimutation case was identified. Eleven had BRCA variants of uncertain significance. Of the patients with abnormal testing, six of 22 women with pathogenic BRCA variants underwent risk-reducing salpingo-oophorectomy (RRSO). CONCLUSIONS: Our study demonstrates that in a region where AAs represent 27% of the population, the proportion of AA patients referred to a Gynecologic Cancer Risk Assessment Clinic remains low. Pathogenic variant and variant of uncertain significance rates were high in patients tested, likely representing a selection bias of high-risk patients. Endeavors should continue to identify minorities at risk for ovarian cancer and institute measures to provide thorough genetic counseling and testing.

Estimating potential for savings for low risk endometrial cancer using the Endometrial Cancer Alternative Payment Model (ECAP): A companion paper to the Society of Gynecologic Oncology Report on the Endometrial Cancer Alternative Payment Model.

OBJECTIVE: To design an endometrial cancer (EC) alternative payment (ECAP) model focused on surgical management of EC, as well as identify drivers of cost in order to develop opportunities for cost-savings while maintaining quality of care. METHODS: National practice patterns and reimbursements were compared between private payers (MarketScan data, years 2009-13) and public payers (Medicare, year 2014) of EC patients who underwent hysterectomy. An episode of care for EC included the hysterectomy, stratified by surgical approach (laparotomy versus robotic versus laparoscopy), and in- and outpatient reimbursements from 30days preoperatively to 60days postoperatively. Reimbursements were categorized into cost centers. A decision model informed modifiable components influencing overall reimbursements for EC surgical care. Variations in length of stay (LOS), emergency department (ED visits), and readmissions were analyzed to create an optimal care model. RESULTS: A total of MarketScan (n=29,558) and Medicare (n=377) patients were included. Mean total reimbursement for an episode of care was $19,183 (SD $10,844) for Medicare and $30,839 (SD $19,911) for MarketScan. Mean reimbursements were greatest for abdominal cases in Medicare ($25,553; SD $11,870) and MarketScan ($35,357; SD $21,670), followed by robotic and laparoscopic. Among MarketScan patients, 7.6% of women were readmitted within 60days after surgery and 11.7% had an evaluation in the ED. The median reimbursement per patient for readmission was $14,474 (IQR $8584 to $26,149), and for ED visit was $6327 (IQR $1369 to $29,153). In an optimized care model, increasing the rate of minimally invasive surgery by 5% while reducing LOS by 10% and ED visits/readmissions by 10%, lowered the average case reimbursement by $903 (2.9%) for MarketScan and $1243 (5.9%) for Medicare. CONCLUSION: An ECAP model demonstrates that reimbursements vary by public versus commercial payers in the U.S. for the surgical management of endometrial cancer patients, and that opportunities for cost savings exist. Nominal increases in the rate of minimally invasive surgery and reduction in the rate of ED visits/readmissions and length of stay can result in substantial savings for endometrial cancer care.

Society of Gynecologic Oncology Future of Physician Payment Reform Task Force report: The Endometrial Cancer Alternative Payment Model (ECAP).

Health care in the United States is in the midst of a significant transformation from a "fee for service" to a "fee for value" based model. The Medicare Access and CHIP Reauthorization Act of 2015 has only accelerated this transition. Anticipating these reforms, the Society of Gynecologic Oncology developed the Future of Physician Payment Reform Task Force (PPRTF) in 2015 to develop strategies to ensure fair value based reimbursement policies for gynecologic cancer care. The PPRTF elected as a first task to develop an Alternative Payment Model for thesurgical management of low risk endometrial cancer. The history, rationale, and conceptual framework for the development of an Endometrial Cancer Alternative Payment Model are described in this white paper, as well as directions forfuture efforts.

Values and worries of ovarian cancer patients.

INTRODUCTION: Older women with ovarian cancer (OC) are less likely to receive guideline concordant treatment. Differences in values and worries about treatment may explain why. METHODS: Women with OC in 2013-2015 were surveyed about values and worries at the time of initial treatment. Existing values (11 item, e.g., maintaining quality of life) and worries (12 items, e.g., treatment side effects) scales were adapted based on OC literature. Responses were very/somewhat/a little/not at all important or worried. Principal Component Analyses (PCA) identified groups of values and worries that best explained scales' variation. We examined proportions reporting very/somewhat important/worried on ≥1 item in each component by age (older ≥65years, younger <65years). RESULTS: Of 170 respondents, 42.3% were older. PCA components for values were: functional well-being (3 survey items, proportion of variance explained [PoVE] 26.3%), length of life and sexual functioning (3 items, PoVE 20.1%), attitudes (3 items, PoVE 14.2%), and not becoming a burden (2 items, PoVE 13.7%). PCA components for worries were: economic (4 items, PoVE 27.2%), uncertainty (6 items, PoVE 26.0%), and family impact (2 items, PoVE 16.3%). Older women were less likely to indicate very/somewhat worried to ≥1 item in the economic (51.4% vs 72.4%, p=0.006), uncertainty (80.6% vs. 98.0%, p=0.001), and family impact component (55.6% vs. 70.4%, p=0.03). No other age differences were found. CONCLUSIONS: While worry during OC treatment decision-making may differ across age groups, values do not. Research should assess how differences in worry might affect OC medical decision-making for older and younger women.

A phase I trial of intraperitoneal GEN-1, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer, administered with pegylated liposomal doxorubicin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers: An NRG Oncology/Gynecologic Oncology Group study.

OBJECTIVE: The study's purpose was to assess safety and efficacy of escalating doses of weekly GEN-1 with pegylated liposomal doxorubicin (PLD) in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers (EOC). METHODS: Patients had persistent or recurrent platinum-resistant EOC. The trial was a standard 3+3 phase I dose escalation design with patients receiving intravenous PLD 40mg/m2 (dose level 1 and 2) or 50mg/m2 (dose level 3) every 28days and intraperitoneal GEN-1 at 24mg/m2 (dose level 1) or 36mg/m2 (dose level 2 and 3) on days 1, 8, 15, and 22 of a 28day cycle. Cycles were repeated every 28days until disease progression. Patients were monitored for toxicity, clinical efficacy, and evidence of systemic and intraperitoneal immunologic effect. RESULTS: Sixteen evaluable patients received a median of 4cycles (range 1-8). No dose limiting toxicities were found. The adverse side effects were 4 grade 3 anemia, 2 grade 3 abdominal pain, 7 grade 3 neutropenia, and 2 grade 4 neutropenia. A clinical benefit of 57.1% (PR=21.4%; SD=35.7%) was found in the 14 patients with measurable disease. The highest number of partial responses (28.6%) and stable disease (57.1%) were found at dose level 3. The maximum tolerated dose was not reached. Increases in IL-12, IFN-γ, and TNF-α levels were found in peritoneal fluid following GEN-1 treatment. CONCLUSIONS: GEN-1 in combination with PLD has encouraging clinical benefit and biological activity in recurrent or persistent EOC and warrants further investigation with escalating doses of GEN-1.

Endpoints in clinical trials: What do patients consider important? A survey of the Ovarian Cancer National Alliance.

OBJECTIVE: In order to understand the patient's perspective in regards to meaningful surrogate clinical trial endpoints and the impact of treatment-related toxicity, and quality of life, we surveyed women with gynecological cancers to ascertain their preferences. METHODS: A 28-question anonymous online survey was posted on the OCNA website (www.ovariancancer.org). Survey questions included demographic factors, tumor data, and patients' preference regarding side effects and therapy endpoints. Data was analyzed for frequency and percentage of each response. Student t-test, Fisher's exact test and Wilcoxon rank sums were preformed. RESULTS: There were 1413 survey responses. Participants reported that for a new agent to be meaningful, the minimum extension of progression-free survival (PFS) and overall survival (OS) should be five or more months, 77% and 85% of the time, respectively. Most subjects (55%, n=612) were interested in an agent that would keep tumor growth relatively static without change in OS. Addressing the impact of adverse aspects from a hypothetical new agent as a function of response, there was significant migration (p<0.0001) to acceptance of greater toxicity and cost under the scenario of a 5-6months OS gain, despite three-fold higher neurotoxicity, as compared to a PFS gain of 3-4months/no OS gain without toxicity. Response patterns weren't altered by recurrence status. CONCLUSIONS: Herein, we show that magnitude of outcome is a desired effect, even given the prospect of significant toxicity and cost. However, these preferences appear to differ between those with primary and recurrent disease.

Phase 1b safety study of farletuzumab, carboplatin and pegylated liposomal doxorubicin in patients with platinum-sensitive epithelial ovarian cancer.

OBJECTIVE: Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha, over-expressed in epithelial ovarian cancer (EOC) but largely absent in normal tissue. Previously, carboplatin plus pegylated liposomal doxorubicin showed superior progression-free survival and an improved therapeutic index compared with carboplatin/paclitaxel in relapsed platinum-sensitive EOC. This study assessed safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive recurrent EOC. METHODS: This multicenter, single-arm study enrolled patients with platinum-sensitive EOC in first or second relapse for treatment with weekly farletuzumab 2.5mg/kg plus carboplatin AUC5-6 and pegylated liposomal doxorubicin 30mg/m(2) every 4weeks for 6cycles. Subsequently, maintenance with single-agent farletuzumab 2.5mg/kg once weekly or farletuzumab 7.5mg/kg once every three weeks continued until progression. The primary objective was to assess the safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin. RESULTS: Fifteen patients received a median of 12.0cycles (range, 3-26) of farletuzumab as combination therapy or maintenance, for a median of 45.0weeks (range 9-95). Farletuzumab/carboplatin/pegylated liposomal doxorubicin was generally well tolerated, with no farletuzumab-related grades 3-4 adverse events. The most commonly reported adverse events were associated with combination chemotherapy: fatigue (73.3%), nausea (46.7%), and neutropenia (40%). Ten patients had grade ≥3 adverse events, most frequently neutropenia and fatigue. No cardiac toxicity was seen. Best overall responses (RECIST) were a complete response for one patient, partial responses for 10 patients, and stable disease for four patients. CONCLUSIONS: Farletuzumab plus carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive EOC demonstrated a safety profile consistent with that of carboplatin plus pegylated liposomal doxorubicin.