Contentsfewer with combined chemo-radiation.Surgery was generally proceeded particularly in the patients who had responses or at least stable diseases to neoadjuvant treatment.Peri-operative outcomes after neoadjuvant treatment were superior compared to those of primary surgery whereas survival data were still inconsistent.Features which had or tended to have favorable prognosis were younger age, early-stage disease, response to neoadjuvant treatment, low pre-operative CA125, and optimal surgery.Among different modalities of neoadjuvant treatment which has become a frequent mode of treatment, neoadjuvant chemotherapy was more common than radiation therapy alone or chemoradiation.Conclusion: Radiation therapy alone (of different modes) was used as a sole definitive modality of therapy particularly for early-stage diseases which limited to uterine body, cervix, with or without parametrial invasion.Among different modalities of neoadjuvant treatment, neoadjuvant chemotherapy was more common than radiation therapy alone or chemoradiation.

Objective: To compare the survival outcomes of adjuvant radiotherapy and chemotherapy in women with uterine-confined endometrial cancer with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CCC). Methods: Medical records of 80 women who underwent surgical staging for endometrial cancer were retrospectively reviewed. Stage I UPSC and CCC were pathologically confirmed after surgery. Survival outcomes were compared between the adjuvant radiotherapy and chemotherapy groups. Results: Fifty-four (67.5%) and 26 (32.5%) women had UPSC and CCC, respectively. Adjuvant therapy was administered to 59/80 (73.8%) women (25 radiotherapy and 34 chemotherapy). High preoperative serum cancer antigen-125 level (25.1 +/- 20.2 vs. 11.5 +/- 6.5 IU/mL, p<0.001), open surgery (71.2% vs. 28.6%, p=0.001), myometrial invasion (MI)=1/2 (33.9% vs. 0, p=0.002), and lymphovascular space invasion (LVSI; 28.8% vs. 4.8%, p=0.023) were frequent in women who received adjuvant therapy compared to those who did not. However, the histologic type, MI=1/2, and LVSI did not differ between women who received adjuvant radiotherapy and those who received chemotherapy. The 5-year progression-free survival (78.9% vs. 80.1%, p>0.999) and overall survival (77.5% vs. 87.8%, p=0.373) rates were similar between the groups. Neither radiotherapy (hazard ratio [HR]=1.810; 95% confidence interval [CI]=0.297-11.027; p=0.520) nor chemotherapy (HR=1.638; 95% CI=0.288-9.321; p=0.578) after surgery was independently associated with disease recurrence. Conclusion: Our findings showed similar survival outcomes for adjuvant radiotherapy and chemotherapy in stage I UPSC and CCC of the endometrium. Further large study with analysis stratified by MI or LVSI is required.

OBJECTIVE:To evaluate oncologic outcomes of minimally invasive radical hysterectomy (RH) in early cervical cancer before and after the application of parametrial invasion (PMI) criterion on magnetic resonance imaging (MRI) and vaginal colpotomy (VC).METHODS:A total of 216 International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer patients who underwent minimally invasive RH was identified between April 2006 and October 2018. Patients were classified into the pre-PMI intracorporeal or VC (IVC) (n=117) and post-PMI VC groups (n=99). In the pre-PMI IVC group, PMI criterion (intact stromal ring) on MRI was not applied and the patients received IVC. In the post-PMI VC group, surgical candidates were selected using the PMI criterion on MRI and all patients received VC only. Oncologic outcomes and prognostic factors associated with disease recurrence were analyzed.RESULTS:The rate of positive vaginal cuff margins in the pre-PMI IVC group was higher than that in the post-PMI VC group (11.1% vs. 1.0%, p=0.003). Two-year disease-free survival was different between the 2 groups (84.5% in pre-PMI IVC vs. 98.0% in post-PMI VC groups, p=0.005). Disrupted stromal ring on MRI (hazard ratio [HR]=20.321; 95% confidence interval [CI]=4.903-84.218; p<0.001) and intracorporeal colpotomy (HR=3.059; 95% CI=1.176-7.958; p=0.022) were associated with recurrence.CONCLUSION:The intact cervical stromal ring on MRI might identify the low-risk group of patients in terms of PMI and lymphovascular/stromal invasion in early cervical cancer. Minimally invasive RH should be performed in optimal candidates with an intact stromal ring on MRI, using VC.

Diagnosis of ovarian cancer is confirmed by microscopic visual analysis of histopathology slides. The development of a system that automatically performs classification of cancer tissue may reduce the burden of pathologists’ workload. In addition, algorithms that predict BRCA1/2 mutation can also reduce cost burden of performing high-cost next-generation sequencing (NGS) test. In this study, a convolution neural network (CNN) algorithm was developed using histopathology images of patients with ovarian cancer and DNA sequence data from The Cancer Genome Atlas and Ajou University Hospital based on genomic CDM. The results showed that the algorithm could distinguish cancer with 81.22% accuracy and BRCA1/2 mutation with 90.37% accuracy. Additionally, by HeatMap visualization, our model localized the lesion well out of the whole-slide image. This suggested that the CNN model can be used as a clinical decision supporting system and as the primary screening system for ovarian cancer and additional NGS test. Introduction Ovarian cancer has the highest mortality rate among women, and 70% is found to be in the third, or higher, stage owing to the absence of early symptoms. Visual analysis of histopathology slides by experienced pathologists is one of the main methods to evaluate the stage and subtypes of ovarian cancers. Recently, additional genetic screening tests such as NGS have been actively performed because a targeted therapy (poly-ADP ribose polymerase (PARP) inhibitors) has been approved for patients with deleterious or suspected deleterious germline or somatic BRCA1/2-mutated advanced ovarian cancer . The clinical decision supporting system, as the primary screening method, can be used to reduce costs and time spent on labor-consuming pathologic diagnosis workflow. In this study, we aimed to develop a deep learning algorithm for automatic classification of cancer tissues and prediction of genetic variants using histopathology images of patients with ovarian cancer and their DNA mutation data based on genomic CDM. Methods Overall study process is composed of data processing and model building (Figure 1). 1. Histopathology image and DNA sequence data Hematoxylin and eosin-stained whole-slide images of 590 normal individuals or patients with high-grade serous carcinoma were downloaded from The Cancer Imaging Archive (TCIA). Among the patients, 282 available DNA sequence data acquired from the next-generation sequencing (NGS) tests were also downloaded from The Cancer Genome Atlas (TCGA). Whole-slide images for the same subtype of ovary cancer and NGS data of 34 patients were obtained from Ajou University Medical Center (AUMC). 2. Mutation status and labeling of tissue images NGS data obtained from TCGA and AUMC were converted to Genomic-CDM, proposed as an extension of OMOP-CDM, and then compared with the state of changes using the data visualization and analysis tool “GeneProfiler”. In particular, variants labeled as having pathogenic effects on genes such as TP53, BRCA1, and BRCA2, which are clinically important in ovarian cancer, were compared. Using the pathologist’s review, images were divided into two groups (1,458 cancer and 1,525 non-cancer). According to the BRCA1/2 mutation status in cancer groups, images were labeled as two groups (1,381 negative and 75 positive). Three regions of interest (ROI) were extracted from each slide and were used to train algorithms. 3. Convolution neural network (CNN) algorithm and HeatMap visualization CNN was used to develop algorithms for cancer classification and BRCA1/2 mutation prediction. The algorithms were learned using the ROI area, which is a part of the overall tissue image. HeatMap visualization was conducted to see if the algorithm accurately finds lesions in the entire image in the absence of the ROI assignment by pathologists. The whole-slide image was cut to the ROI size and then put into the model to predict whether cancer was present. The corresponding predicted values were used to represent colors at the position of the ROI. Result Mutational frequency analysis was conducted using the open source tool “GeneProfiler.” Results showed that the frequencies of pathogenic mutations in AUMC were similar in TCGA, except for the BRCA1 (Figure 2). Of these, the frequency of the BRCA1/2 to be used to predict mutations was 8.15%–35.30%, which was consistent with the results from previous studies. Based on the presence/absence of cancer and BRCA1/2 mutation, images were categorized as cancer/non-cancer group and positive/negative group, respectively; tissue images were labeled using CNN algorithms, and new image samples were used to predict the accuracy of the algorithms. The CNN algorithm developed using the labeled ROI was tested with new samples. The results showed that the accuracy in classifying a cancer tissue was 81.22% (AUC 0.89), and the accuracy in predicting BRCA1/2 mutation in cancer tissues was 90.37% (AUC 0.90; Figure 3a). The results of the HeatMap visualization in the whole image indicated that cancer region tiles showed high cancer prediction scores compared with the overall region as we expected (Figure 3b).

Purpose Genexol-PM is a biodegradable cremophor EL-free polymeric micelle formulation of paclitaxel. Here, we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment. Materials and Methods In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1: 1) to receive Genexol-PM 260 mg/m(2) or Genexol 175 mg/m2 with 5 area under the curve carboplatin every 3 weeks (6 cycles). The primary endpoint was the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR). Results Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00 +/- 0.00 mg/m(2) Genexol-PM or 174.24 +/- 3.81 mg/m(2) Genexol. Median follow-up was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (non-inferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p=0.148). Peripheral neuropathy of >= grade 3 occurred in one patient receiving Genexol. All toxicities were manageable. Conclusion Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes.

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.

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).

•Tumor involvement of the porta hepatis is one of barriers to optimal cytoreduction.•Resection of tumors at the porta hepatis is feasible.•Optimal cytoreduction can be achieved with these procedures for porta hepatis surgery.

Radioresistance often leads to poor survival in concurrent chemoradiotherapy–treated cervical squamous cell carcinoma, and reliable biomarkers can improve prognosis. We compared the prognostic potential of hemoglobin, absolute neutrophil count, and absolute lymphocyte count with that of squamous cell carcinoma antigen in concurrent chemoradiotherapy–treated squamous cell carcinoma. We analyzed 152 patients with concurrent chemoradiotherapy and high-dose-rate intracavitary brachytherapy–treated cervical squamous cell carcinoma. Hemoglobin, absolute neutrophil count, absolute lymphocyte count, and squamous cell carcinoma antigen were quantitated and correlated with survival, using Cox regression, receiver operating characteristic curve analysis, and Kaplan–Meier plots. Both hemoglobin and absolute lymphocyte count in the second week of concurrent chemoradiotherapy (Hb2 and ALC2) and squamous cell carcinoma antigen in the third week of concurrent chemoradiotherapy (mid-squamous cell carcinoma antigen) correlated significantly with disease-specific survival and progression-free survival. The ratio of high-dose-rate intracavitary brachytherapy dose to total dose (high-dose-rate intracavitary brachytherapy ratio) correlated significantly with progression-free survival. Patients with both low Hb2 (≤11 g/dL) and ALC2 (≤639 cells/µL) showed a lower 5-year disease-specific survival rate than those with high Hb2 and/or ALC2, regardless of mid-squamous cell carcinoma antigen (mid-squamous cell carcinoma antigen: ≤4.7 ng/mL; 5-year disease-specific survival rate: 85.5% vs 94.6%, p = 0.0096, and mid-squamous cell carcinoma antigen: >4.7 ng/mL; 5-year disease-specific survival rate: 43.8% vs 66.7%, p = 0.192). When both Hb2 and ALC2 were low, the low high-dose-rate intracavitary brachytherapy ratio (≤0.43) subgroup displayed significantly lower 5-year disease-specific survival rate compared to the subgroup high high-dose-rate intracavitary brachytherapy ratio (>0.43) (62.5% vs 88.2%, p = 0.0067). Patients with both anemia and lymphopenia during concurrent chemoradiotherapy showed poor survival, independent of mid-squamous cell carcinoma antigen, and escalating high-dose-rate intracavitary brachytherapy ratio might improve survival.

AIM:This study investigates the pattern of disease recurrence and identifies the clinicopathologic prognostic factors for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB and IIA cervical carcinoma treated with laparoscopic/robotic radical hysterectomy (LRH/RRH).METHODS:We conducted a retrospective analysis of 128 patients with FIGO stage IB and IIA cervical cancer. Preoperative examination did not uncover definitive evidence of parametrial invasion or lymph node metastasis in any of the patients; therefore, all patients underwent LRH/RRH with retroperitoneal lymphadenectomy between April 2006 and December 2013. Sites of disease recurrence and all possible clinicopathologic factors related to the risk of disease recurrence were determined.RESULTS:Multivariate analysis demonstrated that laparoscopic intracorporeal colpotomy (P < 0.041, odds ratio 7.038, 95% confidence interval 1.059-15.183) represented a strong prognostic factor related to disease recurrence. We categorized the minimally invasive surgery group into LRH through vaginal colpotomy (LRH-VC; 79 patients) and LRH/RRH through intracorporeal colpotomy (LRH/RRH-IC; 49 patients) according to the colpotomic approaches. Disease recurrence was higher in the LRH/RRH-IC group than in the LRH-VC group (16.3% vs 5.1%, P = 0.057), with five patients in the LRH/RRH-IC group experiencing intraperitoneal spreads.CONCLUSIONS:Total laparoscopic/robotic intracorporeal colpotomy under CO2 pneumoperitoneum may carry a risk of positive vaginal cuff margin, as well as intraperitoneal tumor spreads in patients with early-stage cervical cancer treated with LRH/RRH.

OBJECTIVE:To evaluate the learning curve of laparoscopic radical hysterectomy (LRH) for gynecologic oncologists who underwent residency- and fellowship-training on laparoscopic surgery without previous experience in performing abdominal radical hysterectomy (ARH).METHODS:We retrospectively reviewed 84 patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB cervical cancer who underwent LRH (Piver type III) between April 2006 and March 2014. The patients were divided into two groups (surgeon A group, 42 patients; surgeon B group, 42 patients) according to the surgeon with or without ARH experience. Clinico-pathologic data were analyzed between the 2 groups. Operating times were analyzed using the cumulative sum technique.RESULTS:The operating time in surgeon A started at 5 to 10 standard deviations of mean operating time and afterward steeply decreased with operative experience (Pearson correlation coefficient=-0.508, P=0.001). Surgeon B, however, showed a gentle slope of learning curve within 2 standard deviations of mean operating time (Pearson correlation coefficient=-0.225, P=0.152). Approximately 18 cases for both surgeons were required to achieve surgical proficiency for LRH. Multivariate analysis showed that tumor size (>4 cm) was significantly associated with increased operating time (P=0.027; odds ratio, 4.667; 95% confidence interval, 1.187 to 18.352).CONCLUSION:After completing the residency- and fellowship-training course on gynecologic laparoscopy, gynecologic oncologists, even without ARH experience, might reach an acceptable level of surgical proficiency in LRH after approximately 20 cases and showed a gentle slope of learning curve, taking less effort to initially perform LRH.

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.

Objective The purpose of this study is to investigate the incidence of lymph node metastasis in early endometrial cancer patients and to evaluate preoperative clinicopathological factors predicting lymph node metastasis. Methods We identified 142 patients with endometrial cancer between January 2000 and February 2013. All patients demonstrated endometrioid adenocarcinoma with grade 1 or 2 on preoperative endometrial biopsy. Preoperative magnetic resonance imaging showed that tumors were confined to the uterine corpus with superficial myometrial invasion (less than 50%), and there were no lymph nodes enlargements. All patients had complete staging procedures and were surgically staged according to the 2009 FIGO (International Federation of Gynecology and Obstetrics) staging system. Clinical and pathological data were obtained from medical records and statistically analyzed. Results Of the 142 patients, 127 patients (89.4%) presented with stage 1A, 8 (5.6%) with stage IB, 3 (2.1%) with stage II, and 4 (2.8%) with stage III disease. Three patients (2.1%) had lymph node metastasis-2 IIIC1 and 1 IIIC2 disease. Age, preoperative tumor grade, and myometrial invasion less than 50% on preoperative MRI were not associated with lymph node metastasis. A high preoperative serum CA-125 level (>35 IU/mL) was a statistically significant factor for predicting lymph node metastasis on univariate and multivariate analyses. Lymph node metastasis was only found in patients with preoperative grade 2 tumors or a high serum CA-125 level. Conclusion Preoperative tumor grade and serum CA-125 level can predict lymph node metastasis in apparent early endometrial cancer patients.

Objective There have been many comparative reports on laparoscopic radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH) for early-stage cervical cancer. However, most of these studies included patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2 and small (tumor diameter ≤2 or 3 cm) IB1 disease. The purpose of this study was to compare the feasibility, morbidity, and recurrence rate of LRH and ARH for FIGO stage IB and IIA cervical cancer with tumor diameter of 3 cm or greater. Materials and Methods We conducted a retrospective analysis of 88 patients with FIGO stage IB and IIA cervical cancer with tumor diameter of 3 cm or greater. All patients had no evidence of parametrial invasion and lymph node metastasis in preoperative gynecologic examination, pelvic magnetic resonance imaging, and positron emission tomography–computed tomography, and they all underwent LRH or ARH between February 2006 and March 2013. Results Among 88 patients, 40 patients received LRH whereas 48 underwent ARH. The mean estimated blood loss was 588.0 mL for the ARH group compared with 449.1 mL for the LRH group (P < 0.001). The mean operating time was similar in both groups (246.0 minutes in the ARH vs 254.5 minutes in the LRH group, P = 0.589). Return of bowel motility was observed earlier after LRH (1.8 vs 2.2 days, P = 0.042). The mean hospital stay was significantly shorter for the LRH group (14.8 vs 18.0 days, P = 0.044). There were no differences in histopathologic characteristics between the 2 groups. The mean tumor diameter was 44.4 mm in the LRH and 45.3 mm in the ARH group. Disease-free survival rates were 97.9% in the ARH and 97.5% in the LRH group (P = 0.818). Conclusions Laparoscopic radical hysterectomy might be a feasible therapeutic procedure for the management of FIGO stage IB and IIA cervical cancer with tumor diameter of 3 cm or greater. Further randomized studies that could support this approach are necessary to evaluate long-term clinical outcome.

Objective: Laparoscopic radical hysterectomy (LRH) is an alternative surgery to abdominal radical hysterectomy (ARH). There have been many comparative reports on laparoscopic vs. abdominal radical hysterectomy for early-stage cervical cancer. However, most of these studies included patients with FIGO stage IA2 and small (≤2 cm) IB1 disease. The purpose of this study was to compare the safety, morbidity, and recurrence rate of LRH and ARH with pelvic lymphadenectomy for bulky (≥3 cm) FIGO stage IB and IIA cervical cancer.

Objective: To evaluate the long-term outcome of patients with cervical intraepithelial neoplasia (CIN 2-3), adenocarcinoma in situ (AIS), and microinvasive squamous cell carcinoma of the cervix (MICA) after cold knife conization (CKC).