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.

Intraperitoneal and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Ovarian Cancer.

OPINION STATEMENT: In our clinical practice, we have shifted away from the use of adjuvant normothermic intraperitoneal (IP) chemotherapy, particularly following the publication of GOG 252. Our decision is rooted in the accumulating evidence indicating a lack of demonstrable superiority, alongside the recognized toxicities and logistical challenges associated with its administration. This strategic departure is also influenced by the rising utilization of maintenance therapies such as bevacizumab and PARP inhibitors, which present viable alternatives for improving patient outcomes. Our utilization of hyperthermic IP chemotherapy (HIPEC) is currently reserved for a specific cohort of patients, mirroring the patient population studied in the OVHIPEC-1 trial. Specifically, our HIPEC protocol applies to patients presenting with newly diagnosed stage IIIC high-grade epithelial ovarian cancer who are deemed ineligible for primary debulking surgery. Patients must exhibit at least stable disease with neoadjuvant platinum-based chemotherapy, maintain a favorable performance status (ECOG score 0-1), possess good nutritional reserves (with no evidence of protein-calorie malnutrition and an albumin level exceeding 3.5), and not have chronic kidney disease. When HIPEC is planned, it is administered at the time of interval debulking surgery, contingent upon the attainment of optimal surgical outcomes (< 1 cm of residual disease). Our HIPEC protocol adheres to the original OVHIPEC-1 trial guidelines, employing cisplatin at a dosage of 100 mg/m2. We administer at least two antiemetics, antihistamines, and sodium thiosulfate to mitigate known side effects. Postoperatively, patients are admitted to the general surgical floor, reserving the intensive care unit for those in critical condition. We follow Enhanced Recovery After Surgery principles, incorporating early ambulation and feeding into our postoperative care strategy. We have encountered encouraging results with this approach, with most patients having largely uncomplicated postoperative courses and resuming adjuvant chemotherapy within 3 to 4 weeks of surgery.

Molecular testing for endometrial cancer: An SGO clinical practice statement.

The Cancer Genome Atlas publication first described the genomic landscape of endometrial cancer and characterized these cancers into four molecular subtypes with different prognoses. The Proactive Molecular Classifier for Endometrial Cancer was developed to more easily and inexpensively classify endometrial cancers into four similar molecular subtypes which are termed POLE, mismatch repair deficient, p53 abnormal and no specific molecular profile. Beyond these four subtypes, other molecular biomarkers may influence clinical behavior and response to targeted therapies and include beta-catenin, Her2 amplification, PI3K/mTOR/AKT alterations, L1CAM, hormone receptor expression, tumor mutational burden, and ARID1A. There are numerous clinical trials exploring treatment escalation and de-escalation within the four molecular subtypes as well as matching targeted therapies to specific mutational or biomarker profiles. All endometrial cancers should undergo basic molecular classification that includes assessment of mismatch repair status. POLE and p53 status are prognostic and may become actionable in the future. Clinicians who treat patients with endometrial cancer should understand the role of molecular classification in guiding treatment. The goal of this practice statement is to guide appropriate testing, interpretation, and application of molecular information in endometrial cancer.

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.

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.

Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study.

Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has been observed in other cancers, and because bevacizumab is incorporated in several regimens used in the recurrent setting, the duration of treatment may impact survival. We sought to identify whether earlier bevacizumab exposure is associated with prolonged bevacizumab therapy and survival by conducting a multi-institution retrospective study of recurrent OC patients treated with bevacizumab from 2004-2014. Multivariate logistic regression identified factors associated with receiving more than six bevacizumab cycles. Overall survival by duration and ordinal sequence of bevacizumab therapy were evaluated using logrank testing and Cox regression. In total, 318 patients were identified. 89.1% had stage III or IV disease; 36% had primary platinum resistance; 40.5% received two or fewer prior chemotherapy regimens. Multivariate logistic regression demonstrated that primary platinum sensitivity (Odds Ratio (OR) 2.34, p = 0.001) or initiating bevacizumab at the first or second recurrence (OR 2.73, p < 0.001) were independently associated with receiving more than six cycles of bevacizumab. Receiving more cycles of bevacizumab was associated with improved overall survival whether measured from time of diagnosis (logrank p < 0.001), bevacizumab initiation (logrank p < 0.001), or bevacizumab discontinuation (logrank p = 0.017). Waiting one additional recurrence to initiate bevacizumab resulted in a 27% increased hazard of death (Hazard Ratio (HR) 1.27, p < 0.001) by multivariate analysis. In conclusion, patients with primary platinum sensitive disease who received fewer prior lines of chemotherapy were able to receive more cycles of bevacizumab, which was associated with improved overall survival. Survival worsened when bevacizumab was initiated later in the ordinal sequence of therapies.

Smartphone-Based Facial Scanning as a Viable Tool for Facially Driven Orthodontics?

The current paradigm shift in orthodontic treatment planning is based on facially driven diagnostics. This requires an affordable, convenient, and non-invasive solution for face scanning. Therefore, utilization of smartphones' TrueDepth sensors is very tempting. TrueDepth refers to front-facing cameras with a dot projector in Apple devices that provide real-time depth data in addition to visual information. There are several applications that tout themselves as accurate solutions for 3D scanning of the face in dentistry. Their clinical accuracy has been uncertain. This study focuses on evaluating the accuracy of the Bellus3D Dental Pro app, which uses Apple's TrueDepth sensor. The app reconstructs a virtual, high-resolution version of the face, which is available for download as a 3D object. In this paper, sixty TrueDepth scans of the face were compared to sixty corresponding facial surfaces segmented from CBCT. Difference maps were created for each pair and evaluated in specific facial regions. The results confirmed statistically significant differences in some facial regions with amplitudes greater than 3 mm, suggesting that current technology has limited applicability for clinical use. The clinical utilization of facial scanning for orthodontic evaluation, which does not require accuracy in the lip region below 3 mm, can be considered.

Fabrication and In Vitro Characterization of Novel Hydroxyapatite Scaffolds 3D Printed Using Polyvinyl Alcohol as a Thermoplastic Binder.

This paper presents a proof-of-concept study on the biocolonization of 3D-printed hydroxyapatite scaffolds with mesenchymal stem cells (MSCs). Three-dimensional (3D) printed biomimetic bone structure made of calcium deficient hydroxyapatite (CDHA) intended as a future bone graft was made from newly developed composite material for FDM printing. The biopolymer polyvinyl alcohol serves in this material as a thermoplastic binder for 3D molding of the printed object with a passive function and is completely removed during sintering. The study presents the material, the process of fused deposition modeling (FDM) of CDHA scaffolds, and its post-processing at three temperatures (1200, 1300, and 1400 °C), as well it evaluates the cytotoxicity and biocompatibility of scaffolds with MTT and LDH release assays after 14 days. The study also includes a morphological evaluation of cellular colonization with scanning electron microscopy (SEM) in two different filament orientations (rectilinear and gyroid). The results of the MTT assay showed that the tested material was not toxic, and cells were preserved in both orientations, with most cells present on the material fired at 1300 °C. Results of the LDH release assay showed a slight increase in LDH leakage from all samples. Visual evaluation of SEM confirmed the ideal post-processing temperature of the 3D-printed FDM framework for samples fired at 1300 °C and 1400 °C, with a porosity of 0.3 mm between filaments. In conclusion, the presented fabrication and colonization of CDHA scaffolds have great potential to be used in the tissue engineering of bones.

Society of Gynecologic Oncology recommendations for fellowship education during the COVID-19 pandemic and beyond: Innovating programs to optimize trainee success.

In approximately ten months' time, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over 34 million people and caused over one million deaths worldwide. The impact of this virus on our health, relationships, and careers is difficult to overstate. As the economic realities for academic medical centers come into focus, we must recommit to our core missions of patient care, education, and research. Fellowship education programs in gynecologic oncology have quickly adapted to the "new normal" of social distancing using video conferencing platforms to continue clinical and didactic teaching. United in a time of crisis, we have embraced systemic change by developing and delivering collaborative educational content, overcoming the limitations imposed by institutional silos. Additional innovations are needed in order to overcome the losses in program surgical volume and research opportunities. With the end of the viral pandemic nowhere in sight, program directors can rethink how education is best delivered and potentially overhaul aspects of fellowship curriculum and content. Similarly, restrictions on travel and the need for social distancing has transformed the 2020 fellowship interview season from an in-person to a virtual experience. During this time of unprecedented and rapid change, program directors should be particularly mindful of the needs and health of their trainees and consider tailoring their educational experiences accordingly.

Endometrial cancer: A society of gynecologic oncology evidence-based review and recommendations, part II.

In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. This manuscript, Part II in a two-part series, includes specific recommendations on treatment of recurrent disease, post treatment surveillance and survivorship, considerations for younger women, and special situations. Part I covered histopathology and molecular pathology, risk factors, presentation and diagnostic approach, surgical approach and adjuvant therapy.

Endometrial cancer: A society of gynecologic oncology evidence-based review and recommendations.

INTRODUCTION: In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. Despite these advances, the incidence of endometrial cancer as well as the deaths attributable to the disease have continued to rise; from 1987 to 2014 there has been a 75% increase in cases and almost 300% increase in endometrial cancer deaths. Fortunately, since then, there has been progress in the treatment of patients with endometrial cancer with increased utilization of molecular pathology, greater understanding of genetic predisposition, enhanced methods for lymph node assessment, a broader understanding of the efficacy of radiation and chemotherapy, and a more efficient approach to survivorship and surveillance. The purpose of this document is to present a comprehensive review of this progress. MANUSCRIPT DEVELOPMENT PROCESS: The authors reviewed the available evidence, contributed to the development of this manuscript, provided critical review of the guidelines, and finalized the manuscript recommendations. The review was also presented to and approved by the Society of Gynecologic Oncology (SGO) Clinical Practice Committee, SGO Publications Committee, and the SGO board members prior to submission for publication. The recommendations for this manuscript were developed by a panel of gynecologic oncologists who were members of the SGO Clinical Practice and Education Committees. Panelists reviewed and considered evidence from current uterine cancer literature. The terminology used in these guidelines was adopted from the ASCCP management guidelines [1] using a two-part rating system to grade the strength of recommendation and quality of evidence (Table 1). The rating for each recommendation is given in parentheses.

A multicenter open-label randomized phase II trial of paclitaxel plus EP-100, a novel LHRH receptor-targeted, membrane-disrupting peptide, versus paclitaxel alone for refractory or recurrent ovarian cancer.

OBJECTIVE: This randomized open-label phase II study evaluated the safety and clinical activity of EP-100 plus weekly paclitaxel in patients with recurrent ovarian cancer expressing positive LHRH receptor. METHODS: In a limited "run-in" dose escalation phase for EP-100, six patients were treated with ascending dose levels (13 mg/m2, 20 mg/m2, 30 mg/m2). In the randomized phase, patients received weekly paclitaxel (80 mg/m2 intravenously) plus twice weekly EP-100 (30 mg/m2 intravenously; combination arm) or weekly paclitaxel alone (80 mg/m2 intravenously; paclitaxel arm). The primary study endpoint was overall response rate (ORR). RESULTS: Forty-four patients were then randomized to either the experimental combination arm (n = 23) or the standard of care paclitaxel monotherapy arm (n = 21). The ORR was 35% (95%CI 16%-57%) for the combination arm and 33% (95% CI 15%-57%) for the paclitaxel arm. An interesting observation from an unplanned analysis was that a subset of patients with target liver lesions showed a greater overall response rate to the combination (69%) compared to paclitaxel alone (16%). The frequency of treatment-related grade 3-4 adverse events was similar between treatment arms: 48% vs 43% for the combination and paclitaxel arms, respectively. CONCLUSIONS: ORR in the EP-100 combination arm was similar to that in the group treated with paclitaxel alone; however, a subset of patients with liver metastases appeared to benefit from the combination. The addition of EP-100 did not appear to augment the adverse event profile of paclitaxel and was well tolerated.

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.

Postoperative narcotic use in patients with ovarian cancer on an Enhanced Recovery After Surgery (ERAS) pathway.

OBJECTIVES: To determine the impact of an ERAS pathway on post-discharge narcotic use for patients with ovarian cancer undergoing open surgery. METHODS: This was a retrospective cohort study of women who underwent open ovarian cancer surgeries in 2014 prior to ERAS ("pre-ERAS") and in 2016/2018 after ERAS was instituted ("ERAS"). Patients taking chronic narcotics were excluded. A statewide prescription monitoring program was used to identify narcotic prescriptions filled in the three months after surgery. Quantity of narcotic medication is referenced in morphine milligram equivalents (MME). RESULTS: 42 pre-ERAS and 94 ERAS patients were included. The groups were similar in age, BMI, diabetes, tobacco use, mean number of prior abdominal/pelvic surgeries, and advanced stage disease. ERAS patients had a shorter hospital stay (6.7 days pre-ERAS vs 4.2 days ERAS, p = 0.003), used less narcotic in the 24 h prior to discharge (74.0 MME pre-ERAS vs 25.8 MME ERAS, p = 0.002), and filled prescriptions at time of discharge for less narcotic (519.9 MME pre-ERAS vs 339.7 MME ERAS, p = 0.011). After hospital discharge, ERAS patients filled fewer additional prescriptions (52.4% pre-ERAS, vs 29.4% ERAS, p = 0.012). In total, ERAS patients filled prescriptions for 55% fewer narcotics in the three months after surgery than the pre-ERAS group (1101.4 MME pre-ERAS vs 492.1 MME ERAS, p < 0.001). CONCLUSIONS: Institution of an ERAS protocol appears to decrease the narcotic needs of patients in the three months after ovarian cancer surgery.

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.

Intraperitoneal ports placed at the time of bowel resection for treatment of ovarian cancer: Complications and surgical outcomes.

OBJECTIVES: To determine if intraperitoneal (IP) ports placed concurrently with bowel resection during surgical treatment of ovarian cancer is associated with more complications than those ports placed without concurrent bowel resection. METHODS: The medical records of all patients who had an IP port placed at our institution between 2005 and 2016 were reviewed. Two groups were analyzed: IP ports placed with bowel resection (IP-BR) and those without (IP). RESULTS: Of 306 patient charts reviewed, 31% had a surgery with IP port placement and concurrent bowel resection (IP-BR). Demographics were similar except for mean BMI (25.6 IP-BR vs 27.4 IP, p = 0.007). More IP-BR patients had stage IIIC disease (83.3% IP-BR vs 56.9% IP, p ≤0.01). Patients were cytoreduced to R0 in 48.7% IP-BR vs 56.4% IP (p = 0.253). For adjuvant treatment, IV chemotherapy was administered before IP chemotherapy in 90.4% IP-BR (median 2 cycles), and 50.3% IP, (median 2 cycles, p < 0.01). Ultimately 80.2% IP-BR (median 4 cycles) and 77.8% IP (median 5 cycles) received IP chemotherapy (p = 0.65). Rates of total IP port complications were similar (19.2% IP-BR vs 23.2% IP, p = 0.397), including IP port infections (0% IP-BR vs 0.7% IP, p = 0.5). Eleven percent of IP-BR patients had a bowel complication (e.g. obstruction or perforation) while IP port was in situ vs 2.7% IP (p = 0.01). Only 2.7% IP-BR and 6% IP discontinued IP chemotherapy due to IP port complication (p = 0.3). CONCLUSIONS: Patients who have IP ports placed concurrently with a bowel resection do not appear to have more complications, nor lower rates of IP chemotherapy administration.

Post-diagnosis use of antihypertensive medications and the risk of death from ovarian cancer.

OBJECTIVE: To examine associations between post-diagnosis use of antihypertensive (AH) medications including thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACEIs), beta blockers (BBs) [both non-selective (NSBBs) and selective (SBBs)] and calcium channel blockers (CCBs) and ovarian cancer-specific survival. METHODS: This cohort study used SEER-Medicare data on 2195 women 66+ years of age who were diagnosed with ovarian cancer during 2007-2012 and who survived for at least 12 months. Use of an AH class was defined as two or more fills during the year after diagnosis. Ovarian cancer-specific death was assessed starting one year after diagnosis and continued through the end of 2013. Associations between AH use and ovarian cancer-specific mortality were assessed using Cox proportional hazard models, comparing users of a given class of AH to non-AH users. RESULTS: Overall, 718 (33%), 690 (31%), 521 (24%), 154 (7%) of women used a TD, ACEI, BB, or CCB, respectively, with some women (48%) using more than one class of drug. Ovarian cancer-specific mortality was found to be lower among women who used an ACEI (adjusted hazard ratio [aHR] 0.76, 95% confidence interval [CI] 0.63-0.92), a TD (aHR 0.82, 95%CI 0.68-0.99), or a NSBB (aHR 0.60, 95%CI 0.43-0.83), but no such association was seen in women who took a SBB or CCB. CONCLUSION: We observed that women who took certain forms of an AH medication during the year following a diagnosis of ovarian cancer were thereafter at a relatively reduced risk of dying from their disease. However, the potential for residual confounding by disease severity argues for a cautious interpretation.

Revisiting Minimally Invasive Surgery in the Management of Early-Stage Cervical Cancer.

Minimally invasive surgery (MIS) was previously considered an acceptable alternative to open radical hysterectomy in the management of early-stage cervical cancer (ESCC), but adequately powered, high-quality prospective trials evaluating survival outcomes were lacking. Recently, a large randomized phase III trial, the Laparoscopic Approach to Cervical Cancer (LACC) trial, showed that MIS for ESCC is associated with a higher risk of recurrence and death compared with open surgery. We review the LACC trial findings in depth, as well as a recent National Cancer Database analysis using propensity score weighting that supports the LACC trial findings. Additional studies are needed to better understand the mechanisms explaining the worse survival associated with MIS for ESCC. This review discusses considerations for integrating the findings of the LACC trial into clinical practice. Based on the high-quality evidence now available, open radical hysterectomy should be offered as standard of care for stage IA2-IB1 cervical cancer and patients should be guided appropriately to make informed shared decision-making if they still desire MIS.

The end of life costs for Medicare patients with advanced ovarian cancer.

OBJECTIVE: To describe the Medicare payments at the end of life for patients with advanced ovarian cancer, and assess factors responsible for payment variation METHODS: Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified a cohort of women with stage III/IV epithelial ovarian cancer diagnosed between 1995 and 2007. We defined the end of life as the last 90days prior to death. Total medical costs were estimated from overall Medicare payments, and adjusted for geography and for inflation to the 2009 U.S. dollar. A generalized linear regression was performed to assess factors associated with variability in cost. RESULTS: Of 5509 patients, 78.9% died from ovarian cancer. In the 90days prior to death, 65.2% of patients had an inpatient admission, 53.7% received chemotherapy, 19.3% had a palliative procedure, and 62.5% had hospice services. The mean total payment per patient in the last 90days of life was $24,073 (range 0-$484,119) over the study time period. The mean cost of inpatient admissions was $14,529 (range 0-$483,932). On a multivariate analysis, costs at the end of life did not vary based on length of patient survival (p=0.77). Factors associated with significantly increased costs in the last 90days of life were medical comorbidity, chemotherapy, time spent as an inpatient, and admissions associated with emergency room visits. CONCLUSIONS: Reducing the prescription of chemotherapy and increasing the use of hospice services for ovarian cancer patients at the end of life will aid in lowering costs.