Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

Low-Volume Metastases in Apparent Early-Stage Endometrial Cancer: Prevalence, Clinical Significance, and Future Perspectives.

Endometrial cancer (EC) is the most diagnosed gynecologic malignancy, and its incidence and mortality are increasing. The prognosis is highly dependent on the disease spread. Surgical staging includes retroperitoneal evaluation to detect potential lymph node metastases. In recent years, systematic lymphadenectomy has been replaced by sentinel lymph node (SLN) biopsy and ultrastaging, allowing for the detection of macrometastases, micrometastases, and isolated tumor cells (ITCs). Micrometastases and ITCs have been grouped as low-volume metastases (LVM). The reported prevalence of LVM in studies enrolling more than one thousand patients with apparent early-stage EC ranges from 1.9% to 10.2%. Different rates of LVM are observed when patients are stratified according to disease characteristics and their risk of recurrence. Patients with EC at low risk for recurrence have low rates of LVM, while intermediate- and high-risk patients have a higher likelihood of being diagnosed with nodal metastases, including LVM. Macro- and micrometastases increase the risk of recurrence and cause upstaging, while the clinical significance of ITCs is still uncertain. A recent meta-analysis found that patients with LVM have a higher relative risk of recurrence [1.34 (95% CI: 1.07-1.67)], regardless of adjuvant treatment. In a retrospective study on patients with low-risk EC and no adjuvant treatment, those with ITCs had worse recurrence-free survival compared to node-negative patients (85.1%; CI 95% 73.8-98.2 versus 90.2%; CI 95% 84.9-95.8). However, a difference was no longer observed after the exclusion of cases with lymphovascular space invasion. There is no consensus on adjuvant treatment in ITC patients at otherwise low risk, and their recurrence rate is low. Multi-institutional, prospective studies are warranted to evaluate the clinical significance of ITCs in low-risk patients. Further stratification of patients, considering histopathological and molecular features of the disease, may clarify the role of LVM and especially ITCs in specific contexts.

Robotic-assisted hysterectomy for benign gynecologic disease in the United States: in-hospital use of opioid and non-opioid analgesics.

To compare the in-hospital opioid and non-opioid analgesic use among women who underwent robotic-assisted hysterectomy (RH) vs. open (OH), vaginal (VH), or laparoscopic hysterectomy (LH). Records of women in the United States who underwent hysterectomy for benign gynecologic disease were extracted from the Premier Healthcare Database (2013-2019). Propensity score methods were used to create three 1:1 matched cohorts stratified in inpatients [RH vs. OH (N = 16,821 pairs), RH vs. VH (N = 6149), RH vs. LH (N = 11,250)] and outpatients [RH vs. OH (N = 3139), RH vs. VH (N = 29,954), RH vs. LH (N = 85,040)]. Opioid doses were converted to morphine milligram equivalents (MME). Within matched cohorts, opioid and non-opioid analgesic use was compared. On the day of surgery, the percentage of patients who received opioids differed only for outpatients who underwent RH vs. LH or VH (maximum difference = 1%; p < 0.001). RH was associated with lower total doses of opioids in all matched cohorts (each p < 0.001), with the largest difference observed between RH and OH: median (IQR) of 47.5 (25.0-90.0) vs. 82.5 (36.0-137.0) MME among inpatients and 39.3 (19.5-66.0) vs. 60.0 (35.0-113.3) among outpatients. After the day of surgery, fewer inpatients who underwent RH received opioids vs. OH (78.7 vs. 87.5%; p < 0.001) or LH (78.6 vs. 80.6%; p < 0.001). The median MME was lower for RH (15.0; 7.5-33.5) versus OH (22.5; 15.0-55.0; p < 0.001). Minor differences were observed for non-opioid analgesics. RH was associated with lower in-hospital opioid use than OH, whereas the same magnitude of difference was not observed for RH vs. LH or VH.

A Phase I trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies.

PURPOSE: AB160 is a 160 nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles non-covalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of VEGF. Preclinical data showed that AB160 resulted in greater tumor targeting and tumor inhibition compared to sequential treatment with ABX then BEV. Given individual drug activity, we investigated the safety and toxicity of AB160 in patients with gynecologic cancers. PATIENTS AND METHODS: A 3+3 phase I trial was conducted with 3 potential dose levels in patients with previously treated endometrial (EC), cervical (CC), and platinum-resistant ovarian cancer (OC) patients to ascertain the recommended Phase II dose (RP2D). AB160 was administered intravenously on Days 1, 8 and 15 of a 28-day cycle (ABX 75-175 mg/m2, BEV 30-70 mg/m2). Pharmacokinetic analyses were performed. RESULTS: No dose-limiting toxicities (DLTs) were seen among the 3 DLs tested. Grade 3/4 toxicities included neutropenia, thromboembolic events, and leukopenia. DL2 (ABX 150 mg/m2, BEV 60 mg/m2) was chosen as the RP2D. Seven of the 19 patients with measurable disease (36.8%) had confirmed partial responses (95% CI: 16.3%-61.6%). Pharmacokinetic analyses demonstrated that AB160 allowed 50% higher paclitaxel dosing and that paclitaxel clearance mirrored that of therapeutic antibodies. CONCLUSIONS: The safety profile and clinical activity of AB160 supports further clinical testing in patients with gynecologic cancers; the RP2D is DL2 (ABX 150 mg/m2, BEV 60 mg/m2).

Relationship between frailty and nutrition: Refining predictors of mortality after primary cytoreductive surgery for ovarian cancer.

OBJECTIVE: We aimed to examine the interplay between frailty and nutritional status on 90-day mortality after primary cytoreductive surgery (PCS) for ovarian cancer (OC). METHODS: Patients with OC who underwent PCS from 1/2/2006-4/30/2018 at a single institution were identified. Frailty index (FI) includes 30 items and is calculated summing across all the item scores and dividing by the total; frailty was defined as FI ≥0.15. Nutritional status was considered impaired when preoperative serum albumin was <3.5 g/dL. Logistic regression was used to analyze the association between FI (continuous) and albumin status (binary) and 90-day postoperative mortality. RESULTS: A total of 533 patients (mean age, 64.4 years) were included, the majority were stage IIIC disease and serous histology. Albumin was <3.5 g/dL in 87 patients (16.3%) and 113 patients (21.2%) were considered frail. Median FI was 0.07 (IQR 0.03, 0.13). Postoperative 90-day mortality occurred in 24 patients (4.5%). Mortality within 90 days was higher amongst patients with low albumin (12/87, 13.8%), regardless of frailty status (13.8% [9/65] non-frail and 13.6% [3/22] frail patients). Ninety-day mortality in patients with normal albumin (n = 446) was over twice as likely in frail versus non-frail patients (5.5% [5/91] vs. 2.0% [7/355], respectively, p = 0.08). A model to assess 90-day mortality that included both FI and low albumin significantly improved the overall discrimination compared to low albumin alone (AUC 0.76 vs. 0.68 p = 0.03). CONCLUSION: Our findings suggest that frailty and nutrition are both related to 90-day mortality. Preoperative interventions to improve functional and nutritional characteristics are needed.

Practice patterns and complications of hysterectomy for invasive cervical cancer after the Laparoscopic Approach to Cervical Cancer trial.

BACKGROUND: After the publication of the Laparoscopic Approach to Cervical Cancer trial, the standard surgical approach for early-stage cervical cancer is open radical hysterectomy. Only limited data were available regarding whether the change to open abdominal hysterectomy observed after the Laparoscopic Approach to Cervical Cancer trial led to an increase in postoperative complication rates as a consequence of the decrease in the use of the minimally invasive approach. OBJECTIVE: This study aimed to analyze whether there was a correlation between the publication of the Laparoscopic Approach to Cervical Cancer trial and an increase in the 30-day complications associated with surgical treatment of invasive cervical cancer. STUDY DESIGN: Data from the American College of Surgeons National Surgical Quality Improvement Program were used to compare the results in the pre-Laparoscopic Approach to Cervical Cancer period (January 2016 to December 2017) vs the results in the post-Laparoscopic Approach to Cervical Cancer period (January 2019 to December 2020). The rates of each surgical approach (open abdominal or minimally invasive) hysterectomy for invasive cervical cancer during the 2 periods were assessed. Subsequently, 30-day major complication, minor complication, unplanned hospital readmission, and intra- or postoperative transfusion rates before and after the publication of the Laparoscopic Approach to Cervical Cancer trial were compared. RESULTS: Overall, 3024 patients undergoing either open abdominal hysterectomy or minimally invasive hysterectomy for invasive cervical cancer were included in the study. Of the patients, 1515 (50.1%) were treated in the pre-Laparoscopic Approach to Cervical Cancer period, and 1509 (49.9%) were treated in the post-Laparoscopic Approach to Cervical Cancer period. The rate of minimally invasive approaches decreased significantly from 75.6% (1145/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 41.1% (620/1509) in the post-Laparoscopic Approach to Cervical Cancer period, whereas the rate of open abdominal approach increased from 24.4% (370/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 58.9% (889/1509) in the post-Laparoscopic Approach to Cervical Cancer period (P<.001). The overall 30-day major complications remained stable between the pre-Laparoscopic Approach to Cervical Cancer period (85/1515 [5.6%]) and the post-Laparoscopic Approach to Cervical Cancer period (74/1509 [4.9%]) (adjusted odds ratio, 0.85; 95% confidence interval, 0.61-1.17). The overall 30-day minor complications were similar in the pre-Laparoscopic Approach to Cervical Cancer period (103/1515 [6.8%]) vs the post-Laparoscopic Approach to Cervical Cancer period (120/1509 [8.0%]) (adjusted odds ratio, 1.17; 95% confidence interval, 0.89-1.55). The unplanned hospital readmission rate remained stable during the pre-Laparoscopic Approach to Cervical Cancer period (7.9% per 30 person-days) and during the post-Laparoscopic Approach to Cervical Cancer period (6.3% per 30 person-days) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.58-1.04)]. The intra- and postoperative transfusion rates increased significantly from 3.8% (58/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 6.7% (101/1509) in the post-Laparoscopic Approach to Cervical Cancer period (adjusted odds ratio, 1.79; 95% confidence interval, 1.27-2.53). CONCLUSION: This study observed a significant shift in the surgical approach for invasive cervical cancer after the publication of the Laparoscopic Approach to Cervical Cancer trial, with a reduction in the minimally invasive abdominal approach and an increase in the open abdominal approach. The change in surgical approach was not associated with an increase in the rate of 30-day major or minor complications and unplanned hospital readmission, although it was associated with an increase in the transfusion rate.

Vaginal stenosis treatment using computed tomography and fluoroscopy guidance.

INTRODUCTION: Vaginal stenosis is a common complication following construction of a neovagina with vascularized myocutaneous flaps. This is primarily because of inconsistent or inappropriate vaginal dilator use. Image-guided recanalization, especially for obstructed genitourinary tracts, is an emerging idea in interventional radiology. Although multiple surgical techniques have been reported to treat vaginal agenesis or obstruction, the idea of image-guided recanalization of vaginal stenosis is a relatively new management strategy for vaginal stenosis. CASE: We present a challenging case of a patient who initially presented with the complaint of increasing pelvic pressure after the creation of a neovagina via vaginoplasty. She had a distal neovagina created after extensive surgical resection for a large infiltrating pelvic rectal adenocarcinoma. A computed tomography scan revealed a fluid-filled neovaginal abscess. Examination under anesthesia revealed complete stenosis of the neovagina with no identifiable tract for dilation. INTERVENTION: A computed tomography scan and fluoroscopy-guided sharp recanalization of the stenosed neovagina was performed, followed by serial fluoroscopic balloon angioplasty to dilate the stenosed neovagina. Finally, the patient underwent a gynecologic surgery for the excision of remaining granulation tissue to produce a more permanent patent neovagina, followed by regular and proper use of vaginal dilators to ensure patency. CONCLUSION: This case report demonstrates that image-guided techniques can be used to aid in vaginal recanalization in the postoperative setting.

Incidence of venous thromboembolism in patients with advanced stage ovarian cancer undergoing neoadjuvant chemotherapy: Is it time for thromboprophylaxis?

OBJECTIVES: Our objectives were to determine the incidence, timing, and risk factors for venous thromboembolisms (VTEs) in patients with advanced stage epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT). We explored the utilization of direct-acting oral anticoagulants (DOACs) for VTE treatment. METHODS: This retrospective cohort study included patients with advanced stage EOC receiving NACT followed by interval cytoreductive surgery (ICS) at a single institution. Risk factors were compared between patients with versus without VTE between EOC diagnosis and 180 days after ICS. Bleeding complications were compared between patient who received a DOAC versus non-DOAC. RESULTS: VTE cases occurred amongst 33 of the 154 (21.4%) patients with 4 (2.6%) concurrent with EOC diagnosis, 9 (5.8%) between EOC diagnosis and NACT start, 13 (8.4%) between NACT start and ICS, and 7 (4.5%) within 180 days after ICS. There were no statistically significant differences in risk factors assessed (age, body mass index, functional status, histology, Khorana score, and smoking history) between patients with versus without VTE. Eleven patients (33.3%) received a DOAC for VTE treatment. There were no significant differences in number of intraoperative blood transfusions (p = 0.38), blood loss (p = 0.95), or bleeding complications (p = 0.53) between patients treated with a DOAC versus a non-DOAC. CONCLUSION: There is a high incidence of VTE events (21.4%) in patients with advanced stage EOC undergoing NACT. Two-thirds of the VTEs may have been prevented with thromboprophylaxis as they occurred between EOC diagnosis and ICS. These data support consideration of thromboprophylaxis in all patients with advanced stage EOC undergoing NACT.

A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006).

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.

Not all stage I and II endometrial cancers are created equal: Recurrence-free survival and cause-specific survival after observation or vaginal brachytherapy alone in all subgroups of early-stage high-intermediate and high-risk endometrial cancer.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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 with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (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. CONCLUSIONS: Observation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 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.

Excision of Deep Endometriosis of the Rectosigmoid: Individualizing Care to the Presenting Pathology.

STUDY OBJECTIVE: To highlight different surgical approaches for managing deep infiltrating endometriosis involving the rectosigmoid colon. DESIGN: Demonstration of specific surgical techniques with educational narrated video footage. SETTING: 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 lesions >3 cm in size, involving >50% of the bowel circumference, or for multifocal lesions. Various suture and stapler methods exist for this technique. INTERVENTIONS: 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. CONCLUSION: 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.

Surgical Science-Simbionix Robotic Hysterectomy Simulator: Validating a New Tool.

STUDY OBJECTIVE: 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. DESIGN: Prospective education study (Messick validity framework). SETTING: Multicenter, academic medical institutions. PARTICIPANTS: 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. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSION: 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.

Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study.

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.

Image-guided tumor ablation in gynecologic oncology: Review of interventional oncology techniques and case examples highlighting a collaborative, multidisciplinary program.

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.

Appropriate triage allows aggressive primary debulking surgery with rates of morbidity and mortality comparable to interval surgery after chemotherapy.

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 67.5 years, P=0.01), were less likely to have low albumin (16.8% vs. 32.4%, P<0.001), had longer median operative times (315 vs 263 min, P <0.001), more high complexity surgeries and fewer low complexity surgeries (27.2% vs. 11.8% and 18.5% vs 36.3% respectively, P<0.001). The rates of the following outcomes were comparable for PDS and IDS, respectively: successful cytoreduction (complete, 62.5% vs 66.7%, P=0.47 and optimal, 95.3% vs 98.0%, P=0.36), 30-day grade 3+ complications (IPTW-adjusted 18.3% vs. 12.9%, P=0.22), 90-day mortality (IPTW-adjusted, 2.2% vs. 3.8%, P=0.42), length of hospitalization (P=0.29), and postoperative chemotherapy delivery (P=0.83). 3-year overall survival was higher for PDS group (IPTW-adjusted 64.1% vs. 42.6%, P=0.001). CONCLUSIONS: Use of our validated triage strategy allowed us to offer 70% of women with advanced EOC PDS surgery. Despite more complex surgery, M/M after this approach is low and comparable to IDS, with similar rates of complete resection and superior OS. Use of a validated triage system should be utilized when considering PDS vs neoadjuvant chemotherapy.

Phase II trial of ribociclib and letrozole in patients with relapsed oestrogen receptor-positive ovarian or endometrial cancers.

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).

Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients.

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.

Frailty is a determinant of suboptimal chemotherapy in women with advanced ovarian cancer.

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 < 0.001) and paclitaxel (57.9 vs. 80.5%, p = 0.07) despite no differences in dose delays (34.5 vs. 42.1%), dose reductions (65.5 vs. 68.6%), and severe neutropenia (44.8 vs. 39.3%). After adjusting for age, frailty was associated with shorter progression-free (HR 1.58, 95% CI: 0.99-2.50) and overall survival (HR 2.14, 95% CI: 1.35-3.41). 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.