Call me Ishmael: addressing the white whale of team communication in the operating room with labelled surgical caps at an academic medical centre.

INTRODUCTION: Effective communication in the operating room (OR) is crucial. Addressing a colleague by their name is respectful, humanising, entrusting and associated with improved clinical outcomes. We aimed to enhance team communication in the perioperative environment by offering personalised surgical caps labelled with name and provider role to all OR team members at a large academic medical centre. MATERIALS AND METHODS: This was a quasi-experimental, uncontrolled, before-and-after quality improvement study. A survey regarding perceptions of team communication, knowledge of names and roles, communication barriers, and culture was administered before and after cap delivery. Survey results were measured on a 5-point Likert Scale; descriptive statistics and mean scores were compared. All cause National Surgical Quality Improvement Project (NSQIP) morbidity and mortality outcomes for surgical specialties were examined. RESULTS: 1420 caps were delivered across the institution. Mean survey scores increased for knowing the names and roles of providers around the OR, feeling that people know my name and feeling comfortable communicating without barriers across disciplines. The mean score for team communication around the OR is excellent was unchanged. The highest score both before and after was knowing the name of an interdisciplinary team member is important for patient care. A total of 383 and 212 providers participated in the study before and after cap delivery, respectively. Participants agreed or strongly agreed that labelled surgical caps made it easier to talk to colleagues (64.9%) while improving communication (66.0%), team culture (60.5%) and patient care (56.8%). No significant differences were noted in NSQIP outcomes. CONCLUSIONS: Personalised labelled surgical caps are a simple, inexpensive tool that demonstrates promise in improving perioperative team communication. Creating highly reliable surgical teams with optimal communication channels requires a multifaceted approach with engaged leadership, empowered front-line providers and an institutional commitment to continuous process improvement.

A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer.

BACKGROUND: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer. PRIMARY OBJECTIVE: The primary objective is to evaluate the efficacy of intra-peritoneal Olvi-Vec followed by platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer. STUDY HYPOTHESIS: This phase III study investigates Olvi-Vec oncolytic immunotherapy followed by platinum-based chemotherapy and bevacizumab as an immunochemotherapy evaluating the hypothesis that such sequential combination therapy will prolong progression-free survival (PFS) and bring other clinical benefits compared with treatment with platinum-based chemotherapy and bevacizumab. TRIAL DESIGN: This is a multicenter, prospective, randomized, and active-controlled phase III trial. Patients will be randomized 2:1 into the experimental arm treated with Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or the control arm treated with platinum-doublet chemotherapy and bevacizumab. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have recurrent, platinum-resistant/refractory, non-resectable high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer. Patients must have had ≥3 lines of prior chemotherapy. PRIMARY ENDPOINT: The primary endpoint is PFS in the intention-to-treat population. SAMPLE SIZE: Approximately 186 patients (approximately 124 patients randomized to the experimental arm and 62 to the control arm) will be enrolled to capture 127 PFS events. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Expected complete accrual in 2024 with presentation of primary endpoint results in 2025. TRIAL REGISTRATION: NCT05281471.

Intraoperative Multivessel Embolization Reduces Blood Loss and Transfusion Requirements Compared to Internal Iliac Artery Balloon Placement during Cesarean Hysterectomy for Placenta Accreta Spectrum.

PURPOSE: To evaluate the effectiveness and safety of prophylactic multivessel selective embolization (MVSE) compared to those of internal iliac artery occlusion balloon (IIABO) placement in patients undergoing cesarean hysterectomy for placenta accreta spectrum (PAS). MATERIALS AND METHODS: An institutional review board-approved retrospective series was conducted with consecutive patients with PAS at a single institution between 2010 and 2021. MVSE was performed in a hybrid operating room after cesarean section prior to hysterectomy. IIABO was performed with balloons placed into the bilateral internal iliac arteries, which were inflated during hysterectomy. Median blood loss, transfusion requirements, percentage of cases requiring transfusion, and adverse events were recorded. RESULTS: A total of 20 patients treated with embolization and 34 patients with balloon placement were included. Placenta percreta and previa were seen in 60% and 90% of patients, respectively. Median blood loss in the MVSE group was 713 mL (interquartile range [IQR], 475-1,000 mL) compared to 2,000 mL (IQR, 1,500-2,425 mL) in the IIABO group (P < .0001). The median total number of units of packed red blood cell transfusions (0 vs 2.5) and percentage of cases requiring a transfusion (20% vs 65%) were less in the MVSE group (P < .01). A median of 4 vessels (IQR, 3-9) were embolized during MVSE. No major adverse events or nontarget embolization consequences were observed. CONCLUSIONS: Prophylactic MVSE is a safe procedure that reduces operative blood loss and transfusion requirements compared to those of IIABO in patients undergoing cesarean hysterectomy for presumed higher-degree PAS.

Surgical pit crew: initiative to optimise measurement and accountability for operating room turnover time.

BACKGROUND AND OBJECTIVES: Turnover time (TOT), defined as the time between surgical cases in the same operating room (OR), is often perceived to be lengthy without clear cause. With the aim of optimising and standardising OR turnover processes and decreasing TOT, we developed an innovative and staff-interactive TOT measurement method. METHODS: We divided TOT into task-based segments and created buttons on the electronic health record (EHR) default prelogin screen for appropriate staff workflows to collect more granular data. We created submeasures, including 'clean-up start', 'clean-up complete', 'set-up start' and 'room ready for patient', to calculate environmental services (EVS) response time, EVS cleaning time, room set-up response time, room set-up time and time to room accordingly. RESULTS: Since developing and implementing these workflows, measures have demonstrated excellent staff adoption. Median times of EVS response and cleaning have decreased significantly at our main hospital ORs and ambulatory surgery centre. CONCLUSION: OR delays are costly to hospital systems. TOT, in particular, has been recognised as a potential dissatisfier and cause of delay in the perioperative environment. Viewing TOT as one finite entity and not a series of necessary tasks by a variety of team members limits the possibility of critical assessment and improvement. By dividing the measurement of TOT into respective segments necessary to transition the room at the completion of one case to the onset of another, valuable insight was gained into the causes associated with turnover delays, which increased awareness and improved accountability of staff members to complete assigned tasks efficiently.

A randomized patient education trial investigating treatment-related distress and satisfaction with the use of an at-home gynecologic brachytherapy educational video.

BACKGROUND: Physician explanation of gynecologic brachytherapy can be overwhelming or induce patient anxiety, and may be time-constrained given clinical limitations. We report the first randomized trial of an educational video intervention in gynecologic brachytherapy on patient-reported outcomes. METHODS: Between February 2020 and January 2022, 80 gynecologic cancer patients prescribed brachytherapy were randomly assigned to either standard informed consent (Arm A) or a supplemental 16 min brachytherapy educational video (https://vimeo.com/403385455/d0716e3cc8) via the internet (Arm B). Primary outcome was treatment-related distress (National Comprehensive Cancer Network (NCCN) distress scale scored 0 (no distress) to 10 (maximum distress)). Secondary outcome was patient satisfaction (summated Likert-scale scored 11-55). Surveys were administered at baseline, after first treatment, and prior to brachytherapy completion. RESULTS: All patients completed the prescribed brachytherapy. In Arm B, 19/40 (48%) patients and 10/40 (25%) patients' family/friends viewed the video. For patients that completed all surveys (Arm A n=29, Arm B n=28), there was no difference between arms in the sociodemographic, clinical, or treatment variables. Distress scores were low at baseline (Arm A median 4, Arm B median 4, p=0.65) and there was no detectable change in distress between arms on surveys 1 and 2 (ß 0.36, p=0.67) or surveys 1 and 3 (ß -1.02, p=0.29) in multivariable analysis. Satisfaction scores were high at baseline (Arm A median 54, Arm B median 54.5, p=0.64) and there was no detectable change in satisfaction between arms on surveys 1 and 2 (ß 0.22, p=0.93) or surveys 1 and 3 (ß 0.63, p=0.85) in multivariable analysis. CONCLUSIONS: Among patients randomized to an educational video tool for gynecologic brachytherapy, approximately 50% of the cohort and 25% of the cohort's family/friends used the video. Overall, patients had low distress scores and high satisfaction scores with no significant differences between the standard and video intervention arms. Further work is needed to understand factors contributing to gynecologic brachytherapy anxiety. TRIAL REGISTRATION NUMBER: NCT04363957.

Incomplete cisplatin regimens in chemoradiation and its effect on outcomes for locally advanced cervical cancer.

OBJECTIVE: To identify factors associated with receipt of incomplete cisplatin during chemoradiation for locally advanced cervical cancer and its impact on outcomes. METHODS: Patients with locally advanced cervical cancer treated with chemoradiation at our institution between November 2015 and August 2020 were retrospectively identified. Patients who received ≤4 cycles were identified as the 'incomplete' cohort and those who received 5-6 cycles as the 'complete' cohort. The primary endpoint of incomplete chemotherapy was evaluated with multivariable logistic regression. Secondary endpoints of locoregional failure, overall survival, and distant failure were evaluated in multivariable Cox and Fine-Gray models. RESULTS: Of 140 patients with locally advanced cervical cancer that underwent chemoradiation, 22 (15.7%) received an incomplete cisplatin regimen (8 with 0 cycles, 14 with 1-4 cycles). The most common reasons for receiving incomplete treatment were comorbidities/infections (41%), unmet laboratory parameters (27%), and cisplatin intolerance (14%). In multivariable models, only poor (2-4) Eastern Cooperative Oncology Group performance status was a significant predictor as these patients were 41 times more likely to receive incomplete chemotherapy (odds ratio (OR), 95% confidence interval (CI) 4.57 to 375.15, p<0.001). Median follow-up time was 20 months (range 4-64). In multivariable models, receipt of incomplete cisplatin was significantly associated with higher recurrence (locoregional failure hazard ratio (HR) 3.02, 95% CI 1.08 to 8.45, p=0.03; distant failure HR 2.71, 95% CI 1.13 to 6.47, p=0.02) and worse survival (overall survival HR 4.91, 95% CI 1.27 to 18.98, p=0.02). CONCLUSION: Incomplete cisplatin regimen was associated with worse oncologic outcomes. Poor performance status was the only factor associated with receiving an incomplete regimen. This notable proportion of patients may be a target for better tolerated novel targeted anticancer agents in order to improve outcomes.

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.

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.

Tumor FAK orchestrates immunosuppression in ovarian cancer via the CD155/TIGIT axis.

High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by an immunosuppressive tumor microenvironment containing few tumor infiltrating lymphocytes (TILs) and an insensitivity to checkpoint inhibitor immunotherapies. Gains in the PTK2 gene encoding focal adhesion kinase (FAK) at Chr8 q24.3 occur in ∼70% of HGSOC tumors, and elevated FAK messenger RNA (mRNA) levels are associated with poor patient survival. Herein, we show that active FAK, phosphorylated at tyrosine-576 within catalytic domain, is significantly increased in late-stage HGSOC tumors. Active FAK costained with CD155, a checkpoint receptor ligand for TIGIT (T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains), in HGSOC tumors and a selective association between FAK and TIGIT checkpoint ligands were supported by patient transcriptomic database analysis. HGSOC tumors with high FAK expression were associated with low CD3 mRNA levels. Accordingly, late-stage tumors showed elevated active FAK staining and significantly lower levels of CD3+ TILs. Using the KMF (Kras, Myc, FAK) syngeneic ovarian tumor model containing spontaneous PTK2 (FAK) gene gains, the effects of tumor intrinsic genetic or oral small molecule FAK inhibitior (FAKi; VS-4718) were evaluated in vivo. Blocking FAK activity decreased tumor burden, suppressed ascites KMF-associated CD155 levels, and increased peritoneal TILs. The combination of FAKi with blocking TIGIT antibody (1B4) maintained elevated TIL levels and reduced TIGIT+ T regulatory cell levels, prolonged host survival, increased CXCL13 levels, and led to the formation of omental tertiary lymphoid structures. Collectively, our studies support FAK and TIGIT targeting as a rationale immunotherapy combination for HGSOC.

A Novel Fellowship in Perioperative Administration, Quality and Informatics: A Pilot Experience for Training Surgical Leaders.

Value-based, outcome-oriented care supported with innovative technology is the future of surgery. We established a novel fellowship in Perioperative Administration, Quality, and Informatics. The aim is to equip future surgeon scholars with the requisite knowledge base and skillset to serve as institutional leaders capable of transforming surgical healthcare delivery. The model was designed as a project-based, "operations-focused" education with supplemental didactics and mentored by surgical leaders and institutional executives. We describe our initial experience, successes, and challenges such that a similar model may be replicated elsewhere.

Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer.

BACKGROUND: Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combination of a checkpoint inhibitor (nivolumab) and an antiangiogenic agent (cabozantinib) in immunotherapy-naïve endometrial cancer and in patients whose disease progressed on previous immunotherapy with baseline biopsy for immune profiling. PATIENTS AND METHODS: In this phase II trial (ClinicalTrials.gov NCT03367741, registered December 11, 2017), women with recurrent endometrial cancer were randomized 2:1 to nivolumab with cabozantinib (Arm A) or nivolumab alone (Arm B). The primary endpoint was Response Evaluation Criteria in Solid Tumors-defined progression-free survival (PFS). Patients with carcinosarcoma or prior immune checkpoint inhibitor received combination treatment (Arm C). Baseline biopsy and serial peripheral blood mononuclear cell (PBMC) samples were analyzed and associations between patient outcome and immune data from cytometry by time of flight (CyTOF) and PBMCs were explored. RESULTS: Median PFS was 5.3 (90% CI 3.5 to 9.2) months in Arm A (n=36) and 1.9 (90% CI 1.6 to 3.4) months in Arm B (n=18) (HR=0.59, 90% CI 0.35 to 0.98; log-rank p=0.09, meeting the prespecified statistical significance criteria). The most common treatment-related adverse events in Arm A were diarrhea (50%) and elevated liver enzymes (aspartate aminotransferase 47%, alanine aminotransferase 42%). In-depth baseline CyTOF analysis across treatment arms (n=40) identified 35 immune-cell subsets. Among immunotherapy-pretreated patients in Arm C, non-progressors had significantly higher proportions of activated tissue-resident (CD103+CD69+) ɣδ T cells than progressors (adjusted p=0.009). CONCLUSIONS: Adding cabozantinib to nivolumab significantly improved outcomes in heavily pretreated endometrial cancer. A subgroup of immunotherapy-pretreated patients identified by baseline immune profile and potentially benefiting from combination with antiangiogenics requires further investigation.

Positron Emission Tomography-Guided Bone Marrow-Sparing Radiation Therapy for Locoregionally Advanced Cervix Cancer: Final Results From the INTERTECC Phase II/III Trial.

PURPOSE: To test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer. METHODS AND MATERIALS: In an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS. RESULTS: In total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P = .048) and in the combined cohort (13% vs 35%, χ2P = .01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P = .216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group. CONCLUSIONS: PET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.

Improved Prognosis of Treatment Failure in Cervical Cancer with Nontumor PET/CT Radiomics.

Radiomics has been applied to predict recurrence in several disease sites, but current approaches are typically restricted to analyzing tumor features, neglecting nontumor information in the rest of the body. The purpose of this work was to develop and validate a model incorporating nontumor radiomics, including whole-body features, to predict treatment outcomes in patients with previously untreated locoregionally advanced cervical cancer. Methods: We analyzed 127 cervical cancer patients treated definitively with chemoradiotherapy and intracavitary brachytherapy. All patients underwent pretreatment whole-body 18F-FDG PET/CT. To quantify effects due to the tumor itself, the gross tumor volume (GTV) was directly contoured on the PET/CT image. Meanwhile, to quantify effects arising from the rest of the body, the planning target volume (PTV) was deformably registered from each planning CT to the PET/CT scan, and a semiautomated approach combining seed-growing and manual contour review generated whole-body muscle, bone, and fat segmentations on each PET/CT image. A total of 965 radiomic features were extracted for GTV, PTV, muscle, bone, and fat. Ninety-five patients were used to train a Cox model of disease recurrence including both radiomic and clinical features (age, stage, tumor grade, histology, and baseline complete blood cell counts), using bagging and split-sample-validation for feature reduction and model selection. To further avoid overfitting, the resulting models were tested for generalization on the remaining 32 patients, by calculating a risk score based on Cox regression and evaluating the c-index (c-index > 0.5 indicates predictive power). Results: Optimal performance was seen in a Cox model including 1 clinical biomarker (whether or not a tumor was stage III-IVA), 2 GTV radiomic biomarkers (PET gray-level size-zone matrix small area low gray level emphasis and zone entropy), 1 PTV radiomic biomarker (major axis length), and 1 whole-body radiomic biomarker (CT bone root mean square). In particular, stratification into high- and low-risk groups, based on the linear risk score from this Cox model, resulted in a hazard ratio of 0.019 (95% CI, 0.004, 0.082), an improvement over stratification based on clinical stage alone, which had a hazard ratio of 0.36 (95% CI, 0.16, 0.83). Conclusion: Incorporating nontumor radiomic biomarkers can improve the performance of prognostic models compared with using only clinical and tumor radiomic biomarkers. Future work should look to further test these models in larger, multiinstitutional cohorts.

Practice patterns and survival in FIGO 2009 stage 3B endometrial cancer.

OBJECTIVE: To describe the practice patterns and outcomes of patients with stage 3B endometrial cancer. METHODS: We queried the National Cancer Database for all surgically staged, stage 3 patients between 2012 and 2016. Patients who received any pre-operative therapy were excluded. Demographics, tumor factors, and adjuvant therapy for the stage 3 substages were compared. Logistic regression was used to identify factors associated with adjuvant therapy. Kaplan Meier curves were generated and compared using the log-rank test. Multivariable Cox Proportional Hazards Model was used to adjust for prognostic factors. Findings with p < 0.05 were considered significant. RESULTS: Of 7363 patients with stage 3 disease, 478 (6%) had stage 3B; 1732 (23%) had stage 3A, 3457 (48%) had stage 3C1, and 1696 (23%) had stage 3C2 disease. Post-surgical treatment consisted of: combined chemotherapy (CT) and radiation (RT) (49%), CT alone (28%), RT alone (9%), 14% received no postoperative therapy. Among all stage 3 substages, patients with stage 3B disease were the least likely to receive any CT, and the most likely to receive RT alone. After adjusting for known prognostic factors, patients with stage 3A (Hazard ratio (HR) of death = 0.64) and 3C1 (HR of death = 0.79) disease had significantly worse overall survival compared to stage 3B; survival was not demonstrably different from patients with stage 3C2 disease. Patients with stage 3B disease who received CT + RT had the best overall survival. CONCLUSION: Survival of patients with stage 3B disease is similar to that of patients with para-aortic node metastases and is inferior to all others with stage 3 endometrial cancer. Less frequent CT and a higher rate of post-operative RT alone, describes a distinct practice from that seen in other stage 3 patients.

Bilateral Breast Radiation Associated Angiosarcoma After Radiotherapy for Bilateral Invasive Ductal Adenocarcinoma.

Angiosarcoma is a rare, highly malignant endothelial cell carcinoma. Radiotherapy on breast cancer increases the risk of developing an angiosarcoma. We report an extremely rare case of bilateral breast radiation-associated angiosarcoma (RAA). Patient had a strong breast cancer family history, and genetic testing identified KRAS, PIK3CA, RPTOR, and VHL mutation, along with MYC amplification. The overall prognosis of RAA is poor as RAA is characterized by early metastasis, frequent local recurrence, and short overall survival time. The patient eventually passed away because of breast cancer metastasis to the lung and liver.

Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization: the PASTIME protocol.

BACKGROUND: Multidisciplinary care of placenta accreta spectrum cases improves pregnancy outcomes, but the specific components of such a multidisciplinary collaboration varies between institutions. As experience with placenta accreta spectrum increases, it is crucial to assess new surgical techniques and protocols to help improve maternal outcomes and to advocate for hospital resources. OBJECTIVE: This study aimed to assess a novel multidisciplinary protocol for the treatment of placenta accreta spectrum that comprises cesarean delivery, multivessel uterine embolization, and hysterectomy in a single procedure within a hybrid operative suite. STUDY DESIGN: This was a matched prepost study of placenta accreta spectrum cases managed before (2010-2017) and after implementation of the Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol (2018-2021) at a tertiary medical center. Historical cases were managed with internal iliac artery balloon placement in selected cases with the decision to inflate the balloons intraoperatively at the discretion of the primary surgeon. Intraoperative Embolization cases were compared with historical cases in a 1:2 ratio matched on the basis of placenta accreta spectrum severity and surgical urgency. The primary outcome was a requirement for transfusion with packed red blood cells. Secondary outcomes included estimated surgical blood loss, operative and postoperative complications, procedural time, length of stay, and neonatal outcomes. RESULTS: A total of 15 Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization cases and 30 matched historical cases were included in the analysis. There were no demographic differences noted between the groups. A median (interquartile range) of 0 units (0-2 units) of packed red blood cells were transfused in the Intraoperative Embolization group compared with 2 units (0-4.5 units) in the historical group (P=.045); 5 of 15 (33.3%) Intraoperative Embolization cases required blood transfusions compared with 19 of 30 (63.3%) cases in the historical group (P=.11). The estimated blood loss was significantly less in the Intraoperative Embolization group with a median (interquartile range) of 750 mL (450-1050 mL) compared with 1750 mL (1050-2500 mL) in the historical group (P=.003). There were no cases requiring massive transfusion (≥10 red blood cell units in 24 hours) in the Intraoperative Embolization group compared with 5 of 30 (16.7%) cases in the historical group (P=.15). There were no intraoperative deaths from hemorrhagic shock using the Intraoperative Embolization protocol, whereas this occurred in 2 of the historical cases. The mean duration of the interventional radiology procedure was longer in the Intraoperative Embolization group (67.8 vs 34.1 minutes; P=.002). Intensive care unit admission and postpartum length of stay were similar, and surgical and postoperative complications were not significantly different between the groups. The gestational age and neonatal birthweights were similar; however, the neonatal length of stay was longer in the Intraoperative Embolization group (median duration, 32 days vs 15 days; P=.02) with a trend toward low Apgar scores. Incidence of arterial umbilical cord blood pH <7.2 and respiratory distress syndrome and intubation rates were not statistically different between the groups. CONCLUSION: A multidisciplinary pathway including a single-surgery protocol with multivessel uterine embolization is associated with a decrease in blood transfusion requirements and estimated blood loss with no increase in operative complications. The Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol provides a definitive surgical method that warrants consideration by other centers specializing in placenta accreta spectrum treatment.

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.

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.

Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: An NRG Oncology study.

BACKGROUND: Successfully combining targeted agents with chemotherapy is an important future goal for cancer therapy. However, an improvement in patient outcomes requires an enhanced understanding of the tumor biomarkers that predict for drug sensitivity. NRG Oncology/Gynecologic Oncology Group (GOG) Study GOG-86P was one of the first attempts to combine targeted agents (bevacizumab or temsirolimus) with chemotherapy in patients with advanced endometrial cancer. Herein we performed exploratory analyses to examine the relationship between mutations in TP53, the most commonly mutated gene in cancer, with outcomes on GOG-86P. METHODS: TP53 mutational status was determined and correlated with progression-free survival (PFS) and overall survival (OS) on GOG-86P. RESULTS: Mutations in TP53 were associated with improved PFS and OS for patients that received bevacizumab as compared to temsirolimus (PFS: HR 0.48, 95% CI 0.31, 0.75; OS: HR: 0.61, 95% CI 0.38, 0.98). By contrast, there was no statistically significant difference in PFS or OS between arms for cases with WT TP53. CONCLUSIONS: This exploratory study suggests that combining chemotherapy with bevacizumab, but not temsirolimus, may enhance PFS and OS for patients whose tumors harbor mutant p53. These data set the stage for larger clinical studies evaluating the potential of TP53 mutational status as a biomarker to guide choice of treatment for endometrial cancer patients. Clintrials.gov: NCT00977574.