Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

Same day service: A genetic testing station model to improve germline genetic testing in patients with ovarian cancer.

OBJECTIVE: Genetic testing for ovarian cancer (OC) patients is essential to consideration of PARP inhibitor therapy. To improve access, we piloted a Genetic Testing Station (GTS) allowing patients to have a same-day genetic testing visit facilitated by Genetic Counselor Assistants (GCAs) under the supervision of Genetic Counselors (GCs). METHODS: The GTS was implemented December 2018 and operated through February 2020. Gynecologic Oncologists offered ovarian cancer patients a same-day GTS visit with a GCA. The patient received education via videos designed by GCs and then provided consent, a brief family history, and a sample for a standardized 133-gene panel. Results were provided by a GC. Patients were retrospectively identified by querying the medical record for OC patients seen 12 months prior to and 18 months after GTS implementation. RESULTS: A total of 482 patients pre-GTS were compared to 625 patients post-GTS. Genetic testing increased from 68.5% to 75.4% (p = 0.012) after implementation, primarily in patients with epithelial histologies (80% vs 89% in pre-GTS vs post-GTS, p = 0.005). Time from referral for genetic testing to obtaining results was evaluated in the post-GTS cohort, comparing patients who had traditional counseling to those who utilized the GTS. Time to obtaining results was 21 days in the GTS group (95% CI [10, 34]) compared to 56 days (95% CI [41,76]) in the traditional genetic counseling group. CONCLUSIONS: The GTS reduces barriers to care and facilitates discussion of precision treatment within a timely fashion while optimizing GC clinic time. Access improvement remains integral to improving uptake of genetic testing.

Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study.

OBJECTIVE: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). METHODS: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 109 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). RESULTS: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3-12.1) and median PFS was 2.8 months (95% CI: 2.6-3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. CONCLUSION: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.

NCCN Guidelines Insights: Cervical Cancer, Version 1.2020.

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)-dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.

Survival differences of Asian and Caucasian epithelial ovarian cancer patients in the United States.

OBJECTIVE: To compare the racial differences in treatment and survival of Asian-Americans and White patients with epithelial ovarian cancer. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results Program between 1988 and 2009 and analyzed using Chi-squared tests, Kaplan-Meier methods, and Cox regression analysis. RESULTS: Of the 52,260 women, 3932 (7.5%) were coded as Asian, and 48,328 (92.5%) were White. The median age of Asians at diagnosis was 56 vs. 64 years for the Whites (p<0.001). Asians were more likely to undergo primary surgery, have an earlier stage of disease, have a diagnosis of a non-serous histology, and have lower grade tumors. The 5-year disease-specific survival (DSS) of Asians was higher compared to Whites (59.1% vs. 47.3%, p<0.001). On a subset analysis, Vietnamese, Filipino, Chinese, Korean, Japanese, and Asian Indian/Pakistani ethnicities had 5-year DSS of 62.1%, 61.5%, 61.0%, 59.0%, 54.6%, and 48.2%, respectively (p=0.015). On multivariate analysis, age at diagnosis, year of diagnosis, race, surgery, stage, and tumor grade were all independent prognostic factors for survival. Asians were further stratified to U.S. born versus those who were born in Asia and immigrated. Asian immigrants presented at a younger age compared to U.S. born Asians. Immigrants were found to have an improved 5-year DSS when compared to U.S. born Asians and Whites of 55%, 52%, and 48%, respectively (p<0.001). CONCLUSION: Asians were more likely to be younger, undergo primary surgery, have an earlier stage of disease, non-serous histology, lower grade tumors, and higher survival.

Foreign- vs US-born Asians and the association of type I uterine cancer.

OBJECTIVE: The purpose of this study was to determine the association of type I endometrioid uterine cancer in US-born vs immigrant Asian women. STUDY DESIGN: Data were obtained from the Surveillance, Epidemiology, and End Results Program from 2001-2009. Chi-squared, Kaplan-Meier, and binomial logistic regression analyses were used for statistics. RESULTS: Of 4834 Asian women with uterine cancer, 62% were US-born and 38% were immigrants. Of these women, 2972 (61%) had type I (grade 1 or 2, endometrioid histologic type) uterine cancer. Compared with patients with type II disease (grade 3, clear cell and serous histologic type), patients with type I disease were younger (age 55 vs 59 years; P < .01) and had lower stage disease (90% vs 71%; P < .01). US-born Asian women had a significantly higher proportion of type I uterine cancers in contrast to their immigrant counterparts (65% vs 56%; P < .01). Of all immigrants, the proportion of type I cancers was lowest in Japanese women followed by Chinese and Filipino women, respectively (48% vs 52% vs 58%; P < .01). The 5-year disease-specific survivals of US-born vs immigrant Asian women with type I cancer was 92% for both groups. Over 3 time periods (2001-2003, 2004-2006, and 2007-2009), there was an increase in type I cancers among US-born Asian women (61% to 65% to 68%; P < .01). CONCLUSION: US-born Asian women are more likely to be diagnosed with type I uterine cancer compared with immigrants. Over the study period, there was a trend towards an increase in type I cancers among US-born Asian women.

Survival differences in women with serous tubal, ovarian, peritoneal, and uterine carcinomas.

OBJECTIVE: The fallopian tube has been implicated as the primary origin of pelvic serous cancers. We proposed to determine the survival outcomes of serous tubal, ovarian, peritoneal, and uterine cancer patients. STUDY DESIGN: Data were obtained from the National Cancer Institute between 2004 and 2009. Kaplan-Meier and Cox proportional hazards models were used for analysis. RESULTS: Of 12,336 high-grade serous cancer patients, 563 were tubal (TC), 8560 ovarian (OC), 1037 primary peritoneal (PPC), and 2176 uterine cancer (USC). The median ages of these patients were 63 vs 62 vs 67 vs 68 years, respectively. The majority were white (89% vs 88% vs 91% vs 74%). The overall 5 year, disease-specific survival was 37%. The survivals of those with TC, OC, PPC, and USC were 50%, 37%, 26%, and 40% (P < .01). There was no detailed staging on PPC cancers. Adjusted for stage, the survival of those with stage I, II, III, and IV TC were 73%, 62%, 44%, and 22% (P < .01), OC were 83%, 64%, 34%, and 15% (P < .01), and USC were 88%, 72%, 55%, and 17% (P < .01). On multivariate analysis, younger age, white race, earlier stage, and tubal origin were independent predictors for improved survival. CONCLUSION: In advanced-staged serous cancer patients, tubal cancer patients have better survivals compared with ovarian, peritoneal, and uterine cancer.

Clinical Sequencing Contributes to a BRCA-Associated Cancer Rediagnosis That Guides an Effective Therapeutic Course.

Cancer is currently classified and treated using an approach based on tissue of origin. Ambiguous or incorrect diagnoses, however, are common and often go unnoticed. Clinical cancer sequencing can provide diagnostic precision, therapeutic direction, and hereditary cancer risk assessment. This report presents a patient with an initial diagnosis of metastatic pancreatic adenocarcinoma (PDA), a disease with a dismal prognosis. Tumor sequencing revealed genomic abnormalities inconsistent with PDA, instead suggesting serous ovarian cancer. This molecular rediagnosis was further refined by the identification of a BRCA2 truncating mutation in the tumor, subsequently confirmed to be a germline event. These findings prompted the initiation of platinum-based chemotherapy, which produced a life-altering response, and referral to genetic counseling for her offspring. These results suggest that clinical tumor sequencing can simultaneously clarify diagnoses, guide therapy, and inform familial risk, even in patients with end-stage metastatic disease, making the case for the development of specific strategies to deploy sequencing coupled with big data in oncology to improve clinical cancer management.

Evidence-based prescribing of opioids after laparotomy: A quality-improvement initiative in gynecologic oncology.

Introduction: Across specialties, surgeons over-prescribe opioids to patients after surgery. We aimed to develop and implement an evidence-based calculator to inform post-discharge opioid prescription size for gynecologic oncology patients after laparotomy. Methods: In 2021, open surgical gynecologic oncology patients were called 2-4 weeks after surgery to ask about their home opioid use. This data was used to develop a calculator for post-discharge opioid prescription size using two factors: 1) age of the patient, 2) oral morphine equivalents (OME) used by patients the day before hospital discharge. The calculator was implemented on the inpatient service from 8/21/22 and patients were contacted 2-4 weeks after surgery to again assess their opioid use at home. Results: Data from 95 surveys were used to develop the opioid prescription size calculator and are compared to 95 post-intervention surveys. There was no difference pre- to post-intervention in demographic data, surgical procedure, or immediate postoperative recovery. The median opioid prescription size decreased from 150 to 37.5 OME (p < 0.01) and self-reported use of opioids at home decreased from 22.5 to 7.5 OME (p = 0.05). The refill rate did not differ (12.6 % pre- and 11.6 % post-intervention, p = 0.82). The surplus of opioids our patients reported having at home decreased from 1264 doses of 5 mg oxycodone tabs in the pre-intervention cohort, to 490 doses in the post-intervention cohort, a 61 % reduction. Conclusions: An evidence-based approach for prescribing opioids to patients after laparotomy decreased the surplus of opioids we introduced into our patients' communities without impacting refill rates.

Synthetic Lethality Beyond BRCA: A Phase I Study of Rucaparib and Irinotecan in Metastatic Solid Tumors With Homologous Recombination-Deficiency Mutations Beyond BRCA1/2.

PURPOSE: Combining poly ADP-ribose polymerase (PARP) and topoisomerase I inhibitors has demonstrated synergistic effects in in vivo models. This phase I trial evaluated rucaparib and irinotecan in metastatic solid tumors with homologous recombination deficiency. METHODS: This study enrolled patients in three cohorts to determine the tolerability and preliminary efficacy of (1) rucaparib 400 mg PO twice a day (days 1-7, 15-21) and irinotecan 65 mg/m2 intravenously once every 2 weeks; (2) rucaparib 400 mg PO twice a day (D1-7, 15-21) and irinotecan 100 mg/m2 once every 2 weeks; and (3) rucaparib 400 mg per os twice a day (D1-7) and irinotecan 100 mg/m2 once every 3 weeks. RESULTS: Twenty patients were enrolled: 95% with previous platinum, 40% with previous irinotecan, and 20% with previous PARP inhibitor. The maximally tolerated was determined as rucaparib 400 mg twice a day days 1-7 and irinotecan 100 mg/m2 once every 3 weeks. Four dose-limiting toxicities (all grade 3-4 neutropenia) occurred during dose escalation with only neutropenia as other grade 3-4 toxicities (25%; grade 3 [n = 3], grade 4 [n = 2]). Treatment-related grade 1-2 adverse events included neutropenia (45%), diarrhea (45%), nausea (40%), and fatigue (30%). Of 17 patients with evaluable disease, six patients (35%) derived clinical benefit (n = 2 with PR, n = 4 with stable disease for over 6 months). Three patients remained on study >1 year: two with ATM mutations (small bowel carcinoma and pancreatic neuroendocrine tumor) and one patient with a PALB2 mutation (primary peritoneal cancer). CONCLUSION: Pulse dosing of rucaparib and once every 3 weeks irinotecan was well tolerated for up to 18 months with durable responses in BRCA-, PALB2-, and ATM-mutated cancers despite progression on previous platinum.

Factors associated with publication of plenary presentations at the Society of Gynecologic Oncologists annual meeting.

OBJECTIVE: To determine the rate and factors associated with publication of plenary abstract presentations from the Society of Gynecologic Oncologists annual meeting. METHODS: Plenary presentations were reviewed from 2000 to 2005. A PubMed search was performed to identify subsequent peer-reviewed publication of these presentations. Chi-squared test and logistic regression were used for statistical analyses. RESULTS: Of 378 main, focused or express plenary presentations, 173 (45.8%) involved multiple and 205 (54.2%) single institutions. The types of study include: chart review (29.4%), cohort study (28.0%), translational (23.5%), and randomized clinical trial (6.9%). 309 (81.7%) of presentations were subsequently published. The median time from presentation to publication was 14months (range: 1-85). Studies from multiple vs. single institutions were more likely to be published (87.9% vs. 76.6%; p=0.005). In addition, randomized controlled trials were more likely to be published compared with chart review, cohort, and translation research (92.3% vs. 83.8%, 77.4%, and 74.2%; p<0.01). On multivariate analysis, multi-institutional studies (OR=2.28, 95% CI=1.28-4.04; p=0.005) and type of study (OR=1.64, 95% CI=1.19-2.26; p=0.002) were independent factors associated with publication. In addition, multi-institutional studies had longer times from presentation to publication compared with their counterparts. CONCLUSIONS: A high percentage of plenary presentations at the Society of Gynecologic Oncologists annual meeting resulted in subsequent publication. Multi-institutional studies and randomized clinical trials were more likely to be published.

Utilization of and charges for robotic versus laparoscopic versus open surgery for endometrial cancer.

BACKGROUND AND OBJECTIVES: To analyze the utilization and hospital charges associated with robotic (RS) versus laparoscopic (LS) versus open surgery (OS) in endometrial cancer patients. METHODS: Hospital discharge data were extracted from Florida Agency for Health Care Administration between October 2008 and December 2009. RESULTS: Of 2,247 patients (median age: 64 years), 29% had RS, 10% had LS, and 61% had OS. The mean length of hospital stay was 1.6, 1.8, and 3.9 days for RS, LS, and OS, respectively (P < 0.001). The median hospital charge was $51,569, $37,202, and $36,492, for RS, LS, and OS (P < 0.001), with operating room charges ($22,600, $13,684, and $11,272) accounting for the major difference. Robotic surgery utilization increased by 11% (23-34%) over time. CONCLUSIONS: In this statewide analysis of endometrial cancer patients, the utilization of robotic surgery increased and is associated with higher hospital charges compared to laparoscopic and open procedures.