Retreatment with progestin for recurrence after complete response with fertility-sparing treatment in patients with endometrial cancer.

OBJECTIVE: To assess the outcomes of retreatment using progestin for recurrence after a complete response with fertility-sparing treatment in patients with early endometrial cancer. METHODS: We retrospectively reviewed the data of patients with presumed stage IA, grade 1 endometrioid endometrial cancer who developed intra-uterine recurrence after a complete response with fertility-sparing treatment using progestin. Oncological and pregnancy outcomes were analyzed after repeated fertility-sparing treatment. Logistic and Cox regression analyses were performed to analyze the prognostic factors associated with a complete response with secondary fertility-sparing treatment and recurrence-free survival after secondary fertility-sparing treatment, respectively. RESULTS: Fifty patients with a median age of 31 years (range 23-40) underwent secondary fertility-sparing treatment. With a median secondary progestin treatment duration of 9 months (range 3-55), the complete response rate was 78% (39/50) and no patients had extra-uterine spread of disease. Among the 26 (67%) patients who attempted to conceive after complete response, 10 became pregnant (3 spontaneous abortions, 7 live births). Eighteen (46.1%) patients had a second recurrence, with a median recurrence-free survival after secondary fertility-sparing treatment of 14 months (range 3-36); 15 patients received tertiary fertility-sparing treatment and nine (60%) achieved a complete response. Polycystic ovary on ultrasound (OR 5.82, 95% CI 1.1 to 30.6, p=0.037) was associated with an increased complete response rate with secondary fertility-sparing treatment. Multivariable analysis revealed that recurrence-free survival after initial hormonal treatment >6 months (HR 0.11, 95% CI 0.02 to 0.51, p=0.005) and pregnancy after secondary fertility-sparing treatment (HR 0.27, 95% CI 0.08 to 0.98; p=0.047) were significantly associated with longer recurrence-free survival after secondary fertility-sparing treatment. CONCLUSIONS: Repeated progestin treatment was associated with a 78% response rate and it was safe in patients with intra-uterine recurrent endometrial cancer. Thus, it might help preserve fertility after first and second recurrences.

Optimal duration of fertility-sparing hormonal treatment for early-stage endometrioid endometrial cancer.

OBJECTIVES: To analyze the oncologic outcomes of long-term fertility-sparing treatment (FST) in patients with early-stage endometrial cancer (EC) and to determine the optimal duration of FST that would not hamper survival outcomes. METHODS: Patients undergoing FST for presumed stage IA, grade 1 EC between 2005 and 2018 were retrospectively analyzed. Oncologic outcomes were compared between the group with ≤6 months of FST and the group with >6 months of FST. Segmented regression analysis was used to estimate the dynamic changes in cumulative complete response (CR) rates according to FST duration. RESULTS: A total of 122 patients received oral progestin, with concurrent levonorgestrel-releasing intrauterine device use in 108 (88.5%) and 105 (86.1%) achieved CR with a median time to achieve CR of 10 (3-42) months. Of the patients not achieving CR at 6 months of FST, 95.1% (78/82) continued further FST. The overall CR rate (88.9% [32/36] vs. 84.9% [73/86], P = 0.436] was not significantly different between the groups with ≤6 and > 6 months of FST. The changes in cumulative CR rates were significantly different between the two segments divided by 15 months from the initial FST (P = 0.0015, segmented regression analysis). The overall progressive disease (PD) rate was 3.3% (4/122), and PD was first detected during 9-12 months of FST. CONCLUSION: Patients not achieving CR and not showing PD at 6 months of FST could continue further FST. If disease progression is excluded, 15 months of FST can be considered as the cutoff for the optimal FST duration.

Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer.

OBJECTIVE: Hormonal management is an alternative treatment for preserving fertility in patients with presumed early stage endometrioid endometrial cancer. This study aimed to define the pregnancy and oncologic outcomes and factors of successful conception after hormone therapy for endometrioid endometrial cancer. METHODS: We retrospectively analyzed patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer who underwent fertility-sparing treatment. Concurrent medroxyprogesterone and levonorgestrel-release intra-uterine devices were used for treatment. The pregnancy outcomes and oncologic outcomes were compared between the pregnant and non-pregnant groups. RESULTS: Seventy-one patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer had complete remission, and 49 of them tried to conceive. Twenty-two (44.9%) patients became pregnant; the total number of pregnancies was 30. These pregnancies resulted in seven abortions (23.3%), one pre-term birth (3.3%), and 20 full-term births (66.6%). The total live birth rate was 66.6 % (20/30). The median duration of hormonal treatment was 11.9 months (range 4-49) and 12.0 months (range 3-35) in the pregnant and non-pregnant groups, respectively. On multivariate analysis, age, body mass index, treatment duration, medroxyprogesterone dose, and number of dilatation and curettage biopsies were not significantly associated with pregnancy failure, but the association with grade (OR 6.2, 95% CI 1.0 to 38.9; P<0.05) was statistically significant. The median disease-free survival duration was 26 months (range 20-38) and 12 months (range 4-48) in the pregnant and non-pregnant groups, respectively (P<0.05, log-rank test). CONCLUSIONS: A lower grade might be a positive factor for future pregnancy. Moreover, successful pregnancy might be a factor in preventing recurrence.

Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer.

BACKGROUND: This open-label phase III trial evaluated efficacy and safety of S-1 plus cisplatin vs. cisplatin alone as first-line chemotherapy in patients with stage IVB, recurrent, or persistent cervical cancer. METHODS: Patients were randomised (1:1) to S-1 plus cisplatin (study group) or cisplatin alone (control group). In each cycle, cisplatin 50 mg/m2 was administered on Day 1 in both groups. S-1 was administered orally at 80-120 mg daily on Days 1-14 of a 21-day cycle in the study group. The primary endpoint was overall survival (OS). RESULTS: A total of 375 patients were enrolled, of whom 364 (188, study group; 176, control group) received treatment. Median OS was 21.9 and 19.5 months in the study and control groups, respectively (log-rank P = 0.125; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.67-1.05). Median progression-free survival (PFS) was 7.3 and 4.9 months in the study and control groups, respectively (HR 0.62, 95% CI 0.48-0.80, P < 0.001). The adverse event (AE) rate increased in the study group despite the absence of any unexpected AEs. CONCLUSIONS: S-1 plus cisplatin did not show superiority over cisplatin alone in OS but significantly increased PFS in patients with stage IVB, recurrent, or persistent cervical cancer. Since the standard therapy has changed in the course of this study, further studies are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population.

Prediction model for para-aortic lymph node metastasis in patients with locally advanced cervical cancer.

OBJECTIVE: Concurrent chemoradiotherapy is usually administered to patients with locally advanced cervical cancer (LACC). Extended-field chemoradiotherapy is required if para-aortic lymph node (PALN) metastasis is detected. This study aimed to construct a prediction model for PALN metastasis in patients with LACC before definitive treatment. METHODS: Between 2009 and 2016, all consecutive patients with LACC who underwent para-aortic lymphadenectomy at two tertiary centers were retrospectively analyzed. A multivariate logistic model was constructed, from which a prediction model for PALN metastasis was developed and internally validated. Before analysis, risk grouping was predefined based on the likelihood ratio. RESULTS: In total, 245 patients satisfied the eligibility criteria. Thirty-four patients (13.9%) had pathologically proven PALN metastases. Additionally, 16/222 (7.2%) patients with negative PALNs on positron emission tomography/computed tomography (PET/CT) had PALN metastasis. Moreover, 11/105 (10.5%) patients with both negative PALNs and positive pelvic lymph nodes on PET/CT had PALN metastasis. Tumor size on magnetic resonance imaging and PALN status on PET/CT were independent predictors of PALN metastasis. The model incorporating these two predictors displayed good discrimination and calibration (bootstrap-corrected concordance index=0.886; 95% confidence interval=0.825-0.947). The model categorized 169 (69%), 52 (22%), and 23 (9%) patients into low-, intermediate-, and high-risk groups, respectively. The predicted probabilities of PALN metastasis for these groups were 2.9, 20.8, and 76.2%, respectively. CONCLUSION: We constructed a robust model predicting PALN metastasis in patients with LACC that may improve clinical trial design and help clinicians determine whether nodal-staging surgery should be performed.

Management of Endometrial Hyperplasia With a Levonorgestrel-Releasing Intrauterine System: A Korean Gynecologic-Oncology Group Study.

OBJECTIVE: The aim of the study was to evaluate the efficacy of the levonorgestrel intrauterine system (LNG-IUS) for treatment of endometrial hyperplasia (EH). METHODS: A prospective multicenter study was conducted from November 2010 to March 2014. Patients with histologically confirmed EH were treated with LNG-IUS. At 3, 6, and 9 months after LNG-IUS insertion, follow-up endometrial aspiration biopsies with the LNG-IUS in the uterus were undertaken. At the 12th month of follow-up, endometrial tissues were obtained via 2 methods: endometrial aspiration biopsy with the LNG-IUS in the uterus, followed by dilatation and curettage (D&C) after LNG-IUS removal. The primary outcome was the regression rate at 12 months after LNG-IUS insertion, and the secondary outcome was the consistency of the results between the endometrial aspiration biopsy and the D&C. RESULTS: The study population comprised 75 patients, including 37 with simple hyperplasia without atypia; 3 with atypical simple hyperplasia; 23 with complex hyperplasia without atypia, and 12 with atypical complex hyperplasia. Of these patients treated with the LNG-IUS, 38 (50.7%) were followed up at 12 months after LNG-IUS insertion. The complete regression rate at 12 months was 94.7% (36/38): 100% (6/6) of patients with atypical EH and 93.7% (30/32) with EH without atypia. In all of the cases (100%, 36/36), patients achieved complete regression within 3 months of LNG-IUS insertion. A comparison of the pathologic results from endometrial aspiration biopsy and D&C was carried out for 15 patients. In the histologic results by endometrial aspiration biopsy, 14 patients were diagnosed as "normal endometrium" and 1 as "insufficient tissue for pathologic evaluation." Among the 14 cases of normal endometrium by endometrial aspiration biopsy, 1 was diagnosed as "residual EH" by D&C, and the 1 case with insufficient tissue was diagnosed as normal endometrium by D&C. CONCLUSIONS: Levonorgestrel intrauterine system is an effective and favorable method for treatment of EH.

The impact of positive peritoneal cytology on prognosis in patients with cervical cancer: a meta-analysis.

BACKGROUND: The impact of positive peritoneal cytology on the prognosis of cervical cancer is controversial. Thus, we performed a meta-analysis to determine its impact on recurrence, and to investigate correlations between abnormal cytology and/or lymph node metastasis in cervical cancer. METHODS: A systematic literature review was conducted through July 2014. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated by standard meta-analysis techniques with the fixed-effects models, if there was no significant statistical heterogeneity across studies by using I(2). RESULTS: Of 303 studies retrieved, 6 were included in the meta-analysis. These six case-control observational studies included 1360 cervical cancer patients who showed negative peritoneal cytology and 64 who showed positive peritoneal cytology. Over the combined study period, 20 of 45 in the positive peritoneal cytology group experienced recurrence, whereas 88 of 539 controls did. The meta-analysis based on the fixed-effects model indicated a significant increase in the risk of recurrence in the positive peritoneal cytology group relative to the control group (OR: 4.47; 95% CI: 2.33-8.58, P<0.001, I(2)=0.0%). Moreover, the results of our meta-analysis suggested that the positive peritoneal cytology group displayed more lymph node metastasis than the negative peritoneal cytology group (OR: 3.73; 95% CI: 2.13-6.53, P<0.001, I(2)=0.0%). CONCLUSIONS: Although based mainly on retrospective observational studies, our meta-analysis indicates that abnormal peritoneal cytology may be strongly associated with poor prognosis in patients with cervical cancer. Future research should verify this relationship through prospective observational studies over a longer term.

Impact of resident participation on surgical outcomes in laparoscopically assisted vaginal hysterectomy.

OBJECTIVE: To compare surgical outcomes in patients with benign diseases who underwent laparoscopically assisted vaginal hysterectomy (LAVH) to determine the association between surgical outcomes and resident participation in the gynecologic field. METHODS: A single-center retrospective study was conducted of patients diagnosed with benign gynecologic diseases who underwent LAVH between January 2010 and December 2015. Clinicopathologic characteristics and surgical outcomes were compared between the resident involvement and non-involvement groups. The primary endpoint was the 30-day postoperative morbidity. Observers were propensity matched for 17 covariates for resident involvement or non-involvement. RESULTS: Of the 683 patients involved in the study, 165 underwent LAVH with resident involvement and 518 underwent surgery without resident involvement. After propensity score matching (157 observations), 30-day postoperative morbidity occurred in 6 (3.8%) and 4 (2.5%) patients in the resident involvement and non-involvement groups, respectively (P = 0.501). The length of hospital stay differed significantly between the two groups: 5 days in the resident involvement group and 4 days in the non-involvement group (P < 0.001). On multivariate analysis, Charlson Comorbidity Index >2 (odds ratio [OR] 8.01, 95% confidence interval [CI] 2.68-23.96; P < 0.001), operative time (OR 1.02, 95% CI 1.01-1.03; P < 0.001), and estimated blood loss (OR 1.00, 95% CI 1.00-1.00; P < 0.001) were significantly associated with 30-day morbidity, but resident involvement was not statistically significant. CONCLUSION: There was no significant difference in the 30-day morbidity rate when residents participated in LAVH. These findings suggest that resident participation in LAVH may be a viable approach to ensure both residency education and patient safety.

Prognostic value of preoperative metabolic tumor volume and total lesion glycolysis in patients with epithelial ovarian cancer.

PURPOSE: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are measures of metabolic activity of tumors determined by fluorine-18 fluorodeoxyglucose ([(18)F]FDG) uptake on PET/CT images. The purpose of this study was to investigate the relationship between functional tumor parameters (MTV and TLG) and clinical outcomes in patients with epithelial ovarian cancer (EOC). METHODS: Fifty-five patients with EOC who had undergone [(18)F]FDG PET/CT before surgical staging were included in this retrospectively study. For each patient, we determined the highest (SUV(max) and SUV(avg)), the cumulative TLG, and the sum of all MTV, and compared their predictive value of recurrence and the effects of pretreatment functional tumor activity on progression-free interval (PFI). RESULTS: The median duration of PFI was 11 (range 3-43) months, and 20 patients (36.4%) experienced recurrence. Poor outcome was associated with higher values for both the MTV (P = 0.022, hazard ratio 5.571, 95% confidence interval 1.279-24.272) and the TLG (P = 0.037, hazard ratio 2.967, 95% confidence interval 1.065-8.265). The Kaplan-Meier survival graphs showed a significant difference in PFI between the groups categorized by MTV and TLG, respectively (P = 0.01 for MTV, P = 0.0287 for TLG, log rank test). CONCLUSIONS: Pretreatment metabolic parameters such as MTV and TLG showed statistically significant association with recurrence in patients with EOC. These values can be useful quantitative criteria for disease prognostication in patients with EOC before treatment.

20 year experience of postoperative radiotherapy in IB-IIA cervical cancer patients with intermediate risk factors: impact of treatment period and concurrent chemotherapy.

OBJECTIVE: To compare the long-term clinical outcomes of adjuvant radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT) in cervical cancer patients with intermediate risk factors. METHODS: Between 1990 and 2010, 110 cervical cancer patients with 2 or more intermediate risk factors (deep stromal invasion, lymphovascular space invasion, and large tumor size) underwent adjuvant RT (n=56) or CCRT (n=54) following radical surgery. Because CCRT had been performed since 2000, patients were divided into 3 groups regarding treatment period and the addition of chemotherapy, RT 1990-1999 (n=39), RT 2000-2010 (n=17) and CCRT 2000-2010 (n=54). Majority of concurrent chemotherapeutic regimens were carboplatin and paclitaxel (n=48). RESULTS: Five-year relapse-free survival (RFS) rates for RT 1990-1999, RT 2000-2010 and CCRT 2000-2010 were 83.5%, 85.6% and 93.8%, respectively. CCRT 2000-2010 had a significant decrease in pelvic recurrence (p=0.012) and distant metastasis (p=0.027). There were no significant differences in overall survival and RFS between RT 1990-1999 and RT 2000-2010. Acute grade 3 and 4 hematologic toxicities were more frequently observed in CCRT 2000-2010 (p<0.001). However, acute grade 3 and 4 gastrointestinal (GI) and chronic toxicities did not differ between the groups. CONCLUSIONS: This study shows that the addition of concurrent chemotherapy to postoperative RT in cervical cancer patients with intermediate risk factors may improve RFS without increasing acute GI and chronic toxicities, although hematologic toxicities increased significantly.

Loop electrosurgical excision procedure findings for identification of patients with early-stage cervical cancer suitable for less radical surgery.

OBJECTIVE: To define a subset of patients with early-stage cervical cancer at low risk for parametrial invasion through pathologic parameters of loop electrosurgical excision procedure (LEEP). MATERIALS AND METHODS: A retrospective analysis of data from 131 patients who underwent LEEP before radical hysterectomy or radical trachelectomy for stage IA2 to IB1 cervical cancer was performed. Subgroup analysis was performed to define a group of patients at the lowest risk for parametrial invasion based on LEEP findings. RESULTS: Overall, 7 (5.3%) of 131 patients showed parametrial involvement, all of whom had residual tumors in hysterectomy specimens. Risk factors for residual disease included a tumor width greater than 30 mm and a positive endocervical or deep resection margin. A subgroup analysis demonstrated that LEEP parameters, including a depth of invasion of 5 mm or less and a negative endocervical resection margin, were able to define the subgroup of patients at low risk for parametrial invasion. In 24 patients (18.3%) who met these criteria, there was no evidence of parametrial spread as well as nodal metastasis. CONCLUSION: A subgroup of patients with early-stage cervical cancer selected by the 2 LEEP variables, depth of invasion of 5 mm or less and a negative endocervical resection margin, demonstrated no risk for parametrial invasion.

Definitive radiotherapy for treatment of primary vaginal cancer: effectiveness and prognostic factors.

OBJECTIVE: This study was performed to evaluate treatment outcomes and define prognostic factors for primary vaginal cancer treated with definitive radiotherapy. MATERIALS AND METHODS: We retrospectively analyzed 38 patients with primary vaginal cancer who received radiotherapy with curative intent between January 1981 and August 2008. Of these 38 patients, 6 were excluded from this analysis because of other uncontrolled malignancy (n = 1), uncommon histology (n = 4), or insufficient medical records (n = 1). Twenty-three patients (72%) presented with early-stage disease (International Federation of Gynecology and Obstetrics stages 0, I, or II). Eleven patients (34%) were treated with external beam radiotherapy (EBRT) alone and 21 patients (66%) with EBRT plus brachytherapy (BT). Low-dose rate cesium-137 was used with intracavitary technique for most of the patients who received BT. Five patients received chemotherapy. The median total dose in patients who received EBRT and EBRT+BT was 50.4 Gy (range, 39.6-70.4 Gy) and 78.9 Gy (range, 72.0-87.0 Gy), respectively. RESULTS: The median duration of follow-up was 38 months. Five-year overall survival, cause-specific survival, disease-free survival, local control, and regional control rates for the analyzed patients were 75%, 88%, 58%, 62% and 90%, respectively. Thirteen patients had treatment failure as follows: local (n = 7), distant (n = 1), local plus regional (n = 1), local plus distant (n = 2), and local plus regional plus distant (n = 2). Primary tumor size was a significant prognostic factor for disease-free survival (P = 0.039). CONCLUSIONS: Definitive radiotherapy is an effective treatment modality for primary vaginal cancer. Local failure was the major failure pattern, and achievement of local control is important for disease control and survival.

Body mass index and survival in patients with epithelial ovarian cancer.

AIM: There is controversy regarding the effect of obesity on the treatment and survival of ovarian cancer. This study examined the impact of obesity on the treatment and survival outcomes of epithelial ovarian cancer. METHODS: The medical records of patients undergoing surgery for epithelial ovarian cancer (EOC) between January 2000 and February 2010 were reviewed. Patient demographics, surgical outcomes, clinicopathological factors and survival were evaluated and compared according to the body mass index (BMI). The Asian BMI criteria for Koreans were used. RESULTS: Of a total of 486 patients identified, 31 (6.4%) were underweight (BMI<18.5), 224 (46.1%) were normal (18.5≤BMI<23), 179 (36.8%) were overweight (23≤BMI<27.5) and 52 (10.3%) were obese (27.5≥BMI). All surgical outcome parameters except for wound problems failed to show a significant association with BMI. Similarly, there were no differences in the stage, recurrence rate, pathological features or chemotherapy characteristics, including platinum resistance rates, between the BMI groups. However, overweight and obese patients were significantly older than the underweight and normal body weight patients (P<0.01). A history of cardiovascular disease and diabetes mellitus were more common in these overweight and obese patients (P<0.01 for both). There were no differences in progression free survival (P>0.05) or overall survival (P>0.05) according to the BMI. No difference in progression free survival (P>0.05) or overall survival (P>0.05) could be found, even in the subcohort of stages III and IV. CONCLUSION: Obesity itself does not affect the surgical and clinicopathological outcomes or even survival in EOC patients.

Post-treatment [¹8F]FDG maximum standardized uptake value as a prognostic marker of recurrence in endometrial carcinoma.

PURPOSE: The purpose of this study was to determine whether post-treatment [(18)F]fluorodeoxyglucose (FDG) uptake measured as the maximum standardized uptake value (SUV(max)) by integrated positron emission tomography (PET)/computed tomography (CT) imaging has prognostic significance in patients with endometrial carcinoma. METHODS: Patients previously treated by primary surgical staging for endometrial carcinoma were imaged with integrated FDG PET/CT during surveillance. PET/CT findings were compared with histological or clinical evaluation, and the relationship between SUV(max) on PET/CT and recurrence was examined. RESULTS: A total of 61 patients were eligible for analysis. Medical records were retrospectively reviewed for clinical data, treatment modalities and outcome. The median duration of follow-up was 31 months (range 6-102 months) post-treatment. SUV(max) levels were inversely associated with disease-free survival (DFS). Patients were divided into two groups according to SUV(max) (< 4.25 versus ≥ 4.25). The Kaplan-Meier survival graph showed a significant difference in DFS between groups [p < 0.001, hazard ratio (HR) 12.959, 95% confidence interval (CI) 3.650-46.011]. In multivariate analyses, post-treatment SUV(max) (uncategorized values) evaluated by surveillance PET/CT (p = 0.001, HR 1.199, 95% CI 1.077-1.334) and serous adenocarcinoma histology (p = 0.028, HR 5.594, 95% CI 1.207-25.931) were significantly associated with recurrence. CONCLUSION: Post-treatment FDG uptake as measured by SUV(max) showed a significant association with recurrence in patients with endometrial carcinoma and may be used as a new useful prognostic marker.

Significance of numbers of metastatic and removed lymph nodes in FIGO stage IB1 to IIA cervical cancer: Primary surgical treatment versus neoadjuvant chemotherapy before surgery.

OBJECTIVE.: The objective of this study was to compare the significance of numbers of metastatic (MLN) and removed lymph nodes (RLN) between primary surgical treatment (PST) and neoadjuvant chemotherapy followed by surgery (NCS) in patients with FIGO stage IB1 to IIA cervical cancer. METHODS.: Among 1124 patients with cervical cancer, PST (n=451) and NCS (n=73) groups were enrolled for evaluating the association between numbers of MLN and RLN, and clinical outcomes including the pattern of recurrence and survival according to the 2 treatments. RESULTS.: Mean values of progression-free survival (PFS) were 100.8 vs. 87.6 vs. 57.7 months in 0 vs. 1-2 vs. ≥3 MLN, suggesting that ≥3 MLN was associated with poor PFS (adjusted HR, 2.71; 95% CI, 1.02 to 7.21). However, there was no association between the number of MLN and survival in NCS group. The increased number of MLN was also associated with the increase of distant metastasis in PST group (44.0% vs. 72.7% vs. 78.6%; p=0.02), whereas there was no association between the number of MLN and the pattern of recurrence in NCS group. Moreover, mean values of PFS were 57.2 (<20 RLN) vs. 77.9 months (≥20 RLN) in PST group with lymph node metastasis (p=0.04), demonstrating that ≥20 RLN improved PFS in PST group (adjusted HR, 0.48; 95% CI, 0.25 to 0.95). CONCLUSIONS.: The increased number of MLN may be more significant for predicting poor survival and distant metastasis, and the increased number of RLN may be associated with better survival in the patients treated with PST than those treated with NCS.

Activation of mTOR signaling pathway associated with adverse prognostic factors of epithelial ovarian cancer.

OBJECTIVE: Activation of the mammalian target of rapamycin (mTOR) pathway enhances cell survival and growth by regulating the efficiency of protein translation. This study was conducted to evaluate the association of activated mTOR signaling molecules with the clinicopathologic characteristics in epithelial ovarian cancer. METHODS: Immunohistochemical staining with antibodies against p-4EBP1, p-mTOR, and p-p70S6K were performed on specimens of 103 patients with ovarian cancer. Tumors were classified as chemoresistant in cases where time to recurrence after the end of chemotherapy was shorter than 6months. RESULTS: Expressions of p-mTOR, p-4EBP1, and p-p70S6K were detected in 47.6%, 85.4%, and 64.1% of all patients, respectively. p-4EBP1 overexpression was associated with advanced stage (p=0.04), histologic grade (p<0.01), residual mass (p<0.01), shorter disease-free survival rate (p=0.01) and chemoresistance (p=0.02). p-p70S6K was associated with residual mass with marginal significance (p=0.06). p-4EBP1 expression was correlated with p-p70S6K expression (r=0.42, p<0.01), whereas p-mTOR was not associated with expression of its downstream effectors or prognostic factors. CONCLUSIONS: Our findings suggest that p-4EBP1 expression was associated with poor prognostic factors of ovarian cancer and that p-4EBP1 overexpression may be a prognostic biomarker of ovarian cancer.

Prognostic value of metabolic tumor volume measured by FDG-PET/CT in patients with cervical cancer.

OBJECTIVE: To determine if preoperative metabolic tumor volume (MTV) measured by integrated (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) imaging has prognostic value in patients with cervical cancer treated primarily with radical hysterectomy. METHODS: Patients with FIGO stage IB to IIA cervical cancer were imaged with FDG-PET/CT before radical surgery. MTV was measured from attenuation-corrected FDG-PET/CT images using a standard uptake value (SUV)-based automated contouring program. We evaluated the relationship of MTV to disease-free survival (DFS). RESULTS: A total of 63 patients were included in the study. The cut-off value for predicting recurrence was determined using a receiver operating characteristic (ROC) curve. MTV in this study was found to be correlated with lymph node (LN) metastasis, parametrium (PM) involvement, FIGO stage, and SUV(max). In univariate analysis, MTV≥23.4 mL (HR 1.017, 95% confidence interval (CI) 1.005-1.029, P=0.004), SUV(max)≥9.5 (HR 5.198, 95% CI 1.076-25.118, P=0.04), LN metastasis (HR 12.338, 95% CI 1.541-98.813, P=0.018), PM involvement (HR 14.274, 95% CI 1.785-114.149, P=0.012), and lymphovascular space invasion (HR 8.871, 95% CI 1.104-71.261, P=0.04), were related to DFS. In multivariate analyses, age (HR 0.748, 95% CI 0.587-0.952, P=0.018) and MTV≥23.4 mL (HR 49.559, 95% CI 1.257-1953.399, P=0.037) were determined to be independent prognostic factors of DFS. CONCLUSION: Preoperative MTV is an independent prognostic factor for DFS in patients with cervical cancer treated by radical surgery.

An occult invasive cervical cancer found after a simple hysterectomy: a 10-year experience in a single institution.

OBJECTIVE: The aim of this study was to identify patients who are at risk of a recurrence and those needing adjuvant treatment by risk grouping in invasive cervical cancer after a simple hysterectomy (SH). METHODS: During 2000-2009, 26 patients who underwent SH and were finally diagnosed with stages higher than IA1 were reviewed retrospectively. The American Joint Committee on Cancer (AJCC) pathologic staging system was adopted. Based on the pathologic findings, the criteria for risk scoring was set: 1 for depth of invasion (DOI) is between 3-5 mm, and 2 for DOI greater than 5 mm; 1 for longest diameter (LD) is between 0.7-20 mm, and 2 for LD greater than 20 mm; 1 for lymphovascular space invasion positive; and 3 each for parametrium, resection margin, and lymph node positive. The final score was calculated by summing up the risk scores. The receiver operation characteristic curve was created to confirm the best cutoff value. RESULTS: All patients were stage IA2 to IB2, of which the number of patients in stages IA2, IB1, and IB2 were 1, 24, and 1, respectively. Eleven patients did not receive any further treatment. Of the remaining 15 patients, 11 received radiation therapy, 3 underwent concurrent chemoradiation therapy, and 1 received chemotherapy alone. No patient underwent a radical parametrectomy. During a median follow-up of 67 months (range, 9-122 months), 3 patients (11.5%) showed a recurrence. Patient whose score was 1 to 3, 4 to 5, and 6 or higher was classified into low-risk, intermediate-risk, and high-risk groups, respectively. All patients in the low-risk group did not recur without any adjuvant treatment (sensitivity, 100%; specificity 34.8-65.2%). CONCLUSIONS: Adjuvant treatment can be omitted in low-risk group patients with invasive cervical cancer detected after SH.

Conservative treatment with medroxyprogesterone acetate plus levonorgestrel intrauterine system for early-stage endometrial cancer in young women: pilot study.

OBJECTIVE: To assess the feasibility of using medroxyprogesterone acetate (MPA) and levonorgestrel intrauterine system (LNG-IUS) to treat early-stage endometrial cancer in young women who want to preserve their reproductive potential. METHODS: Prospective observational study of 5 young patients (mean [SD] age, 38.4 [4.8] years; range, 33-41 years) with a grade 1 endometrial cancer that is presumably confined to the endometrium. The subjects were given a daily oral dose of 500 mg of MPA and LNG-IUS placement. They were followed with dilation and curettage every 3 months. RESULTS: Complete remission was shown in 4 of 5 patients, and one patient showed partial remission. Biopsy results were negative in 2 patients at 3 months, in 1 patient at 6 months, and in 1 patient at 12 months. No treatment-related complications occurred. No recurrence was found during the follow-up period (mean [SD], 10.2 [3.6] months; range, 6-16 months). CONCLUSIONS: The concomitant use of MPA with LNG-IUS is feasible for conservative treatment of early-stage endometrial cancer in young women who want to preserve their reproductive potential.

Hypoxia-inducible factor 1α polymorphisms and early-stage cervical cancer.

BACKGROUND: Human papillomavirus can stabilize and induce hypoxia-inducible factor 1α (HIF-1α) protein, which is associated with diminished response to treatment and poor prognosis for cervical cancer. Hypoxia-inducible factor 1α polymorphisms (1772C>T and 1790G>A) in the N-terminal transactivation domain generate significantly increased transcriptional activity and have been linked to poor outcome in various malignancies. OBJECTIVE: The aim of this study was to analyze the possible influence of HIF-1α genetic polymorphisms on cancer susceptibility, tumor aggressiveness, and survival of patients with early-stage cervical cancer. METHODS: One hundred ninety-nine patients with early-stage cervical cancer who were treated with surgical resection were retrospectively investigated. Hypoxia-inducible factor 1α 1772C>T and 1790G>A genetic polymorphisms were compared with 205 healthy subjects and correlated with the clinical outcome of patients with early-stage cervical cancer. RESULTS: The risk of cervical cancer was not affected by HIF-1α 1772C>T and 1790G>A polymorphisms. However, lymph node metastasis was significantly increased in patients who had the 1790 variant (adjusted odds ratio, 5.01; 95% confidence interval, 1.05-23.88; P = 0.043). In survival analysis, HIF-1α 1772C>T and 1790G>A polymorphisms were not related to disease-free survival and overall survival. CONCLUSIONS: Although HIF-1α genetic polymorphisms had little association with cervical cancer risk and prognosis, individual variance of HIF-1α gene may be associated with cervical cancer invasiveness.