Sang-Young Ryu

Current status of gynecological cancer in China

The aim of this review is to examine the current status of gynecological cancer in China focusing on epidemiological data. Epidemiological data on gynecological cancer in China is sparse. Therefore, most of the data were estimated via extrapolation based on a few available datasets. Cervical cancer is relatively rare and the incidence and mortality rate are largely decreasing. However, in young women, the incidence and mortality rates are increasing. The overall and age-specific incidence rates of cervical cancer appear to be varied according to geographical areas. The overall prevalence rate of human papillomavirus (HPV) in China is similar with other eastern Asian countries, but the age-specific HPV prevalence showed sustained high HPV prevalence rates in elderly women. There is not yet an established national program for cervical cancer prevention. The incidence rate of corpus and ovarian cancers in China slightly increased between 2000 and 2005, but is still lower than Japan or Korea. There is no reliable, national-level data on mortality rates of corpus and ovarian cancer in China. Breast cancer is one of the most rapidly increasing cancers in China. The increase was sharper in young women than in elderly women. Both increased risk and change of population size/structure contributed to the increase of breast cancer.

Randomized Clinical Trial of Weekly vs. Triweekly Cisplatin-Based Chemotherapy Concurrent With Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

PURPOSE To compare compliance, toxicity, and outcome of weekly and triweekly cisplatin administration concurrent with radiotherapy in locally advanced cervical cancer. METHODS AND MATERIALS In this open-label, randomized trial, 104 patients with histologically proven Stage IIB-IVA cervical cancer were randomly assigned by a computer-generated procedure to weekly (weekly cisplatin 40 mg/m(2), six cycles) and triweekly (cisplatin 75 mg/m(2) every 3 weeks, three cycles) chemotherapy arms during concurrent radiotherapy. The difference of compliance and the toxicity profiles between the two arms were investigated, and the overall survival rate was analyzed after 5 years. RESULTS All patients tolerated both treatments very well, with a high completion rate of scheduled chemotherapy cycles. There was no statistically significant difference in compliance between the two arms (86.3% in the weekly arm, 92.5% in the triweekly arm, p > 0.05). Grade 3-4 neutropenia was more frequent in the weekly arm (39.2%) than in the triweekly arm (22.6%) (p = 0.03). The overall 5-year survival rate was significantly higher in the triweekly arm (88.7%) than in the weekly arm (66.5%) (hazard ratio 0.375; 95% confidence interval 0.154-0.914; p = 0.03). CONCLUSIONS Triweekly cisplatin 75-mg/m(2) chemotherapy concurrent with radiotherapy is more effective and feasible than the conventional weekly cisplatin 40-mg/m(2) regimen and may be a strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.

Is adjuvant chemoradiotherapy overtreatment in cervical cancer patients with intermediate risk factors

PURPOSE To determine whether adjuvant chemoradiotherapy (CRT) improves the outcome of cervical cancer patients with intermediate risk factors. METHODS AND MATERIALS Between January 2000 and June 2006, the medical records of 735 patients who had undergone radical surgery for Stage IB-IIA cervical cancer were reviewed retrospectively. Of the 735 patients, 172 with two or more intermediate risk factors (i.e., lymphovascular space involvement, deep stromal invasion, and tumor size≥2 cm) were grouped as follows according to the adjuvant treatment received: 34 patients, no further treatment; 49 patients, RT; and 89 patients, CRT. The significance of the clinical parameters and recurrence-free survival of each group were analyzed. RESULTS Of the 172 patients with any of the intermediate risk factors, 137 (79.6%) had two or more intermediate risk factors. Of the 172 patients, 12 developed recurrences (6.4%)->(7.0%), with 6 in the pelvis and 6 in distant sites. All 12 recurrences occurred in those who had two or more intermediate risk factors (sensitivity, 100%); however, only six recurrences were detected in patients who met the Gynecologic Oncology Group criteria for the intermediate-risk group (sensitivity, 50%; Z test, p<.05). A statistically significant difference was found in the 3-year recurrence-free survival rate among the no further treatment, RT, and CRT groups (67.5%, 90.5%, and 97.5%, respectively; p<.05). The incidence of Grade 3-4 hematologic and gastrointestinal toxicities was not significantly different statistically between the RT and CRT groups (6.1% and 13.4%, respectively; p > .05). CONCLUSION Postoperative adjuvant CRT can improve the outcome of cervical cancer patients with intermediate risk factors, with low increase in toxicity.

Risk Assessment Tool for Distant Recurrence After Platinum-Based Concurrent Chemoradiation in Patients With Locally Advanced Cervical Cancer: A Korean Gynecologic Oncology Group Study

PURPOSE Our study aimed to develop a model to predict distant recurrence in locally advanced cervical cancer, which can be used to select high-risk patients in enriched clinical trials. PATIENTS AND METHODS Our study was a retrospective analysis of a multi-institutional cohort of patients treated between 2001 and 2009. According to the order of data submission, data from three institutions were allocated to a model development cohort (n = 434), and data from the remaining two institutions were allocated to an external validation cohort (n = 115). Patient information including [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) data and clinical outcome was modeled using competing risk regression analysis to predict 5-year cumulative incidence of distant recurrence. RESULTS The competing risk analysis revealed that the following four parameters were significantly associated with distant recurrence: pelvic and para-aortic nodal positivity on FDG-PET, nonsquamous cell histology, and pretreatment serum squamous cell carcinoma antigen levels. This four-parameter model showed good discrimination and calibration, with a bootstrap-adjusted concordance index of 0.70. Also, the validation set showed good discrimination with a bootstrap-adjusted concordance index of 0.73. A user-friendly Web-based nomogram predicting 5-year probability of distant recurrence was developed. CONCLUSION We have developed a robust model to predict the risk of distant recurrence in patients with locally advanced cervical cancer. Further, we discussed how the selective enrichment of the patient population could facilitate clinical trials of systemic chemotherapy in locally advanced cervical cancer.

Phase II evaluation of CKD-602, a camptothecin analog, administered on a 5-day schedule to patients with platinum-sensitive or -resistant ovarian cancer

BACKGROUND To evaluate the toxicity and efficacy of a newly developed topoisomerase I inhibitor, CKD-602 in second-line therapy of ovarian cancer. METHODS We enrolled 24 patients with recurrent ovarian cancer, of median age 54 years (range, 39-64). Eleven patients had measurable lesions on CT scan, and the other 13 had increased serum CA-125 levels. Eighteen patients had platinum-sensitive disease (minimum treatment free interval > or =6 months) and 6 had platinum-resistant disease (minimum treatment free interval <6 months). CKD-602 (0.5 mg/m(2)/day) was administered intravenously for 5 days every 3 weeks. The median number of courses per patient was 6 (range, 1 to 12). Response was evaluated by the evaluation of the size of the mass by CT scan and CA-125 response. RESULTS The overall response rate was 45.0% (9/20), with 4 patients exhibiting partial responses and 5 patients exhibiting 75% CA-125 responses in 20 evaluable patients. Of the 9 responsive patients, 8 were platinum-sensitive (8/15, 53.3%) and 1 was platinum-resistant (1/5, 20.0%). An additional 5 patients showed stable disease, whereas 6 patients exhibited progressive lesions. Of 24 patients, the most common toxicity was hematological, with grades 3 or 4 neutropenia developing in all 24 patients (100%) and in 94 cycles (71.7%). Grade 3 thrombocytopenia developed in 4 patients (16.7%) and 6 cycles (4.6%). None of the patients experienced grades 3 and 4 gastrointestinal toxicities, including nausea, vomiting, and anorexia. CONCLUSIONS The newly developed topoisomerase I inhibitor, CKD-602, showed activity against both platinum-sensitive and -resistant ovarian cancer, with acceptable toxicity.

Detection of Recurrence by 18F-FDG PET in Patients with Endometrial Cancer Showing No Evidence of Disease

This study assessed the feasibility of F-18-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) in the post-therapy surveillance for patients with endometrial cancer showing no evidence of disease (NED). From April 1997 to June 2007, 127 patients with endometrial cancer showing NED were performed 18F-FDG PET scan. The feasibility of 18F-FDG PET for the early detection of recurrence in patients with endometrial cancer was evaluated retrospectively. Of the 127 patients, 32 patients showed positive lesions on 18F-FDG PET scan. Nineteen (19/127 cases, 15%) of them were confirmed to have a recurrence clinically or histologically. The sensitivity, specificity and positive and negative predictive value of 18F-FDG PET for detecting recurrences in patients with endometrial cancer were 100%, 88%, 59% and 100%, respectively. In conclusion, 18F-FDG PET may be a useful method for the post-therapy surveillance in patients with endometrial cancer.

Platelet-derived endothelial cell growth factor as a prognostic factor for radiotherapy outcome in patients with adenocarcinoma of the uterine cervix

OBJECTIVE The aim of this study was to evaluate the platelet-derived endothelial cell growth factor (PD-ECGF) and VEGF expressions of tumor cells as prognostic factors for radiotherapy outcome in patients with adenocarcinoma of the uterine cervix. METHODS In 47 formalin fixed, paraffin-embedded tissues from adenocarcinoma of the uterine cervix which had been treated with radiation (1970-1995), PD-ECGF and VEGF expressions were determined using immunohistochemistry, and the relationships between PD-ECGF or VEGF expressions and local control or survival were assessed. RESULTS PD-ECGF and VEGF expressions were successfully detected in the cytoplasm and/or nucleus of adenocarcinoma cells of the uterine cervix. Of the 47 patients, 44.6 (21/47 cases) and 57.4% (27/47 cases) were positive for PD-ECGF and VEGF, respectively. There was no correlation between PD-ECGF or VEGF expressions and age, grade, or histologic subtypes. Stage and high expression of PD-ECGF showed a significant correlation to local control (P = 0.0025, P = 0.0057, respectively) and were significant independent prognostic factors for 5-year survival in multivariate analysis (P = 0.0039, P = 0.0032, respectively). CONCLUSION This study demonstrated that PD-ECGF expression was a significant prognostic factor for radiotherapy outcome in patients with adenocarcinoma of the uterine cervix. Preradiation assessment of PD-ECGF expression may be helpful in selecting high-risk patients, providing them with opportunities to receive more sophisticated and individualized treatments.

Characteristics of thyroid incidentalomas detected by pre-treatment [18F]FDG PET or PET/CT in patients with cervical cancer

Objective Considering the increased use of [18F]FDG PET or PET/CT, the clinical significance of thyroid incidentalomas is the subject of controversy. The aim of this study was to determine the incidence of malignancies associated with thyroid incidentalomas detected by pre-treatment PET or PET/CT in patients with cervical cancer. Methods We retrospectively reviewed the medical records of patients with cervical cancer who had thyroid incidentalomas detected by pre-treatment PET or PET/CT and were treated at our institute between January 2001 and December 2009. Results Of 327 patients who underwent pre-treatment PET or PET/CT, 33 patients had thyroid incidentalomas (10.1%) and 4 patients were diagnosed with thyroid malignancies by percutaneous needle aspiration (PCNA) or surgery. To put it concretely, of 33 patients with thyroid incidentaloma, 16 patients had a diffuse uptake and 17 patients had a focal uptake. Four of 17 patients with focal uptake were diagnosed with thyroid malignancies (23.5%). One patient with a focal uptake had an atypical cell based on PCNA, but did not undergo additional studies. The mean SUVmax of thyroid malignancies did not differ from that of benign thyroid diseases. Conclusion Thyroid incidentalomas are frequently detected by pre-treatment PET or PET/CT in patients with cervical cancer. Focal uptake on PET or PET/CT has a high risk of thyroid cancer.

Survival impact based on the thoroughness of pelvic lymphadenectomy in intermediate- or high-risk groups of endometrioid-type endometrial cancer: A multi-center retrospective cohort analysis

OBJECTIVE To investigate whether the number of lymph nodes obtained during lymphadenectomy affects the survival of patients with intermediate- or high-risk endometrioid-type endometrial cancer. METHODS A total of 476 patients who were diagnosed with FIGO stage IB to IIIC2 endometrioid adenocarcinoma through surgical staging, including hysterectomy and pelvic lymphadenectomy with or without paraaortic lymphadenectomy between 2000 and 2013 were retrospectively enrolled from four tertiary centers in Korea. Sentinel lymph node mapping was not performed in any patient. The number of nodes obtained and positive nodes, was extracted from pathologic report. RESULTS Paraaortic lymphadenectomy was performed in 298 (62.6%) patients and 164 (34.4%) had stage IIIC disease. The isolated paraaortic lymph node metastasis rate decreased as the number of pelvic nodes obtained increased. In the total study population, an increase of negative pelvic and paraaortic nodes was associated with improved recurrence-free survival (RFS) and overall survival (OS) independent of other prognostic factors. In the node-positive group, an increase of negative pelvic nodes was an independent prognostic factor for RFS [hazard ratio (HR), 0.946; 95% confidence interval (CI), 0.906-0.988] and OS [HR, 0.907; 95% CI, 0.849-0.968]. In stage IIIC2 patients, 14 or less negative pelvic nodes was associated with poor RFS and OS. CONCLUSIONS Removing as many pelvic nodes as possible is required to warrant accurate nodal staging and improve survival in patients with intermediate- or high-risk endometrial cancer. Sentinel lymph node mapping can be a resolution to minimize lymph node dissection without compromising staging accuracy.

Efficacy of Fibrin Sealant in Reducing Hemorrhage after a Loop Electrosurgical Excision Procedure

Background/Aims: We examined the association of fibrin sealant use with post-operative hemorrhage in patients who underwent a loop electrosurgical excision procedure (LEEP). Methods: We retrospectively collected clinicopathologic data of 344 patients who underwent LEEP at our institute between 2007 and 2009. We defined hemorrhage which occurred between 1 and 30 days after LEEP and required electrocautery to achieve hemostasis as severe secondary hemorrhage (SSH). We determined whether or not the use of fibrin sealant during LEEP was associated with a decreased occurrence of SSH. In addition, we examined the associations of other clinicopathologic variables with SSH and fibrin sealant use. Results: SSH occurred in 6 of 200 patients (3%) with fibrin sealant and in 12 of 144 patients (8%) without fibrin sealant. Based on univariate analysis, the use of fibrin sealant was associated with SSH (p = 0.028). However, age, surgeons and pathologic diagnosis were not associated with SSH. Based on multivariate analysis, the use of fibrin sealant was associated with less SSH (p = 0.033, OR = 0.328, 95% CI 0.117–0.917). Conclusion: Fibrin sealant use reduces the incidence of severe post-operative hemorrhage after LEEP.