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Contains fulltext : 241226.pdf (Publisher’s version ) (Closed access) BACKGROUND: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously been shown to extend progression-free survival versus placebo when given to patients with relapsed high-grade serous or endometrioid ovarian cancer who were platinum sensitive and who had a BRCA1 or BRCA2 (BRCA1/2) mutation, as part of the SOLO2/ENGOT-Ov21 trial. The aim of this final analysis is to investigate the effect of olaparib on overall survival. METHODS: This double-blind, randomised, placebo-controlled, phase 3 trial was done across 123 medical centres in 16 countries. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status at baseline of 0-1, had histologically confirmed, relapsed, high-grade serous or high-grade endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, and had received two or more previous platinum regimens. Patients were randomly assigned (2:1) to receive olaparib tablets (300 mg in two 150 mg tablets twice daily) or matching placebo tablets using an interactive web or voice-response system. Stratification was by response to previous chemotherapy and length of platinum-free interval. Treatment assignment was masked to patients, treatment providers, and data assessors. The primary endpoint of progression-free survival has been reported previously. Overall survival was a key secondary endpoint and was analysed in all patients as randomly allocated. Safety was assessed in all patients who received at least one treatment dose. This trial is registered with ClinicalTrials.gov, NCT01874353, and is no longer recruiting patients. FINDINGS: Between Sept 3, 2013 and Nov 21, 2014, 295 patients were enrolled. Patients were randomly assigned to receive either olaparib (n=196 [66%]) or placebo (n=99 [34%]). One patient, randomised in error, did not receive olaparib. Median follow-up was 65·7 months (IQR 63·6-69·3) with olaparib and 64·5 months (63·4-68·7) with placebo. Median overall survival was 51·7 months (95% CI 41·5-59·1) with olaparib and 38·8 months (31·4-48·6) with placebo (hazard ratio 0·74 [95% CI 0·54-1·00]; p=0·054), unadjusted for the 38% of patients in the placebo group who received subsequent PARP inhibitor therapy. The most common grade 3 or worse treatment-emergent adverse event was anaemia (which occurred in 41 [21%] of 195 patients in the olaparib group and two [2%] of 99 patients in the placebo group). Serious treatment-emergent adverse events were reported in 50 (26%) of 195 patients receiving olaparib and eight (8%) of 99 patients receiving placebo. Treatment-emergent adverse events with a fatal outcome occurred in eight (4%) of the 195 patients receiving olaparib, six of which were judged to be treatment-related (attributed to myelodysplastic syndrome [n=3] and acute myeloid leukaemia [n=3]). INTERPRETATION: Olaparib provided a median overall survival benefit of 12·9 months compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Although statistical significance was not reached, these findings are arguably clinically meaningful and support the use of maintenance olaparib in these patients. FUNDING: AstraZeneca and Merck.

ObjectivesStaging procedure in borderline ovarian tumors is a topic of controversy. Upstaging in non-serous borderline ovarian tumors that are confined to the ovary is rare. The aim of this study was to assess the impact of surgical staging on clinical outcomes in mucinous borderline ovarian tumors.MethodsThis was a retrospective study conducted at the Asan Medical Center, Seoul, Korea between January 1990 and December 2015, that included 432 patients with mucinous borderline ovarian tumors and at least 6 months follow-up. These patients were divided into a ‘staging group’ and ‘unstaged group’. The staging group referred to patients who, in addition to hysterectomy and/or adnexal surgery, underwent at least one of the following: cytology, omental biopsy/omentectomy, peritoneal biopsy, lymph node biopsy/lymphadenectomy, or appendectomy. The unstaged group referred to patients who did not undergo any staging procedure but underwent adnexal surgery (cystectomy or oophorectomy).ResultsMedian patient age was 40 (range 9–87) years. A total of 367 patients (85%) underwent a staging procedure (staging group) and 65 (15.0%) patients did not (unstaged group). Among the staging group, 258, 4, 100, and 5 patients were FIGO stage IA, IB, IC, or II-III, respectively. Overall recurrence was confirmed in 15 patients and median time to recurrence was 13.4 (range 0.4–127.3) months. One patient was in the unstaged group and had borderline recurrence. Fourteen were in the staging group, and 11 of them had borderline and three had invasive recurrence. Extraovarian disease was found at recurrence only in two patients. There was no significant difference in recurrence-free survival (p=0.39) and in overall survival between the staging group and the unstaged group (p=0.40). In total, 16 (4.4%) of 367 patients who underwent a staging procedure were upstaged.ConclusionStaging in mucinous borderline ovarian tumors may be omitted if there is no obvious evidence of gross extraovarian disease.

BACKGROUND: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS: In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA-mutation cohort), and the intention-to-treat population. RESULTS: A total of 1140 patients underwent randomization. In the BRCA-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2% vs. 10.5%, p < 0.001). In contrast, endometrial lesions were not associated with HPV infection (8.1% vs. 4.5%, p = 0.12). The HPV-DNA testing in women with AGC may be a useful tool for predicting clinically significant cervical lesions.

BACKGROUND: Secondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube (“ovarian”) cancer is widely practiced but has not been evaluated in phase 3 investigation. METHODS: We randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy (paclitaxel–carboplatin or gemcitabine–carboplatin) and use of bevacizumab were at the discretion of the investigator. The primary end point was overall survival. RESULTS: A total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups. The hazard ratio for death (surgery vs. no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; P=0.08), which corresponded to a median overall survival of 50.6 month and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively). Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery. CONCLUSIONS: In this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.)

Objective To investigate the expression of different histone deacetylases and their association with disease characteristics and survival outcomes in uterine leiomyosarcoma patients. Methods The immunohistochemical expression of different histone deacetylases and p53 by tissue microarray and histological subtypes were assessed in tumor tissue samples of 42 eligible patients. Results Histone deacetylases 1–4, 6 and 8 showed prevalent and strong (3+) expression (88.1, 90.5, 95.2, 92.9, 83.3 and 100%, respectively). Histone deacetylases 5, 7 and 9 showed infrequent strong expression (33.3, 50 and 38.1%, respectively). There were trends of higher disease-free survival rates according to the combination of weaker expression of histone deacetylase 5, 7 or 9 with positive p53 expression or with non-epithelial subtype. The patients with triple-positive favorable prognostic factors (any of weaker histone deacetylase 5, 7 and 9 expression, p53 positive, and non-epithelioid subtype) had the better survival outcomes while the patients with other combinations had the worse survival outcomes. In multivariate analysis, histone deacetylase 5 in combination with epithelioid subtype was an independent predictor for disease-free survival. Conclusions Expression of histone deacetylase 5, 7 and 9 is a potential prognostic marker in uterine leiomyosarcoma when combined with pathologically relevant prognostic factors (p53 and histological subtype). This prevalent and strong histone deacetylase expression warrants further study in well-designed investigations of histone deacetylases as therapeutic targets in uterine leiomyosarcoma.

The aim of this study is to determine the rate of clinically significant histopathologic lesions in women identified with atypical glandular cells (AGC). Five-hundered and forty patients with AGC, from a cohort of 1013 with AGC, met inclusion criteria for this study by having a proper histologic evaluation. Clinically significant histologic results were obtained in 170 cases with AGC (31.5%). Of the 170 clinically significant cases, 86 of 540 (15.9%) were diagnosed with malignant lesions. The findings of clinically significant lesions in more than 30% of patients support the recommendation that women identified with AGC require extensive histologic examination.

Currently, the indications for progestin therapy are limited to endometrioid adenocarcinoma that are International Federation of Gynecology and Obstetrics (FIGO) grade 1, FIGO stage IA, and confined to the endometrium. However, there have been attempts to broaden the indications of progestin therapy to patients with higher FIGO grades and/or with superficial myometrial invasion. We experienced a case with myoinvasive endometrioid adenocarcinoma treated with oral progestin, whose follow-up endometrial curettage specimen showed an apparent complete histologic regression; however, the final hysterectomy specimen disclosed myoinvasive endometrioid adenocarcinoma within the superficial myometrium, with absence of residual tumor in the endometrium. We describe this case to demonstrate that complete histologic regression of the endometrial lesion in a follow-up curettage specimen after progestin treatment does not guarantee histologic regression of the carcinoma within the myometrium. Our case indicates that current indications for progestin treatment should not be broadened to patients with superficial myometrial invasion.

PURPOSE This study evaluated whether coping strategies (positive reframing, planning, and active coping) and depression mediate the relationship between sense of coherence (SOC) and quality of life (QoL) using a serial multiple mediator model in patients with gynecologic cancer who are undergoing chemotherapy. METHODS A sample of 148 participants, with a mean age of 52.17 years (range 20-75) and diagnosed with gynecological cancer (e.g., cervix, ovary and endometrium) was surveyed in a cross-sectional study. Data were collected using a structured self-reporting questionnaire. A serial multiple mediator model was analyzed to explain sequential causality among two mediators (coping strategy and depression) and to investigate the direct and indirect effects of the mediator model in SPSSWIN 26.0 and PROCESS macro program. RESULTS The conceptual serial mediation model of SOC, positive reframing, depression, and QoL revealed a significant positive total effect (coefficient c = 13.099, SE = 1.647, p

The lymph node status is the most important prognostic factor for endometrial cancer. This study aimed to assess whether sentinel lymph node mapping (SLNM) is applicable in endometrial cancer. A retrospective review of patients with endometrial cancer who were diagnosed and treated in Asan Medical Centre from September 2015 to December 2017 was conducted. One hundred patients underwent robotic (da Vinci®) or laparoscopic surgical treatment, including SLNM with indocyanine green (ICG) fluorescence detection using the Firefly® and NIR/ICG systems. At least one lymph node area was observed in 100% of SLNM cases. Sentinel node detection and frozen biopsy were performed in all cases, and all patients with metastasis were found on SLNM. The sensitivity and negative predictive value were both 100% in the patient-by-patient and station-by-station analyses. SLNM appears to be a feasible method to reduce the morbidity and increase the detection rate in early-stage endometrial carcinoma.What is already known on this subject? There are studies that it is safe to diagnose the possibility of lymph node metastasis through sentinel lymph node mapping in endometrial cancer.What do the results of this study add? In this study, it is shown that the accuracy of sentinel lymph node mapping is 100% accurate.What are the implications of these findings for clinical practise and/or further research? Therefore, total lymphadenectomy will not be necessary for the future.

To compare the oncologic outcomes between chemoradiotherapy (CRT) and radical hysterectomy followed by tailored adjuvant therapy in patients with early cervical cancer presenting with pelvic lymph node metastasis. We retrospectively analyzed the medical records of women with early cervical cancer presenting with positive pelvic nodes identified on pretreatment imaging assessment. Propensity score matching was employed to control for the heterogeneity between two groups according to confounding factors. Overall survival, disease-free survival, and pattern of failure were compared between the two groups. A total of 262 patients were identified, among them, 67 received definitive CRT (group A), and 195 received hysterectomy (group B). Adjuvant therapy was administered to 88.7% of group B. There were no significant differences between group A and group B regarding the 5-year overall survival rates (89.2% vs. 89.0%) as well as disease-free survival rates (80.6% vs. 82.7%), and patterns of failure. Distant metastasis was the major failure pattern identified in both groups. In multivariate analysis, non-squamous histology was significantly associated with poorer overall survival. As there are no significant differences in 5-year OS, DFS, and patterns of failure, definitive CRT could avoid the combined modality therapy without compromising oncologic outcomes.

PURPOSE A phase II study (ClinicalTrials.gov identifier: NCT00628251 ) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. PATIENTS AND METHODS In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician’s choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population. RESULTS Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy. CONCLUSION Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.

ObjectivesThe aim of this study was to compare surgical and oncologic outcomes of open and laparoscopic surgery in patients with borderline ovarian tumors (BOTs).Materials and MethodsThis study included patients with BOTs who underwent open (n = 433) or laparoscopic (n = 210) surgery between 1990 and 2015. Surgical outcomes, perioperative morbidity, and disease-free survival and overall survival were compared.ResultsThere was no significant difference in age, histologic type of tumor, and laterality of tumor. However, body mass index was slightly higher for the open surgery group (P = 0.046). The open surgery group had a higher serum cancer antigen 125 level (P < 0.001), larger tumor size (P < 0.001), more frequent radical surgery (P = 0.001), higher stage (P = 0.034), and higher incidence of invasive implants (P = 0.035). The operative time (P < 0.001), time interval to return of bowel movement (P < 0.001), and length of postoperative hospital stay (P < 0.001) were significantly shorter and estimated blood loss was significantly less (P < 0.001) in the laparoscopic group. Perioperative complications were documented in 5 (2.4%) patients in the laparoscopic surgery group and 17 (3.9%) in the open surgery group (P = 0.064). Twenty-three (5.3%) patients in the open surgery group and 9 (4.3%) in the laparoscopic surgery group had recurrence (P = 0.902) at a median follow-up of 57 months. The 10-year disease-free survival was 96% and 97% for the open and laparoscopic groups, respectively (P = 0.851), with no significant difference between the groups after adjusting for independent factors (odds ratio, 1.0; 95% confidence interval, 0.4–2.4; P = 0.999). The 10-year overall survival was 99% for both groups, respectively (P = 0.441).ConclusionsLaparoscopic surgery and open surgery showed similar survival outcomes in BOTs. The surgical outcomes of laparoscopic surgery were more favorable.

To evaluate the immunohistochemical (IHC) expression of hormone receptors and analyze the prognostic implication of these receptors in patients with endometrial stromal sarcoma (ESS). Fifty-one patients with ESS whose paraffin blocks and pathologic slides, which were obtained after hysterectomy, were available and included in this study. Clinicopathologic data were gathered from patients' medical records, and IHC staining of hormone receptors was performed using tissue microarrays. Estrogen receptor (ER)-alpha was expressed in 37 patients (72.5%), and strong immunoreactivity was observed in 27 patients (52.9%). However, ER-beta expression was observed in only two patients (3.9%). Progesterone receptor (PR) expression was identified in 36 patients (70.6%), and strong immunoreactivity was found in 26 patients (51%). Androgen receptor (AR) expression was observed in 30 patients (58.8%), and strong immunoreactivity was noted in 14 patients (27.5%). Gonadotropin-releasing hormone receptor (GnRH-R) expression was observed in 49 patients (96.1%), but no patient exhibited strong immunoreactivity. All patients expressed CYP19A1, and 43 patients (84.3%) had strong immunoreactivity. ER-alpha, PR, and AR positivity was associated with significantly better overall survival (OS). No patient with AR positivity died of ESS. When the patients were categorized according to ER-alpha, PR, and AR immunoreactivity, triple-positive ESS had the best OS, and triple-negative ESS was linked to the worst OS. Expression of hormone receptors was associated with favorable survival outcome in ESS. Hormone receptors that showed strong expression deserve further evaluation to clarify their importance as a therapeutic target and predictor of treatment response.

Surgical treatment is the mainstay of the management of early-stage cervical cancer. Abdominal radical hysterectomy and trachelectomy have long been the standard surgical approach to early-stage cervical cancer, achieving excellent survival outcomes. Recently, laparoscopic radical hysterectomy and trachelectomy have become the preferred alternative to abdominal surgery because laparoscopic approaches lead to better surgical outcomes without compromising survival outcomes. Since the robotic surgery platform was approved for the use of gynaecologic surgery in 2005, robotic radical hysterectomy and trachelectomy have been increasingly used in the surgical management of early-stage cervical cancer. However, the role of robotic surgery is poorly defined. This review examines the role of robotic surgery in the surgical management of cervical cancer by comparing the published data on its use with those of abdominal and laparoscopic surgeries.

Purpose The symptom clusters in patients with ovarian cancer undergoing chemotherapy have not been well evaluated. We investigated the symptom clusters and effects of symptom clusters on the quality of life of patients with ovarian cancer. Method We recruited 210 ovarian cancer patients being treated with chemotherapy and used a descriptive cross-sectional study design to collect information on their symptoms. To determine inter-relationships among symptoms, a principal component analysis with varimax rotation was performed based on the patient's symptoms (fatigue, pain, sleep disturbance, chemotherapy-induced peripheral neuropathy, anxiety, depression, and sexual dysfunction). Results All patients had experienced at least two domains of concurrent symptoms, and there were two types of symptom clusters. The first symptom cluster consisted of anxiety, depression, fatigue, and sleep disturbance symptoms, while the second symptom cluster consisted of pain and chemotherapy-induced peripheral neuropathy symptoms. Our subgroup cluster analysis showed that ovarian cancer patients with higher-scoring symptoms had significantly poorer quality of life in both symptom cluster 1 and 2 subgroups, with subgroup-specific patterns. The symptom clusters were different depending on age, age at disease onset, disease duration, recurrence, and performance status of patients with ovarian cancer. In addition, ovarian cancer patients experienced different symptom clusters according to cancer stage. Conclusions The current study demonstrated that there is a specific pattern of symptom clusters, and symptom clusters negatively influence the quality of life in patients with ovarian cancer. Identifying symptom clusters of ovarian cancer patients may have clinical implications in improving symptom management.

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/m 2 ( 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/m 2 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/m 2 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/m 2 were significant predictors for poor treatment response and high recurrence. Therefore, it is important to maintain patients' normal BMIs during progestin therapy.

Objective The study aims to identify preoperative predictors of complete cytoreduction and early recurrence and death in epithelial ovarian, tubal, and peritoneal cancer after neoadjuvant chemotherapy (NACT). Methods We performed a retrospective analysis of 85 patients who underwent 3 cycles of NACT. Patients were divided into 2 groups according to residual tumor at interval debulking surgery (IDS), and clinicopathologic, surgical, and follow-up data were compared. Results Cancer antigen 125 (CA-125) levels before the IDS after completion of NACT were higher in the residual tumor group (42.0 vs 116.6 U/mL, P = 0.006). The drop rate of CA-125 after NACT was higher in the no residual tumor group (96.8% vs 89.9%, P = 0.001). Patients with residual tumor showed lower disease-free and overall survival outcomes than patients with no residual tumor. In univariate analysis, CA-125 of 100 U/mL or less before IDS and a drop rate after NACT greater than 80% were preoperative predictive factors for complete cytoreduction. In multivariate analysis, a drop rate of CA-125 after NACT greater than 80% was an independent preoperative predictive factor for complete cytoreduction (P = 0.002). Progressive disease on follow-up image during NACT was an independent preoperative predictive factor for early recurrence and death (P Conclusions A significant drop of CA-125 after NACT and progressive disease on follow-up image are independent preoperative predictors for complete cytoreduction and early recurrence and death.

Objective To identify risk factors for distant recurrence in node-positive cervical cancer patients who underwent radical hysterectomy and pelvic lymph node dissection (PLND) with para-aortic lymph node sampling (PALNS) or para-aortic lymph node dissection (PALND). Methods A total of 299 patients in whom lymph node metastasis was confirmed after radical surgery at Asan Medical Center for stage IA2 to IIB cervical cancer from February 2001 to December 2012 were identified. In all, 72 (24.1%) patients underwent PLND only and 227 (75.9%) underwent PLND with PALNS or PALND. Four patients were excluded due to diagnosed with small cell carcinoma. The clinicopathologic data of 223 patients were retrospectively analyzed. Distant recurrence was defined as recurrence at a site over the pelvic radiation field. Results Among all 223 study patients, the mean number of positive lymph nodes was 4.46. There were 54 (24.2%) patients with distant metastasis. Multivariate analyses using the Cox proportional hazards model showed that histologic types (HR=3.031, P ≤0.001 for adenocarcinoma, HR=2.302, P =0.066 for adenosquamous carcinoma), number of positive lymph nodes (HR=1.077, P ≤0.001), and surgical stage (HR=1.264, P =0.022) were independent risk factors for distant recurrence of cervical cancer. A scoring system for the prediction of distant recurrence was generated by incorporating these factors and showed good discrimination and calibration (concordance index of 0.753). In an internal validation set, this scoring system showed good discrimination with a C-statistics of 0.777. According to the Hosmer-Lemeshow test, the chi-square was 0.650 and the P -value was 0.723. Conclusions We have developed a robust scoring system that can predict the risk of distant recurrence in node-positive cervical cancer patients after radical operation. This scoring system was used to identify a group of patients who required systemic control of distant micrometastasis. This group of patients is an appropriate target for consolidation chemotherapy after concurrent chemoradiation therapy.

BACKGROUND: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. METHODS: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m2) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. FINDINGS: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7-34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0-17·6]) and the placebo group (15·0 months [12·6-16·1]) groups (hazard ratio 0·93 [95% CI 0·79-1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. INTERPRETATION: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. FUNDING: Amgen. ispartof: LANCET ONCOLOGY vol:20 issue:6 pages:862-876 ispartof: location:England status: published

Objective To determine the accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade in patients with mucinous ovarian tumors. Methods This study included 1,032 patients with mucinous ovarian tumors who underwent frozen section diagnosis during surgery. Sensitivity, specificity, and diagnostic accuracy of frozen section diagnosis was calculated. Univariate and multivariate regression analyses were performed to determine factors associated with diagnosis upgrade in the final pathology report. Results The sensitivity and specificity of frozen section diagnosis were 99.1% (95% confidence interval [CI]=98%–99.6%) and 82.2% (95% CI=77.9%–85.7%), respectively, for benign mucinous tumors; 74.6% (95% CI=69.1%–79.4%) and 96.7% (95% CI=95.2%–97.8%), respectively, for mucinous borderline ovarian tumors; and 72.5% (95% CI=62.9%–80.3%) and 98.8% (95% CI=97.9%–99.3%), respectively, for invasive mucinous carcinomas. The multivariate analysis revealed that mixed tumor histology (odds ratio [OR]=2.8; 95% CI=1.3–6.3; p=0.012), tumor size >12 cm (OR=2.5; 95% CI=1.5–4.3; p=0.001), multilocular tumor (OR=2.9; 95% CI=1.4–6.0; p=0.006), and presence of a solid component in the tumor (OR=3.1; 95% CI=1.8–5.1; p12 cm, multilocular tumor, and presence of a solid component in the tumor were independent risk factors for final pathological diagnosis upgrade based on frozen section diagnosis.

Objectives To perform a systematic review and meta-analysis of the prognostic value of post-treatment ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) in uterine cervical cancer patients treated with radiotherapy (RT) with or without chemotherapy. Methods PubMed and Embase databases were searched up to July 22, 2018, for studies which evaluated the response outcomes of ¹⁸F-FDG PET following RT, and their prognostic significance in uterine cervical cancer was assessed with overall survival (OS) or progression-free survival (PFS) as endpoints. Hazard ratios (HRs) were meta-analytically pooled using the random-effects model. Results Eleven studies with 12 patient cohorts including 1,104 patients were included. For a quantitative synthesis of OS, 7 cohorts were included. Two cohorts which reported disease-specific survival instead of OS were also included with flexibility. Pooled HR of complete metabolic response (CMR) compared to partial metabolic response (PMR) was 0.19 (95% confidence interval [CI]=0.11-0.31). Pooled HR of CMR compared to progressive metabolic disease (PMD) was more evident at 0.07 (95% CI=0.04-0.12), and that of CMR compared to both PMR and PMD was 0.20 (95% CI=0.12-0.34). Quantitative synthesis for PFS was performed with a total of 8 cohorts. Pooled HR of CMR was 0.17 (95% CI=0.10-0.29) compared to PMR, 0.02 (95% CI=0.01-0.06) compared to PMD and 0.12 (95% CI=0.07-0.19) compared to both PMR and PMD. Conclusion Response results of post-RT ¹⁸F-FDG PET were significant prognostic factors in patients with uterine cervical cancer, and ¹⁸F-FDG PET could be a reasonable follow-up imaging modality.

Objective To evaluate the efficacy of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment and to compare the diagnostic accuracy of endometrial aspiration biopsy with dilatation & curettage (D&C) in young women with early-stage endometrial cancer (EC) who wished to preserve their fertility. Methods A prospective phase II multicenter study was conducted from January 2012 to January 2017. Patients with grade 1 endometrioid adenocarcinoma confined to the endometrium were treated with combined oral MPA (500 mg/day)/LNG-IUS. At 3 and 6 months of treatment, the histologic change of the endometrial tissue was assessed. The regression rate at 6 months treatment and the consistency of the histologic results between the aspiration biopsy and the D&C were evaluated. Results Forty-four patients were enrolled. Nine voluntarily withdrew and 35 patients completed the protocol treatment. The complete regression (CR) rate at 6 months was 37.1% (13/35). Partial response was shown in 25.7% of cases (9/35). There were no cases of progressive disease and no treatment-related complications. A comparison of the pathologic results from aspiration biopsy and D&C was carried out for 33 cases. Fifteen cases were diagnosed as "EC" by D&C. Among these, only 8 were diagnosed with EC from aspiration biopsy, yielding a diagnostic concordance of 53.3% (κ=0.55). Conclusion Combined oral MPA/LNG-IUS treatment for EC showed 37.1% of CR rate at 6 months. Considering the short treatment periods, CR rate may be much higher if the treatment continued to 9 or 12 months. So, this treatment is still a viable treatment option for young women of early-stage EC. Endometrial aspiration biopsy with the LNG-IUS in place is less accurate than D&C for follow-up evaluation of patients undergoing this treatment. Trial registration ClinicalTrials.gov Identifier: NCT01594879.

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.

Objectives To evaluate the outcome of fertility-sparing surgery among young women with early-stage clear cell carcinoma of the ovary. Methods In a retrospective study, data were reviewed for patients aged 45 years or younger who had FIGO stage I clear cell carcinoma of the ovary and had attended one institution in South Korea between December 1999 and December 2009. Outcomes were compared between women undergoing fertility-sparing surgery, defined as preservation of the uterus and at least one adnexa, and those undergoing radical surgery. Results Overall, 47 patients were included (22 underwent fertility-sparing surgery, 25 radical surgery). After a median follow-up of 72 months (range 8–175), 5 (23%) patients who underwent fertility-sparing surgery and 5 (20%) in the radical surgery group had recurrent disease ( P = 0.820). The mean time to recurrence was 19 months after fertility-sparing surgery versus 20 months after radical surgery ( P = 0.935). The anatomical location of recurrence did not differ. There was no difference in 5-year disease-free survival (77% vs 84%; P = 0.849) or 5-year overall survival (91% vs 88%; P = 0.480). Conclusion Fertility-sparing surgery was found to be a safe alternative for young women with FIGO stage I clear cell carcinoma of the ovary who wish to preserve fertility.

Background Palliative chemotherapy should be used with caution when attempting to alleviate symptoms in patients with end-stage cancer. However, palliative chemotherapy continues to be utilized in cancer patients during their last stages of life. In this study, we analyzed the pattern of chemotherapy administered during the last 6 months of life in patients with end-stage gynecologic cancer who were treated with active palliative chemotherapy for the past 10 years. Method We retrospectively analyzed the data for patients with gynecologic cancer who died after undergoing active palliative chemotherapy without receiving hospice management at Asan Medical Center from 2006 to 2015. Patients were divided into two groups: those who died between 2006 and 2010, and those who died between 2011 and 2015. Based on the electronic medical records, the demographic and baseline characteristics of the patients, hospital admission during the last 6 months, invasive procedures, palliative chemotherapy patterns, and the time of the last chemotherapy session were confirmed. Results A total of 193 patients with gynecologic cancer were eligible for this study. 92 patients died during 2006 to 2010, and 101 patients died during 2011 to 2015. The mean frequency of admission during the last 6 months was 5.12 for those who died in 2006–2010 and 6.06 for those who died during 2011–2015 (p = 0.003); similarly, the mean frequency of palliative chemotherapy during the last 6 months was 3.84 (2006–2010) vs. 4.93 times (2011–2015; p

To determine whether the pelvic lymph node ratio (LNR) has significant prognostic value for survival and disease recurrence in node-positive, early stage cervical cancer patients. The medical records of 872 consecutive women who received postoperative adjuvant chemoradiotherapy were reviewed. Of these, 397 women with pathologically proven lymph nodal metastasis were included in this analysis and categorized into 3 groups according to their LNR: low (0.4, n = 25). The association between LNR and oncological outcome was evaluated using the Kaplan–Meier method and multivariate analysis. A total of 13,491 LNs were retrieved from 397 women, with a median harvest of 32 nodes per patient. There was a strong positive correlation between the number of metastatic LNs and LNR (r = 0.83, P

Background Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients. Given the importance of lymph node metastasis, it is imperative that patients harboring metastasis are identified and can undergo appropriate treatment. Sentinel lymph node (SLN) mapping has drawn attention as a lymph node mapping technique. We evaluated the feasibility and efficacy of (SLN) mapping using indocyanine green (ICG) in cervical cancer. Methods We performed a single-center, retrospective study of 103 surgically treated cervical cancer patients who underwent SLN mapping. After using ICG to detect SLN during surgery, we removed the SLNs followed by laparoscopic or robotic-assisted radical surgery and bilateral pelvic lymphadenectomy. Results Stage IB1 was the most common (61.17%). At least one SLN was detected in all cases. Eighty-eight patients (85.44%) had bilateral pelvic SLNs. The mean number of SLN per patient was 2.34. The side-specific sensitivity was 71.43%, the specificity was 100%, the negative predictive value (NPV) was 93.98%, and the false negative rate (FNR) was 28.57%. In cases of tumors smaller than 2 cm with negative lymph node metastasis on imaging, the study revealed a side-specific sensitivity of 100%, a specificity of 100%, a NPV of 100%, and a FNR of 0%. Large tumor size (≥ 4 cm), a previous history of a loop electrosurgical excision procedure (LEEP), depth of invasion (≥ 50%), the microscopic parametrial (PM) invasion, and vaginal extension were significantly associated with the false-negative detection of SLN. Moreover, the microscopic PM invasion was the only risk factor of the false-negative detection of SLN in multivariate analysis. Conclusion SLN mapping with ICG in cervical cancer is feasible and has high detection rate. The sensitivity of 100% was high enough to perform SLN biopsy alone in an early stage in which the tumor is less than 2 cm, with no lymphadenopathy on image examination. However, for large or invasive tumors, we would have to be cautious about performing SLN biopsy alone. Trial registration Retrospectively registered 2017-0600.

Objective To investigate the expression of androgen receptor (AR) and its correlation with disease status and survival outcome in uterine leiomyosarcoma with other hormone receptors. Methods The medical records and paraffin blocks of 42 patients were reviewed. The immunohistochemical expression of AR, estrogen receptor (ER), progesterone receptor (PR), gonadotropin releasing hormone (GnRH), and cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) were assessed using tissue microarray. Results In total, AR expression was observed in 11 patients (26.2%). International Federation of Gynecology and Obstetrics (FIGO) stage and AR were independent factors for disease-free survival (DFS) in multivariate regression analysis (odds ratio [OR]=5.8; 95% confidence interval [CI]=1.2-28.4 and OR=0.2; 95% CI=0.05-0.90; p=0.029 and 0.032, respectively). There were no deaths in the AR expression group, whereas the 5-year overall survival (OS) was 54.8% in the no expression group (p=0.014). Co-expression of ER and/or PR with AR was associated with significantly better 5-year DFS and OS than those with negative AR (72.7% vs. 28.6% and 100% vs. 64.3%; p=0.020 and 0.036, respectively). AR may be an independent prognostic marker regardless of ER/PR. Conclusion AR can be a potential prognostic biomarker in uterine leiomyosarcoma.

Objective The aim of this study was to evaluate the diagnostic value of integrated ¹⁸F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) for suspected recurrence of epithelial ovarian cancer (EOC) with non-disseminated lesions. Methods We retrospectively reviewed the medical records of recurrent EOC patients who underwent secondary cytoreduction from January 2000 to December 2013. A total of 134 patients underwent secondary cytoreduction after imaging with either ¹⁸F-FDG-PET/CT or contrast-enhanced computed tomography (CECT). Results In a patient-based analysis of 134 patients, 124 (92.5%) were confirmed to be positive for malignancy. Among 72 patients with suspected non-disseminated recurrence on ¹⁸F-FDG-PET/CT, 65 (89.0%) were confirmed to have recurrence, giving 98.5% sensitivity, 87.7% accuracy, and 88.9% positive predictive value (PPV). In the 65 patients with recurrence, residual tumor remained in 14 patients, giving an accuracy of patient selection for secondary cytoreduction of 69.4% (50/72) and it is higher than that of CECT (64.0%). In 169 lesions removed from patients who underwent preoperative ¹⁸F-FDG-PET/CT, 135 (79.9%) were confirmed to be positive for malignancy and 124 were accurately detected by ¹⁸F-FDG-PET/CT, giving 91.9% sensitivity, 81.1% accuracy, and 85.5% PPV. Foreign body granuloma was found in 33.3% of 21 lesions with false-positive ¹⁸F-FDG-PET/CT findings (7/21). The mean preoperative cancer antigen 125 (CA-125) level in false-positive patients was 28.8 U/mL. Conclusion Compared with CECT, ¹⁸F-FDG-PET/CT shows higher sensitivity in lesion-based analysis and better accuracy of patient selection for secondary cytoreduction. However, there is still a need for integration of the results of ¹⁸F-FDG-PET/CT, CECT, and CA-125 levels to aid treatment planning.

Objective To evaluate survival impact of low anterior resection (LAR) in patients with epithelial ovarian cancer (EOC) grossly confined to the pelvis. Methods We retrospectively reviewed 397 patients who underwent primary staging surgery for treatment of 2014 International Federation of Gynecology and Obstetrics (FIGO) stage II–IIIA EOC: 116 (29.2%) IIA, 212 (53.4%) IIB, and 69 (17.4%) IIIA. Patients with grossly enlarged retroperitoneal lymph nodes positive for metastatic carcinoma were excluded. Of 92 patients (23.2%) with gross tumors at the rectosigmoid colon, 68 (73.9%) underwent tumorectomy and 24 (26.1%), LAR for rectosigmoid lesions. Survival outcomes between patients who underwent tumorectomy and LAR were compared using Kaplan-Meier curves. Results During the median follow-up of 55 months (range, 1–260), 141 (35.5%) recurrences and 81 (20.4%) deaths occurred. Age (52.8 vs. 54.5 years, p=0.552), optimal debulking (98.5% vs. 95.0%, p=0.405), histologic type (serous, 52.9% vs. 50.0%, p=0.804), FIGO stage (p=0.057), and platinum-based adjuvant chemotherapy ≥6 cycles (85.3% vs. 79.2%, p=0.485) were not different between groups. No significant difference in 5-year progression-free survival (PFS; 57.9% vs. 62.5%, p=0.767) and overall survival (OS; 84.7% vs. 63.8%, p=0.087), respectively, was noted between groups. Postoperative ileus was more frequent in patients subjected to LAR than those who were not (4/24 [16.7%] vs. 11/373 [2.9%], p=0.001). The 5-year PFS (60.3% vs. 57.9%, p=0.523) and OS (81.8% vs. 87.7%, p=0.912) between patients who underwent tumorectomy and those who did not were also similar. Conclusion Survival benefit of LAR did not appear to be significant in EOC patients with grossly pelvis-confined tumors.

The histoculture drug response assay (HDRA) has been correlated clinically to a number of cancer types (please see Chaps. 7 - 11 of the present volume). The present chapter reviews the clinical trials of the HDRA for ovarian cancer. A prospective clinical trial of the HDRA for advanced epithelial ovarian cancer (AEOC) was performed at Asan Medical Center, Seoul, Korea. The clinical trial compared the efficacy of first-line therapy paclitaxel and carboplatinum in the HDRA and the clinical response for the patients whose tumors were tested in the HDRA. A series of patients (104) were treated with adjuvant combination chemotherapy of paclitaxel and carboplatinum after primary cytoreductive surgery. Tumor fragments were cultured on Gelfoam® and tested with paclitaxel and carboplatinum and evaluated with the MTT endpoint. Patients were categorized into two groups as either sensitive to both drugs (SS) or not sensitive to one or both drugs (R) based on HDRA results. The recurrence rate was much lower in the SS group compared to the R group, 29.2% vs. 69.8%, respectively. The SS group had a significantly longer progression-free survival compared to the R group, 34.0 months vs. 16.0 months, respectively. In another clinical trial, the HDRA was performed on 85 cases of ovarian cancer and 97% were evaluable. HDRA results were correlated to clinical response of 15 patients who received cisplatinum-based therapy that included doxorubicin and cyclophosphamide (CAP therapy). The true-positive rate was 88%, the true-negative rate was 86%, the sensitivity was 88%, the specificity was 86%, and the accurate prediction rate was 87% when HDRA results were compared to the response of the treated patients.

Purpose: To investigate disease-free survival (DFS) and prognostic factors following the administration of postoperative (chemo)radiotherapy in patients with early-stage cervical cancers. Methods: The medical records of 1,069 patients from 10 participating institutions were reviewed. Statistically and clinically established factors were considered as candidates for constructing the prediction model. This model was validated, using bootstrapping to correct for optimistic bias. Results: The 5-year DFS rate was 81.1%, with a median follow-up period of 59.6 months. The statistically significant prognostic factors were as follows: pelvic lymph node metastasis, histologic type, parametrial invasion, lymphovascular space invasion, and tumor size. The nomogram for DFS was constructed, and it demonstrated a good discrimination performance, with an internally validated concordance index of 0.72. Conclusions: Our predictive model exhibited accurate predictions and may be useful in designing clinical trials to study if further chemotherapy can reduce the recurrence of disease in high-risk patients.

Objective: To compare the intraoperative and postoperative outcomes of laparoendoscopic single-site surgery (LESS) versus conventional laparoscopic surgery in women with ovarian mature cystic teratoma. Methods: A retrospective review of 303 women who underwent LESS (n=139) or conventional laparoscopic surgery (n=164) due to ovarian mature cystic teratoma was performed. Intra- and postoperative outcomes were compared between the two groups. Results: There was no intergroup difference in age, body weight, height, body mass index, comorbidities, tumor size, bilaterality of tumor, or the type of surgery. However, more patients in the LESS group had a history of previous abdominal surgery (19.4% vs. 6.7%, P=0.001). Surgical outcomes including operating time (89 vs. 87.8 minutes, P=0.734), estimated blood loss (69.4 vs. 68.4 mL, P=0.842), transfusion requirement (2.2% vs. 0.6%, P=0.336), perioperative hemoglobin level change (1.3 vs. 1.2 g/dL, P=0.593), postoperative hospital stay (2.0 vs. 2.1 days, P=0.119), and complication rate (1.4% vs. 1.8%, P=0.999) did not differ between LESS and conventional groups. Postoperative pain scores measured using a visual analogue scale were significantly lower in the LESS group at 8 hours (P=0.021), 16 hours (P=0.034), and 32 hours (P=0.004) after surgery, and 32 of 139 patients (23%) in the LESS group and 78 of 164 patients (47.6%) in the conventional group required at least one additional analgesic (P

Objective To analyze the oncologic and reproductive outcomes of pediatric and young adolescents with malignant ovarian germ cell tumors (MOGCTs). Methods Pediatric or young adolescent girls aged 16years or under with MOGCT were eligible for this study. Results Forty-two pediatric or adolescent girls with MOGCT met the inclusion criteria. The median age was 12years (range, 6–16years) and 29 patients were premenarchal. The most common histologic type was immature teratoma, and 30 patients (54.3%) had stage I MOGCT. All patients underwent fertility-sparing surgery, which was defined as the preservation of at least one adnexa and the uterus. No patient had residual disease after surgery. Thirteen patients had tumor spillage, two patients had a positive peritoneal cytology, and two patients had lymph node metastasis. After surgery, 31 patients received adjuvant chemotherapy with bleomyocin, etoposide, and cisplatin (BEP) (median, 4cycles; range, 1–6 cycles). After a median follow-up time of 93months (range, 22–217 months), six patients had a recurrence of the disease, and one patient died. The 5-year disease-free and overall survival rates were 85% and 97%, respectively. Among the surviving 41 patients, seven were premenarchal, 30 had regular menstruation, and three had irregular menstruation. No patient had premature ovarian failure. Conclusion All patients received uniform treatment consisting of fertility-sparing complete cytoreductive surgery followed by BEP chemotherapy. Regardless of histologic type and FIGO stage, the oncologic outcomes were excellent and the reproductive outcomes were favorable.

Objective Malignant Brenner tumors (MBTs) of the ovary are very rare, and their definition, biology, and treatment modality have not been established. This study investigated the clinical characteristics of MBTs and the importance of chemotherapy for recurrent disease. Materials and methods We conducted a retrospective analysis of 10 patients with MBT of the ovary treated at a single tertiary center from 1991 to 2013. Results The median age was 55.5 years (range, 37–68 years). Nine of the 10 patients were symptomatic. The median size of the ovarian tumors was 10.5 cm (range, 2.5–25.0 cm). The cancer antigen-125 level was elevated in three patients. Six patients had a stage I tumor, one had a stage II tumor, two had a stage III tumor, and one had a stage IV tumor. Six patients received systemic adjuvant chemotherapy after surgery. The mean follow-up duration was 54.5 months (range, 8–173 months). Disease recurrence occurred in four of the 10 patients. The median time to recurrence was 11 months (range, 9–18 months). Two patients with locoregional recurrence showed favorable results after chemotherapy, regardless of the initial stage of the tumor. The patient with the stage IIIC tumor is alive at 13 months after recurrence on current chemotherapy. The patient with the stage IV tumor showed no evidence of the disease > 12 years after the last chemotherapy. Lastly, two patients with distant recurrence died after showing a long-term survival of 49 months and 88 months, respectively, after recurrence and intensive chemotherapy. Conclusion Our results showed that systemic chemotherapy is beneficial in patients with recurrence of a primary MBT of the ovary, especially in the locoregional recurrence.

Endometrialcanceristhemostcommongynecologiccancerin developed countries. Approximately 3%–14% of endometrial cancersarediagnosedinyoungwomenunder40whowantto preserve their fertility.The incidence ofendometrial cancer in thisage groupisincreasing, forwhich fertility-sparingtherapy is increasingly used because it is one of the most important quality of life issues in these women. Progestin therapy is the most common type of fertility-sparing therapy. In this review, the most up-to-date findings regarding fertility-sparing progestin therapy for young women with primary and recurrent endometrial cancer is addressed in terms of diagnosis, treatment, follow-up, and oncologic and reproductive outcomes. Fertility-sparing progestin therapy is highly effective in selected young women with primary and recurrent endometrial cancer. The selection of appropriate patients through comprehensive pretreatment evaluation is of paramount importance to achieve the best outcomes without compromisingsurvival.Becauseofthehighrateofrecurrence after successful fertility-sparing therapy, close surveillance is mandatory, and prophylactic hysterectomy is the best option for patients who have completed family planning. Pregnancy outcomes are very promising with the aid of assisted reproductive technologies. Continuous daily oral medroxyprogesteroneacetateandmegestrolacetatearethepreferred progestins for fertility-sparing therapy, but future studies should be performed to determine the optimal dose and treatment duration of these agents. The Oncologist 2015; 20:270–278 ImplicationsforPractice:Inyoungwomenwithendometrialcancer,thecurerateisveryhigh.Therefore,theefficacyoftreatment shouldnotbelimitedtotheoncologicoutcomes.Thequality-of-lifeissueisasimportantasoncologicoutcomesinthesepatients. Fertilitypreservationisoneofthemostimportantquality-of-lifeissues.Basedontheresultsofnumerousstudies,fertility-sparing progestin therapy can be safely performed in endometrioid adenocarcinoma confined to the endometrium. It also can be reasonably recommended to selected women with more advanced disease and recurrent disease. However, careful follow-up is important because of the high rate of recurrence.

ObjectiveThe purpose of this study was to identify preoperative clinicopathological predictive factors for lymph node (LN) metastasis in women diagnosed with uterine papillary serous carcinoma (UPSC).MethodsWomen diagnosed with UPSC in our institution from 1997 to 2012 were identified. All patients underwent hysterectomy and bilateral salpingo-oophorectomy plus pelvic and/or para-aortic lymphadenectomy. The predictive values of the risk factors for LN metastasis were analyzed using χ2 and multivariate logistic regression analyses.ResultsA total of 94 patients met our study criteria. A CA-125 cutoff of 47.5 IU/mL on the receiver operating characteristic curve provided the best sensitivity and specificity (56.5% vs 90.1%, respectively) for LN metastasis prediction. The sensitivities and specificities of old age (≥60 years), body mass index of 25 kg/m2 or greater, deep myometrial invasion, tumor size greater than 2 cm, tumor size greater than 4 cm, preoperative CA-125 greater than 47.5 IU/mL, LN metastasis on imaging, and extrauterine spread on imaging for the presence of a positive LN were 39.1%, 34.8%, 30.4%, 34.8%, 21.7%, 56.5%, 43.5%, and 52.2%, and 52.1%, 45.1%, 78.9%, 57.7%, 83.1%, 90.1%, 93.0%, and 90.1%, respectively. Preoperative CA-125 (P < 0.001), LN metastasis on preoperative imaging (P < 0.001), and extrauterine spread on preoperative imaging (P = 0.009) were risk factors for LN metastasis on univariate analysis. Multivariate analysis revealed that preoperative CA-125 (P = 0.001) was the only independent risk factor for LN metastasis.ConclusionsPreoperative CA-125 is a preoperative predictive factor for LN metastasis in UPSC.

Objective Accurately predicting cytoreducibility in advanced-ovarian cancer is needed to establish preoperative plans, consider neoadjuvant chemotherapy, and improve clinical trial protocols. We aimed to develop a positron-emission tomography/computed tomography-based nomogram for predicting incomplete cytoreduction in advanced-ovarian cancer patients. Methods Between 2006 and 2012, 343 consecutive advanced-ovarian cancer patients underwent positron-emission tomography/computed tomography before primary cytoreduction: 240 and 103 patients were assigned to the model development or validation cohort, respectively. After reviewing the detailed surgical documentation, incomplete cytoreduction was defined as a remaining gross residual tumor. We evaluated each individual surgeon's surgical aggressiveness index (number of high-complex surgeries/total number of surgeries). Possible predictors, including surgical aggressiveness index and positron-emission tomography/computed tomography features, were analyzed using logistic regression modeling. A nomogram based on this model was developed and externally validated. Results Complete cytoreduction was achieved in 120 patients (35%). Surgical aggressiveness index and five positron-emission tomography/computed tomography features were independent predictors of incomplete cytoreduction. Our nomogram predicted incomplete cytoreduction by incorporating these variables and demonstrated good predictive accuracy (concordance index=0.881; 95% CI=0.838–0.923). The predictive accuracy of our validation cohort was also good (concordance index=0.881; 95% CI=0.790–0.932) and the predicted probability was close to the actual observed outcome. Our model demonstrated good performance across surgeons with varying degrees of surgical aggressiveness. Conclusion We have developed and validated a nomogram for predicting incomplete cytoreduction in advanced-ovarian cancer patients which may help stratify patients for clinical trials, establish meticulous preoperative plans, and determine if neoadjuvant chemotherapy is warranted.

Aims: We investigated the prognosis of patients with small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) in relation to treatment modalities. Methods: We retrospectively reviewed the medical records and pathological reports of 102 patients who were histologically diagnosed with SCNEC at 5 different institutes. Time to progression (TTP) and overall survival (OS) were analyzed for each treatment modality. Results: Of the patients with early-stage [International Federation of Obstetrics and Gynecology (FIGO) stage IB2 or below] SCNEC, 57.8 and 79.3% underwent radical hysterectomy followed by adjuvant therapy. In advanced-stage SCNEC, concurrent chemoradiation therapy was given to 51.4% of the patients. The overall recurrence rate was 51.6%. In early- and advanced-stage SCNEC, the TTP was not different (22.3 vs. 13.3 months, p = 0.104), but the OS was different (40.7 vs. 21.4 months, p = 0.029). Parametrial involvement and lymph vascular space invasion were found to be associated with an unfavorable prognosis. Interestingly, survival was the most unfavorable in patients with early-stage SCNEC who had never received chemotherapy. FIGO stage and use of chemotherapy were identified as independent prognostic factors in SCNEC patients. Conclusions: SCNEC requires systemic chemotherapy as part of the initial treatment, along with surgery or radiation, even in patients with early-stage disease.

We used a 3-dimensional (3D) printer to create anatomical replicas of real lesions and tested its application in cervical cancer. Our study patient decided to undergo radical hysterectomy after seeing her 3D model which was then used to plan and simulate this surgery. Using 3D printers to create patient-specific 3D tumor models may aid cervical cancer patients make treatment decisions. This technology will lead to better surgical and oncological outcomes for cervical cancer patients. J. Surg. Oncol. 2016;114:150-152. © 2016 Wiley Periodicals, Inc.

Objective: To determine the role of preoperative serum cancer antigen 125 (CA 125) in malignant ovarian germ cell tumors (MOGCTs). Materials and methods: Using information from medical databases of Asan Medical Center (Seoul, Korea), we investigated 161 patients with histologically diagnosed MOGCTs and whose preoperative serum CA 125 had been checked. We determined the optimal cutoff value of CA 125 as > 249.5 U/mL in MOGCTs using a receiver operating characteristic curve. Results: The median patient age was 24 years (range, 6–52 years). The most common histologic type was immature teratoma. Most patients had stage I disease. Thirty-two patients (19.9%) had elevated preoperative serum CA 125 levels over 249.5 U/mL. On univariate analysis, tumor size, advanced stage, the presence of ascites, ovarian surface involvement, and tumor rupture were significantly associated with elevated preoperative CA 125 levels (>249.5 U/mL). In the median follow-up time of 87 months (range, 9–271 months), 14 patients had a recurrence, and 5 died of the disease. Patients with an elevated serum preoperative CA 125 level (>249.5 U/mL) had poorer disease-free survival, but this was not statistically significant. However, elevated preoperative CA 125 (>249.5 U/mL) was significantly associated with poorer overall survival. Conclusions: Elevated preoperative serum CA 125 may have prognostic value in patients with MOGCTs. Keywords: CA-125 antigen, Ovarian germ cell cancer, Prognosis

IntroductionThe aim of this study was to evaluate the significance of ovarian endometriosis on the prognosis of ovarian clear cell carcinoma (OCCC).MethodsPatients with OCCC were divided into 2 groups according to the presence of ovarian endometriosis: group 1, no coexisting ovarian endometriosis; group 2, clear cell carcinoma arising from ovarian endometriosis or the presence of ovarian endometriosis elsewhere in the ovary. Clinicopathologic characteristics, disease-free survival (DFS), and overall survival (OS) were compared between the 2 groups.ResultsOf 155 patients with OCCC, 77 were categorized into group 1 and 78 into group 2. Group 2 patients were younger than group 1 (median age, 48 vs 51 years; P = 0.005) and had higher incidence of early-stage disease (stage I, 77% vs 58%; P = 0.001) and lower incidence of lymph node metastasis (4% vs 17%; P = 0.008). Group 2 patients were observed to have a significantly higher 5-year DFS (P < 0.001) and OS (P = 0.001) compared with group 1. In stage I disease, group 2 had a significantly higher 5-year DFS (P = 0.004) and OS (P = 0.016) than did group 1. In the multivariate analysis, coexisting endometriosis and advanced International Federation of Obstetrics and Gynecology stage were significant factors for both DFS and OS rates.ConclusionsOvarian clear cell carcinoma with endometriosis was found more frequently in younger women and had a higher incidence of early-stage disease and a lower incidence of lymph node metastasis compared with OCCC without endometriosis. Ovarian endometriosis was associated with improved prognostic factors and a better DFS and OS even in stage I disease. Ovarian endometriosis was an independent prognostic factor for OCCC.

Symptoms of patients with cancer need to be evaluated with a standard instrument. The Memorial Symptom Assessment Scale-Short Form (MSAS-SF) is a symptom assessment tool that has been validated in many languages.The aim of the present study was to validate the Korean-version Memorial Symptom Assessment Scale-Short Form (MSAS-SF) in patients with gynecologic cancer.We translated the MSAS-SF into Korean, and 175 gynecologic cancer inpatients completed the MSAS-SF, Functional Assessment Cancer Therapy-General (FACT-G), and gathered demographic and clinical data and Karnofsky Performance Status (KPS). Reliability was assessed for internal consistency with Cronbach's alpha coefficient. Pearson's correlation coefficient was calculated between the MSAS-SF and FACT-G subscales for convergent validity. T-test analysis was used to compare differences in MSAS-SF subscales by cancer stage and KPS for discriminant validity.The Cronbach's alpha coefficients for the MSAS-SF subscales ranged from 0.80 to 0.91. The Korean-version MSAS-SF subscales showed convergent validity with FACT-G subscales. The correlation coefficients were -0.640 (P 0.001) and -0.628 (P 0.001) for global distress index and total MSAS score with FACT-G total score. The scores of MSAS-SF subscales showed appropriate differences by cancer stage and KPS.The Korean-version MSAS-SF is a valid tool for the reliable assessment of patients with gynecologic cancer in Korea.

Purpose To provide evidence-based, resource-stratified global recommendations to clinicians and policymakers on the management and palliative care of women diagnosed with invasive cervical cancer. Methods ASCO convened a multidisciplinary, multinational panel of cancer control, medical and radiation oncology, health economic, obstetric and gynecologic, and palliative care experts to produce recommendations reflecting resource-tiered settings. A systematic review of literature from 1966 to 2015 failed to yield sufficiently strong quality evidence to support basic- and limited-resource setting recommendations; a formal consensus-based process was used to develop recommendations. A modified ADAPTE process was also used to adapt recommendations from existing guidelines. Results Five existing sets of guidelines were identified and reviewed, and adapted recommendations form the evidence base. Eight systematic reviews, along with cost-effectiveness analyses, provided indirect evidence to inform the consensus process, which resulted in agreement of 75% or greater. Recommendations Clinicians and planners should strive to provide access to the most effective evidence-based antitumor and palliative care interventions. If a woman cannot access these within her own or neighboring country or region, she may need to be treated with lower-tier modalities, depending on capacity and resources for surgery, chemotherapy, radiation therapy, and supportive and palliative care. For women with early-stage cervical cancer in basic settings, cone biopsy or extrafascial hysterectomy may be performed. Fertility-sparing procedures or modified radical or radical hysterectomy may be additional options in nonbasic settings. Combinations of surgery, chemotherapy, and radiation therapy (including brachytherapy) should be used for women with stage IB to IVA disease, depending on available resources. Pain control is a vital component of palliative care. Additional information is available at www.asco.org/rs-cervical-cancer-treatment-guideline and www.asco.org/guidelineswiki . It is the view of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Background We aimed to evaluate the efficacy and the safety of uterine preservation in patients with early-stage uterine adenosarcoma who want to preserve future fertility. Methods We performed a retrospective review of patients with stage I uterine adenosarcoma diagnosed and treated at a single institute from 1998 through 2014. Results Among the total of 31 patients, uterine preservation surgery was performed in 7 of the nulliparas. Of the 7 patients receiving uterine preservation surgery, 3 showed no evidence of disease (NED), 2 had persistent disease confined to the uterus, and 2 were alive with disease (AWD) after recurrence. One patient with an NED status had a vaginal delivery at term. In the uterine preservation group, 1 patient had sarcomatous overgrowth at the time of diagnosis and experienced disease recurrence. In the hysterectomy group, 3 of 24 patients had tumor recurrence. Of the five patients with tumor recurrence, four (80%) had sarcomatous overgrowth at diagnosis and it was significantly associated with recurrence by univariate analysis (OR 13.3, p = 0.027). Conclusions Uterine preservation represents a possible treatment option for young female patients who want to maintain fertility. However, a detailed explanation of the risk of recurrence is necessary, especially in patients with sarcomatous overgrowth, which seems to be associated with a higher risk of recurrence. Trial registration Retrospectively registered.

Objective To evaluate the prognostic value of metabolic parameters measured by preoperative ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) in patients with uterine carcinosarcoma (UCS). Methods Data of 55 eligible patients with UCS who underwent preoperative ¹⁸F-FDG PET/CT and surgical staging were analyzed retrospectively. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV₂.₅), and total lesion glycolysis (TLG₂.₅) of the primary tumors were measured using a SUV threshold of 2.5. The optimal cutoff value of each parameter was determined by time-dependent receiver operating characteristic curve, and its impact on progression-free survival and overall survival was evaluated by Cox proportional hazards model. Results During a median follow-up period of 29 (range, 1.5-109.4) months, 47.3% (26/55) of the patients experienced disease progression, and the disease-associated mortality rate was 43.6% (24/55). Univariate analysis determined that hazard ratios (HRs) for disease progression for SUVmax (≥8.33), MTV₂.₅ (≥63.92 mL), and TLG₂.₅ (≥396.16) were 1.930 (95% confidence interval [CI]=0.793-4.701), 3.264 (95% CI=1.466-7.268), and 2.692 (95% CI=1.224-5.924), respectively. And, HRs for death were 1.979 (95% CI=0.774-5.060), 2.764 (95% CI=1.217-6.274), and 2.721 (95% CI=1.198-6.182), respectively. While peritoneal cytology, histology, and tumor diameter were independent prognostic factors in multivariate analysis, MTV and TLG were not. Conclusion Though MTV and TLG of primary UCS were not independent predictors compared to surgically obtained data, MTV and TLG of primary UCS may provide useful information on prognosis especially in patients who are not able to undergo surgical staging.