Comparison of Outcomes in Bowel Resections by Gynecologic Oncologists Versus General Surgeons During Maximal Cytoreductive Surgery for Advanced Ovarian Cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3006).

BACKGROUND: This report describes the oncologic outcomes for patients with advanced ovarian cancer who had bowel surgery performed by gynecologic oncologists (GOs) and compares the outcomes with those for bowel surgery performed by general surgeons (GSs) during maximal cytoreductive surgery. METHODS: Patients from six academic institutions who had FIGO stage III or IV ovarian cancer and underwent any bowel surgeries during maximal cytoreductive surgery were eligible for the study. The patients were divided into two groups according to whether bowel surgery was performed by a GO or a GS. In both groups, the GOs were mainly involved in extra bowel debulking procedures. Perioperative and survival outcomes were compared between the two groups. RESULTS: The 761 patients in this study included 113 patients who underwent bowel surgery by a GO and 648 who had bowel surgery by a GS. No discernible differences were observed in age, American Society of Anesthesiology (ASA) score, FIGO stage, histologic type, timing of cytoreductive surgery (primary or interval debulking surgery), or complications between the two groups. The GO group exhibited a shorter operation time than the GS group. Kaplan-Meier analysis showed no survival differences between the two groups. In the Cox analysis, non-serous cell types and gross residual diseases were associated with adverse effects on overall survival. However, performance of bowel surgery by a GO did not have an impact on survival. CONCLUSION: Performance of bowel surgery by a GO during maximal cytoreductive surgery is both feasible and safe. These results should be reflected in the training system for GOs regarding bowel surgery, and further research is needed to confirm that GOs can play a more leading role in performing extra-uterine procedures.

Surgery for Recurrent Epithelial Ovarian Cancer.

PURPOSE OF REVIEW: To review evidence around the value and challenges of surgery for recurrent epithelial ovarian cancer (ROC). Both cytoreductive and palliative aspects will be addressed RECENT FINDINGS: Prospective and retrospective evidence demonstrates a significantly longer remission derived from the combination of surgical and systemic modalities as opposed to systemic treatment alone in carefully selected ROC-patients who have relapsed more than 6 months from the end of their 1st line platinum-based chemotherapy. Nevertheless, this benefit appears to be limited when total macroscopic tumor clearance is not achieved. Selection algorithms to identify optimal surgical candidates are of paramount importance to prevent surgical morbidity without the equivalent oncological benefit. In the palliative setting, the risks and benefits of salvage surgery need to be counterbalanced with the advances of conservative techniques for optimal care. Well-defined selection algorithms to identify those who will benefit from surgery in the relapsed setting appear to be the key to oncologic and surgical success.

Extra-abdominal cytoreductive techniques in ovarian cancer: how far can (should) we go?

Complex surgery is an essential component in the management of advanced ovarian cancer. Furthermore, achieving complete gross resection in cytoreductive surgery appears to be associated with significant survival benefits in patients with advanced ovarian cancer. The goal of this review is to demonstrate the advancement of surgical techniques in gynecologic oncology surgery, including resection of disease within the intrathoracic and inguinal regions. This progress has expanded the option of surgery to more patients, especially those who would have previously been deemed inoperable. In this review we describe the most notable studies and reports of surgical resection of ovarian cancer involving cardiophrenic/supradiaphragmatic lymph nodes, mediastinum, lung pleura or parenchyma, and the inguinal region. We also describe the growing role that video-assisted thoracic surgery has played in advanced ovarian cancer diagnosis and management. The studies, series, and reports described demonstrate that comprehensive surgical procedures outside of the abdomen or pelvis can be both safe and feasible in properly selected patients. They also suggest that resection of disease outside of the abdomen or pelvis may benefit appropriately selected patients. Future studies are necessary to identify which patients may benefit most from upfront surgery versus neoadjuvant chemotherapy when ovarian cancer metastasis is present in the thoracic or inguinal regions.

Cost-effectiveness of hyperthermic intraperitoneal chemotherapy following interval cytoreductive surgery for stage III-IV ovarian cancer from a randomized controlled phase III trial in Korea (KOV-HIPEC-01).

BACKGROUND: To evaluate the cost-effectiveness of the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) following interval cytoreductive surgery (ICS) for stage III-IV ovarian cancer from a randomized controlled phase III trial. METHODS: A comparative cost-effective analysis was performed using a Markov health-state transition model derived from the current trial cohort (ClinicalTrials.gov Identifier: NCT01091636). The incremental cost-effectiveness ratio (ICER) was evaluated by dividing the incremental costs by incremental quality-adjusted life-years (QALYs) with a time horizon of 10 years. Costs were calculated from the perspective of Korean healthcare, and health utility values were extracted from published sources. RESULTS: Based on data from the trial, the mean QALY in the ICS group was 7.16 compared to 10.8 in ICS followed by the HIPEC group. With an incremental QALY of 3.64, the ICS followed by HIPEC, was estimated to obtain an ICER of KRW 954,598 (USD 708.3) per QALY. CONCLUSION: The findings of the study suggest that ICS followed by HIPEC, is cost-effective with a significant gain in QALYs. These results may support the current reimbursement of HIPEC from Korean insurance services and the management of long-term conditions.

Impact of warm saline irrigation, hyperthermic intraperitoneal chemotherapy on postoperative pain in primary ovarian cancer from the KOV-HIPEC-01 randomized trial.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a treatment option at the time of cytoreductive surgery after neoadjuvant chemotherapy. The effect of active warming of HIPEC on postoperative pain needs to be investigated. This study aimed to investigate whether HIPEC reduces postoperative pain. METHODS: From the KOV-HIPEC-01 trial, a randomized controlled trial of HIPEC for advanced primary ovarian cancer, 184 patients with a residual tumor size <1 cm were randomly assigned to the HIPEC and control groups at a 1:1 ratio. The consumption of analgesics and pain scales were analyzed. Hyperthermic intraperitoneal chemotherapy was administered after cytoreductive surgery. The primary objective was to compare the consumption of opioids measured in morphine milligram equivalents and non-opioids measured as the maximum daily dose between the HIPEC and control groups. The secondary objective was to compare the minimum and maximum pain intensities on numeric rating scales between the two groups using a linear mixed model. RESULTS: Lesser consumption of non-opioids, with a lower mean maximum daily dose on postoperative days 1 and 2, was observed. The HIPEC group also experienced lower maximum pain intensities on postoperative day 1. No overall differences in the minimum or maximum pain intensities were observed on postoperative day 7. CONCLUSION: The addition of HIPEC to cytoreductive surgery did not lead to increased postoperative pain, as demonstrated by a reduction in the use of analgesics and lower scores on postoperative pain scales during the early postoperative period.

Is minimally invasive radical surgery safe for patients with cervical cancer ≤2 cm in size? (MISAFE): Gynecologic Oncology Research Investigators coLLborAtion study (GORILLA-1003).

OBJECTIVE: To identify clinicopathological factors associated with disease recurrence for patients with 2018 FIGO stage IA with lymphovascular invasion to IB1 cervical cancer treated with minimally invasive surgery (MIS). METHODS: A total of 722 patients with cervical cancer between January 2010 and February 2021 were identified. Clinicopathological factors related to disease recurrence were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. To determine prognostic factors for DFS, a Cox proportional hazard regression model was used. RESULTS: Of 722 patients, 49 (6.8%) experienced disease recurrence (37 pelvis, 1 para-aortic lymph node, and 11 peritoneum). Five-year DFS and OS rates were 90.7% and 98.1%, respectively. In multivariate analysis, risk factors associated with disease recurrence were residual disease in the remaining cervix (OR, 3.122; 95% CI, 1.152-8.461; p = 0.025), intracorporeal colpotomy (OR, 3.252; 95% CI, 1.507-7.017; p = 0.003), and positive resection margin (OR, 3.078; 95% CI, 1.031-9.193; p = 0.044). The non-conization group had a higher percentage of stage IB1 (77.4% vs. 64.6%; p = 0.004) and larger tumor (10 mm vs. 7 mm; p < 0.001) than the conization group. Intracorporeal colpotomy and residual disease in the remaining cervix were independent variables associated with disease recurrence in patients undergoing MIS following conization. CONCLUSION: During MIS, patients with cervical cancer ≤2 cm in size can be vulnerable to peritoneal recurrences. Patients diagnosed with invasive cancer through conization often have low-risk pathological features, which may affect their survival outcomes.

Fertility-sparing hormonal treatment in patients with stage I endometrial cancer of grade 2 without myometrial invasion and grade 1-2 with superficial myometrial invasion: Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-2001).

OBJECTIVES: To evaluate oncologic and pregnancy outcomes of fertility-sparing treatment (FST) using progestin in patients with stage I grade 2 endometrioid endometrial cancer (EC) without myometrial invasion (MI) or grade 1-2 with superficial MI. METHODS: Multicenter data of patients with stage I grade 2 EC without MI or grade 1-2 EC with superficial MI, who received FST between 2005 and 2021, were analyzed. Cox regression analysis identified independent factors for progressive disease (PD) during the FST. RESULTS: Altogether, 54 patients received FST [medroxyprogesterone acetate (500-1000 mg) in 44, megestrol acetate (40-800 mg) in 10] with concurrent levonorgestrel-releasing intrauterine devices use in 31. With median time to achieve a complete response (CR) of 10 (3-24) months, 39 patients (72.2%) achieved CR. Of the 15 patients who attempted to conceive after achieving CR, 7 (46.7%) became pregnant (2 abortions, 5 live births). During a median FST duration of 6 (3-12) months, nine patients (16.6%) were diagnosed with PD. Fifteen (38.5%) experienced recurrence with a median recurrence-free survival of 23 (3-101) months. In the multivariable analysis, tumor size before FST ≥2 cm (HR 5.456, 95% CI 1.34 to 22.14; p = 0.018) was significantly associated with a high PD rate during FST. CONCLUSION: The overall response rate to FST was promising, however, the PD rate was significant during the first 12 months of FST. Therefore, performing thorough endometrial biopsy and imaging studies is essential to strictly evaluate the extent of the disease every 3 months from FST initiation.

Intranodal Lymphangiography and Embolization for the Treatment of Early Postoperative Lymphatic Leaks after Pelvic Surgery.

PURPOSE: To assess outcome and predictors of outcome after lymphatic embolization (LE) for early postoperative lymphatic leak after pelvic surgery. MATERIAL AND METHODS: Lymphangiography (LG) procedures performed between May 2015 and February 2020 for postoperative intraperitoneal lymphatic leaks after pelvic surgery were reviewed. Treatment indication was lymphatic drainage of >500 mL/d persisting for >1 week. LE was performed by injecting glue into the iliac lymph node. Fisher exact and Wilcoxon rank-sum tests were used for comparative analysis, and logistic regression was used to assess predictors of outcome. RESULTS: LG was performed in 71 patients. A leak was demonstrated in 69 patients who underwent LE. The mean drainage was 1,329 mL/d ± 773. Catheters were removed in 49 (69.0%) patients after 1 procedure and in 69 (97.2%) patients after a mean of 1.3 procedures. The mean drainage at the time of catheter removal was 157 mL/d ± 100. Failure occurred in 12 (16.9%) cases, including 2 (2.8%) cases of unsuccessful catheter removal and 10 (14.1%) cases of catheter reinsertion owing to recurrent ascites (n = 3) and lymphoceles (n = 7). Older age and drainage of >1,500 mL/d were associated with failure (P = .004). Drainage of >1,500 mL/d was associated with a post-LE catheter dwell time of longer than 1 week (P = .024). Minor adverse events were noted in 4 (5.6%) patients who presented with transient leg swelling. CONCLUSIONS: LE was effective for treating pelvic surgery-related lymphatic leaks. Reintervention may be required. Drainage of >1,500 mL/d was associated with clinical failure and a post-LE catheter dwell time of longer than 1 week.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA-3001).

BACKGROUND: To identify those most likely to benefit from secondary cytoreductive surgery (SCS), we evaluated the survival outcomes and factors predictive of prognosis in patients with recurrent ovarian cancer. METHODS: We retrospectively reviewed the medical records of patients with recurrent ovarian cancer treated at five high-volume Korean hospitals between 2010 and 2021. Recurrence characteristics, treatment methods, and potential predictors of survival were compared between the chemotherapy and surgery groups. RESULTS: Among all 670 patients, 88.1% had initial stage III/IV disease, and 215 (32.1%) underwent SCS. Among patients who underwent SCS, only those who achieved complete resection exhibited improved survival. Even in patients with residual disease < 1 cm after SCS, we observed no significant survival benefit (p = 0.942). In the multivariate Cox analysis, residual disease at primary surgery, progression-free interval, recurrence sites (≤3 regions or limited carcinomatosis), ascites, and SCS were significant predictors of survival. Meanwhile, the only factor predictive of complete resection after SCS was recurrence sites (p < 0.001). CONCLUSIONS: The benefits of SCS appear to be exclusive to cases of complete resection. We propose limited regional platinum-sensitive recurrence (≤3 regions or limited carcinomatosis) without ascites as the optimum selection criteria for SCS.

Significance of cholecystectomy in cytoreductive surgery for advanced ovarian cancer.

BACKGROUND: There have been no studies concerning the complications or benefits of cholecystectomy in ovarian cancer. In this study, we aimed to evaluate the outcomes of cholecystectomy performed during various time periods of the disease course and suggest a management strategy for cholecystectomy in ovarian cancer. METHODS: We retrospectively reviewed the medical records of patients with advanced ovarian cancer who underwent cholecystectomy during the cytoreductive surgery from 2009 to 2020. Cholecystectomy was primarily indicated when the gallbladder and surrounding structures were considered to have metastatic tumor invasion. If the final pathologic results showed free of malignant tumor, patients were placed into the no-infiltration group. Clinical outcomes including the recurrence rate and complications were analyzed. RESULTS: A total of 62 patients underwent cholecystectomy, 48 of whom (77.4%) underwent cholecystectomy during primary or interval debulking surgery, whereas 14 (22.6%) underwent cholecystectomy during the follow-up period (five with benign disease and 9 with disease recurrence). Among the patients, 32 (51.6%) patients were included in the no-infiltration group in the final pathology. There were no complications observed in the no-infiltration group (n = 32). Seven (78%) of the nine patients who received cholecystectomy for disease recurrence had metastatic disease in the porta-hepatis or lesser sac at the time of primary surgery. However, no recurrent lesions were observed around the porta-hepatis in patients who received cholecystectomy during primary treatment. CONCLUSION: Considering the safety of the procedure, as well as the risk of disease recurrence or cholecystitis, a cholecystectomy can be offered to patients with ovarian cancer who have metastatic lesions around the gallbladder and porta-hepatis at the time of primary surgery.

Randomized multicenter phase II trial of prophylactic irradiation of para-aortic lymph nodes in advanced cervical cancer according to tumor hypoxia: Korean Radiation Oncology Group (KROG 07-01) study.

We conducted a prospective phase II study on whether extended-field irradiation (EFI) confers survival benefits depending on hypoxic markers in locally advanced uterine cervical cancer (LAUCC). RNA-seq was performed to identify immune and hypoxic gene signatures. A total of 288 patients were randomized to either EFI or pelvic radiotherapy (PRT). All patients completed chemoradiotherapy. Overall, significantly higher 5-year para-aortic recurrence free survival (PARFS) rate occurred in EFI (97.6%) than in PRT group (87.2%), with marginal tendency to improve disease-free survival (DFS; 78% vs 70%, P = .066). Subgroup analyses were performed based on carbonic anhydrase 9 (CA9)-only positive, CA9/hypoxia-inducible factor (HIF) double positive and CA9 negative. In the CA9-only positive, EFI successfully increased 5-year PARFS (100% vs 76.4%, P = .010), resulting in significantly improved long-term DFS (85.7% vs 54.7%, P = .023) compared to the PRT, while there was no such benefit of EFI in the CA9/HIFs double positive. RNA-seq analysis identified distinct immunehigh subgroup with negative correlation with hypoxia gene signatures (R = -.37, P < .01), which showed a higher 5-year DFS than the immunelow (P = .032). Hypoxia-related genes were upregulated in the CA9/HIFs double positive compared to CA9 negative (P < .05). Only 17.4% of patients in CA9-negative group showed immunelow signatures, while 40.0% of patients in the double-positive group exhibited immunelow signatures. In conclusion, EFI improved PARFS significantly in all patients, but therapeutic efficacy of EFI in terms of improved DFS was solely observed in CA9-only positive LAUCC, and not in CA9/HIFs double-positive subgroup. RNA-seq analysis suggested that hypoxia-induced immunosuppression may be related to treatment resistance in LAUCC.

A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer.

BACKGROUND: PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer. METHODS: Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101. DISCUSSION: PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04678102 .

Gastrointestinal/genitourinary perforation and fistula formation with or without bevacizumab in patients with previously irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators Collaboration (GORILLA) group (GORILLA-1001).

BACKGROUND: This study aims to evaluate the incidence of and identify risk factors for gastrointestinal (GI) and genitourinary (GU) fistula or perforation formation with or without bevacizumab in patients with recurrent cervical cancer who underwent pelvic radiation therapy (RT). METHODS: Medical records of patients with recurrent cervical cancer who previously underwent pelvic RT between 2007 and 2020 were retrospectively reviewed. Clinicopathological factors were compared between groups that are stratified according to: 1) fistula/perforation (+) versus (-); and 2) bevacizumab plus conventional chemotherapy (BC) versus chemotherapy alone (C). Univariate and multivariate regression analyses were performed to identify risk factors for fistula/perforation. Overall survival (OS) was compared between the different groups. RESULTS: Of 219 participants, fistula/perforation of any grade occurred in 36 patients (16.4%); 27 fistulas and 9 perforations. Bevacizumab was more frequently used in Bevacizumab was more frequently used ( +) group than fistula/perforation (-) group (p = 0.015). Multivariate analysis showed that bevacizumab administration was the only independent risk factor for fistula or perforation (HR, 3.27; 95% CI, 1.18-9.10; P = 0.023). F/P was observed more frequently in women receiving BC (n = 144) than those receiving C (n = 75) (20.8% vs. 8.0%; P = 0.019). During median follow-up of 33.7 months (1.2-185.6 months), no significant OS difference was observed between fistula/perforation ( +) vs. (-) (hazards ratio [HR], 1.78; median 84.2 months [95% CI, 59.3-109.0] vs. 129.5 months [95% CI, 114.1-144.9]; P = 0.065) or BC vs. C (HR, 1.03; median 119.8 months [95% CI, 97.3-142.3] vs. 115.7 months [95% CI, 96.0-135.4]; P = 0.928). CONCLUSIONS: This study suggests that incorporation of bevacizumab in chemotherapy regimens for treating recurrent cervical cancer in patients who underwent pelvic RT incurs considerable risk for GI/GU fistula or perforation. There were no other independent risk factors for developing GI/GU fistula or perforation in this study population.

Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol.

BACKGROUND: The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. METHODS: This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. DISCUSSION: We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery. TRIAL REGISTRATION: ClinicalTrials.gov ; NCT04370496 ; registration date, May 2020.

Treatment outcomes and complications in FIGO stage IIIC and IVB endometrioid endometrial cancer patients presenting as nodal spreads following systematic lymphadenectomy and adjuvant therapy.

OBJECTIVE: To evaluate the treatment outcomes and complications of patients with FIGO stage IIIC and IVB endometrioid endometrial cancer (EC) presenting primarily as nodal spreads following systematic lymphadenectomy and adjuvant therapy. MATERIAL AND METHODS: Forty-four FIGO stage IIIC and IVB endometrioid EC patients between July 2003 and March 2020 received staging procedures including systematic lymphadenectomy. The survival outcomes and late treatment-related complications were compared between adjuvant chemoradiation-based group and chemotherapy-based group. RESULTS: Of the 44 patients, 16 (36.4%) had stage IIIC1, 26 (59.1%) had stage IIIC2, and 2 (4.5%) had stage IVB disease. The median follow-up time was 54 months (range, 10-185 months). There was no statistical difference in mortality between the microscopic and macroscopic nodal groups (6.2% vs 4.3%, p > 0.999). Eleven patients (25.0%) and 33 patients (75.0%) received adjuvant chemoradiation and chemotherapy, respectively. The 5-year disease-free and overall survival rates were not different between the two groups (disease-free survival, 81.8% vs 82.1%, p = 0.743; overall survival, 90.9% vs 95.8%, p = 0.537). The incidence rates of grade 2 lymphedema (36.4% vs 9.1%, p = 0.032) and grade 2/3 gastrointestinal complications (36.4% vs 0.0%, p < 0.001) were higher in the chemoradiation-based group than those in the chemotherapy-based group. CONCLUSIONS: Systematic lymphadenectomy and adjuvant chemotherapy might be the preferred treatment for FIGO stage IIIC and IVB endometrioid EC patients presenting as nodal spreads given that no difference in patient survival was found, but a higher incidence of treatment-related complications was observed in the chemoradiation-based group.

Reduction of cycles of neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian or primary peritoneal cancer (ROCOCO): study protocol for a phase III randomized controlled trial.

BACKGROUND: Primary debulking surgery (PDS) and adjuvant chemotherapy is the standard treatment for advanced ovarian, fallopian or primary peritoneal cancer. However, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) has been introduced as an alternative, showing similar efficacy and decreased postoperative complications compared with PDS. Although there is still no evidence for whether three or four cycles of NAC used clinically could be adequate, reducing one cycle of NAC is expected to remove more visible tumours and thereby improve prognosis. Thus, we proposed with this study to evaluate the efficacy and safety of reducing one cycle of NAC for advanced ovarian, fallopian or primary peritoneal cancer. METHODS: This study is a prospective, multi-centre, open-label, randomized phase III trial. A total of 298 patients with advanced ovarian, fallopian or primary peritoneal cancer will be recruited and randomly assigned to either three (control group) or two cycles of NAC (experimental group). After the NAC, we will conduct IDS with maximal cytoreduction and then administer the remaining three or four cycles for a total of six cycles of adjuvant chemotherapy. The primary end point is progression-free survival, and the secondary end points are time to tumour progression, overall survival, tumour response after NAC, IDS and adjuvant chemotherapy, radiologic investigation after IDS, tumour response by positron emission tomography-computed tomography after NAC, quality of life, adverse events, success rate of optimal cytoreduction, surgical complexity, postoperative complications and safety of IDS. We will assess these factors at screening, at every cycle of chemotherapy, at IDS, after the completion of chemotherapy, every 3 months for the first 2 years after the planned treatment and every 6 months thereafter for 3 years. DISCUSSION: We hypothesize that reducing one cycle of NAC will contribute to more resection of visible tumours despite 10% reduction of optimal cytoreduction, which could improve survival. Moreover, two cycles of NAC may increase postoperative complications by 5% compared with three cycles, which may be acceptable. TRIAL REGISTRATION: This study has been prospectively registered at ClinicalTrials.gov on Oct. 2nd, 2018 (NCT03693248, URL: https://clinicaltrials.gov/ct2/show/NCT03693248).

Comparison of posterior rectal dissection techniques during rectosigmoid colon resection as part of cytoreductive surgery in patients with epithelial ovarian cancer: Close rectal dissection versus total mesorectal excision.

OBJECTIVE: The aim of this study was to evaluate the clinical outcomes of close rectal dissection (CRD) compared with those of total mesorectal excision (TME) as the posterior rectal dissection procedure during rectosigmoid colectomy performed as part of cytoreductive surgery in patients with epithelial ovarian cancer. METHODS: We retrospectively reviewed the medical records of 163 patients who underwent posterior rectal dissection for rectosigmoid resection, including low anterior resection or subtotal colectomy, as part of ovarian cancer surgery from 2006 to 2018. The TME technique was mainly performed by colorectal surgeons, and the CRD technique preserving the mesorectal tissue was performed by an experienced gynecologic oncology surgeon. The patients were divided into the TME group and the CRD group, and their clinical outcomes were analyzed. RESULTS: A total of 163 patients with ovarian cancer underwent rectosigmoid colon resection. Among the patients, 87 (53.4%) underwent CRD and 76 (46.6%) underwent TME as the posterior rectal dissection technique. The disease severity according to FIGO stage (p = .390) and the residual disease status (p = .412) were not statistically different between the 2 groups. However, the postoperative incidences of anastomotic leakage (p = .045) and prolonged ileus (>7 days, p = .055) were higher in the TME group. The pelvic recurrence rate and progression-free survival did not differ between the 2 groups (p = .663 and .790, respectively). CONCLUSIONS: Considering the perioperative outcomes, CRD may be an alternative technique for rectal dissection in ovarian cancer with less perioperative morbidity and equivalent oncologic outcomes.

Perioperative outcomes of extensive bowel resection during cytoreductive surgery in patients with advanced ovarian cancer.

BACKGROUND AND OBJECTIVES: To achieve optimal cytoreduction, extensive bowel resections are sometimes required in patients with advanced ovarian cancer. Few studies have focused on the extent or number of resections of bowel surgeries and their feasibility. METHODS: We retrospectively reviewed the medical records of patients with advanced ovarian cancer who underwent bowel surgery as part of debulking procedures at Ajou University Hospital from 2006 to 2018. Patients who received extensive bowel resections (two-segment resections or subtotal colectomy) were identified, and their perioperative outcomes were evaluated. RESULTS: A total of 172 patients underwent bowel surgery. Of them, 128 (74.4%) underwent one-segment bowel resection, 25 (14.5%) underwent two-segment bowel resections, and 19 (11.1%) underwent subtotal colectomy. Although the operative time, transfusion rate, and postoperative bleeding events were higher in patients who underwent extensive bowel resection, the rates of perioperative complications were not significantly higher in this group. Anastomotic leakage occurred in two (1.5%) patients in the one-segment resection group, one (4.2%) patient in the multiple resection group, and two (10.5%) patients in the subtotal colectomy group. CONCLUSIONS: Multiple bowel resections (up to two segments) are feasible and can be safely performed with an acceptable complication rate in patients with advanced ovarian cancer.

Practice patterns of surgery for advanced ovarian cancer: analysis from international surveys.

BACKGROUND: We investigated the practice patterns of surgery for advanced ovarian cancer (AOC) through relevant international surveys. METHODS: After searching for 878 studies on surgery for AOC till 2017, we extracted 18 questions with similar query and answer formats from eight studies. Among them, 5 and 13 were classified as comprehensive and procedure information. RESULTS: In comprehensive information, there was a higher preference for optimal cytoreduction defined as no visible tumor (44%) compared with residual tumors <1 cm (38%) or <2 cm (2%) and omental disease involving the spleen or pancreas was more important as an intraoperative finding precluding optimal cytoreduction (35%) since 2010. The preference for neoadjuvant chemotherapy was the highest at its use for 1-10% (36%), which was preferred in Europe over USA. The positive expectation of preoperative determination of optimal cytoreduction was higher in Europe than in USA (44 vs. 27%; P < 0.05). In procedure information, conventional gynecological surgery was mainly performed by gynecological oncologists, whereas more than 50% of upper abdominal or urological surgeries were conducted by other surgeons. European clinicians showed a higher response rate of diaphragmatic stripping and resection than those from USA (88 vs. 60%; 69 vs. 24%; P < 0.05). CONCLUSION: No visible tumor as the criterion for optimal cytoreduction was preferred in AOC, and aggressive surgery beyond conventional gynecological surgery tended to be performed by other surgeons. Moreover, the preference of neoadjuvant chemotherapy and the positive expectation of preoperative determination of optimal cytoreduction were higher in Europe than in USA.

Risk factors for septic adverse events and their impact on survival in advanced ovarian cancer patients treated with neoadjuvant chemotherapy and interval debulking surgery.

OBJECTIVES: The aim of this study was to analyze risk factors for septic complications during adjuvant chemotherapy and their impact on survival in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). METHODS: We retrospectively reviewed the medical records of 69 patients with advanced epithelial ovarian cancer from 2004 to 2017. All patients underwent three cycles of NACT followed by IDS and adjuvant chemotherapy. We identified grade 3 or 4 hematologic complications and severe adverse events accompanied by neutropenia, including sepsis or septic shock, that occurred during treatment. Clinicopathologic data including demographic factors, preoperative medical conditions, surgical procedures, and survival times were evaluated. RESULTS: Of 69 patients, 27 (39.1%), 6 (8.8%), and 2 (2.9%) patients experienced grade 3 or 4 neutropenia, anemia, and thrombocytopenia, respectively, during NACT. Thirteen patients (18.8%) had a neutropenic fever with sepsis and 2 patients (2.9%) died of septic shock during adjuvant chemotherapy. Concurrent medical disease, splenectomy during IDS, and anemia or thrombocytopenia during NACT were significant risk factors for septic adverse events. In multivariate analysis, anemia (hemoglobin < 8 g/dL, p = 0.004) during NACT was the only significant factor associated with septic adverse events during adjuvant chemotherapy. Although there was no significant difference in progression-free survival, overall survival was significantly shorter in patients with septic adverse events (median, 82.3 vs. 17.3 months, p = 0.007). CONCLUSIONS: Grade 3 anemia during NACT may be an early indicator for septic adverse events during adjuvant chemotherapy. Considering the adverse impact on survival, scheme and dose of adjuvant chemotherapy should be tailored, and careful follow-up evaluation should be ensured in this patient group.