Laparoscopic predictability of minimally invasive interval debulking in advanced ovarian cancer: The MIID-SOC trial.

BACKGROUND: We sought to create a laparoscopic-based model to predict the ability to perform a minimally invasive (MIS) cytoreductive surgery in advanced epithelial ovarian cancer patients who have received neoadjuvant chemotherapy (NACT). METHODS: Fifty women were enrolled in a multi-institutional prospective pilot study (NCT03378128). Each patient underwent laparoscopic evaluation of 43 abdominopelvic sites followed by surgeon dictated surgical approach, either continue MIS or laparotomically. However, if the procedure continued MIS, the placement of a hand-assist port for manual palpation was mandated to emulate a laparotomic approach and all 43 sites were re-evaluated. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each site to predict MIS resectability. Each parameter was assigned a numeric value based on the strength of statistical association and a total predictive index score (PIV) was assigned for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict the MIS approach. RESULTS: Twenty-seven patients (61%) underwent MIS surgery. The following abdominopelvic sites were selected for inclusion in the model: gastrosplenic ligament, rectum, left mesocolon, transverse colon, right colon, cecum, appendix, liver capsule, intrahepatic fossa/gallbladder, ileum/jejunum. Using the PIV, a ROC was generated with an AUC = 0.695. In the final model, a PIV <2 identified patients able to undergo an optimal MIS cytoreductive surgery with an accuracy of 68.2%. The specificity, or the ability to identify patients who would not be able to undergo an optimal MIS interval cytoreductive surgery, was 66.7%. CONCLUSION: This predictive index model may help to guide future inclusion criteria in randomized studies evaluating the MIS approach in advanced epithelial ovarian cancer.

Tyrosine kinase inhibitor toxicities: A society of gynecologic oncology review and recommendations.

OBJECTIVE: Oral tyrosine kinase inhibitors (TKIs) have new indications for treatment in gynecologic malignancies. These targeted drugs have both unique and overlapping toxicities, which require careful attention and management. New combination therapies with immune-oncology agents have demonstrated promise in endometrial cancer. This review examines common adverse events associated with TKIs and provides readers with an evidence-based review on current uses and strategies for the management of these medications. METHODS: A comprehensive review of the medical literature on TKI use in gynecologic cancer was undertaken by a committee approach. Details of each drug, its molecular target, and relevant data on both clinical efficacy and side effects were compiled and organized for clinical use. Information on drug-related secondary effects and management strategies for specific toxicities, including dose reduction and concomitant medications, were gathered. RESULTS: TKIs can potentially offer improved response rates and durable responses for a group of patients who were previously without an effective standard second-line therapy. The combination of lenvatinib and pembrolizumab represents a more targeted approach to the drivers of endometrial cancer; however, there remains significant drug-related toxicity, and thus dose reduction and dose delay are frequently required. Toxicity management requires frequent check-ins and management strategies to help patients find the highest tolerable dose. TKIs are expensive and patient financial toxicity is as critical a measure of a drug's utility as any drug side effect. Many of these drugs have patient assistance programs, which should be fully utilized to minimize cost. CONCLUSIONS: Future studies are needed to expand the role of TKIs into new molecularly driven groups. Attention to cost, durability of response, and long-term toxicity management is needed to ensure all eligible patients have access to treatment.

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.

Does trocar puncture of the bladder during midurethral sling impact postoperative urinary storage and voiding symptoms?

INTRODUCTION AND HYPOTHESIS: The incidence of trocar bladder puncture during midurethral sling (MUS) surgery varies widely. We aim to further characterize risk factors for bladder puncture and examine its long-term impact on storage and emptying. METHODS: This is an Institutional Review Board-approved, retrospective chart review of women who underwent MUS surgery at our institution from 2004 to 2018 with ≥12 months of follow-up. Unless prolonged catheterization was necessary, a voiding trial was performed prior to discharge, or the next morning in outpatients, regardless of puncture. Preoperative and postoperative details were obtained from office charts and operative records. RESULTS: Of 1,500 women, 1,063 (71%) had retropubic (RP) and 437 (29%) had transobturator MUS surgery. Mean follow-up was 34 months. Thirty-five women (2.3%) sustained a bladder puncture. RP approach and lower BMI were significantly associated with puncture. No statistical association was found between bladder puncture and age, previous pelvic surgery, or concomitant surgery. Mean day of discharge and day of successful voiding trial were not statistically different between the puncture and nonpuncture groups. There was no statistically significant difference in de novo storage and emptying symptoms between the two groups. Fifteen women in the puncture group had cystoscopy during follow-up and none had bladder exposure. Level of the resident performing trocar passage was not associated with bladder puncture. CONCLUSIONS: Lower BMI and RP approach are associated with bladder puncture during MUS surgery. Bladder puncture is not associated with additional perioperative complications, long-term urinary storage/voiding sequelae, or delayed bladder sling exposure. Standardized training minimizes bladder punctures in trainees of all levels.

Enhanced recovery after surgery (ERAS) protocol is associated with lower post-operative opioid use and a reduced office burden after minimally invasive surgery.

OBJECTIVE: Enhanced recovery after surgery (ERAS) has decreased hospital opioid use, but less attention has been directed towards its impact on clinic burden with respect to post-operative care. Our objective was to determine the impact of an ERAS protocol on post-operative opioid prescribing, and the subsequent number of pain medication refill requests and unscheduled patient-provider interactions in the 30-day post-operative period. METHODS: IRB-approved retrospective study comparing post-operative opioid prescription practices 10 months before and 10 months after ERAS protocol implementation after minimally invasive gynecologic surgery. Opioid doses in morphine milligram equivalents (MMEs), number of unscheduled visits, and phone calls were compared before and after ERAS implementation. RESULTS: A total of 791 patients were included; 445 without and 346 with ERAS implementation. ERAS was associated with higher rates of same day discharge (49% vs 39%, p = 0.003) and lower readmission rates (2.0% vs 5.6%, p = 0.011). Post-operatively, patients who received the ERAS protocol were prescribed less opioids (197.8 vs. 223.5 MMEs, p = 0.0087). There was a trend towards less refill requests with ERAS (1.7% vs 3.6%, p = 0.11). ERAS was associated with a decreased number of post-operative phone calls (38% vs 46%, p = 0.023), including calls for pain (10% vs 16%, p = 0.021), and fewer unscheduled visits related to pain (1.5% vs 5.8%, p = 0.001). CONCLUSIONS: Implementation of the ERAS protocol resulted in a decrease in post-operative opioid prescribing. Despite the lower amount of prescribed post-operative opioids, the ERAS protocol translated into a decrease in the need for post-operative interactions with the clinic staff, specifically encounters associated with pain.

Beyond Serous: Treatment Options for Rare Endometrial Cancers.

OPINION STATEMENT: Rare endometrial cancers are high-grade, aggressive malignancies which are often diagnosed at an advanced stage, and account for disproportionately more deaths than their more common low-grade counterparts. Standard of care includes a combination of surgery, radiation, and chemotherapy. Surgery consists of complete hysterectomy, and more recent evidence supports replacing a full lymphadenectomy with sentinel node mapping. Paclitaxel and carboplatin remain the mainstays of chemotherapy, while current studies incorporating immunotherapy will inform future practice. Whether and how to incorporate radiation remains controversial, and certain histologic subtypes, such as carcinosarcomas, may benefit from radiation more than others. Owing to their relative rarity, it is difficult to conduct clinical trials in this patient population, which has hindered the development of effective therapies for rare malignancies. Molecular profiling has offered insight into the pathogenesis of rare endometrial cancers, providing actionable targets for personalized therapy.

Evaluation of the Viability of Untreated Leiomyomas Using Computed Tomography-Detected Calcification Patterns.

OBJECTIVE: To evaluate the relationship between computed tomography (CT)-detected calcification patterns and Magnetic Resonance Imaging (MRI) enhancement as a surrogate for viability in untreated uterine leiomyomas. METHODS: We queried 2 university hospital databases to identify patients with: (1) at least 1 calcified leiomyoma on CT greater than 1 cm (2) contrast-enhanced MRI of the pelvis performed within 5 years of the CT, and (3) no prior history of uterine fibroid embolization (UFE). Computed tomography was used to analyze calcification pattern and contrast-enhanced MRI to analyze size and viability. RESULTS: There were 12,862 reports that fit the criteria. After exclusion, 50 patients with 74 calcified untreated leiomyomas were analyzed. Three calcification patterns were identified: rim (n = 22), diffuse (n = 9), and coarse either less than or greater than 50% (n = 43). Four of 22 (18%) of leiomyomas with rim calcification were viable. Three of 9 (33%) of leiomyomas with diffuse calcification were viable. All leiomyomas with coarse calcifications were viable, 43 of 43 (100%). CONCLUSIONS: Leiomyomas with coarse calcifications are viable, whereas the majority with rim or diffuse calcification are not. This information may be helpful when triaging symptomatic women to treatment.

Factors Associated with Same Day Discharge after Laparoscopic Surgery in Gynecologic Oncology.

STUDY OBJECTIVE: To identify factors associated with same day discharge (SDD) after laparoscopic surgery in gynecologic oncology. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: Total of 800 patients having minimally invasive surgery in the division of gynecologic oncology during a 20-month period. INTERVENTION: Minimally invasive surgery cases were reviewed for determinants of SDD to identify factors that could improve the SDD rate. MEASUREMENTS AND MAIN RESULTS: During the study period, 800 minimally invasive procedures were performed with a 43.0% SDD rate. Patients who had SDD were younger (52.3 years vs 58.0 years; p <.001), had a lower body mass index (31.1 kg/m2 vs 33.7 kg/m2; p <.001), were less likely to have a malignancy (28.2% vs 55.5%; p <.001), had a lower estimated blood loss (36 vs 72 mL; p <.001), and were more likely to have received an enhanced recovery after surgery protocol (49.8% vs 39.3%; p <.003). Total surgical time was shorter in women with SDD (156 minutes vs 208 minutes) as was total narcotic use in morphine equivalents (MEq) (milligram intravenous MEq, 23.1 mg MEq vs 28.8 mg MEq). SDD was also associated with earlier start time (p <.001). Laparoscopic cases were most likely to have SDD (51.4%) as compared with robotic assisted surgery (16.1%) or minilaparotomy (10.5%). There was a wide range of SDD among surgeons ranging from 19.8% to 56.2% (p <.001). In a multivariate analysis, the factors predicting SDD in order of predictive factors were surgical time (p <.001), recovery time (p <.001), start time (p <.001), surgeon (p <.001), age (p <.001), estimated blood loss (p <.001), and type of surgery (p = .005). CONCLUSION: Multiple factors affect SDD. Modifiable factors for SDD include the start time, surgeon preference, and patient expectations for SDD. Given these data, centers should prioritize surgical order by which patients are more likely to go home, and surgeons should analyze their own data with respect to achieving higher SDD rates.

Improved Rates of Same-day Discharge in Patients Undergoing Surgery for Endometrial Cancer Following the COVID-19 Pandemic.

STUDY OBJECTIVE: To determine the effect of the coronavirus disease 2019 (COVID-19) pandemic on the rate of same-day discharge (SDD) after minimally invasive surgery for endometrial cancer. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: A total of 166 patients underwent a minimally invasive surgery procedure for the indication of endometrial cancer at a large academic institution from September 1, 2019, to October 1, 2020-80 patients before the implementation of the COVID-19 restrictions and 86 patients after. INTERVENTIONS: COVID-19 pandemic with visitor restrictions and hospital policy changes placed on March 17, 2020. MEASUREMENTS AND MAIN RESULTS: SDD rate was increased by 18% after the start of the COVID-19 pandemic (40% vs 58%, p = .02). There were no differences between the 2 groups with regard to operative time (p = .07), estimated blood loss (p = .21), uterine weight (p = .12), age (p = .06), body mass index (p = .42), or surgery start time (p = .15). In a multivariable logistic regression model, subjects in the COVID-19 group had 3.08 times (95% confidence interval, 1.40-6.74; p = .01) higher odds of SDD than those in the pre-COVID-19 group. There was no difference in 30-day readmission rates (7.5% vs 5.8%, p = .66). CONCLUSION: There was a significant increase in the SDD of patients with endometrial cancer since the start of the COVID-19 pandemic. The pandemic has strained hospital resources and motivated patients and physicians to avoid hospitalization. This shows that with proper motivation, an increase in SDD rates is possible without an increase in complications or rehospitalization.

Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Uterine carcinosarcomas: From pathology to practice.

OBJECTIVE: Uterine carcinosarcoma (UCS) is a rare but aggressive cancer. In early-stage disease data guiding treatment is sparse. The purpose of this review is to summarize the findings from the 2019 NRG oncology group summer symposium meeting as well as a review of the current literature, with a particular focus on molecular targets, ongoing clinical trials, and treatment of early and advanced/recurrent disease. METHODS: A combination of expert presentations and an extensive literature search was undertaken to summarize the literature in this review. MEDLINE was queried for peer-reviewed publications on UCS. This search was not limited by year or study design, but was limited to English language publications. ClinicalTrials.gov was queried for ongoing trials in UCS. RESULTS: UCS is a rare cancer that is biphasic, with the carcinomatous component driving its aggressive nature. Level 3 evidence regarding early stage disease is lacking, but retrospective data suggests adjuvant therapy is warranted. The recent results of GOG 261 have contributed valuable information towards treatment strategy, including use of paclitaxel and carboplatin for UCS. Clinical trials are ongoing to investigate new targeted agents in UCS. CONCLUSION: Ongoing endometrial cancer clinical trials now include UCS patients. In combination with advances in molecular profiling, this will provide patients with UCS improved therapeutic options. Until that time, surgical resection and traditional cytotoxic chemotherapy remains standard of care.

Palpable Lumps after Mastectomy: Radiologic-Pathologic Review of Benign and Malignant Masses.

Patients who have undergone mastectomy, with or without reconstruction, are not universally screened with mammography or US. Therefore, clinical breast examination by the physician and patient-detected palpable abnormalities are crucial for detecting breast cancer or recurrence. Diagnostic US is the first-line modality for evaluation of postmastectomy palpable masses, with occasional adjunct use of diagnostic mammography for confirming certain benign masses. In the setting of a negative initial imaging evaluation with continued clinical concern, diagnostic MRI may aid in improving sensitivity. Knowledge of the typical multimodality imaging appearances and locations of malignant palpable abnormalities-such as invasive carcinoma recurrence, cancer in residual breast tissue, radiation-induced sarcoma, and metastatic disease-is crucial in diagnosis and treatment of these entities. In addition, familiarity with the range of benign palpable postmastectomy processes-including fat necrosis, fat graft, seroma, granuloma, neuroma, fibrosis, and infection-may help avoid unnecessary biopsies and reassure patients. The authors review common and rare benign and malignant palpable masses in mastectomy patients, describe multimodality diagnostic imaging evaluation of each entity, review radiologic and pathologic correlation, and acquaint the radiologist with management when these findings are encountered. ©RSNA, 2021.

Perioperative Recovery and Narcotic Use in Laparoscopic versus Robotic Surgery for Endometrial Cancer.

STUDY OBJECTIVE: To compare intraoperative and perioperative narcotic use, recovery room time, and total hospital stay for patients treated with robotic vs laparoscopic surgery for endometrial cancer. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: All patients having minimally invasive surgery in the division of gynecologic oncology during a 20-month period. INTERVENTION: Laparoscopic cases were compared with robot-assisted cases with respect to perioperative outcome. MEASUREMENT AND MAIN RESULTS: Hospital billing records were used to identify all patients with endometrial cancer treated from January 1, 2018 through July 31, 2019 undergoing either laparoscopic or robotic surgery. Data were collected including total narcotic use converted to intravenous morphine milligram equivalent (MME), total amount of time in recovery, and length of hospital stay. A total of 139 laparoscopic and 101 robotic surgeries were eligible for analysis. There was no difference between the groups with respect to blood loss, alcohol use, or smoking. Patients undergoing laparoscopy had a significantly lower body mass index compared with patients undergoing robotic surgery (32.9 vs 38.0 kg/m2; p <.001). Univariate analysis showed no difference between the 2 groups with respect to narcotic use in surgery (21.7 vs 21.1 MME; p = .64), recovery (4.3 vs 4.5 MME; p = .70), or total dose (26.0 vs 25.6 MME; p = .78). However, patients who underwent a robotic approach had a longer recovery room time (128 minutes vs 163 minutes; p <.001 and a longer surgical time (288 minutes vs 204 minutes; p = .001). Patients in the robotic group were also more likely to undergo full lymphadenectomy than patients in the laparoscopy group (38.0% vs 20.8% p <.001). In a multivariate analysis, the only significant factors for predicting total narcotic dose were age, use of a preoperative enhanced recovery after surgery program, and surgical time. Patients who had laparoscopy were more likely to achieve same-day discharge (39.3% vs 17.8%; p <.001), but in the multivariate analysis, the type of surgery did not predict same-day discharge. CONCLUSION: There was no difference in narcotic use in the perioperative period with robotic surgery compared with laparoscopy. Recovery time was longer for robotic surgery, but this was not significant in multivariate analysis. Same-day discharges were less frequent with robotics, which may be more related to the physician's choice rather than the procedure.

Outcomes of Minimally Invasive versus Open Radical Hysterectomy for Early Stage Cervical Cancer Incorporating 2018 FIGO Staging.

STUDY OBJECTIVE: To compare outcomes after minimally invasive surgery (MIS) vs open radical hysterectomy for early stage cervical cancer incorporating 2018 Federation of Gynecology and Obstetrics (FIGO) staging. DESIGN: A retrospective analysis. SETTING: A single teaching hospital. PATIENTS: Patients after radical hysterectomy for stage IA1 with lymphovascular invasion, IA2, or IB1 squamous, adenosquamous, or adenocarcinoma of the cervix between 2007 and 2018, mirroring the Laparoscopic Approach to Cervical Cancer trial criteria. INTERVENTIONS: The use of MIS surgery for performing radical hysterectomy. MEASUREMENTS AND MAIN RESULTS: The outcomes were compared between patients undergoing MIS vs open approaches. A total of 126 patients met the inclusion criteria. The approach was open in 44 patients (35%) and MIS in 82 patients (65%); 49% were laparoscopic and 51% were robotic. Distribution based on the 2009 FIGO staging showed 1 stage IA1 with lymphovascular invasion, 15 stage IA2, and 110 stage IB1 patients. Although not statistically significant, the 3-year disease-free survival (DFS) was higher in the open compared to the MIS group (95% vs 87%; p = .17), and the overall survival was higher in the open compared to the MIS group (97% vs 92%; p = .25). Fourteen patients whose disease recurred were Stage IB1 by FIGO 2009 staging; 11/14 were reclassified to a higher stage by 2018 FIGO staging (5/5 open, 6/9 MIS). Adjuvant therapy was recommended for all these patients based on the Sedlis criteria (10/14) or other risk factors (4/14). Despite this, only 1/9 of MIS patients whose disease recurred received adjuvant therapy compared with 3/5 patients whose disease recurred in the open group (p = .05). CONCLUSION: In a cohort of patients similar to that of the Laparoscopic Approach to Cervical Cancer trial, 2018 FIGO staging may be useful to refine indications for MIS radical hysterectomy in early stage cervical cancer. However, disparate outcomes between MIS and open approaches may be explained by differences in compliance with National Comprehensive Cancer Network guidelines for adjuvant therapy.

Comparison of Perioperative Outcomes between Minimally Invasive Sentinel Node Biopsy and Full Lymphadenectomy for Endometrial Cancer.

STUDY OBJECTIVE: To review the perioperative differences between patients undergoing a minimally invasive sentinel lymph node dissection and those undergoing a full lymphadenectomy. DESIGN: Retrospective review. SETTING: Teaching hospital. PATIENTS: All patients undergoing a minimally invasive procedure for endometrial cancer that included nodal evaluation. INTERVENTIONS: Patients who underwent a sentinel lymph node biopsy were compared with those who underwent a full lymphadenectomy at the time of minimally invasive surgery by either laparoscopic or robot-assisted surgery. MEASUREMENTS AND MAIN RESULTS: A total of 241 minimally invasive surgery procedures for endometrial cancer were performed during the 20-month study period. Nodal dissection was indicated and performed in 156 (65%) of these patients, with 93 undergoing a sentinel lymph node biopsy and 63 a full lymphadenectomy. There was no difference between the sentinel group and the lymphadenectomy group with respect to age, estimated blood loss (p = .23), use of a preoperative enhanced recovery after surgery program (p = .82), or body mass index (34.0 kg/m2 vs 33.7 kg/m2; p = .87). The use of full lymphadenectomy was very dependent on the surgeon (p <.001). There was no difference in narcotic use in milligram intravenous equivalents of morphine in surgery (20.9 vs 22.2; p = .37), recovery (4.6 vs 4.9; p = .73), or total dose (25.4 vs 27.0; p = .33). The surgical procedure was longer with lymphadenectomy (185.2 minutes vs 214.2 minutes; p <.001) and the relative risk of discharge from recovery was lower (0.71; 95% confidence interval, 0.51-0.97; p = .03). The hospital stay was longer with lymphadenectomy (16.3 hours vs 25.5 hours; p <.001) and same-day discharge less frequent (48.5% vs 13.8%; p <.001). A multivariate analysis confirmed that sentinel node biopsy was associated with an increased relative risk of discharge of 1.68 (95% confidence interval 1.11-2.53; p = .01) CONCLUSION: Total narcotic requirements are similar between sentinel node biopsy and lymphadenectomy. However, sentinel node biopsy is associated with a shorter surgical time, recovery time, and hospital stay.

Pre-emptive Non-narcotic Pain Medication before Minimally Invasive Surgery in Gynecologic Oncology.

STUDY OBJECTIVE: To review the impact of enhanced recovery after surgery (ERAS) after minimally invasive surgery (MIS) with respect to perioperative narcotics, time in the recovery room, and total time in hospital. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: All patients having MIS in the division of gynecologic oncology during a 20-month period. INTERVENTION: MIS cases were compared before and after the implementation of an ERAS protocol that incorporated orally administered acetaminophen, gabapentin, and celecoxib. MEASUREMENT AND MAIN RESULTS: A total of 800 MIS cases were performed during the period (77% laparoscopy, 18% robotic, 5% mini-lap). Of these, 449 cases were treated without and 351 with the ERAS protocol. There were no significant differences between the groups with respect to age, BMI, surgery type, smoking, surgical indication, blood loss, or diagnosis. Total narcotic use in milligram intravenous equivalents of morphine (mg IV Eq) was significantly less in the ERAS patients (28.5-mg IV Eq vs 23.6-mg IV Eq; p <.001). There was a trend toward less narcotics in recovery (4.8-mg IV Eq vs 4.1-mg IV Eq; p = .08). Postoperative recovery room time was not different between the groups (129 minutes vs 131 minutes; p = .66). ERAS was associated with a higher rate of same day discharge (38.5% vs 49.0%; p = .003) and a shorter length of hospital stay (22.9 hours vs 18.5 hours; p = .008), with a hazard ratio for discharge of 0.82 (0.71-0.94). However, the same day discharge rate varied widely between treating physicians (20% to 56%). CONCLUSIONS: Implementation of an ERAS protocol for MIS appears to reduce total perioperative narcotic use but does not reduce recovery room time. There was a reduction in total hospital time, but this may be dependent on practice patterns of individual physicians.

Results of an early safety analysis of a study of the combination of pembrolizumab and pelvic chemoradiation in locally advanced cervical cancer.

BACKGROUND: Immune checkpoint inhibitors are being considered for locally advanced cervical cancer (LACC) together with standard-of-care pelvic chemoradiation (CRT). However, the safety of the combination and its optimal schedule are unknown. Defining the safety of the combination is a primary objective of a study examining concurrent and sequential schedules. This article presents a safety analysis that was fully accrued and met reporting requirements. METHODS: Pembrolizumab was given after CRT (arm 1) or during CRT (arm 2) according to a randomized phase 2 design. Patients who were 18 years old or older and had LACC (stages IB-IVA according to the 2009 International Federation of Gynecology and Obstetrics system) were randomized 1:1 to the treatment regimens. The CRT was identical in the 2 arms. Pembrolizumab was administered every 3 weeks for 3 doses; no maintenance was allowed. All patients receiving any treatment were evaluated for safety. Safety assessments included the incidence and severity of adverse events (AEs) and the occurrence of protocol-defined dose-limiting toxicity (DLT) through 30 days after the last pembrolizumab infusion. RESULTS: As of August 2019, 52 of the 88 planned patients had completed treatment and were evaluable for toxicity. Treatment-related grade 2 or higher toxicity was experienced by 88%; 11 had at least 1 grade 4 AE, and another 23 had at least 1 grade 3 AE. Grade 1 or higher diarrhea was reported in 34 patients (65%; 50% of these were grade 1), and there was no difference between arms (63% in arm 1 vs 68% in arm 2). Two patients experienced 3 DLTs. Most patients completed cisplatin (100% in arm 1 vs 82% in arm 2); 83% in both arms completed all pembrolizumab. CONCLUSIONS: Preliminary results support the safety and feasibility of adding pembrolizumab to pelvic CRT concurrently or sequentially. LAY SUMMARY: Pembrolizumab is a humanized antibody against programmed cell death protein 1 that is used in cancer immunotherapy. Preliminary data suggest that pembrolizumab can be safely combined with chemotherapy and pelvic radiation in the treatment of locally advanced cervical cancer. Future studies of the addition of immunotherapy to traditional chemoradiation are planned to determine the best way to deliver the treatment and whether any improvement is seen with the addition of immunotherapy to traditional therapy.

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

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

Molecular variations in uterine carcinosarcomas identify therapeutic opportunities.

OBJECTIVE: To perform comprehensive genomic profiling on a large cohort of patients with uterine carcinosarcomas to identify potential therapeutic targets. METHODS: Molecular profiling was conducted on 168 retrospectively de-identified patients with uterine carcinosarcomas using the Caris Life Sciences platform. Specimens were evaluated for aberrations in protein expression by immunohistochemistry, DNA sequence mutation using a 592-gene next generation sequencing panel, copy number amplification using next generation sequencing or in situ hybridization, and fusion events using NextGen RNA sequencing. Tumor mutational load and microsatellite instability were also evaluated. RESULTS: We identified 168 patients with uterine carcinosarcoma; median age of the cohort was 67 years. The most common mutations were observed in the following genes: TP53 (86%), PIK3CA (34%), FBXW7 (23%), PTEN (18%), KRAS (16%), PPP2R1A (10%). Tumor mutational load was low to moderate in most cases (50% and 45%, respectively). HER2/neu (ERBB2) was amplified in 9% of tumors. Immunohistochemistry protein expression was elevated in TOP2A (95%), TS (80%), PTEN (76%), and TUBB3 (66%). Mismatch repair deficiency was rare (4%). CONCLUSIONS: Multiple somatic mutations and copy number alterations in genes that are therapeutic targets were identified in half of cases. Uterine carcinosarcomas represent an aggressive histology with limited treatment options and poor outcomes, and clinical trials are needed to validate new therapeutic targets.

A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study.

INTRODUCTION: Cabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer. METHODS: This was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m2 given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens. RESULTS: Median PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77-1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17-4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24-2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm. CONCLUSIONS: Median PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer.