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.

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.

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.

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.

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.

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.

A study of clinicopathologic factors as indicators for early prediction of suboptimal debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer.

AIM: This study aimed to evaluate early clinicopathologic factors predicting gross residual disease after neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer. METHODS: We analyzed clinicopathologic data of 68 patients with ovarian cancer who were treated with neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) between March 2006 and December 2016. All the patients received three cycles of NAC followed IDS. We evaluated all possible clinicopathologic characteristics, including reduction rates of serum CA-125 after each NAC and seven initial abdominopelvic computed tomography (CT) findings related to disease severity. RESULTS: After IDS, no gross residual disease was found in 46 (67.6%) patients and 22 (33.4%) patients had gross residual disease. Multivariate analysis identified that reduction rate of CA-125 after 2nd NAC, body mass index (BMI) and small bowel lesion in the initial CT findings were significantly associated with gross residual disease after IDS (P = 0.005, 0.030, 0.001, respectively). The optimal cutoff value predicting gross residual disease were less than 50% of CA-125 reduction rate after 2nd NAC and low BMI (<23 kg/m2 ). The combined receiver operating characteristic curve analysis of these factors showed good performance for predicting gross residual disease after IDS (area under the curve = 0.845). CONCLUSION: A model using small bowel mesentery involvement on CT, BMI (<23 kg/m2 ) and less than 50% reduction of the initial CA-125 level after the 2nd NAC is highly predictive of gross residual disease after IDS in advanced ovarian cancer patients. These results may be helpful in further treatment planning and patients counseling.

Salvage radiotherapy with or without concurrent chemotherapy for pelvic recurrence after hysterectomy alone for early-stage uterine cervical cancer.

PURPOSE: Treatment outcomes of patients with pelvic recurrence after hysterectomy alone for uterine cervical cancer who received salvage radiotherapy (RT) with or without concurrent chemotherapy were investigated. METHODS: Salvage RT for recurrent cervical cancer confined to the pelvic cavity after hysterectomy alone was received by 33 patients. The median interval between initial hysterectomy and recurrence was 26 months. Whole-pelvic irradiation was delivered to median dose of 45 Gy, followed by a boost with a median dose of 16 Gy to the gross tumor volume. Cisplatin-based concurrent chemotherapy was administered to 29 patients. RESULTS: The median follow-up period was 53 months for surviving patients. Most patients (97.0%) completed salvage RT of ≥45 Gy. Complete response (CR) was achieved in 23 patients (69.7%). Pelvic sidewall involvement and evaluation with positron-emission tomography-computed tomography were significantly associated with CR. The 5­year progression-free survival (PFS), local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 62.7, 79.5, 72.5, and 60.1%, respectively. Initial International Federation of Gynecology and Obstetrics stage, pelvic sidewall involvement, and CR status were significant factors for PFS and OS rates in multivariate analysis. The incidence of severe acute and late toxicities (≥grade 3) was 12.1 and 3.0%, respectively. CONCLUSION: Aggressive salvage RT with or without concurrent chemotherapy for recurrent cervical cancer confined to the pelvic cavity was feasible, with promising treatment outcomes and acceptable toxicities. However, even more intensive novel treatment strategies should be investigated for patients with unfavorable prognostic factors.

Long-term results of early adjuvant concurrent chemoradiotherapy for high-risk, early stage uterine cervical cancer patients after radical hysterectomy.

BACKGROUND: The aim of the present study was to investigate the long-term survival outcomes and toxicities associated with our experienced early administration of adjuvant concurrent chemoradiotherapy (CCRT). METHODS: Ninety-eight patients with pelvic lymph node metastasis, positive resection margin, and/or parametrial invasion who received adjuvant CCRT between 1995 and 2011 were analyzed retrospectively. The first cycle of platinum-based adjuvant chemotherapy was initiated within 2-3 weeks after surgery (median, 12 days) and continued every 4 weeks for a total of 4 cycles. Adjuvant radiotherapy was performed during the second and third cycles of chemotherapy. RESULTS: After a median follow-up period of 119 months for survivors, 13 patients (13.3%) experienced recurrence and 11 patients died of cancer during the follow-up period. The 5-year recurrence-free survival and cancer specific survival rates were 87.6% and 90.6%, respectively. Ninety-four patients (95.9%) received ≥3 cycles of chemotherapy. Total radiation dose of ≥45 Gy was delivered in 91 patients (92.9%). Grade 3-4 hematologic and gastrointestinal toxicities developed in 37 (37.8%) and 14 (14.3%) patients during CCRT, respectively. CONCLUSION: The present study confirmed the long-term safety and encouraging survival outcomes of early administration of adjuvant CCRT, suggesting the benefits of early time to initiation of adjuvant treatments.

Treatment outcomes in patients with FIGO stage IB-IIA cervical cancer and a focally disrupted cervical stromal ring on magnetic resonance imaging: A propensity score matching study.

OBJECTIVE: The aim of this study was to compare treatment outcomes of primary concurrent chemoradiation therapy (CCRT) versus radical hysterectomy (RH) followed by adjuvant RT or CCRT in patients with FIGO stage IB-IIA cervical cancer with focal disruption of the cervical stromal ring on magnetic resonance imaging (MRI). METHODS: We retrospectively analyzed the clinicopathological data of 156 patients with FIGO stage IB-IIA cervical cancer showing a focal disruption of the stromal ring on MRI between March 2000 and March 2015. Treatment outcomes were compared between the RT-based (n=54) group and RH-based group (n=54) after propensity score matching of each of the patients using a logistic regression model, including age, tumor size on MRI, pelvic lymph node enlargement on MRI, and histology. RESULTS: Five-year disease-free survival rate was 83.1% for the RT-based group and 77.4% for the RH-based group (p=0.228). Five-year disease-specific survival rate was 84.3% for the RT-based group and 83.5% for the RH-based group (p=0.434). Incidence rates of late grade 3 genitourinary adverse reactions (14.8% vs. 0.0%, p=0.006) were significantly higher in the RH-based group than those in the RT-based group. CONCLUSIONS: Primary CCRT might be the preferred treatment for FIGO stage IB-IIA cervical cancer patients with focal disruption of cervical stromal ring on MRI given that no difference in patient's survival was found, but higher incidence of treatment-related complications was observed in the RH-based group. Also, primary radical surgery should be done more cautiously in these patients.

Preoperative nomogram for prediction of microscopic parametrial infiltration in patients with FIGO stage IB cervical cancer treated with radical hysterectomy.

OBJECTIVE: This study aimed to establish a nomogram to predict microscopic parametrial infiltration (PMI) by combining preoperative clinicopathologic factors in FIGO stage IB cervical cancer patients treated by radical hysterectomy (RH). METHODS: We retrospectively analyzed clinicopathologic data of 298 patients with FIGO stage IB cervical cancer treated by RH between February 2000 and March 2015. The nomogram was developed based on multivariate logistic regression analysis of preoperative clinicopathologic data. The accuracy and discriminative ability of the nomogram were evaluated by a concordance index and calibration curve. The low-risk group was predefined as having a predicted probability of PMI <10%. RESULTS: Multivariate analysis identified diameter-based tumor volume and disruption of the cervical stromal ring on magnetic resonance imaging, serum squamous cell carcinoma antigen level, and menopausal status as independent prognostic factors associated with PMI. The concordance index of the nomogram was 0.940 (95% CI, 0.908-0.967), and calibration plots revealed good agreement between the observed probabilities and nomogram-predicted probabilities (Hosmer Lemeshow test, p=0.574). The nomogram classified 200 out of 298 patients (67.1%) as low risk. In the low-risk group, the predicted probability of PMI was 3.5% and the actual PMI rate was 2.5% (5 out of 200). CONCLUSIONS: We developed a preoperative nomogram predicting microscopic PMI in surgically treated FIGO stage IB cervical cancer patients. The probabilities derived from this nomogram may have the potential to provide valuable guidance for physicians regarding the primary management of FIGO stage IB cervical cancer patients.

Predicting Model of Lymph Node Metastasis Using Preoperative Tumor Grade, Transvaginal Ultrasound, and Serum CA-125 Level in Patients With Endometrial Cancer.

OBJECTIVE: The purpose of this study was to evaluate the predicting model for lymph node metastasis using preoperative tumor grade, transvaginal sonography (TVS), and serum cancer antigen 125 (CA-125) level in patients with endometrial cancer. MATERIALS AND METHODS: Between January 2000 and February 2013, we identified 172 consecutive patients with surgically staged endometrial cancer. Transvaginal sonography was performed by an expert gynecologic radiologist in all patients. All patients had complete staging surgery including total hysterectomy with bilateral pelvic and para-aortic lymphadenectomy and were staged according to the 2009 International Federation of Gynecology and Obstetrics classification. Various clinicopathologic data were obtained from medical records and were retrospectively analyzed. RESULTS: Of 172 patients, 138 patients presented with stage I (118 IA and 20 IB), 12 had stage II, 18 had stage III (2 IIIA, 1 IIIB, 8 IIIC1, and 7 IIIC2), and 2 had stage IV diseases. Most patients had endometrioid adenocarcinoma (88.4%), and others (12.6%) had nonendometrioid histology. Eighteen patients (10.5%) were found to have lymph node metastasis. Deep myometrial invasion on preoperative TVS (≥50%), high serum CA-125 level (≥ 35 IU/mL), preoperative grade 2 or 3 tumors were significant preoperative factors predicting lymph node metastasis. There was no significant association between preoperative histology and lymph node metastasis. We calculated the simple model predicting lymph node metastasis based on preoperative tumor grade, TVS findings, and CA-125 level using logistic regression analysis. The sensitivity and specificity of this model were 94% and 57%, respectively (area under the curve, 0.84; 95% confidence interval [CI], 0.74-0.93; P < 0.01). CONCLUSIONS: Preoperative tumor grade, myometrial invasion on preoperative TVS, and CA-125 can accurately predict lymph node metastasis in patients with endometrial cancer. The current study suggests the possibility that TVS could be positively used for preoperative evaluation strategy in the low-resource countries instead of expensive imaging modalities such as magnetic resonance imaging or positron emission tomography-computed tomography.

Transvaginal Sonography-Guided Core Biopsy of Adnexal Masses as a Useful Diagnostic Alternative Replacing Cytologic Examination or Laparoscopy in Advanced Ovarian Cancer Patients.

OBJECTIVE: The aim of this study was to evaluate transvaginal sonography (TVS)-guided core biopsy of the adnexal masses for neoadjuvant chemotherapy (NACT) in patients with advanced ovarian malignancies. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 52 patients who had undergone TVS-guided core biopsies in our gynecologic cancer center between May 2009 and October 2015. TVS-guided core biopsies were performed on patients with advanced ovarian malignancies who were considered as candidates for NACT and patients with adnexal masses who required a differential diagnosis of non-gynecologic tumors. RESULTS: Thirty-seven patients (71.2%) were scheduled to undergo NACT owing to the presence of coexisting illness, age, tumor burden, and location of metastatic sites. Fifteen patients (28.8%) underwent TVS-guided core biopsies to determine if they had primary or secondary ovarian tumors. Histopathologic examinations revealed primary ovarian tumors in 44 patients (84.6%). Nongynecologic tumors including gastrointestinal stromal tumor and metastatic tumor from gallbladder, gastric, and colorectal cancer were found to be the second most common disease (n = 5 [9.6%]). Findings in the samples were nondiagnostic in 4 patients (5.8%). With respect to the histological concordance rate between TVS-guided core biopsy and surgical specimen, diagnostic accuracy was 93.6%. There were no biopsy-related complications. CONCLUSIONS: TVS-guided core biopsy may be a feasible procedure to diagnose adnexal masses, particularly in patients with advanced ovarian malignancies who are more likely to benefit from NACT.

Robotic single-site versus laparoendoscopic single-site hysterectomy: a propensity score matching study.

BACKGROUND: The aim of this study was to compare the surgical outcomes of robotic single-site (RSS-H) and laparoendoscopic single-site total hysterectomy (LESS-H) and to evaluate the feasibility of RSS-H in patients with benign gynecologic disease. METHODS: The RSS-H was performed using the da Vinci single-site surgical platform, and the LESS-H using a single multi-channel port system at the umbilicus. Among 467 consecutive patients who had undergone total hysterectomy for benign gynecologic disease, surgical outcomes were compared between RSS-H group (n = 25) and LESS-H group (n = 442) after propensity score matching. RESULTS: All operations were completed robotically and laparoscopically without conversion to laparotomy, respectively. The RSS-H group had longer operating times and less operative bleeding compared to the LESS-H group. While the LESS-H showed 1.4% of major complication rate, the RSS-H had no perioperative complication. Even after propensity score matching, the RSS-H still showed longer operating times (170.9 vs 94.1 min, p < 0.0001) and less operative bleeding (median estimated blood loss, 20 vs 50 ml, p = 0.009; mean hemoglobin drop, 1.6 vs 2.0 g/dl, p = 0.038) than the LESS-H. CONCLUSIONS: The RSS-H could be a feasible and safe procedure in appropriately selected patients with benign gynecologic disease, and further experience and technical refinements will continue to improve operative results. Prospective randomized trials will permit the evaluation of the potential benefits of the RSS surgery as a minimally invasive surgical approach.