Korean Gynecologic Oncology Group Study Research Articles

Somatic genomic landscape of East Asian epithelial ovarian carcinoma and its clinical implications from prospective clinical sequencing: A Korean Gynecologic Oncology Group study (KGOG 3047).

Through the wide adaptation of next-generation sequencing (NGS) technology within clinical practice, molecular profiling of the tumor has been the principal component of personalized treatment. In our study, we have generated a large collection of cancer genomes on East Asian epithelial ovarian carcinoma (EOC) patients and demonstrate the feasibility and utility of NGS platforms to explore the dynamic interrelations of major cancer driver alterations and their impacts on clinical prognosis and management. A total of 652 EOC patients have undergone clinical NGS panels to determine the prevalence of germline and somatic mutations. Notably, TP53 was the most frequently altered event (73%), followed by both BRCA1 and BRCA2 (22% each) and MYC (19%) through pan-EOC analysis. When analyzed based on individual histopathological levels, TP53 mutation was highly dominant in high-grade serous and mucinous histology, whereas mutations in PIK3CA and ARID1A were mostly observed in clear cell carcinoma, and KRAS, BRAF, and CDKN2A mutations were enriched in endometrioid, low-grade serous, and mucinous tumors, respectively. The network-based probabilistic model showed significant co-occurrences of TP53 with BRCA1 and ALK with BRCA2, NOTCH1, and ROS1, whereas mutual exclusivity of TP53 with KRAS and PIK3CA was evident. Furthermore, we utilized machine-learning algorithms to identify molecular correlates that conferred increased sensitivity to platinum and olaparib treatments including somatic mutations in BRCA1, ATM, and MYC. Conversely, patients with ALK mutation were considerably resistant to both treatment modalities. Collectively, our results demonstrate the clinical feasibility of prospective genetic sequencing to facilitate personalized treatment opportunities for patients with EOC.

Comparisons of survival outcomes between bevacizumab and olaparib in BRCA-mutated, platinum-sensitive relapsed ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG 3052).

ObjectiveTo compare survival outcomes between bevacizumab (BEV) and olaparib (OLA) maintenance therapy in BRCA-mutated, platinum-sensitive relapsed (PSR) high-grade serous ovarian carcinoma (HGSOC).MethodsFrom 10 institutions, we identified HGSOC patients with germline and/or somatic BRCA1/2 mutations, who experienced platinum-sensitive recurrence between 2013 and 2019, and received second-line platinum-based chemotherapy. Patients were divided into BEV (n=29), OLA (n=83), and non-BEV/non-OLA users (n=36). The OLA and non-BEV/non-OLA users were grouped as the OLA intent group. We conducted 1:2 nearest neighbor-matching between the BEV and OLA intent groups, setting the proportion of OLA users in the OLA intent group from 65% to 100% at 5% intervals, and compared survival outcomes among the matched groups.ResultsOverall, OLA users showed significantly better progression-free survival (PFS) than BEV users (median, 23.8 vs. 17.4 months; p=0.004). Before matching, PFS improved in the OLA intent group but marginal statistical significance (p=0.057). After matching, multivariate analyses adjusting confounders identified intention-to-treat OLA as an independent favorable prognostic factor for PFS in the OLA 65P (adjusted hazard ratio [aHR]=0.505; 95% confidence interval [CI]=0.280−0.911; p=0.023) to OLA 100P (aHR=0.348; 95% CI=0.184−0.658; p=0.001) datasets. The aHR of intention-to-treat OLA for recurrence decreased with increasing proportions of OLA users. No differences in overall survival were observed between the BEV and OLA intent groups, and between the BEV and OLA users.ConclusionCompared to BEV, intention-to-treat OLA and actual use of OLA maintenance therapy were significantly associated with decreased disease recurrence risk in patients with BRCA-mutated, PSR HGSOC.

Comparison of diagnostic accuracy between endometrial curettage and aspiration biopsy in patients treated with progestin for endometrial hyperplasia: a Korean Gynecologic Oncology Group study.

ObjectiveTo compare the diagnostic accuracy of dilatation and curettage (D&C) versus endometrial aspiration biopsy in follow-up evaluation of patients treated with progestin for endometrial hyperplasia (EH)MethodsA prospective multicenter study was conducted from 2015 to 2018. Patients with EH were treated with progestin, one of the following three treatment regimens: oral medroxyprogesterone acetate (MPA) 10 mg/day for 14 days per cycle, continuous MPA 10 mg/day or the levonorgestrel-releasing intrauterine system (LNG-IUS). At 3 or 6 months of treatment, endometrial tissues were obtained via 2 methods in each patient: aspiration biopsy, followed by D&C. The primary outcome was the consistency of the histologic results between the 2 methods. The secondary outcome was the regression rate at 6 months of treatment.ResultsThe study population comprised 65 patients (55 with non-atypical hyperplasia, 10 with atypical hyperplasia). During the follow-up, a comparison of the pathologic results from aspiration biopsy and D&C was carried out for the 65 cases. Thirty-eight cases were diagnosed as EH by D&C. Among these, only 24 were diagnosed with EH from aspiration biopsy, for a diagnostic concordance of 63.2% (ĸ=0.59). Forty-four patients were followed up at 6 months, and the regression rate was 31.8% (14/44). Responses were obtained for 41.7% (5/12) of the cyclic MPA group, 58.3% (7/12) of the continuous MPA group and 10% (2/20) of the LNG-IUS group.ConclusionAs a follow-up evaluation of patients treated with progestin for EH, aspiration biopsy is less accurate than D&C and might not be a reliable method.Trial RegistrationClinicalTrials.gov Identifier: NCT02412072

1061TiP - An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: A Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION

BackgroundA pilot study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer has been started in Korea. Archival tumor samples were tested for HRD and PD-L1 status. Treatment arms will be allocated according to the test results. For HRD+ patients, we tested the synergistic effects of olaparib and other agents; treatment arms will randomly be allocated. (Arm 1: olaparib and cediranib; Arm 2: olaparib and durvalumab). For HRD- patients, we tested the role of biomarker-driven immunotherapy according to PD-L1 expression (Arm 3: durvalumab and chemotherapy in patients with high PD-L1 expression; Arm 4: durvalumab, tremelimumab, and chemotherapy in patients with low PD-L1 expression). Sixty-eight patients will be included from three Korean institutions within 1 year. The primary endpoint is the response rate according to RECIST 1.1 (6 months after treatment initiation). This trial has been registered with clinicaltrials.gov, and the registration number is NCT03699449. Trial designWe designed the present study as biomarker-driven targeted therapy in platinum-resistant recurrent ovarian cancer. Each arm has the following specific hypothesis. Arm 1: olaparib and cediranib have synergistic activity in patients with HRD+. Arm 2: olaparib and durvalumab have synergistic activity in patients with HRD+. Arm 3: durvalumab and chemotherapy (SOC; standard of care) is effective in patients with high PD-L1 expression. Arm 4: durvalumab, tremelimumab, and chemotherapy (SOC; standard of care) have synergistic activity even in patients with low PD-L1 expression. Clinical trial identificationNCT03699449. Legal entity responsible for the studyThe authors. FundingSeverance Hospital Research Fund for Clinical Excellence and Handok Jeseok Foundation. DisclosureJ. Lee: Research grant / Funding (self): Janssen; Research grant / Funding (institution): MSD; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Roche. All other authors have declared no conflicts of interest.

Prognostic Model for Survival and Recurrence in Patients with Early-Stage Cervical Cancer: A Korean Gynecologic Oncology Group Study (KGOG 1028)

PurposeWe aimed to develop and validate individual prognostic models in a large cohort of cervical cancer patients that were primarily treated with radical hysterectomy.Materials and MethodsWe analyzed 1,441 patients with early-stage cervical cancer treated between 2000 and 2008 from the Korean Gynecologic Oncology Group multi-institutional cohort: a train cohort (n=788) and a test cohort (n=653). Models predicting the risk for overall survival (OS), disease-free survival (DFS), lymphatic recurrence and hematogenous recurrence were developed using Cox analysis and stepwise backward selection and best-model options. The prognostic performance of each model was assessed in an independent patient cohort. Model-classified risk groups were compared to groups based on traditional risk factors.ResultsIndependent risk factors for OS, DFS, lymphatic recurrence, and hematogenous recurrence were identified for prediction model development. Different combinations of risk factors were shown for each outcome with best predictive value. In train cohort, area under the curve (AUC) at 2 and 5 years were 0.842/0.836 for recurrence, and 0.939/0.882 for OS. When applied to a test cohort, the model also showed accurate prediction result (AUC at 2 and 5 years were 0.799/0.723 for recurrence, and 0.844/0.806 for OS, respectively). The Kaplan-Meier plot by proposed model-classified risk groups showed more distinctive survival differences between each risk group.ConclusionWe developed prognostic models for OS, DFS, lymphatic and hematogenous recurrence in patients with early-stage cervical cancer. Combining weighted clinicopathologic factors, the proposed model can give more individualized predictions in clinical practice.

Comparison of laparoscopic and abdominal radical hysterectomy in early stage cervical cancer patients without adjuvant treatment: Ancillary analysis of a Korean Gynecologic Oncology Group Study (KGOG 1028)

ObjectiveWe compared two groups of early stage cervical cancer patients treated with different surgical methods without adjuvant treatment using retrospective multicenter data previously collected for Korean Gynecologic Oncology Group (KGOG) study designed for developing prognostic models. MethodWe initially assessed data from the multi-institutional cohort with early stage (IB-IIA) cervical cancer patients treated with radical hysterectomy without adjuvant treatment between 2000 and 2008. Propensity score matching was performed to compare disease-free survival (DFS) and overall survival (OS) of patients with laparoscopic to abdominal radical hysterectomy. Additionally, survival comparison was performed in patients with tumor size <2 cm. ResultsAfter matching, 119 patients with laparoscopic radical hysterectomy were compared with 357 patients with abdominal radical hysterectomy (median follow-up of 63.9 months). Inferior DFS was observed in the laparoscopy group (HR 2.738 [95% CI 1.326–5.650], p = 0.005) with a significant difference in pelvic (HR 5.110 [95% CI 1.817–14.473], p < 0.001) and hematogenous recurrence (HR 3.171 [95% CI 1.059–9.494], p = 0.03), but OS was not significantly different between two groups (p = 0.624). In subgroup analysis in the patient with tumor size <2 cm (laparoscopy 62 vs. laparotomy 186, median follow-up of 69.1 months), laparoscopy was associated with lower rate of DFS (HR 12.987 [95% CI 1.451–116.244], p = 0.003), but no significant difference in OS was observed between groups. Regarding OS, number of events is lacking, and inferior DFS in the laparoscopy group may be compensated by better response to radiation therapy in pelvic recurrence. ConclusionsIn this analysis, laparoscopic radical hysterectomy was associated with lower rates of DFS but not OS in early stage cervical cancer patients without adjuvant treatment. Further larger scale studies are needed.

Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708)

BackgroundOutcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer.MethodsWe conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes.ResultsA total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively).ConclusionsIn this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.

Real-world effectiveness of bevacizumab based on AURELIA in platinum-resistant recurrent ovarian cancer (REBECA): A Korean Gynecologic Oncology Group study (KGOG 3041)

PurposeTo evaluate the effectiveness of bevacizumab with single-agent chemotherapy for platinum-resistant ovarian cancer in a real-world setting. Patients and methodsWe enrolled recurrent platinum-resistant ovarian cancer patients from 27 institutions. All had received bevacizumab with single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin (PLD), topotecan) between 2015 and 2017 for second- or third-line chemotherapy in routine clinical practice. The primary endpoint was progression-free survival (PFS) and safety. Secondary endpoints included the objective response rate (ORR), PFS2, overall survival, duration of chemotherapy, and reasons for discontinuing chemotherapy. ResultsOf 391 patients, 259 (66.2%) received bevacizumab with PLD, 94 (24.0%) with topotecan, and 38 (9.7%) with weekly paclitaxel. The median PFS was 6.1 months with all forms of bevacizumab-containing therapy. Although the cohort with weekly paclitaxel had a better PFS than the PLD cohort (P = 0.028), this finding was not found in patients with a previous platinum-free interval of less than three months. The median duration of therapy was five cycles (range, one to 20 cycles), and 29 patients (7.4%) discontinued treatment because of adverse events from bevacizumab-containing regimens. The PLD cohort had fewer grade ≥ 3 adverse events than the other regimens (PLD, 35.8%; weekly paclitaxel, 52.6%; topotecan, 51.1%; P = 0.012), especially events of hematologic toxicities. ConclusionIn Korean ovarian cancer patients, the safety and effectiveness of chemotherapy with bevacizumab in a real-world setting was consistent with the results from a randomized controlled study. The effectiveness and toxicity profiles varied among the chemotherapy regimens, and this finding should be considered in practice.Clinical trials registration: NCT03367182.

Prognostic model for disease-free survival, lymphatic and/or hematogenous recurrence, in patients with early stage cervical cancer treated with radical hysterectomy: A Korean Gynecologic Oncology Group study

Prognostic model for disease-free survival, lymphatic and/or hematogenous recurrence, in patients with early stage cervical cancer treated with radical hysterectomy: A Korean Gynecologic Oncology Group study

Real-world Effectiveness of bevacizumab based on AURELIA in platinum-resistant recurrent ovarian cancer (REBECA) : A Korean Gynecologic Oncology Group study (KGOG 3041).

e17547Background: Adding to bevacizumab to chemotherapy improves progression-free survival for platinum-resistant ovarian cancer. This study evaluates effectiveness of 2nd-line or 3rd-line bevacizu...

Preoperative assessment of lymph node metastasis in endometrial cancer: A Korean Gynecologic Oncology Group study

Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed. Eligible patients with histologically confirmed endometrial cancer underwent magnetic resonance imaging (MRI) and serum cancer antigen 125 (CA 125) testing before surgery. The following criteria were used to identify low-risk patients: 1) endometrioid-type cancer, 2) no evidence of deep myometrial invasion on MRI, 3) no enlarged lymph nodes on MRI, 4) no suspicious metastasis out of the uterine corpus, and 5) serum CA 125 levels less than 35 U/mL. Systematic pelvic and/or para-aortic lymphadenectomy was performed for all patients. The primary endpoint was estimation of the negative predictive value (NPV). From January 2012 to December 2014, 529 patients from 20 hospitals in 3 Asian countries were consecutively enrolled. According to our criteria, 272 patients (51.4%) were categorized into the low-risk group. Fifty-three of the 529 patients (10.0%) had lymph node metastases; these patients included 8 (2.9%) falsely categorized as low-risk. The sensitivity and specificity of the criteria were 84.9% and 55.5%, respectively. The NPV of 97.1% was higher than the predefined target endpoint of 96%. The low-risk criteria based on preoperative tests were confirmed to be reliable and accurate for identifying patients at low risk for lymph node metastasis. These criteria may facilitate patient counseling and surgical decision making. Cancer 2017;123:263-272. © 2016 American Cancer Society.

Prognostic model for disease-free survival, lymphatic and/or hematogenous recurrence, in patients with early stage cervical cancer treated with radical hysterectomy: A Korean Gynecologic Oncology Group Study.

e17000Background: To develop a model to predict 5 year disease-free survival (DFS), lymphatic and/or hematogenous recurrence, in early stage cervical cancer treated with radical hysterectomy, which...

Comparison of diagnostic accuracy between endometrial curettage and pipelle aspiration biopsy in patients treated with progestin for endometrial hyperplasia: a Korean Gynecologic Oncology Group Study (KGOG 2019).

A prospective multicenter trial has been started in Korea to evaluate the diagnostic accuracy of endometrial aspiration biopsy compared with dilatation and curettage in patients treated with progestin for endometrial hyperplasia. For conservative treatment of endometrial hyperplasia, orally administered progestins are most commonly used method with various treatment regimens and more recently, the levonorgestrel-releasing intrauterine system also has been used successfully to treat endometrial hyperplasia. However, there is no report about the accuracy of endometrial sampling during hormonal treatment for follow-up evaluation of endometrial hyperplasia. Patients with histologically confirmed endometrial hyperplasia are offered hormonal treatment with any one of the following three options: oral medroxyprogesterone acetate 10 mg/day for 14 days per cycle, continuous oral medroxyprogesterone acetate 10 mg/day or insertion of levonorgestrel-releasing intrauterine system. Histological surveillance is performed at 3 months or 6 months following initial treatment. Endometrial tissues are obtained via endometrial aspiration biopsy using a pipelle and dilatation and curettage. In the case of levonorgestrel-releasing intrauterine system, endometrial aspiration biopsy will be done with levonorgestrel-releasing intrauterine system in uterus and then, after the removal of levonorgestrel-releasing intrauterine system, dilatation and curettage will be done. The biopsy findings will be compared. The primary endpoint is to compare the pathological outcome of endometrial aspiration with dilatation and curettage. The secondary endpoint is the response rate with three types of progestin treatment at 6 months.

Preoperative risk assessment for lymph node metastasis in endometrial cancer (PALME study): Results of the Korean Gynecologic Oncology Group study

Preoperative risk assessment for lymph node metastasis in endometrial cancer (PALME study): Results of the Korean Gynecologic Oncology Group study

Concurrent chemoradiation with paclitaxel in high-risk endometrial cancer patients after surgery: A Korean Gynecologic Oncology Group study

Objectives: To evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer.

Intermediate-risk grouping of cervical cancer patients treated with radical hysterectomy: a Korean Gynecologic Oncology Group study

Background:In this study, we sought to identify a criterion for the intermediate-risk grouping of patients with cervical cancer who exhibit any intermediate-risk factor after radical hysterectomy.Methods:In total, 2158 patients with pathologically proven stage IB–IIA cervical cancer with any intermediate-risk factor after radical hysterectomy were randomly assigned to two groups, a development group and a validation group, at a ratio of 3 : 1 (1620 patients:538 patients). To predict recurrence, multivariate models were developed using the development group. The ability of the models to discriminate between groups was validated using the log-rank test and receiver operating characteristic (ROC) analysis.Results:Four factors (histology, tumour size, deep stromal invasion (DSI), and lymphovascular space involvement (LVSI)) were significantly associated with disease recurrence and included in the models. Among the nine possible combinations of the four variables, models consisting of any two of the four intermediate-risk factors (tumour size ⩾3 cm, DSI of the outer third of the cervix, LVSI, and adenocarcinoma or adenosquamous carcinoma histology) demonstrated the best performance for predicting recurrence.Conclusion:This study identified a ‘four-factor model' in which the presence of any two factors may be useful for predicting recurrence in patients with cervical cancer treated with radical hysterectomy.

Synchronous primary cancers of the endometrium and ovary in young women: A Korean Gynecologic Oncology Group Study

ObjectiveSome authors have recommended the use of diagnostic laparoscopy as a pretreatment assessment step for conservative hormonal treatment in young women with endometrial cancer. The aim of this study was to determine the incidence of synchronous primary cancer of the endometrium and ovary in young women. MethodsThe medical records of 3240 patients with endometrial cancer who underwent primary surgery between 1995 and 2010 were collected from 7 institutions and were retrospectively reviewed. Low-risk endometrial cancer was defined as tumors without myometrial invasion; normal or benign-looking ovaries; normal CA-125; grade 1 endometrioid histology; and early stage endometrial cancer on pretreatment assessment. ResultsFifteen percent (471/3240) were younger than 40years of age. The incidence of synchronous ovarian cancer in young women with endometrial cancer was 4.5% (21/471). In patients with low-risk endometrial cancer, synchronous cancers were not identified. ConclusionThe incidence of synchronous ovarian malignancies in young women with endometrial cancer was quiet low (4.5%), unlike previous studies have revealed (11–29%). Therefore, diagnostic laparoscopy is not mandatory in patients with low-risk early stage endometrial cancer selected for conservative treatment to confirm the absence of ovarian malignancy.

Outcomes of ovarian preservation in a cohort of premenopausal women with early-stage endometrial cancer: A Korean Gynecologic Oncology Group study

ObjectiveThe aim of this study was to evaluate the impact of ovarian preservation on the recurrence and survival rates of premenopausal women with early-stage endometrial cancer. MethodsUsing medical records of premenopausal women who received primary surgical treatment for stage I–II endometrial cancer, the demographics and survival rates were compared retrospectively for patients who had ovarian preservation and those who underwent bilateral salpingo-oophorectomy. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) based on propensity score were performed to adjust for selection bias between the two groups. ResultsA total of 495 women were identified, including 176 patients who had ovarian preservation. The ovarian preservation group was younger (P<0.001) and had an earlier year of diagnosis (P=0.014), a lower prevalence of lymphadenectomy (P<0.001), and a marginally significant association with lower tumor grade (P=0.052). The Kaplan–Meier curve and the log rank test showed no difference in either recurrence-free survival (P=0.742) or overall survival (P=0.462) between the two groups. In a multivariate Cox model adjusted by IPTW and covariates, ovarian preservation had no effect on either recurrence (hazard ratio [HR], 0.73; 95% CI, 0.29–1.81) or overall survival (HR, 1.33; 95% CI, 0.43–4.09). ConclusionsOvarian preservation does not appear to be associated with an adverse impact on the outcomes of premenopausal women with early-stage endometrial cancer. The present study has useful implications for physicians counseling young women who want to preserve their ovaries.

Use of complex surgical procedures, patterns of tumor spread, and CA-125 predicts a risk of incomplete cytoreduction: A Korean Gynecologic Oncology Group study (KGOG-3022)

ObjectivesWe aimed to develop a risk model to predict a risk of suboptimal cytoreduction in primary surgery of ovarian cancer. MethodsThe clinical records and computed tomography (CT) data of 358 patients with stages II–IV epithelial ovarian cancer were reviewed. Tumor spread patterns identified by principal component analysis, CA-125, and a newly developed surgical skill index were integrated into a logistic model along with other variables. Internal validation was performed using bootstrapped re-sampling and calibration was assessed by goodness-of-fit test. ResultsAmong the 358 patients, optimal cytoreduction, which was defined as no residual tumor, was achieved in 145 patients (40.5%). The surgical capacity of an individual institution was estimated by a surgical skill index, which was the frequency of complex surgeries in patients with advanced disease. In a multivariate model, two distinctive CT patterns of tumor spread (diffuse spread pattern and upper abdominal extension pattern), a surgical skill index, and serum CA-125 independently predicted a risk of suboptimal cytoreduction (P=0.006, P=0.013, P=0.031, and P=0.001, respectively). The model showed a C-statistic of .73 (95% confidence interval .67 to .79), which was significantly higher than tumor stage or ascites. Rigorous internal validation by bootstrapped re-sampling successfully confirmed the model. ConclusionsWe identified two distinct tumor spread patterns of ovarian cancer, which can be integrated to improve a prediction model. Our model may be useful in patient referral or clinical trials for patient stratification.

Chemoradiation With Paclitaxel and Carboplatin in High-Risk Cervical Cancer Patients After Radical Hysterectomy: A Korean Gynecologic Oncology Group Study

To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m(2), carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.