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PURPOSE The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor–positive ovarian cancer. METHODS This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light. RESULTS From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor–positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported. CONCLUSION This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.

The role of abdominal hysterectomy for benign disease has decreased with time, given the broad application of minimally invasive hysterectomy. Abdominal hysterectomy is indicated when minimally inv...

ObjectiveTo evaluate trends in outpatient versus inpatient hysterectomy for endometrial cancer and assess enabling factors, cost and safety.MethodsIn this retrospective cohort study, patients aged 18 years or older who underwent hysterectomy for endometrial cancer between January 2008 and September 2015 were identified in the Premier Healthcare Database. The surgical approach for hysterectomy was classified as open/abdominal, vaginal, laparoscopic or robotic assisted. We described trends in surgical setting, perioperative costs and safety. The impact of patient, provider and hospital characteristics on outpatient migration was assessed using multivariate logistic regression.ResultsWe identified 41 246 patients who met inclusion criteria. During the time period studied, we observed a 41.3% shift from inpatient to outpatient hysterectomy (pConclusionsA significant shift from inpatient to outpatient setting was observed for hysterectomies performed for endometrial cancer over time. Minimally invasive surgery, particularly the robotic approach, facilitated this migration, preserving clinical outcomes and leading to reduction in costs.

OBJECTIVE: Morbidity and mortality (M/M) after primary debulking surgery (PDS) is often cited as a rationale for neoadjuvant chemotherapy and interval debulking surgery (IDS). We tested if using an evidence-based algorithm to identify patients fit for surgery would reduce M/M after PDS to that seen after IDS. METHODS: We included women who underwent PDS or IDS for advanced epithelial ovarian cancer (EOC) (1/2012–7/2016) guided by the use of a prospective triage algorithm. Outcomes were compared after applying inverse-probability of treatment weighting (IPTW) to adjust for covariate imbalance. RESULTS: Of 334 included patients, 232 (69.5%) underwent PDS and 102 (30.5%) were triaged to IDS. Relative to IDS group, PDS patients were younger (63.9 vs 67.5years, P=0.01), were less likely to have low albumin (16.8% vs. 32.4%, P

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.

Background Standard of care in patients with advanced ovarian cancer (AOC) is upfront surgery followed by chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) is an alternative in selected patients. Most data exist with IDS following 3–4 cycles chemotherapy, however, some patients experience a delay of IDS. So far, the impact of a “delayed” interval debulking surgery (DID) is poorly defined. Methods We analyzed data from eight international gynecology-oncology referral centers. Patients were included if they had newly diagnosed AOC and were prone to DID (minimum 5 cycles of NACT) between 2011 and 2017. Results 308 patients underwent DID. 89.6% had a high-grade serous ovarian cancer. The median number of pre-op NACT was 6 cycles (range 5–9) and 6.1% of patients received additionally bevacizumab. The majority of patients had stage-IV disease (51.3%). Median duration of surgery was 210 min (range 34–561), the median surgical complexity score was 4 (range 1–16). Complete resection was achieved in 60.1%. The median number of post-op chemotherapy cycles was 2 (range 0–5). The rate of severe complications (Clavien-Dindo£3°) was 9.7% and 30 days post-op mortality was 0.3%. The median PFS and OS in patients with complete resection was 19.5 and 49.2 months compared to 14.8 and 33.0 months in patients with incomplete resection (p = 0.001), respectively. We did not observe any survival benefit for patients with cytoreduction to small residuals (1–10 mm) compared to residual disease >1 cm. Conclusion Our data may suggest that offering surgery to patients with persistent disease after 5+ cycles could be associated with favorable outcome if a complete resection is achieved. Patients who had residual disease postoperatively may experience rather peri-operative treatment burden than any benefit from DID.

Objective To analyze clinical characteristics and survival of patients with primary vaginal cancer. Methods Retrospective analysis of patients with primary squamous, adenocarcinoma and adenosquamous cell carcinoma of the vagina identified from the Mayo Clinic Cancer Registry between 1998 and 2018. Results A total of 124 patients were identified: stage I, 39 patients; stage II, 44, stage III, 20 and stage IV, 21. Patients with stage III and IV were older as compared to stage I and II. (mean ages 61 vs 67) (p = 0.024). Squamous cell carcinoma made up 71% of tumors. History of other malignancy was present in 24% patients. Median follow-up time was 60 months (range 1–240). Five-year PFS in stage I, II, III and IV was 58.7%, 59.4%, 67.3% and 31.8%, respectively (p = 0.039). Five-year DSS was 84.3%, 73.7%, 78.7% and 26.5% respectively (p 4 cm, entire vaginal involvement, and lymph node (LN) metastasis were poor prognosticators in univariate analysis. Primary surgery in stage I/II patients had similar survival outcomes as compared to primary radiation, but post-operative RT rate was 55%. Brachytherapy alone was associated with a high local recurrence (80%) in stage I/II patients. The addition of brachytherapy had improved 5-year PFS and DSS than EBRT alone in patients with stage III/IVA. (p Conclusion Surgery or radiation is effective treatment for vaginal cancer stage I and II. The addition of brachytherapy to external pelvic radiation increases survival in stages III-IV.

Objective To compare the survival outcomes and surgical radicality between women who underwent open versus robotic radical hysterectomy (RH) for early cervical cancer. Methods In this institutional retrospective study, patients with clinical stage IA2- IIA (FIGO 2009) squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who underwent either open or robotic RH between 2000 and 2017 were identified. Parametrial width and vaginal length were re-measured from pathology slides. An inverse propensity score weighting model was used to adjust selection bias. Results A total of 333 patients were included (181 open, 152 robotic). The median follow-up time was 130 months for the open group and 53 months for the robotic group. There were 31 (17.1%) recurrences in the open and 21 (13.8%) in the robotic group. The 5-year progression-free survival (PFS) for the robotic and open group were 79.0% and 90.5%, respectively (HR 2.37, 95% CI 1.40–4.02). Five-year overall survival (OS) were 85.8% and 95.3%, respectively (HR 3.17, 95% CI 1.76–5.70). The mean parametrial width was similar between the open and robotic groups (2.5 vs 2.4 cm, p = 0.99). Unique recurrences (38.1%, 8/21) were noted in the robotic group: 2 port-site, 4 peritoneal, and 2 carcinomatosis. The time to vaginal recurrence was shorter in the robotic group than the open group (p = 0.001). Conclusion Patients who underwent robotic RH had inferior PFS and OS compared to open surgery. Surgical radicality according to pathology measurements was similar between the two approaches.

In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission., The folate receptor alpha (FRα) is overexpressed in the majority of high-grade serous ovarian cancers and has been proposed as a candidate vaccine antigen. Here the authors report the safety and immunogenicity of Th17-inducing dendritic cells pulsed with FRα-derived epitopes in an early phase I clinical trial with ovarian cancer patients.

Objective We previously reported an algorithm that identifies women at high risk of postoperative morbidity & mortality (M/M) as a tool to triage between neoadjuvant chemotherapy and primary surgery for epithelial ovarian cancer (EOC). We sought to independently validate its performance using multicenter data. Methods Women who underwent surgery for stage IIIC/IV EOC between 1/1/2014 and 12/31/2017 were identified from the National Surgical Quality Improvement Program database and classified as “high risk” or “triage appropriate” using our algorithm. Outcomes were compared between triage appropriate and high-risk women using the chi-square test. Results 1777 women met inclusion criteria; the mean age was 62.6 years and 81.9% had stage IIIC disease. Nationally, the surgical complexity scores were low (69.8% low, 25.2% intermediate and 5.0% high). “High risk” women had 2-fold higher rate of severe 30-day complication or death (6.2% vs 3.5%; p = 0.01), a 3-fold higher rate of 30-day mortality (1.4% vs 0.5%; p = 0.08), and a higher risk of death following a severe complication (11.1% vs. 0%, p = 0.11). A sensitivity analysis excluding women with unknown albumin who didn't meet other high risk criteria showed similar results: severe 30-day complications or death (6.2% vs 3.5%; p = 0.02) and 30-day mortality (1.4% vs 0.3%; p = 0.04) for “high risk” vs “triage appropriate” women. Conclusions Primary cytoreductive surgery to minimal residual disease remains the goal for EOC. We verify that our algorithm can identify women at risk of M/M using national multicenter data, despite a low complexity surgical setting and using 30-day mortality (vs. 90-day). Objective surgical risk assessment for ovarian cancer should be standard of care and can be incorporated into practice using the Mayo triage algorithm.

Objective To determine relevant provider opinions on uterus transplantation (UTx). Patients and Methods We invited 1933 providers in obstetrics and gynecology, transplant surgery, transplant medicine, internal medicine, and family medicine at a large, integrated health care system to complete an online survey containing a series of questions on their attitudes about the ethics and clinical utility of UTx. The survey was open from June 4, 2018, through July 2, 2018. We received 449 responses overall (23.2% response rate). Results Of 433 physicians who responded, 195 (45.0%) believe that UTx is ethically justified, and just over a third (160 of 446 [35.9%]) would introduce the possibility of UTx to a patient with absolute uterine factor infertility (AUFI). Respondents indicated the risks to donor, recipient, and child carried the most weight in their ethical evaluation and were most supportive of UTx in a patient with congenital uterine absence (334 of 743 [45.0%]; participants were allowed to choose more than one answer). A majority stated that a living or cadaveric donor would be an acceptable donor source (238 of 395 [60.3%]). Conclusion Provider support for UTx is qualified by safety concerns and its expansion to patient populations other than women with AUFI. This survey suggests that most providers limit their support of UTx to patients with the most demonstrated clinical need, childless women with AUFI.

ObjectiveThe choice of adjuvant treatment for women with stage II endometrial cancer is challenging, given the known increase in morbidity with external beam radiation compared with vaginal brachytherapy, and the lack of consensus on its benefits. We summarized the evidence on survival and recurrence for stage II endometrial cancer, defined as cervical stromal invasion, after adjuvant postoperative external beam radiotherapy and vaginal brachytherapy.MethodsWe searched the MEDLINE, EMBASE, CENTRAL, and Scopus databases from inception to January 2019 to identify studies that compared adjuvant postoperative external beam radiotherapy with or without vaginal brachytherapy and vaginal brachytherapy alone in stage II endometrial cancer. Our primary outcome was the locoregional recurrence rate, defined as recurrence in the pelvis or vagina. Secondary outcomes included the rate of recurrence at any site, distant recurrence rate, vaginal recurrence rate, pelvic recurrence rate, and 5 year overall survival. Study selection, assessment, and data abstraction were performed by an independent set of reviewers. Random effects models were used to synthesize quantitative data.ResultsWe included 15 cohort studies reporting data on 1070 women. Most women with stage II endometrial cancer (848/1070, 79.3%) were treated with external beam radiotherapy with or without vaginal brachytherapy. Subgroup analysis was stratified by whether >90% of the women included underwent pelvic lymph node assessment (sampling or full dissection). Locoregional recurrence (pelvic and vaginal recurrence) was significantly reduced with external beam radiotherapy with or without vaginal brachytherapy compared with vaginal brachytherapy alone (14 studies (n=1057); odds ratio (OR) 0.33 (95% confidence interval (CI) 0.16 to 0.68); I2=5%) regardless of pelvic lymph node assessment. Most women (81.8%) who recurred locoregionally had a least one uterine risk factor (grade 3 tumor, myometrial invasion >50%, or lymphovascular invasion). There was no difference in overall survival with external beam radiotherapy with or without vaginal brachytherapy compared with vaginal brachytherapy alone (five studies (n=463); OR 0.78 (95% CI 0.34 to 1.80); I2=48%).ConclusionsExternal beam radiotherapy with or without vaginal brachytherapy decreased the locoregional recurrence threefold for stage II endometrial cancer, regardless of pelvic lymph node assessment. Most women who suffered recurrence locoregionally had a least one high risk factor. Vaginal brachytherapy alone may be sufficient therapy for node negative stage II endometrial cancer without uterine risk factors, while those with uterine risk factors should be considered for external beam radiotherapy with or without vaginal brachytherapy to improve locoregional control.

Objective To investigate progression-free survival (PFS) and overall survival (OS) between women who underwent surgical versus radiographic assessment of pelvic lymph nodes (PLN) and para-aortic lymph nodes (PALN) prior to chemoradiation therapy for cervical cancer. Methods In this retrospective cohort analysis, patients with stage IB2 - IIIB squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who completed concurrent chemoradiation therapy (CCRT) between 2000 and 2017 from the Mayo Clinic Cancer Registry were identified. A 1:2 propensity score matching between surgical and imaging groups was performed and PFS and OS were compared between groups. Results 148 patients were identified and after propensity score matching, 35 from the surgical group and 70 from the imaging group were included in the analysis. There were no statistical differences in baseline characteristics between the 2 groups. The median follow-up time was 41 months (range 7–218) for the surgical group and 51.5 months (range 7–198) for the imaging group. Five-year PFS was 62.6% for the surgical group and 72.4% in imaging group (HR 1.11, 95% CI 0.54–2.30, p = 0.77). Five-year OS was 70.2% for the surgical group and 70.5% for the imaging group (HR 1.02, 95% CI 0.46–2.29, p = 0.96). FIGO stage, PALN metastasis, and parametrial involvement were found to be poor prognosticators for PFS and OS in univariate analysis. Only PALN metastasis significantly predicted unfavorable PFS (HR 2.76, 95% CI 1.23–6.18, p = 0.01) and OS (HR 3.46, 95% CI 1.40–8.55, p = 0.01) in multivariate analysis. There were no differences in locoregional recurrence and distant metastasis between the two groups (p = 0.33 and 0.59 respectively). Conclusion Patients with cervical cancer who underwent radiographic assessment of PLN and PALN had comparable survival outcomes to surgical assessment.

To highlight different surgical approaches for managing deep infiltrating endometriosis involving the rectosigmoid colon.Demonstration of specific surgical techniques with educational narrated video footage.Bowel endometriosis is reported in 3.8% to 37% of patients with endometriosis [1]. Most commonly, the rectosigmoid colon is involved. Pelvic ultrasound and magnetic resonance imaging may be useful in diagnosis and for surgical planning [2]. Treatment options include observation, medications, or surgery. There are various surgical techniques that can be used for excision of deep infiltrating endometriosis involving the rectosigmoid colon. Serosal shaving, discoid resection, and complete resection are the possible types of surgical interventions that are demonstrated in this surgical education video at an academic medical center. Serosal shaving is used for lesions with minimal involvement of the muscularis. It can be done sharply or with electrosurgery and it is imperative to assess bowel integrity after shaving. Discoid resection is used for lesions with muscularis involvement,3 cm in size, and encompassing less than one-third to a half of the bowel circumference. Full-thickness discoid bowel resection can be done in various ways including manual resection with primary suture closure, regular stapler transabdominally, or EEA stapler (Medtronic EEA Circular Stapler, Minneapolis, MN) transrectally. Segmental resection is used for lesions3 cm in size, involving50% of the bowel circumference, or for multifocal lesions. Various suture and stapler methods exist for this technique.Based on the imaging and intraoperative findings, a surgical technique was chosen and demonstrated. The types of surgical techniques demonstrated include laparoscopic serosal shaving, discoid resection with manual resection and primary suture closure, discoid resection with EEA stapler, and segmental resection.Knowledge of different surgical approaches to excise endometriosis is essential to appropriately address a patient's unique pathology. The choice of which surgical technique to use should include consideration of the location of the lesion, depth and circumference of involvement, and the number of nodules present.

To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC).We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors.Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with2 factors among grade 3, LVSI, or stage IB had a 3-year CSS95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology.Observation or VB only may be sufficient in stage I endometrioid HIR ECs with2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.

To gather validity evidence for and determine acceptability of Surgical Science-Simbionix Hysterectomy Modules for the DaVinci Xi console simulation system (software; 3D Systems by Simbionix [now Surgical Science-Simbionix], Littleton, CO, and hardware; Intuitive Surgical, Inc., Sunnyvale, CA) and evaluate performance benchmarks between novice and experienced or expert surgeons.Prospective education study (Messick validity framework).Multicenter, academic medical institutions.Residents, fellows, and faculty in obstetrics and gynecology were invited to participate at 3 institutions. Participants were categorized by experience level: fewer than 10 hysterectomies (novice), 10 to 50 hysterectomies (experienced), and more than 50 hysterectomies (expert). A total of 10 novice, 10 experienced, and 14 expert surgeons were included.Participants completed 4 simulator modules (ureter identification, bladder flap development, colpotomy, complete hysterectomy) and a qualitative survey. Simulator recordings were reviewed in duplicate by educators in minimally invasive gynecologic surgery using the Modified Global Evaluative Assessment of Robotic Skills (GEARS) rating scale.Most participants felt that the simulator realistically simulated robotic hysterectomy (64.7%) and that feedback provided by the simulator was as or more helpful than feedback from previous simulators (88.2%) but less helpful than feedback provided in the operating room (73.5%). Participants felt that this simulator would be helpful for teaching junior residents. Simulator-generated metrics correlated with GEARS performance for the bladder flap and ureter identification modules in multiple domains including total movements and total time for completion. GEARS performance for the bladder flap module correlated with experience level (novice vs experienced/expert) in the domains of interest and total score but did not consistently correlate for the other procedural modules. Performance benchmarks were evaluated for the bladder flap module for each GEARS domain and total score.The modules were well received by participants of all experience levels. Individual simulation modules appear to better discriminate between novice and experienced/expert users than overall simulator performance. Based on these data and participant feedback, the use of individual modules in early residency education may be helpful for providing feedback and may ultimately serve as 1 component of determining readiness to perform robotic hysterectomy.

ObjectiveSubstituting lymphadenectomy with sentinel lymph node biopsy for staging purposes in endometrial cancer has raised concerns about incomplete nodal resection and detrimental oncological outcomes. Therefore, this study aimed to investigate the association between the type of lymph node assessment and overall survival in endometrial cancer accounting for node status and histology.MethodsWomen with stage I–III endometrial cancer who underwent hysterectomy and lymph node assessment from January 2012 to December 2015 were identified in the National Cancer Database. Patients who underwent neoadjuvant therapy, had previous cancer, and whose follow-up was less than 90 days were excluded. Multivariable Cox proportional hazards regression analyses were performed to assess factors associated with overall survival.ResultsOf 68 614 patients, 64 796 (94.4%) underwent lymphadenectomy, 1777 (2.6%) underwent sentinel node biopsy only, and 2041 (3.0%) underwent both procedures. On multivariable analysis, neither sentinel lymph node biopsy alone nor sentinel node biopsy followed by lymphadenectomy was associated with significantly different overall survival compared with lymphadenectomy alone (HR 0.92, 95% CI 0.73 to 1.17, and HR 0.91, 95% CI 0.77 to 1.08, respectively). When stratified by lymph node status, sentinel node biopsy alone or followed by lymphadenectomy was not associated with different overall survival, both in patients with negative (HR 0.95, 95% CI 0.73 to 1.24, and HR 1.04, 95% CI 0.85 to 1.27, respectively) or positive (HR 0.91, 95% CI 0.54 to 1.52, and HR 0.77, 95% CI 0.57 to 1.04, respectively) lymph nodes. These findings held true when sentinel node biopsy alone and sentinel node biopsy plus lymphadenectomy groups were merged, and on stratification by histotype (type one vs type 2) or inclusion of only complete lymphadenectomy (at least 10 pelvic nodes and at least one para-aortic node removed). In all analyses, age, Charlson-Deyo score, black race, AJCC pathological T stage, grade, lymphovascular invasion, brachytherapy, and adjuvant chemotherapy were independently associated with overall survival.DiscussionNo difference in overall survival was found in patients with endometrial cancer who underwent sentinel node biopsy alone, sentinel node biopsy followed by lymphadenectomy, or lymphadenectomy alone. This observation remained regardless of node status, histotype, and lymphadenectomy extent.

PURPOSE The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery. MATERIALS AND METHODS Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics. RESULTS Of 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard ( P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory. CONCLUSION HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.

Highlights • There are multiple disease and treatment related barriers to participating in an exercise based prehabilitation program. • Patients with advanced ovarian cancer are interested and motivated to take part in prehabilitation despite barriers. • The oncology care team has notable influence on a patient’s motivation and willingness to participate in prehabilitation., Prehabilitation may modify frailty and increase resilience in a subset of ovarian cancer patients; however there is low adherence to most programs. Our aim was to investigate potential barriers and facilitators of prehabilitation during neoadjuvant chemotherapy (NACT). We identified 15 patients who underwent NACT from 2016 to 2018. Patients underwent a semi-structured one-on-one interview. Transcripts were coded by 4 independent reviewers to identify emerging themes related to patients’ experience, functioning and exercise during chemotherapy. Data saturation occurred after 15 interviews. Patients had a mean age of 64 and were triaged to NACT for unresectable disease in 47% of cases. Patients were overall willing to participate in exercise during chemotherapy, including walking (93%), strength training (87%), and yoga or stretching (33%). Patients identified significant factors which would motivate them to exercise during treatment despite the stated barriers, including perceived benefit to overall health and well-being, improving cancer related outcomes and a supportive treatment community. In addition, the majority of patients cited advice from their physician to participate in an exercise program as highly motivating. Cancer and treatment related symptoms such as fatigue, pain, nausea and vomiting, and respiratory distress, as well as access to care, and social and mental barriers were most often identified by patients as barriers to exercise. Patients with advanced ovarian cancer demonstrated high motivation and willingness to exercise during chemotherapy, particularly when recommended by their healthcare team and when they believe there will be a direct benefit on treatment options or cancer cure.

To evaluate the impact of an evidence-based triage algorithm to decide between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NACT/IDS) for advanced epithelial ovarian cancer (EOC).Surgical morbidity and mortality (M/M) after PDS for stage IIIC-IV EOC at Mayo Clinic after implementation of the triage algorithm (contemporary cohort, 2012-July 2016) were compared to that of a historic PDS cohort (2003-2011).Mean age of the 232 women who met inclusion criteria in the contemporary cohort was 63.9 years. We observed a 71% decrease in 90-day mortality from 8.9% to 2.6% (P = 0.002) between the contemporary and historic cohorts. Accordion grade 3+ postoperative complications within 30 days after surgery decreased from 22.3% to 18.3% (P = 0.19). Among those with a grade 3+ complication, 90-day mortality rates decreased from 28.3% in the historic cohort to 2.4% in the contemporary cohort (P 0.001) suggesting patients were better able to tolerate complex surgery. When compared to the historic PDS cohort, oncologic outcomes were also improved in the contemporary PDS cohort. Complete as well as optimal (residual disease ≤1 cm) cytoreduction rates increased (45.5% vs. 62.5% and 84.5% vs. 95.3%, respectively, P 0.001), and the proportion of women starting chemotherapy within 42 days of surgery increased (57.4% vs. 69.8%, P = 0.001). Three-year overall survival was 53% in the historic cohort and 66% in the contemporary cohort (P 0.001).Use of the Mayo triage algorithm for EOC was associated with reduced 90-day mortality after PDS and improved oncologic outcomes. Surgical risk assessment is a critical aspect of treatment planning in the primary management of EOC and should be incorporated into practice.

Highlights • NRH-L is a rare disease that may lead to non-cirrhotic portal hypertension. • NRH-L may present as a paraneoplastic disorder, complicating oncologic treatment. • This is the first case of NRH-L as a potential paraneoplastic disorder due to PSTT.

Objective To determine the incidence and risk factors for venous thromboembolism (VTE) within six months after primary debulking surgery (PDS) for epithelial ovarian cancer (EOC). Methods In a historical cohort, we estimated the cumulative incidence of clinically diagnosed VTE within 6 months among consecutive women who underwent PDS for EOC at a single institution from 1/1/2003 to 12/31/2011. We evaluated perioperative variables as potential risk factors of VTE within 6 months during the postoperative period using univariate and multivariable Cox proportional hazards models. Results Among 860 women without an immediate history (past 30 days) of a VTE, the cumulative incidence of VTE was 7.5% (95% CI, 5.7–9.3) by 30 days and 13.8% (95% CI, 11.4–16.2) by 6 months following surgery. Macroscopic residual disease (adjusted HR 1.99 [95% CI 1.35–2.94] vs microscopic), increasing estimated blood loss (1.25 [1.05–1.49] per doubling), longer hospital length of stay (3.00 [1.57–5.75]), and experiencing a cardiac event within 30 postoperative days (2.72 [1.55–4.80]) were independently associated with subsequent VTE within 6 months. In-hospital VTE prophylaxis included heterogeneous approaches; dual prophylaxis did not impact 30-day or 6-month VTE rates. Conclusions VTE occurred in 1 in 7 women with EOC within 6 months of PDS—a substantial risk of VTE that extends into the adjuvant chemotherapy period. Novel prophylactic measures should be explored in these women at high risk for VTE.

Enhanced recovery after surgery (ERAS) is an evidence-based approach to perioperative care of the surgical patient. A mounting body of literature in gynecologic surgery has demonstrated that ERAS improves postoperative outcomes, shortens hospital length of stay, and reduces cost without increasing complications or readmissions. Most of the existing literature has concentrated on open surgery, questioning if patients undergoing minimally invasive surgery also derive benefit. Our aim was to systematically review the literature on ERAS after minimally invasive gynecologic surgery (MIGS) with and without bowel surgery. Given the paucity of studies on ERAS in MIGS with bowel surgery (1 study), we expanded our search to include studies of ERAS in patients undergoing minimally invasive colorectal resections alone. Twelve studies were identified through an electronic database search of PubMed, Medline, and Ovid EMBASE. These studies included patients undergoing MIGS for benign and/or malignant indications and showed that ERAS pathways decreased length of stay and/or increased the proportion of same-day discharge surgeries, improved patient satisfaction, and reduced hospital costs while maintaining low postoperative complication and readmission rates. Although limited, data from a single study suggest that ERAS in MIGS with bowel surgery leads to shortened hospital stay, stable postoperative morbidity, and less readmissions. Although the variation between the published protocols underscores the need for standardization, existing literature supports the adoption of ERAS as safe and effective when planning MIGS.

Objectives: Most splenectomies performed in ovarian cancer (OC) debulking are for disease resection; the impact of splenectomy on 30-day complication and oncologic outcomes is unclear. We aimed to determine the association of splenectomy with postoperative complications, overall survival (OS), and progression-free survival (PFS) in the setting of primary debulking surgery (PDS) for OC. Methods: We retrospectively evaluated women who underwent PDS or surgical staging for OC from 1/2003-07/2016. Perioperative variables and 30-day complications defined by ACS-NSQIP were abstracted. Among those with advanced stage (IIIC/IV) disease, complications were graded using the modified Accordion grading scale; severe was defined as grade 3 or 4. A propensity score (PS) matched cohort was evaluated to limit the effect of bias due to confounding variables between patients who did and did not have a splenectomy. The severe complication rate was compared between matched pairs using McNemar's test and time-to-event outcomes were compared using stratified Cox proportional hazards models. Results: Among 1311 patients in the cohort, 153 (11.7%) underwent splenectomy. Patients with splenectomy were more likely to have advanced stage disease (96.1 vs 60.6%), serous histology (89.5 vs 68.8%), ascites (83.0 vs 45.3%), higher median preoperative CA-125 (737 vs 388 U/mL), and residual disease (52.9 vs 31.3%), compared to patients without splenectomy (all p Download : Download high-res image (74KB) Download : Download full-size image Conclusions: We observed that splenectomy during PDS was associated with increased risk of progression and death compared to those not undergoing splenectomy but this risk was no longer observed with a PS-matched cohort. Splenectomy appears to be a marker for disease extent but does not increase the risk of progression or decreased survival in and of itself. Splenectomy was associated with a higher risk of severe postoperative complications including a 9% risk of pancreatic leak. These findings underscore the importance of preoperative surgical risk/benefit assessment and expertise in management of complications.

Objectives: Women with Lynch syndrome (LS) experience a lifetime risk of endometrial and colon cancer of up to 57%, and the risk is approximately equal for each LS gene. Little is known about how LS patients perceive and seek to manage their cancer risks. The objective of this study was to determine the perceived risk of endometrial (EC), ovarian (OC), and colon (CC) cancer among those with LS, to report adherence to EC and CC screening guidelines, and uptake of risk reducing surgical procedures. Methods: A survey instrument was developed using investigator generated items and queries adapted from the Health Information National Trends Survey. The anonymous, web-based survey was advertised on Lynch Syndrome International Facebook page from July 1st to August 1st of 2020. Items were reviewed by an expert panel and a patient advocate. Eligibility for cancer screening was defined as (1) EC screening: ≥35 years with no personal history of EC and an intact uterus, and age appropriate screening was defined as an endometrial biopsy within 1 year; (2) CC screening: ≥25 years with no personal history of CC and intact colon, and age appropriate screening was defined as a colonoscopy within 2 years. Results: Of 169 survey responses, 26 were excluded (2 declined, 4 no LS diagnosis, 11 incomplete, 9 men). Results are based on 143 women. The mean (SD) age was 47.3(11.4) years with 91% residing in North America and 68% college educated. Nearly all (99%) were diagnosed by genetic testing with the most common mutation being in MSH2 (40%). A prior cancer diagnosis was reported in 57% with 29% having EC, 21% CC, and 4% OC. Most women (63%) take a multidisciplinary approach to their LS care, including visits with a primary care provider (73%), GI specialist (93%), or gynecologist (70%). However, 37% prefer to receive advice from a single provider most commonly a PCP (35%) or GI (35%). Among women that retain the at-risk organ and do not have a personal history of cancer in that organ, over 90% accurately report their risk of EC, OC, and CC as being more likely than those without LS. However, significantly fewer rated their own likelihood of cancer as high (Table 1). Hysterectomy was common (78%) and more frequently performed for risk reduction in women Download : Download high-res image (96KB) Download : Download full-size image Conclusions: Women with LS appear to be knowledgeable of their increased risk of EC, OC, and CC compared to those without LS, but they may underestimate their personal risk of EC. There was a high uptake of risk reducing surgical procedures in this population, especially in those

Objectives: Women with stage IB endometrioid endometrial cancer (EEC) are at risk of developing non-vaginal recurrences. However, it is unclear which patients have high enough risk to justify testing systemic therapies. Our aim is to identify significant risk factors for non-vaginal recurrence. Methods: This is a retrospective multicenter study, including patients who underwent complete surgical staging for EEC at Mayo Clinic, Rochester (MN, USA) between January 1999-December 2017, and at Fondazione Policlinico Gemelli (Rome, Italy) between March 2002-March 2017, with a final FIGO stage IB. Patients without lymph node assessment were excluded. Recurrences were categorized into isolated vaginal and non-vaginal (hematogenous, peritoneal, lymphatic, or multi-site). The follow-up was restricted to the first 5 years following surgery. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method. Cox proportional hazards models, stratified by center, were fit to evaluate the association of clinical and pathologic characteristics with the risk of recurrence. Results: Three hundred eighty-six patients were identified. The mean myometrial invasion (MI) of the cohort was 70.4% (SD 13.2). The majority of the patients received either vaginal brachytherapy (VB) or no adjuvant therapy (N=256, 66.3%), 57 patients (14.8%) received EBRT ± chemotherapy ± VB, 38 (9.8%) received chemotherapy ± VB, and 35 (9.1%) unknown. Greater MI was associated with increased histologic grade and lymph vascular space invasion (LVSI). We identified 51 recurrences (14 isolated vaginal, and 37 non-vaginal); the median follow-up of the remaining patients was 4.5 (IQR, 2.3-6.9) years. The 5-year RFS for non-vaginal recurrences was 88.1% (95% CI 84.4-91.9%). There was a strong linear relationship between the percent of MI and the risk of recurrence. Patients with the deepest MI (≥90%) had a rate of recurrence as high as 40%. At univariate analysis, the risk of non-vaginal recurrence increased as the percent of MI increases (vs. MI 50-69.9%), with a hazard ratio (HR) of 3.33 (95% CI, 1.46-7.58) in patients with MI 70 to 89%, and HR of 8.47 (95% CI, 3.26-22.01) with MI≥ 90%. Patients with grade 3 disease had a higher risk of non-vaginal recurrence compared to grade 1-2 (HR 3.58, 95% CI, 1.86-6.88). At multivariate analysis, both histologic grade and depth of MI were independent predictors of recurrence. In particular, the subset of patients with MI≥ 70% and grade 3 tumors have the poorest RFS; however, we noticed also that patients with myometrial invasion ≥ 90% have a very high risk of recurrence independently from histologic grade (Table). Download : Download high-res image (68KB) Download : Download full-size image Conclusions: Considering women with stage IB endometrioid endometrial cancer, the rate of non-vaginal recurrences at 5 years is very high (> 30%): (1) in patients with any grade with MI≥ 90%; and (2) in grade 3 patients with MI≥ 70%. In the future, these pathologic findings could help us identify subgroups of patients in which systemic therapies may be tested.

Objectives: Historically, patients with early-stage high-intermediate risk (HIR) endometrioid endometrial cancer (EC) have been known to benefit from improved recurrence-free survival (RFS) with the use of adjuvant therapy. However, specific subgroups of HIR patients may benefit from observation ± vaginal brachytherapy (VB) only. We sought to evaluate RFS and cause-specific survival (CSS) after observation ± VB in the subgroups of early-stage HIR endometrioid EC. Methods: We identified patients with early-stage HIR endometrioid EC, who underwent a total hysterectomy, bilateral salpingo-oopho-rectomy, and sentinel lymph node biopsy or pelvic ± paraaortic lymphadenectomy at Mayo Clinic and Cleveland Clinic between 1999 and 2016. HIR group was defined based on revised GOG99 criteria used in the GOG249 trial: age ≥70 with 1 risk factor, age ≥50 with 2 risk factors, or all the 3 risk factors (grade 2-3, ≥50% myometrial invasion, or positive lymphovascular space invasion [LVSI]). HIR subgroups were determined by all possible combinations of risk factors, and 3-year RFS, site-specific RFS, and CSS were estimated. Results: Among 1,507 women with stage I or II EC, 447 stage I endometrioid EC patients were identified who fulfilled HIR criteria, and 349 (78.1%) were managed with observation ± VB. Eleven subgroups were defined and evaluated (Table). Among stage IA patients (1-5 subgroups), subgroup 5 (G3 ≥50y LVSI+) had the lowest RFS and CSS of 68.9% (46.6-100.0%) and 86.7% (71.1-100.0%), respectively, whereas the remaining 4 subgroups had 3-year RFS and CSS >90%. In all stage IA subgroups, 3-year lymphatic RFS was >90%; 3-year distant RFS was lowest in subgroup 5 (79.6% [56.9-100.0%] and 97.1% [91.8-100.0%] in subgroup 3 [G2 ≥50y LVSI+]). Additionally, 3-year CSS was 90%. Conversely, all stage IB subgroups experienced distant recurrence; 3-year distant RFS ranged from 73.1% (53.5-99.7%) to 96.5% (91.8-100.0%). 3-year distant RFS lower than 90% was observed in those subgroups with grade 3 or positive LVSI (7, 9, 10, and 11). Conclusions: Our results suggest that observation ± VB can be sufficient in some subgroups of stage I endometrioid HIR patients, specifically stage IA endometrioid HIR EC without the concomitant presence of grade 3 and LVSI. Among stage IB endometrioid HIR EC subgroups, particularly those with grade 3 or LVSI, observation ± VB is associated with lower RFS and CSS. Stratifying HIR patients into risk subgroups would alleviate the risk of overtreatment and undertreatment among patients with early-stage endometrioid EC; in this regard, the molecular characterization will provide a further instrument to achieve this objective.

ObjectiveIt is unclear how to best sequence adjuvant chemotherapy and radiotherapy for advanced endometrial cancer. We studied the outcomes for women treated with chemotherapy before radiotherapy in a chemotherapy-first (chemotherapy for 6 cycles followed radiotherapy) or ‘sandwich’ approach (chemotherapy for 3 cycles followed by radiotherapy and subsequently chemotherapy for 3 cycles).MethodsWomen with stage IIIC endometrial cancer and no gross residual disease treated with chemotherapy before radiotherapy between April 2003 and April 2016 were included. The Kaplan-Meier method was used to estimate recurrence and survival. We performed a meta-analysis of endometrial cancer trials comparing chemotherapy and radiotherapy versus radiotherapy alone.ResultsA total of 102 patients were included. The mean (SD) age was 63.8 (10.6) years; 84 patients received the chemotherapy-first approach and 18 patients received the ‘sandwich’ approach. Pelvic and para-aortic nodes were removed in 99% and 88.2%, respectively. Among all the patients, we observed 1 pelvic (1%), 1 para-aortic (1%), and 5 vaginal (4.9%) recurrences. At 3 years, for the ‘sandwich’ and chemotherapy-first approaches, the vaginal recurrence was 11.8% and 4.2%, pelvic recurrence was 0% and 1.5%, para-aortic recurrence was 0% and 1.2%, distant recurrence was 42.9% and 24.4%, and overall survival was 70.3% and 81.7%, respectively. With ‘chemotherapy before radiotherapy’ 94.9% completed 4+ chemotherapy cycles (vs 71–90% reported in the literature for ‘radiotherapy before chemotherapy’). In a meta-analysis of endometrial cancer trials, distant recurrence rates were reduced with 4+ chemotherapy cycles but not with 3 cycles (p=0.01).ConclusionChemotherapy before radiation sequencing for stage IIIC endometrial cancer was associated with a high proportion of patients completing 4+ chemotherapy cycles and low locoregional lymphatic recurrence rate, despite delaying radiotherapy until after 3–6 cycles of chemotherapy and not administering concurrent cisplatin.

Objective Women with Lynch Syndrome (LS) experience a lifetime risk of endometrial (EC) and colon (CC) cancer of up to 57%, and the risk is approximately equal for each LS gene. Our objective was to determine knowledge of EC and CC risks, screening guidelines, and management recommendations among healthcare providers caring for women with LS. Methods An anonymous survey was sent to providers in primary care, ob/gyn, gynecologic oncology, gastroenterology, and clinical genomics across a healthcare enterprise. Data reported using descriptive statistics. Results 215 of 1198(18%) providers responded and 89% either had or anticipated caring for women with LS. Of 167 providers who completed the survey, 51% were primary care and 38% reported feeling at least somewhat uncomfortable with cancer screening for LS. Among the 77 (46%) currently caring for women with LS, 39% counsel that the risk of CC is approximately equivalent to the risk of EC; 34% counsel that the risk of EC is lower than the risk of CC or consistent with the general population. Additional counseling rates shown in table 1. Conclusions A large portion of providers who care for LS patients feel uncomfortable with making cancer screening recommendations. One-third of providers potentially underestimate a woman’s risk of EC, and most do not recognize that EC could be the presenting cancer for women. Improved education of providers regarding cancer screening and risk reduction options for women with LS may improve adherence to management guidelines.

As interventional oncology services within radiology mature, image-guided ablation techniques are increasingly applied to recurrent gynecologic malignancies. Ablation may be performed using thermal techniques like cryoablation, microwave ablation, or radiofrequency ablation, as well as non-thermal ones, such as focused ultrasound or irreversible electroporation. Feasibility and approach depend on tumor type, size, number, anatomic location, proximity of critical structures, and goals of therapy. Current indications include local control of limited metastatic disease or palliation of painful bone metastases refractory or unsuitable to conventional therapies. Technical aspects of these procedures, including methods to protect nearby critical structures are presented through illustrative examples. Cases amenable to image-guided ablation include, but are not limited to, hepatic or pulmonary metastases, musculoskeletal metastases, retroperitoneal nodal metastases, pelvic side wall disease, abdominal wall disease, and vaginal or vulvar tumors. Protective maneuvers, such as hydro-displacement of bowel, neuromonitoring, and retrograde pyeloperfusion through ureteral stents, permit safe ablation despite close proximity to vulnerable nerves or organs. Image-guided ablation offers an alternative modality to achieve local tumor control without the risks associated with surgery or systemic treatment in appropriately selected patients. A multidisciplinary approach to use of image-guided ablation includes collaboration between gynecologic oncology, interventional radiology, anesthesia, urology and radiation oncology teams allowing for appropriate patient-centered case selection. Long-term follow up and additional studies are needed to determine the oncologic benefits of such techniques.

Objective We describe a phase II clinical trial of the combination of ribociclib and letrozole for treatment of relapsed oestrogen receptor (ER)-positive ovarian cancer (OC) and endometrial cancer (EC). The primary endpoint was the proportion of patients alive, progression-free survival (PFS), and still on treatment at 12 weeks (PFS12), with 45% or greater considered positive. Methods Patients with measurable, relapsed ER-positive OC or EC (platinum-sensitive or resistant) were eligible and treated with 400 mg of oral ribociclib and 2.5 mg of oral letrozole daily. Patient-derived xenografts (PDXs) were created from imaging-guided tumour biopsies. Results Forty patients (20 OC and 20 EC) were enrolled. A PFS12 of 55% was observed in the EC cohort and 50% in the OC cohort. A PFS greater or equal to 24 weeks (PFS24) was seen in 20% (4/20) of the OC cohort and 35% (7/20) of the EC cohort. The greatest benefit was seen in low-grade serous OC (LGSOC) (3/3, 100% PFS24) and grades 1 and 2 EC (5/11, 45% PFS24). All three LGSOC patients obtained at least a partial response lasting for over 2 years, with two of the three patients still on treatment. PDX tumour engraftment was feasible in 45% of patients. Positive survival effects of the combination of ribociclib and letrozole were observed in two of three EC PDX models. Conclusion Ribociclib and letrozole have promising clinical activity in relapsed ER-positive OC and EC, particularly in LGSOC and relapsed ER-positive grade 1 and 2 EC. Generation of PDX models is feasible with positive survival effects observed in EC models. Trial registration number ClinicalTrials.gov registry ( NCT02657928 ).

Background/aim Early-stage uterine serous carcinoma (USC) has one of the highest recurrence rates and mortality among early-stage uterine epithelial cancers. Research into the clinical management of USC has begun to progress, guided by surgical and pathological advances. This article summarizes the available literature regarding diagnosis, management, and possible future uses of molecular analysis of women with early-stage USC. Materials and methods PubMed was searched for all pertinent English language research articles published from January 1, 2006 through March 1, 2020 which included a study population of women diagnosed with stage 1 USC. Due to the scarcity of prospective or large-scale data, studies were not limited by design or numbers of patients. Studies performed at earlier dates were incorporated to provide context. Results A total of 86 studies were included in the review. Multiple well-designed studies have confirmed the safety of a minimally invasive surgical approach for surgical management of USC. The role of sentinel node biopsy has been validated with both prospective and retrospective multi-center data. Stage I USC is associated with a highly variable risk of recurrence, even following completion of adjuvant chemoradiation. This aggressive phenotype has been linked to high numbers of somatic copy number alterations, tumor protein 53, and phosphatidylinositol 3 kinase mutations, which have been shown to be predictive of prognosis. Conclusion Early-stage USC demonstrates a lack of predictable recurrence patterns, with reports noting distant recurrence in patients with disease confined to polyps. Unless no residual tumor is found on hysterectomy, chemotherapy and radiotherapy should be discussed and individualized by stage and treatment goals.

Objective To compare baseline body composition measures (BCM), including sarcopenia, between patients with advanced epithelial ovarian cancer (EOC) undergoing primary cytoreductive surgery (PCS) versus neoadjuvant chemotherapy/interval cytoreductive surgery (NACT/ICS) and evaluate changes in BCM pre-NACT versus pre-ICS. Methods Patients with stage IIIC/IV EOC who underwent PCS or NACT with curative intent between 1/1/2012 and 7/31/2016 were included. Computed tomography scans were evaluated via a semi-automated program to determine BCM. Measures evaluated include skeletal muscle area (SMA), skeletal muscle density (SMD), skeletal muscle index (SMI), and skeletal muscle gauge (SMG). Sarcopenia was defined as SMI Results The study included 200 PCS patients and 85 NACT/ICS patients, of which 76 had both pre-NACT and pre-ICS scans. NACT patients were significantly more likely to be sarcopenic compared to PCS patients (40.0% vs 27.5%, p = 0.04). Mean SMA (107.3 vs 113.4 cm2, p = 0.004) and mean SMG (1344.6 vs. 1456.9 (cm2 x HU)/m2, p = 0.06) were lower in NACT patients. Among NACT/ICS patients, mean SMI significantly decreased −1.4 cm2/m2 (p = 0.005) at the time of surgery, resulting in a non-statistically significant increase in the percentage of sarcopenic patients from baseline (40.8% vs. 50.0%, p = 0.09). Conclusions Sarcopenia is more common in patients with advanced EOC undergoing NACT compared to PCS when using an evidence-based triage system for triage decisions. Body composition changes significantly over the course of NACT. Sarcopenia may be an indicator of debility and another factor for consideration in treatment planning. Further research into body composition's effects on prognosis and altering sarcopenia is necessary.

Objective To evaluate the relationship between frailty and chemotherapy delivery among women with epithelial ovarian cancer (EOC). Methods We included women who underwent primary debulking surgery (PDS) for stage IIIC/IV EOC between 1/2/2003 and 12/30/2011, received adjuvant chemotherapy at our institution, and had data available to calculate a frailty deficit index. Frailty was defined as a frailty deficit index ≥0.15. Relative dose intensity (RDI) of chemotherapy was calculated as the percentage of the standard dose that was administered, and compared between frail and non-frail using the Wilcoxon rank-sum test. Results Failure to receive chemotherapy following PDS was twice as common among frail vs. non-frail women (26.7% vs 14.2%, p = 0.001). Of the 169 women who received chemotherapy at our institution, 17.2% (29/169) were frail. Frail women were older (mean, 67.9 vs 62.3 years, p = 0.01), had higher BMI (mean, 29.6 vs 25.7 kg/m2, p = 0.003), and were less likely to complete 6 cycles of chemotherapy (75.9 vs. 93.6%, p = 0.008). Using an RDI cutoff of 85%, frail women were less likely to have adequate doses of carboplatin (15.8 vs. 66.2%, p Conclusion Frail women with EOC were less likely to receive chemotherapy or the optimal dose of chemotherapy after PDS despite no evidence of treatment-related toxicity. Frail EOC patients demonstrated shorter progression-free and overall survival. Further studies are needed to explore the association between frailty, chemotherapy, and survival.

ObjectivesIt is unclear if sentinel lymph node biopsy is associated with improved surgical outcomes compared with lymphadenectomy in patients with endometrial cancer. In this study we aimed to compare peri-operative surgical outcomes and treatment-related morbidity in patients who underwent robotic-assisted sentinel lymph node biopsy versus systematic pelvic lymphadenectomy or hysterectomy alone for apparent early-stage endometrial cancer.MethodsRecords were reviewed of consecutive patients with International Federation of Gynecology and Obstetrics stages I–III endometrial cancer undergoing robotic-assisted staging from January 1, 2009, through June 30, 2016. For the purpose of this analysis we focused on the actual patients who had sentinel node biopsy only (ie, excluding those who had an associated lymphadenectomy either for failed mapping or during the learning curve). We also excluded patients who had para-aortic lymph node dissection from the lymphadenectomy group. Perioperative and 30-day surgical outcomes were compared between patients who underwent sentinel lymph node assessment and those who had pelvic lymphadenectomy or hysterectomy alone, respectively. Inverse probability of treatment weighting derived from propensity scores was used to minimize allocation bias in the comparison of outcomes between groups.ResultsA total of 621 patients were analyzed: 188 (30.3%) with sentinel lymph node biopsy, 198 (31.9%) with pelvic lymphadenectomy, and 235 (37.8%) with hysterectomy alone. Inverse probability of treatment weights analysis balanced for baseline characteristics (age, body mass index, American Society of Anesthesiologists score, Charlson co-morbidity index, parity, prior cesarean section, and previous abdominal operation) showed no significant differences in intra-operative and post-operative complications, re-admissions, and re-operations between the groups. Compared with pelvic lymphadenectomy, the sentinel lymph node biopsy group had a shorter mean operative time (138.0 vs 222.8 min, pConclusionsIntroduction of sentinel lymph node biopsy reduces operative times and improves peri-operative surgical outcomes of robotic-assisted staging for apparent early-stage endometrial cancer without worsening the morbidity of hysterectomy alone.

To examine the effect of robotic-assisted surgery implementation for treatment of endometrial cancer in the United States on 30-day clinical outcomes and costs.We retrospectively reviewed data of adult patients who underwent total hysterectomy for endometrial cancer in the US hospitals in Premier Healthcare Database between January 1, 2008 and September 30, 2015. We conducted trend analyses comparing the proportions of surgical approaches with the associated clinical outcomes and costs over the study period using Mann-Kendall tests. Clinical outcomes and costs of robotic-assisted surgery, laparoscopic and open surgery have been compared after propensity score 1:1 matching in the most recent 3 years (January 1, 2013-September 30, 2015).Of a total of 35,224 patients, use of robotic-assisted surgery increased from 9.48% to 56.82% while open surgery decreased from 70.4% to 28.1% over the study period. A 2.5% decrease in major complications (P .001), a 2.9% decrease in minor complications (P = .001), and a 2.0% decrease 30-day readmissions (P = .001) was observed across all surgical approaches. Perioperative 30-day total cost slightly decreased from US $11,048 to US $10,322 (P = .08). Among propensity-score matched patients, robotic-assisted surgery was associated with shorter hospitalization than open surgery (median [interquartile range], 2.0 [2.0-3.0] vs 4.0 [3.0-6.0] days) and laparoscopic surgery (2.0 [2.0-3.0] vs 3.0 [2.0-4.0] days), fewer 30-day complications (20.1% vs 33.7%) (all P .001), and comparable perioperative 30-day total costs (median [interquartile range], US $12,200 [US $9,509-US $16,341] vs US $12,018 [US $8,996-US $17,162]; P = .34) with open surgery.Robotic-assisted surgery facilitated the widespread diffusion of a minimally invasive approach nationally for endometrial cancer, with reduction of perioperative morbidity and no increase in overall treatment-related 30-day costs at national level.

The aim of this study was to assess the role of frozen section (FS) in identifying an absence of lymph nodes during sentinel lymph node (SLN) biopsy for apparent early-stage endometrial cancer (EC). Consecutive apparent early-stage EC patients who had SLNs removed after cervical injection with indocyanine green (ICG) from 1 June 2014 to 30 June 2016 were analyzed. An empty node (EN) was defined as an SLN specimen without evidence of lymph node(s). The association of tumor and patient characteristics with an EN was evaluated, and trend analysis to compare the rate of ENs over calendar quarters was performed. A decision-tree model was then created to compare the use of FS versus no FS for SLN evaluation in the hypothetical cohort affected by early-stage EC in the US each year. Over the study period, 300 patients met the inclusion criteria. FS revealed ENs in 24 (8%) patients. No association between patient demographic characteristics (age, body mass index, prior abdominopelvic surgery, international federation of gynecology and obstetrics (FIGO) stage, histology, myometrial invasion, cervical stromal invasion) and presence of ENs was observed. The rate of ENs at FS did not change over time (p = 0.68). The hypothetical analysis showed a 4.3% decrease of inappropriately staged patients with the use of FS on the SLN (95% confidence interval 4.1–4.5). ENs during SLN biopsy for EC staging is not a rare event and can be easily detected with FS. The implementation of FS of SLN might reduce inadequate staging of EC. Individual institutions may want to examine their own EN rates and determine if this would assist them in their SLN practices for EC.

Ovarian, fallopian tube and primary peritoneal carcinomas (OVCA) most commonly present in advanced stages and despite aggressive surgical resection and chemotherapy will likely recur. Although OVCA can recur in the liver, chest or brain, it most commonly recurs within the peritoneal cavity. Peritoneal spread is problematic and often results in bowel obstruction and the inability to maintain nutritional goals. Given the lethality of peritoneal disease as well as the difficulty in treating this recurrence pattern, novel tactics to treat peritoneal dissemination have been a focus of research in OVCA. Heated intraperitoneal chemotherapy (HIPEC) has been well studied and is utilized to treat appendiceal malignancies, which similarly involve the peritoneum. HIPEC has been shown to improve survival and decrease the risk of peritoneal recurrence in patients with appendiceal malignancies. This technique has also been shown to improve outcomes in patients with peritoneal metastases due to colorectal cancers and gastric cancers. Over the past three decades, HIPEC has been used to treat OVCA with mixed results. The aim of this paper is to review the use of HIPEC in the treatment of OVCA in the upfront and recurrent setting.

Objective Two randomized trials failed to demonstrate efficacy of platinum-based chemotherapy (PbCT) for uterine serous carcinoma (USC). Our objective was to reassess the value of PbCT for patients with microscopic residuum (R0). Methods Progression-free survival (PFS) after surgery was analyzed for 409 patients and correlated with adjuvant therapies: vaginal brachytherapy (VBRT), external beam radiotherapy (EBRT), PbCT, or combinations. Results The estimated 5-year PFS for stage I ( n =209) USC was 65.1% for observation only; 90.7%, VBRT only; and 91.1%, PbCT±VBRT (85% received VBRT); VBRT significantly ( P =.004) impacted PFS, but the added value of PbCT remains uncertain. Of 58 stage IIIC, PbCT-treated patients (±EBRT), 5-year PFS was 33.9%; most failures had a vascular disseminated component. Median PFS for 72 stage IV, PbCT-treated patients was 18.6months for R0; 8.0, R1≤1cm residual disease; and 4.6, R2>1cm ( P =.008). The progression rate (PR) during 1 to 2year follow-up for R0 was similar to PR during 0–1year follow-up for R1 ( P =.31), suggesting recurrences in patients with R0 disease before 2years are likely platinum resistant. PRs during follow-up were nearly identical for R0≥2years and R1≥1year ( P =.95), presumably showing limited numbers of platinum-sensitive tumors. Conclusions A comparison of PR for patients treated with PbCT for stage IV R0 and R1 disease suggested that a 1-year lag interval precedes clinical recognition of PbCT refractory/resistant R0 disease. Most patients treated with PbCT who had microscopic residuum had recurrences within 2years (across stages), emphasizing the need for more effective therapy.