Metabolic syndrome and persistent cervical human papillomavirus infection.

OBJECTIVE: Few studies have been conducted on the relationship between metabolic syndrome (MetS) and persistent human papillomavirus (HPV) infection. We investigated whether MetS and associated factors can predict the persistence of HPV infection. PATIENTS AND METHODS: We performed a retrospective cohort study of 80,993 female cases undergoing general medical screenings at Samsung Medical Center and 51,140 cases were included in final analysis. MetS and associated factors were used to develop a model predicting the persistence of HPV infection which was defined as HPV positivity for at least one year. The performance of the model was internally validated using bootstrapping and externally validated by testing the risk score against the test set. RESULTS: Of the 51,140 cases, there were 5833 (11.4%) cases diagnosed with MetS and 7682 (15.0%) cases diagnosed with HPV infection at baseline. The 12- to 24-month persistence rates of HPV were 50.0% (2846/5691). MetS (OR 1.34, 95% CI 1.04-1.71), globulin (by quintile; OR 1.70, 95% CI 1.25-2.30), fibrinogen (x100 value by quintile; OR 1.07, 95% CI 1.02-1.14), total protein (by quintile; OR 0.91, 95% CI 0.84-0.99) and prothrombin time (by quintile; OR 0.94, 95% CI 0.89-0.99) were significantly associated with the persistence of HPV in multivariate analysis. For validation, a prediction model showed good performance for a range of risk scores and categorized cases into low-, intermediate- and high-risk, which were also correlated with HPV persistence (45.8%, 51.9%, and 60.2% respectively, P < 0.001). CONCLUSION: MetS and associated factors were associated with an increased risk of persistent HPV infection.

Chemoradiotherapy response prediction model by proteomic expressional profiling in patients with locally advanced cervical cancer.

OBJECTIVE: Resistance to chemo-radiation therapy is a substantial obstacle that compromises treatment of advanced cervical cancer. The objective of this study was to investigate if a proteomic panel associated with radioresistance could predict survival of patients with locally advanced cervical cancer. METHODS: A total of 181 frozen tissue samples were prospectively obtained from patients with locally advanced cervical cancer before chemoradiation. Expression levels of 22 total and phosphorylated proteins were evaluated using well-based reverse phase protein arrays. Selected proteins were validated with western blotting analysis and immunohistochemistry. Performances of models were internally and externally validated. RESULTS: Unsupervised clustering stratified patients into three major groups with different overall survival (OS, P = 0.001) and progression-free survival (PFS, P = 0.003) based on detection of BCL2, HER2, CD133, CAIX, and ERCC1. Reverse-phase protein array results significantly correlated with western blotting results (R2 = 0.856). The C-index of model was higher than clinical model in the prediction of OS (C-index: 0.86 and 0.62, respectively) and PFS (C-index: 0.82 and 0.64, respectively). The Kaplan-Meier survival curve showed a dose-dependent prognostic significance of risk score for PFS and OS. Multivariable Cox proportional hazard model confirmed that the risk score was an independent predictor of PFS (HR: 1.6; 95% CI: 1.4-1.9; P < 0.001) and OS (HR: 2.1; 95% CI: 1.7-2.5; P < 0.001). CONCLUSION: A proteomic panel of BCL2, HER2, CD133, CAIX, and ERCC1 independently predicted survival in locally advanced cervical cancer patients. This prediction model can help identify chemoradiation responsive tumors and improve prediction for clinical outcome of cervical cancer patients.

CDK7 is a reliable prognostic factor and novel therapeutic target in epithelial ovarian cancer.

OBJECTIVE: Cyclin-dependent kinase 7 (CDK7) engages tumor growth by acting as a direct link between the regulation of transcription and the cell cycle. Here, we investigated the clinical significance of CDK7 expression and its potential as a therapeutic target in epithelial ovarian cancer (EOC). METHODS: CDK7 expression was examined in 436 ovarian tissues including normal to metastatic ovarian tumors using immunohistochemistry, and its clinical implications were analyzed. Furthermore, we performed in vitro and in vivo experiments using CDK7 siRNA or a covalent CDK7 inhibitor (THZ1) to elucidate the effect of CDK7 inhibition on tumorigenesis in EOC cells. RESULTS: The patient incidence of high CDK7 expression (CDK7High) gradually increased from normal ovarian epithelium to EOC (P < 0.001). Moreover, CDK7High was associated with an advanced stage and high-grade histology (P = 0.035 and P = 0.011, respectively) in EOC patients and had an independent prognostic significance in EOC recurrence (P = 0.034). CDK7 inhibition with siRNA or THZ1 decreased cell proliferation and migration, and increased apoptosis in EOC cells, and this anti-cancer mechanism is caused by G0/G1 cell cycle arrest. In in vivo therapeutic experiments using cell-line xenograft and PDX models, CDK7 inhibition significantly decreased the tumor weight, which was mediated by cell proliferation and apoptosis. CONCLUSION: Mechanistic interrogation of CDK7 revealed that it is significantly associated with an aggressive phenotype of EOC, and it has independent prognostic power for EOC recurrence. Furthermore, CDK7 may be a potential therapeutic target for patients with EOC, whether platinum sensitive or resistant.

In Vivo Comparison of MONOFIX, A Novel Barbed Suture with a Triangular Stopper, with Pre-existing Products in a Porcine Model.

STUDY OBJECTIVE: MONOFIX, a new absorbable barbed suture device, has a triangular stopper at the end to hold the suture to the tissue without hooking the looped end or knotting. The aim of this study was to compare the biomechanical strength and histologic features of MONOFIX with other barbed suture devices using a porcine model. DESIGN: Well-designed, controlled trial without randomization. SETTING: Animal laboratory in university hospital. SUBJECTS: Sixteen, 60-kg, mature female domestic pigs (skin closure group) and 5, 60-kg, mature female domestic pigs (fascial closure group). INTERVENTIONS: In the skin closure group, 3-0 MONOFIX versus 2 widely used 3-0 absorbable barbed sutures (3-0 V-Loc 180 or Stratafix). In the fascial closure group, 2-0 MONOFIX versus 1 widely used 2-0 absorbable barbed sutures (2-0 Stratafix). MEASUREMENTS AND MAIN RESULTS: In the skin closure group, the biomechanical wound strength of skin sutured with size 3-0 MONOFIX, V-Loc 180, or Stratafix was evaluated by postoperative day assessment (days 0, 3, 7, 14, and 28). In the fascial closure group, pigs underwent 2 paramedian incisions and were sutured with 2-0 MONOFIX or with 2-0 Stratafix to evaluate histologic reaction. At 6 weeks the tissues around the suture line were excised and microscopically evaluated. The biomechanical strength of the MONOFIX had similar tissue tensile strength compared with the control, regardless of postoperative day. In the fascial closure model, there was no significant difference in the average tissue reaction score between MONOFIX and Stratafix (1.2 ± .3 vs 1.3 ± .3, p = .478). CONCLUSION: This study demonstrated that MONOFIX has equivalent tensile strength and histologic reaction when compared with commonly used barbed suture devices. Accordingly, this preclinical study suggests that the use of MONOFIX is a safe alternative to other barbed suture devices.

Response to Combination Chemotherapy With Paclitaxel/Ifosfamide/Platinum Versus Paclitaxel/Platinum for Patients With Metastatic, Recurrent, or Persistent Carcinoma of the Uterine Cervix: A Retrospective Analysis.

OBJECTIVE: Paclitaxel/ifosfamide/cisplatin triplet has shown a higher response rate than paclitaxel/cisplatin doublet, but the toxicity profile hindered the use of the triplet regimen. In this study, we adjusted the dosage of the triplet regimen and introduced carboplatin in cisplatin-intolerable patients. We tested the efficacy and toxicity of the modified triplet regimen in patients with recurrent or persistent cervical cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with recurrent or persistent cervical cancer who were treated between 2003 and 2015 at Samsung Medical Center. Response rate, progression-free survival (PFS), overall survival (OS), and toxicity of paclitaxel/ifosfamide/platinum (TIP) and paclitaxel/platinum (TP) were compared. RESULTS: The overall response rate of TIP was significantly higher than that of TP (52.7% vs 36.4%, P = 0.031). In the TP group, response rate was higher in patients with progression-free interval longer than 12 months (P = 0.028) and those with squamous cell histology (P = 0.028). In TIP group, patients with older than 50 years (P = 0.017), progression-free interval longer than 12 months (P = 0.046), and squamous cell carcinoma histology (P < 0.001) showed higher response rates; but TIP showed higher response on all occasions. Median OS and median PFS were similar for TP and TIP (OS, 22.43 months vs 18.5 months, P = 0.44; PFS, 6.37 months vs 8.3 months, P = 0.48). CONCLUSIONS: Paclitaxel/ifosfamide/platinum showed a higher response rate than TP in patients with recurrent cervical cancer without an increase in severe complications. Considering the high response rate, TIP may be an option for persistent or recurrent cervical cancer.

Elevated Preoperative CA125 or CA19-9 in Borderline Ovarian Tumors: Could It Be Suggestive of Advanced Stage or a Poor Prognosis?

OBJECTIVES: To investigate whether elevated levels of CA125 (≥35 U/mL) and CA19-9 (≥37 U/mL) suggest advanced-stage disease (defined as stage II or higher) or poor prognosis in patients with borderline ovarian tumors (BOTs). STUDY DESIGN: We retrospectively identified 591 patients with BOTs. Multivariate logistic regressions and Cox proportional hazard regressions were used to determine the clinicopathologic factors associated with the presence of advanced-stage disease and the prognostic factors associated with recurrence-free survival. RESULTS: CA125 was elevated more often in serous than in mucinous tumors (50.6 vs. 35.5%; p = 0.003), whereas CA19-9 was elevated more often in mucinous than serous tumors (33.6 vs. 15.3%; p = 0.001). An elevated CA125 level was independently associated with the presence of advanced-stage disease in serous (p = 0.005) and in mucinous BOTs (p = 0.015). However, preoperative elevation of CA19-9, unlike CA125, was not associated with the advanced-stage disease. Elevated preoperative CA125 level (p = 0.037) was an independent prognostic factor for recurrence-free survival in patients with serous BOTs. However, neither CA125 nor CA19-9 had prognostic significance in mucinous BOTs. CONCLUSIONS: Elevated preoperative CA125, unlike CA19-9, is a diagnostic and prognostic biomarker associated with the presence of advanced-stage disease and risk of relapse in patients with serous BOTs.

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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%. CONCLUSIONS: 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.

Significance of body weight change during fertility-sparing progestin therapy in young women with early endometrial cancer.

OBJECTIVE: To evaluate the influence of body weight change during fertility-sparing progestin therapy on oncologic and reproductive outcomes in young women with early-stage endometrial cancer who did not complete child bearing. METHODS: This multicenter, retrospective study included 154 young patients with well-differentiated, endometrium-confined endometrioid endometrial adenocarcinoma on magnetic resonance imaging who received fertility-sparing progestin therapy. RESULTS: The mean body weight and body mass index (BMI) at baseline and progestin therapy completion was 65.3±16.2 and 66.5±15.9kg (P=0.044), respectively, and 25.51±5.99 and 25.99±5.94kg/m2 (P=0.034), respectively. During progestin therapy, 51 (33.1%), 29 (18.8%), and 74 patients (48.1%) had weight loss, no weight change, and weight gain, respectively, of which 11 (7.1%) had 10% weight loss and 30 (19.5%) had 10% weight gain. A pretreatment BMI of ≥25kg/m2 was significantly associated with a lower complete response rate to progestin therapy (P=0.003) and a high recurrence rate (P=0.033). A posttreatment BMI of ≥25kg/m2 was also a significant factor for high recurrence rate (P=0.049). However, weight change during therapy was not significantly associated with complete response or recurrence rate. Pre and posttreatment BMIs and weight change were not associated with pregnancy and live birth rates. CONCLUSION: Weight change during progestin therapy has little influence on complete response, recurrence, pregnancy, and live birth rates. However, pre and posttreatment BMIs of ≥25kg/m2 were significant predictors for poor treatment response and high recurrence. Therefore, it is important to maintain patients' normal BMIs during progestin therapy.

Minimally invasive compared with open surgery in patients with borderline ovarian tumors.

OBJECTIVE: To compare the surgical and oncological outcomes between laparoscopic (single-port or multi-port) and open surgery in the treatment of patients with borderline ovarian tumors (BOTs). METHODS: A retrospective analysis was performed on 687 patients who underwent single-port laparoscopy (n=89), multi-port laparoscopy (n=223), or open surgery (n=375) due to BOTs. RESULTS: The age, tumor size, tumor marker, and the proportions of radical surgery rate and surgical staging were significantly lower in the single-port laparoscopy and multi-port laparoscopy groups compared with those in the open surgery group (all P<0.001). The operative time, operative blood loss, length of hospital stay, and perioperative complications were also significantly reduced in the two laparoscopic groups compared with those in the open surgery group (all P<0.001). However, there was no significant difference found between the groups with regard to histological type, pathologic stage, and postoperative residual tumor volume. After the median follow-up time of 41.8months, the recurrence-free survival and overall survival rates did not differ between groups. CONCLUSION: Laparoscopy (either the single-port or multi-port) was a preferred alternative to open surgery in the present cohort of BOT patients because it was associated with more favorable surgical outcomes, with no compromise in oncologic outcome.

Parametrial Involvement on Magnetic Resonance Imaging Has No Effect on the Survival of Early-Stage Cervical Cancer Patients.

OBJECTIVES: Parametrial involvement (PMI) in patients with cervical cancer is known to be an unfavourable prognostic factor. The purpose of this study was to investigate the prognostic significance of PMI on magnetic resonance imaging (MRI) in patients with early-stage cervical cancer. METHODS: Three hundred three patients with stage IB or IIA cervical cancer treated by adjuvant radiotherapy or concurrent chemoradiotherapy following primary surgery from 2001 to 2011 were enrolled in this study. We reviewed preoperative MRI and pathologic findings and compared recurrence and survival of group defined according to PMI status. RESULTS: There were 73 patients (24.1%) with PMI based on MRI and 52 patients (17.2%) with PMI based on surgical pathology. The accuracy of MRI for detecting PMI was 77.2% (sensitivity, 53.8%; specificity, 82.1%). In all patients, pathology-based evidence of PMI had a negative effect on both 5-year disease-free survival (73.2% vs 85.3%, P = 0.048) and 5-year overall survival (76.6% vs 91.4%, P = 0.009), but PMI on MRI did not have a significant effect on survival. In subgroups defined according to PMI status on MRI and surgical pathology, subgroups with pathology-based evidence of PMI showed a trend of a lower survival rate, regardless of PMI on MRI, but without statistical significance. CONCLUSIONS: Unlike pathologic results, PMI on MRI was not associated with recurrence or survival in patients with early-stage cervical cancer.

Uterine Fibroids: Correlation of T2 Signal Intensity with Semiquantitative Perfusion MR Parameters in Patients Screened for MR-guided High-Intensity Focused Ultrasound Ablation.

PURPOSE: To evaluate the relationships between T2 signal intensity and semiquantitative perfusion magnetic resonance (MR) parameters of uterine fibroids in patients who were screened for MR-guided high-intensity focused ultrasound (HIFU) ablation. MATERIALS AND METHODS: Institutional review board approval was granted, and informed consents were waived. One hundred seventy most symptom-relevant, nondegenerated uterine fibroids (mean diameter, 7.3 cm; range, 3.0-17.2 cm) in 170 women (mean age, 43.5 years; range, 24-56 years) undergoing screening MR examinations for MR-guided HIFU ablation from October 2009 to April 2014 were retrospectively analyzed. Fibroid signal intensity was assessed as the ratio of the fibroid T2 signal intensity to that of skeletal muscle. Parameters of semiquantitative perfusion MR imaging obtained during screening MR examination (peak enhancement, percentage of relative peak enhancement, time to peak [in seconds], wash-in rate [per seconds], and washout rate [per seconds]) were investigated to assess their relationships with T2 signal ratio by using multiple linear regression analysis. Correlations between T2 signal intensity and independently significant perfusion parameters were then evaluated according to fibroid type by using Spearman correlation test. RESULTS: Multiple linear regression analysis revealed that relative peak enhancement showed an independently significant correlation with T2 signal ratio (Β = 0.004, P < .001). Submucosal intracavitary (n = 20, ρ = 0.275, P = .240) and type III (n = 18, ρ = 0.082, P = .748) fibroids failed to show significant correlations between perfusion and T2 signal intensity, while significant correlations were found for all other fibroid types (ρ = 0.411-0.629, P < .05). CONCLUSION: In possible candidates for MR-guided HIFU ablation, the T2 signal intensity of nondegenerated uterine fibroids showed an independently significant positive correlation with relative peak enhancement in most cases, except those of submucosal intracavitary or type III fibroids.

Prognostic significance of annexin A2 and annexin A4 expression in patients with cervical cancer.

BACKGROUND: The annexins (ANXs) have diverse roles in tumor development and progression, however, their clinical significance in cervical cancer has not been elucidated. The present study was to investigate the clinical significance of annexin A2 (ANXA2) and annexin A4 (ANXA4) expression in cervical cancer. METHODS: ANXA2 and ANXA4 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 46 normal cervical epithelium samples and 336 cervical cancer cases and compared the data with clinicopathological variables, including the survival of cervical cancer patients. RESULTS: ANXA2 expression was lower in cancer tissue (p = 0.002), whereas ANXA4 staining increased significantly in cancer tissues (p < 0.001). ANXA2 expression was more prominent in squamous cell carcinoma (p < 0.001), whereas ANXA4 was more highly expressed in adeno/adenosquamous carcinoma (p < 0.001). ANXA2 overexpression was positively correlated with advanced cancer phenotypes, whereas ANXA4 expression was associated with resistance to radiation with or without chemotherapy (p = 0.029). Notably, high ANXA2 and ANXA4 expression was significantly associated with shorter disease-free survival (p = 0.004 and p = 0.033, respectively). Multivariate analysis indicated that ANXA2+ (HR = 2.72, p = 0.003) and ANXA2+/ANXA4+ (HR = 2.69, p = 0.039) are independent prognostic factors of disease-free survival in cervical cancer. Furthermore, a random survival forest model using combined ANXA2, ANXA4, and clinical variables resulted in improved predictive power (mean C-index, 0.76) compared to that of clinical-variable-only models (mean C-index, 0.70) (p = 0.006). CONCLUSIONS: These findings indicate that detecting ANXA2 and ANXA4 expression may aid the evaluation of cervical carcinoma prognosis.

Impact of lymphadenectomy on survival after recurrence in patients with advanced ovarian cancer without suspected lymph node metastasis.

OBJECTIVE: To investigate the impact of pelvic and para-aortic lymphadenectomy during primary debulking surgery (PDS) on recurrence pattern and survival after recurrence in patients with advanced epithelial ovarian cancer (EOC) without suspected lymph node (LN) metastasis in preoperative imaging studies and intraoperative findings. METHODS: A retrospective review of patients with FIGO stage III and IV EOC without suspected lymph node metastasis was performed. Patients with stage III EOC due to LN metastasis without peritoneal disease were excluded from this study. Survival comparisons for progression-free survival (PFS), overall survival (OS), and survival after recurrence were performed between patients with or without lymphadenectomy. RESULTS: Of the 261 EOC patients fulfilling inclusion criteria, 194 (74.3%) experienced relapse and a further 132 (50.6%) died within a median follow-up period of 48months (range, 6-139months). Patterns of recurrence and CA-125 level at recurrence were not different between patients with lymphadenectomy and without lymphadenectomy; however, patients with lymphadenectomy showed longer survival after recurrence than those without lymphadenectomy (43 vs. 32months, p=0.013). This difference was pronounced in the group with residual tumor <1cm (48 vs. 30months, p=0.010). The survival advantage of lymphadenectomy after recurrence remained significant in multivariate analysis (HR 0.57, 95% CI 0.38-0.84, p=0.005). CONCLUSIONS: Lymphadenectomy during PDS was associated with longer survival, especially survival after recurrence. The underlying mechanism should be elucidated in future studies.

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.

Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2.

PURPOSE: Trebananib, a peptibody that blocks binding of angiopoietin-1 and -2 to Tie2, significantly prolonged progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer in the phase 3 TRINOVA-1 study. We report overall survival (OS) in the intent-to-treat population and clinically relevant subgroups and time to second disease progression (PFS-2). PATIENTS AND METHODS: Women with recurrent disease (platinum-free interval<12months) were randomized to receive intravenous paclitaxel 80mg/m(2) (3weeks on/1week off) plus intravenous trebananib 15mg/kg or placebo, weekly. OS in the intent-to-treat population was a key secondary endpoint. Exploratory analysis of PFS-2 was conducted according to guidance by the European Medicines Agency. RESULTS: Median OS was not significantly improved with trebananib compared with placebo (19.3 versus 18.3months; HR, 0.95; 95% CI, 0.81-1.11; P=0.52) in the intent-to-treat population (n=919). In subgroup analysis, trebananib improved median OS compared with placebo (14.5 versus 12.3months; HR, 0.72; 95% CI, 0.55-0.93; P=0.011) in patients with ascites at baseline (n=295). In the intent-to-treat population, trebananib significantly improved median PFS-2 compared with placebo (12.5 versus 10.9months; HR, 0.85; 95% CI, 0.74-0.98; P=0.024). The incidence and type of adverse events in this updated analysis was consistent with that described in the primary analysis; no new safety signals were detected. CONCLUSIONS: OS was not significantly longer in the intent-to-treat population, although there was an improvement in OS in patients with ascites receiving trebananib. PFS-2 confirmed that the PFS benefit associated with trebananib was maintained through the second disease progression independent of the choice of subsequent therapy.

Health-Related Quality of Life and Sociodemographic Characteristics as Prognostic Indicators of Long-term Survival in Disease-Free Cervical Cancer Survivors.

OBJECTIVES: Health-related quality-of-life (HRQOL) issues of cancer patients are considered an important clinical outcome. We aimed to investigate the prognostic value of HRQOL on long-term survival outcomes in disease-free cervical cancer survivors (CCSs). METHODS: The study sample consisted of 860 disease-free CCSs from 6 Korean cancer hospitals recruited for HRQOL survey during 2005 (median time from diagnosis, 5.9 years). Health-related quality-of-life measures included the European Organization for Research and Treatment of Cancer QLQ-C30 and its Cervical Cancer Module (CX24). Survival data were retrieved from the Korean Statistical Office after 6 years from the survey. Health-related quality-of-life domains along with sociodemographic and clinicopathologic variables were analyzed as prognostic factors for survival from the date of survey. RESULTS: During the median follow-up period of 6.3 years after the survey, 30 (3.5%) patients died from all causes. Age, time since diagnosis, and physical activity were independent prognostic factors, which constituted the baseline model along with cancer stage. When HRQOL domains were tested separately against the baseline model, functional scales (physical, role, social, and emotional functioning), global health status, symptom scales (pain and appetite loss), and cervical cancer module items (body image, sexual inactivity, and sexual worry) were significantly associated with survival (P < 0.05). CONCLUSIONS: These findings suggest that, in addition to well-known prognostic factors, including age, time since diagnosis, and physical activity, HRQOL scores obtained from disease-free CCSs are associated with survival.

Long-term Outcomes of MRI Stage IIB Cervical Cancer.

OBJECTIVE: Magnetic resonance imaging (MRI) can be used to assess parametrial invasion (PMI) in cervical cancer. Discordance between MRI findings and International Federation of Gynecology and Obstetrics (FIGO) staging is not uncommon because FIGO staging depends on physical examination. The purpose of this study was to retrospectively evaluate the long-term outcomes of MRI stage IIB cervical cancer. METHODS: A total of 312 patients with MRI stage IIB cervical cancer were retrospectively found between 2002 and 2011. Of these patients, 171 (group 1) were FIGO stage IIB cervical cancers and 141 (group 2) were MRI stage IIB cervical cancers that were negative PMI on physical examination. Group 1 was treated with chemotherapy and/or radiation therapy, and group 2 was treated with radical hysterectomy and lymph node dissection. The FIGO stages and pathologic findings of group 2 were recorded. Groups 1 and 2 were compared regarding 5-year overall survival rate. RESULTS: The FIGO stages of group 2 were IB1 in 51 (36.2%), IB2 in 28 (19.9%), and IIA in 62 (44%), whereas those of group 1 were all IIB. Group 2 showed lymphovascular space invasion in 71 (50.4%), lymph node metastasis in 48 (34.0%), PMI in 46 (32.6%), and vagina invasion in 9 (6.4%). Five-year overall survival rates of groups 1 and 2 were 73.7% and 84.5%, respectively (P = 0.013). CONCLUSIONS: Magnetic resonance imaging stage IIB cervical cancers with negative PMI on physical examination should be surgically treated because of better survival rate than FIGO stage IIB cervical cancers.

Development and Validation of the Korean Version of Hand-Foot Skin Reaction and Quality of Life Questionnaire (HF-QoL-K).

Given the growing number of cancer patients and the resulting increase in the administration of chemotherapeutic agents, convenient and effective methods for measuring the symptoms and quality of life associated with the hand-foot syndrome (HFS) are needed. Therefore, the aim of this study was to develop and validate the Korean version of the hand-foot skin reaction and quality of life questionnaire (HF-QoL-K), comprising a 20-item symptom domain and an 18-item daily activity domain. After we developed the HF-QoL-K, 209 Korean patients with gynecologic cancer who were undergoing chemotherapeutic agents relating the HFS were asked to fill in the questionnaire. The content validity, internal consistency reliability, and test-retest reliability were evaluated. The internal validity index, Cronbach's alpha coefficient, and intra-class correlation coefficient of the HF-QoL-K were 0.90, 0.958, and 0.825 (95% confidence interval [CI], 0.774-0.865), respectively. The scatter plot (Pearson correlation coefficient, 0.826) and the Bland-Altman plot for test-retest reliability were also acceptable. The HF-QoL-K instrument is a valid and reliable questionnaire for the measurement of the symptoms and quality of life in Korean cancer patients suffering HFS.

Clinical outcomes of primary surgical treatment for acquired vulvar lymphangioma circumscriptum.

OBJECTIVE: To assess the clinical outcomes of surgical treatment for acquired vulvar lymphangioma circumscriptum in patients who received radical surgery and/or adjuvant radiation therapy for cervical cancer. METHODS: A retrospective chart review of eight patients was performed to assess the demographic information, chief complaints, treatment modality for cervical cancer, location, and primary treatment modality for vulvar LC, postoperative changes in symptoms, and/or signs, the development of local recurrence and the outcome of patients. RESULTS: All eight patients were previously diagnosed with cervical cancer FIGO clinical stage IA to IIA and received surgery, radiation therapy, or concurrent chemoradiation therapy. Microscopic examination revealed multiple, dilated, D2-40-positive dermal vascular channels containing eosinophilic proteinaceous material, consistent with LC. Most chief complaints showed considerable improvements on assessment at the outpatient clinic after the primary surgery. No patient showed aggravation of symptoms. Two patients developed local recurrences. One patient developed recurrence on the opposite side 13 months after local excision. We performed a second wide local excision. Another patient developed recurrence 47 months after the primary surgery. Since the lesion was very small and localized, we decided to manage it conservatively, but monitor it very closely. The remaining six patients remained free of recurrence. CONCLUSION: It is not easy for gynecologists to have an initial clinical diagnosis of LC, because there are a number of diseases that exhibit similar clinical manifestation to that of vulvar LC. Even if it is diagnosed correctly, local recurrence often occurs. Relevant symptoms associated with LC are not only distressing, but also affect patients' quality of life. Based on our data, we propose that surgical treatment could provide a more long-lasting answer compared to other treatment modalities, since it is beneficial in terms of clinical outcomes. In the future, a long-term follow-up investigation is required to assess the prognosis and to compare the efficacy and side effects of each modality.

Timing and patterns of recurrence in epithelial ovarian cancer patients with no gross residual disease after primary debulking surgery.

OBJECTIVE: The aim of this study was to analyse patterns and timing of recurrence and their association with clinical outcomes in recurrent epithelial ovarian cancer (EOC) patients with no gross residual disease after primary debulking surgery (PDS). METHODS: This study was conducted on 303 EOC patients with no residual disease after PDS who were treated at the Samsung Medical Center from 2002 to 2012. By reviewing electronic medical records, information on date of clinical/pathological recurrence and pattern of disease presentation for each relapse were retrieved. RESULTS: Within a median follow-up of 53 months (range 3-156), 88 recurrences (29.0%) and 28 cancer-related deaths (9.2%) were observed. Most of the recurrences were distant, discrete and transcoelomic. After complete cytoreduction, the initial stage was associated with location of recurrence, but not with recurrence patterns. Complete cytoreduction reduced the number of recurrences, but it did not affect timing of recurrence. In multivariate analysis for overall survival (OS), patients with distant recurrence, diffuse carcinomatosis and mixed spread pattern of transcoelomic, lymphatic and haematogenous recurrence were found to have higher risk. CONCLUSIONS: We found that timing of recurrence was not affected by complete cytoreduction. Location, type and pattern of recurrence were also significant prognostic factors for OS, in addition to known prognostic predictors such as platinum sensitivity.