JGOG2046: a feasibility study of neoadjuvant chemotherapy followed by debulking surgery for clinically diagnosed FIGO stage IVb endometrial cancer.

BACKGROUND: We evaluated the feasibility of neoadjuvant chemotherapy, followed by debulking surgery, for clinically diagnosed FIGO stage IVb endometrial cancer (protocol number: JGOG2046). METHODS: The experimental treatment consisted of 3 cycles of paclitaxel (180 mg/m2) plus carboplatin (AUC5) followed by debulking surgery, including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and 3 cycles of adjuvant chemotherapy. Patients were considered as eligible if they were pathologically diagnosed as primary endometrial cancer, and had both endometrial tumor and distant metastasis confirmed by imaging examinations. The primary endpoint was the incidence of patients who completed debulking surgery after the neoadjuvant chemotherapy. RESULTS: While 51 patients were enrolled from 23 hospitals, the final study cohort consisted of 49 patients with a mean age of 59.0 years. Although the response ratio of the neoadjuvant chemotherapy was 65.3% (95% CI 50.4-78.3%), 67.3% (95% confidence interval (CI) 52.5-80.1%) underwent debulking surgery after the neoadjuvant chemotherapy and 59.2% (95% CI 45.2-71.8%) completed the protocol treatment including 3 courses of adjuvant chemotherapy. The median disease-free survival time was 9.1 months (95% CI 6.5-11.9), while the median overall survival time was 23.2 months (95% CI 11.9-27.8). A patient with sigmoid colon cancer and another with cervical cancer were included in this study. CONCLUSIONS: Neoadjuvant chemotherapy followed by debulking surgery was a feasible and acceptable treatment for metastatic endometrial cancer. (225 words).

Prognostic factors of 2018 FIGO stage IB-IIA cervical cancer with absence of high/ intermediate surgical-pathological risk factors.

OBJECTIVE: This retrospective analysis of a real-world database of open radical hysterectomy in Japan aimed to reveal the clinicopathological findings and clinical outcomes of low-risk patients with stage IB-IIA cervical cancer. METHODS: A total of 1143 stage IB1, IB2 and IIA1 (reclassified by FIGO 2018 staging system) patients with cervical cancer who underwent radical hysterectomy between January 2004 and December 2008 from the Japanese Gynecologic Oncology Group database were analyzed. Low-risk patients were defined as those without a tumor size exceeding 4 cm, parametrial tumor involvement, deep (outer half) stromal invasion, lymphovascular space invasion or lymph nodal metastasis. RESULTS: 61.2% (772/1262) patients with stage IB1, 32.1% (229/932) with stage IB2 and 16.9% (72/294) of stage IIA1 were classified into the low-risk group. The 5-year overall survival and disease-free survival rates were 98.4 and 93.7%, respectively. Histological classification did not affect the survival rates, but stage IIA cases had significantly lower overall survival and disease-free survival (83.5 and 93.8%, respectively) than stage IB cases. The independent prognostic factors for disease-free survival were older age (≧50), histology, clinical stage and clinical stage as independent prognostic factors for overall survival. Regarding recurrence, older age, non-SCC and stage IIA1 were independent risk factors for local recurrence, but stage IIA1 was the only independent risk factor for distant metastasis. CONCLUSION: We found that stage IIA1 was the strongest risk factor for survival and recurrence of low-risk uterine cervical cancer (FIGO, 2018). In low-risk cases, stage IIA1 should be considered separately from stage IB.

Resolution of large pelvic lymphocele after incidental intracystic hemorrhage caused by percutaneous catheter drainage: Case report.

We report the case of a large pelvic lymphocele after an ovarian cancer operation, which incidentally vanished after bleeding resulting from percutaneous catheter drainage. The patient was a 74-year-old woman with stage IVB ovarian cancer who underwent surgery including pelvic lymph node dissection. Three months after surgery, computed tomography revealed a large (13-cm diameter) pelvic lymphocele with associated bilateral hydronephrosis and left femoral vein thrombosis. The lymphocele was repeatedly drained by percutaneous aspiration, and the day after the second procedure, the drainage fluid became bloody. The catheter was clamped for 3 days and then removed. The lymphocele volume gradually decreased, and it was not seen on a computed tomography scan 70 days after drainage. The lymphocele did not recur prior to her death. In this case, the intracystic hemorrhage was considered to have served as a blood patch for lymph leakage.

Stage III disease of ovarian, tubal and peritoneal cancers can be accurately diagnosed with pre-operative CT. Japan Clinical Oncology Group Study JCOG0602.

PURPOSE: Computed tomography of the abdomen and pelvis is a useful imaging modality for identifying origin and extent of ovarian cancer before primary debulking surgery. However, the International Federation of Gynecology and Obstetrics staging for ovarian cancer is determined based on surgico-pathological findings. The purpose of this study is to determine whether computed tomography staging can be the surrogate for surgico-pathological International Federation of Gynecology and Obstetrics staging in advanced ovarian cancer undergoing neoadjuvant chemotherapy. METHODS: Computed tomography staging was compared with surgico-pathological International Federation of Gynecology and Obstetrics staging in primary debulking surgery arm patients in a randomized controlled trial comparing primary debulking surgery and neoadjuvant chemotherapy (JCOG0602). The cancer of primary debulking surgery arm was identically diagnosed regarding the origin and extent with the cancer of neoadjuvant chemotherapy arm before accrual, using imaging studies (computed tomography and/or magnetic resonance imaging), cytological examination (ascites, pleural effusion or tumor contents fluid) and tumor marker (CA125 > 200 U/mL and CEA < 20 ng/mL). Institutional computed tomography staging was also compared with computed tomography staging by central review. RESULTS: Among 149 primary debulking surgery arm patients, 147 patients who underwent primary debulking surgery immediately were analyzed. Positive predictive values and sensitivity of computed tomography staging for surgical stage III disease (extra-pelvic peritoneal disease and/or retroperitoneal lymph node metastasis) were 99%. Meanwhile, positive predictive values for the presence of small (≤2 cm) extra-pelvic peritoneal disease were low; <20% in omentum. Accuracy of institutional computed tomography staging was comparable with computed tomography staging by central review. CONCLUSIONS: Preoperative computed tomography staging in each institution can be the surrogate for surgico-pathological diagnosis in stage III disease of ovarian cancer patients undergoing neoadjuvant chemotherapy without diagnostic surgery, but reliability of diagnosis of stage IIIB disease is inadequate.Clinical trial registration: UMIN000000523(UMIN-CTR).

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan.

OBJECTIVE: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. METHODS: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. RESULTS: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. CONCLUSION: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

Clinical status and prognostic factors in Japanese patients with uterine leiomyosarcoma.

OBJECTIVE: Uterine leiomyosarcoma (uLMS) is a rare gynecologic malignancy for which the currently available treatments do not consistently provide long-term disease control. This study aimed to reveal the current clinical status of uLMS to support future clinical trials. METHODS: This study enrolled patients with uLMS treated at 53 Japanese institutions from 2000 to 2012. Central pathological review (CPR) was performed. All cases were confirmed by CPR, and epidemiological features, treatment, and prognosis were analyzed statistically. RESULTS: A total of 307 patients were enrolled. A diagnosis of uLMS was confirmed in 266 patients (86.6%) of patients after CPR, of whom data for 259 were analyzed. Of these, 186 (71.8%) patients underwent complete gross resection as primary therapy. Ninety-eight patients received no additional adjuvant therapy, while docetaxel and gemcitabine was the most frequent regimen among 155 patients treated with adjuvant chemotherapy. In all cases, the median overall survival (OS) was 44.2 months. Multivariate analyses of prognostic factors in all cases identified stage III and IV disease, high serum lactate dehydrogenase level, and menopausal status as poor prognostic factors. However, in stage I cases, high serum lactate dehydrogenase level and no adjuvant treatment were identified as poor prognostic factors. The 5-year OS of patients with stage I uLMS treated with adjuvant chemotherapy was significantly better than that of those without adjuvant treatment (67.8% vs 46.7%, P = 0.0461). CONCLUSIONS: Despite complete removal of the primary lesion, the clinical course of patients with uLMS was poor due to recurrence of distant metastasis. The application of a suitable biomarker and effective adjuvant chemotherapy are required to improve the prognosis of patients with uLMS.

Serous carcinoma of the uterine cervix: Clinicopathological features differing from serous carcinomas of other female organs.

AIM: Serous carcinoma of the uterine cervix (USCC) is a very rare malignant tumor, while this histological subtype is common in the ovary, fallopian tube, uterine corpus and peritoneum. Because of its rarity, details of the clinicopathological features of USCC are largely unknown. We retrospectively analyzed the clinicopathological characteristics of five cases of pure USCC. METHODS: We reviewed the medical records and pathological specimens of five USCC cases who were treated at the Gynecology Service of the National Hospital Organization Kyushu Cancer Center, Japan, between 2000 and 2017. The clinicopathological features were also compared with those of serous carcinomas of the endometrium and ovary who were treated during the same period. RESULTS: Five patients were treated at our hospital between 2000 and 2017. Three tumors were stage IB1, one was stage IIB, and one was stage IVB. The median follow-up time was 104 months (range 26-210). Four patients other than stage IVB were treated with radical hysterectomy and have been free of relapse. One patient with stage IVB tumor was treated with platinum-based combination chemotherapy and is currently on maintenance therapy with bevacizumab and remains free of relapse. CONCLUSION: USCC has a distinctive clinicopathological feature that differentiates it from serous carcinomas of other female organs. USCC had been thought to be a poor prognostic disease; however, it could be curable if it is not accompanied by lymph node metastasis or peritoneal dissemination. We might conquer USCC even if it is accompanied by lymph node metastasis with the use of multimodal therapy.

Spin Ice-like Magnetic Relaxation of a Two-dimensional Network based on Manganese(III) Salen-type Single-Molecule Magnets.

Spin ice is an exotic type of magnetism displayed by bulk rare-earth pyrochlore oxides. We discovered a spin ice-like magnetic relaxation of [{Mn(saltmen)}4 {Mn(CN)6 }](ClO4 )⋅13 H2 O (saltmen2- =N,N'-(1,1,2,2-tetramethylethylene)bis(salicylideneiminate)). This magnetic system can be considered as a two-dimensional network of MnIII salen-type single-molecule magnets (SMMs) in which each SMM unit (ST =4) has two orthogonally oriented axial anisotropies and is connected ferromagnetically through the [Mn(CN)6 ]3- unit (S=1). This work illustrates that a two-dimensional SMM network with competition between the ferromagnetic interaction and local noncollinear magnetic anisotropies on SMMs is a new type of magnetic system exhibiting slow relaxation of magnetization with a Davidson-Cole-type broad distribution of the relaxation time.

A multi-institutional observational study on the effects of three-dimensional radiotherapy and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors.

BACKGROUND: The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. METHODS: We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. RESULTS: The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. CONCLUSIONS: The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.

Comparison of Electrosurgical Devices for Cervical Conization: Novel Monopolar Scalpel (VIO) Versus Ultrasonic Scalpel.

OBJECTIVE: The aim of this study was to compare the outcomes associated with the use of a novel monopolar scalpel with those associated with the use of an ultrasonic scalpel for cervical conization of cervical intraepithelial neoplasia. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study in patients treated in our institute between April 2010 and March 2017. We used either the VIO monopolar scalpel (VIO) or Harmonic ultrasonic scalpel (HS) for cervical conization. We analyzed operative outcomes, postoperative complications, and pathological findings associated with the use of the 2 devices. RESULTS: In 500 patients treated with cervical conization, VIO and HS were used in 249 and 251 patients, respectively. No significant difference in patient background was found between the groups. The mean operative time was shorter with VIO than with HS (18.2 min vs. 27.4 min). The mean estimated blood loss was greater with VIO (7.2 g vs. 3.1 g), but the postoperative bleeding rate was higher with HS (5% vs. 20%). Regarding other complications, cervical stenosis was only noted with VIO (4 cases, 1.6%). The positive margin (11% vs. 16%) and positive endocervical curettage rates (7% vs 10%) were not significantly different between the groups. No significant differences were also found in the pathological results and need for additional treatment (the rate of the additional treatment: 20% vs. 23%). CONCLUSIONS: Considering short operating time and less postoperative bleeding, VIO was preferred to HS. However, the excessive coagulation in VIO is considered to lead to cervical stenosis.

Identifying a candidate population for ovarian conservation in young women with clinical stage IB-IIB cervical cancer.

This study seeks to identify risk factors associated with ovarian metastasis and to characterize a population with minimum risk of ovarian metastasis in young women with stage IB-IIB cervical cancer. This was a nation-wide multicenter retrospective study in Japan examining consecutive cases of surgically-treated women with clinical stage IB-IIB cervical cancer who had oophorectomy at radical hysterectomy (n = 5,697). Multivariable analysis was performed to identify independent risk factors for ovarian metastasis. Ovarian metastasis was seen in 70 (1.2%, 95% confidence interval 0.9-1.5) cases. In the entire cohort, adenocarcinoma, lympho-vascular space invasion, uterine corpus tumor invasion, and pelvic/para-aortic nodal metastases remained independent risk factors for ovarian metastasis (all, adjusted-p < 0.05). In a sensitivity analysis of 3,165 women aged <50 years (ovarian metastasis, 1.0%), adenocarcinoma, parametrial tumor involvement, uterine corpus tumor involvement, and pelvic/para-aortic nodal metastases remained independent risk factors for ovarian metastasis (all, adjusted-P < 0.05). In the absence of these five risk factors (representing 46.1% of women aged <50 years), the incidence of ovarian metastasis was 0.14%. With the presence of adenocarcinoma alone (representing 18.9% of women aged <50 years), the incidence of ovarian metastasis was 0.17% and was not associated with increased risk of ovarian metastasis compared to the subgroup without any risk factors (p = 0.87). In conclusion, nearly two thirds of women aged <50 years with clinical stage IB-IIB cervical cancer had no risk factor for ovarian metastasis or had adenocarcinoma alone: these subgroups had ovarian metastasis rates of around 0.1% and may be a candidate population for ovarian conservation at surgical treatment.

Renal function and urological complications after radical hysterectomy with postoperative radiotherapy and platinum-based chemotherapy for cervical cancer.

BACKGROUND: We aimed to clarify renal functional changes long term and serious urological complications in women with cervical cancer who undergo radical hysterectomy followed by pelvic radiotherapy and/or platinum-based chemotherapy to treat the initial disease. METHODS: Data on 380 women who underwent radical hysterectomy at the National Kyushu Cancer Center from January 1997 to December 2013 were reviewed. Main outcome measures were the estimated glomerular filtration rate (eGFR) and monitored abnormal urological findings. RESULTS: Postoperative eGFR was significantly lower than preoperative eGFR in 179 women with surgery alone and in 201 women with additional pelvic radiotherapy and/or chemotherapy (both P < 0.01). Two types of univariate analyses for eGFR reduction in women after treatment showed that older age, advanced stage, pelvic radiotherapy, and platinum-based chemotherapy were significant variables on both analyses. Two types of multivariate analyses showed that platinum-based chemotherapy or pelvic radiotherapy were associated with impaired renal function (odds ratio 1.96, 95% confidence interval 1.08-3.54 and odds ratio 2.85, 95% confidence interval 1.12-7.24, for the respective analyses). There was a higher rate of bladder wall thickening in women with pelvic radiotherapy had than those without it (17.4% vs. 2.7%, P < 0.01). One serious urological complication (intraperitoneal rupture of the bladder) occurred among women who underwent pelvic radiotherapy (0.6% vs. 0%). CONCLUSIONS: Surgeons should be aware that eGFR is reduced after platinum-based chemotherapy and/or postoperative pelvic radiotherapy. Serious and life-threatening urological complications are rare, but surgeons should be aware of the possibility during the long follow-up.

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer.

BACKGROUND: Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese. OBJECTIVE: The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan. METHODS: The guideline was created according to the basic principles in creating the guidelines of JSGO. RESULTS: The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget's disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions. CONCLUSION: Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.

Adjuvant chemotherapy for a primitive neuroectodermal tumor of the uterine corpus: A case report and literature review.

A primitive neuroectodermal tumor (PENT) belongs to the category of a Ewing sarcoma. A PENT of the uterus is rare and has been known to be very aggressive by nature. Owing to the rarity of the tumor, there is no optimal treatment at present. In many cases, after hysterectomy, chemotherapy or radiation therapy has been performed. However, an effective chemotherapy regimen was unclear. In the soft tissue sarcoma area, the chemotherapy approach has recently greatly improved. Vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC-IE) therapy has improved the survival rate of patients with Ewing sarcoma/PENT. Thus, VDC-IE therapy may be used for a uterine PENT. Here, we report a case of a uterine PENT in a premenopausal woman successfully treated with multimodality treatment including VDC-IE therapy and discuss the optimal chemotherapy for a uterine PENT through a literature review.

Phase II basket trial of perifosine monotherapy for recurrent gynecologic cancer with or without PIK3CA mutations.

Objective Perifosine exhibits anti-tumor activity by inhibiting AKT phosphorylation. The purpose of this phase II basket trial was to evaluate the efficacy and safety of perifosine monotherapy for ovarian, endometrial, and cervical cancers. Methods Recurrent or persistent ovarian, endometrial, or cervical cancer patients were assigned to PIK3CA wild-type or mutant groups. Each patient received 600 mg oral perifosine on day 1 followed by a maintenance dose of 100 mg daily. The primary endpoint was disease control rate; secondary endpoints included response rate, progression-free survival, overall survival, and safety. Immunohistochemical staining and targeted sequencing were used to explore new biomarkers in such patients. Results Sixteen and 5 ovarian, 17 and 7 endometrial, and 18 and 8 cervical cancer patients with PIK3CA wild-type and mutant, respectively, were enrolled. Disease control rates (wild-type/mutant) were 12.5/40.0%, 47.1/14.3%, and 11.1/25.0% in ovarian, endometrial, and cervical cancer, respectively. The most common grade 3/4 toxicities were anemia (22.5%) and anorexia (11.3%). Immunohistochemical staining revealed that the disease control rate in patients with negative phosphatase and tensin homolog (PTEN) expression was 50.0%, and the odds ratio of positive to negative patients was 0.24 in all patients. Conclusions Perifosine monotherapy showed good tolerability but expected efficacy was not achieved. Modest efficacy was demonstrated in ovarian cancer patients with PIK3CA mutations and endometrial cancer patients with PIK3CA wild-type; no difference was observed between PIK3CA wild-type and mutant in cervical cancer. Absence of PTEN expression may be predictive of clinical efficacy with perifosine monotherapy.

Improvement in the prognosis of ovarian cancer in the era before addition of molecular targeting therapy.

OBJECTIVE: The prognosis of ovarian cancer has improved because of platinum- and taxane-containing chemotherapy. We investigated the 5-year disease-specific overall survival and prognostic factors of patients with advanced ovarian cancer to elucidate the change in clinical course of ovarian cancer with the advance of chemotherapy for patients who developed relapse in the era before the addition of molecular targeting therapy. METHODS: We reviewed the clinical course of 134 patients with advanced ovarian cancer (FIGO Stage III and IV) treated in the past 11 years (1999-2010). We classified the patients into two groups: those who had been diagnosed with ovarian cancer from 1999 to 2005 (Group A) and those who had been diagnosed from 2006 to 2010 (Group B). We compared the 5-year disease-specific overall survival and median survival rates between these two groups. We also investigated the prognostic factors of 104 patients who developed relapse. RESULTS: The 5-year disease-specific overall survival rate was significantly higher in Group B than A (67.0% vs. 38.6%; P = 0.032). Chemotherapy containing pegylated liposomal doxorubicin hydrochloride, non-clear cell adenocarcinoma and intestinal resection were independent prognostic factors. CONCLUSIONS: The induction of new chemotherapeutic drugs and the increased variation of second- or third-line chemotherapy affected the improvement in overall survival of patients with advanced epithelial ovarian cancer.

Annual Report of the Committee on Gynecologic Oncology, Japan Society of Obstetrics and Gynecology: Patient Annual Report for 2014 and Treatment Annual Report for 2009.

The Japan Society of Obstetrics and Gynecology collects and analyzes annual data on gynecologic cancers from member institutions. We present the Patient Annual Report for 2014 and the Treatment Annual Report for 2009. Data on 7436 patients with cervical cancer, 9673 with endometrial cancer, 5924 with ovarian cancer, and 1909 with ovarian borderline tumor for whom treatment was initiated in 2014 were summarized in the Patient Annual Report. Stage I accounted for 55.6%, stage II for 22.9%, stage III for 10.2%, and stage IV for 11.2% of all patients with cervical cancer. Stage I accounted for 72.3%, stage II for 6.0%, stage III for 14.1%, and stage IV for 7.7% of all patients with endometrial cancer. Stage I accounted for 43.3%, stage II for 9.1%, stage III for 27.6%, and stage IV for 7.2% of all patients with ovarian cancer. Data on the prognosis of 4126 patients with cervical cancer, 4613 with endometrial cancer, and 3205 with ovarian cancer for whom treatment was initiated in 2009 were analyzed in the Treatment Annual Report. Survival was analyzed by using the Kaplan-Meier method, the log-rank test and the Wilcoxon test. The 5-year overall survival rates for patients with cervical cancer were 92.4% for stage I, 76.7% for stage II, 54.3% for stage III, and 25.2% for stage IV. The equivalent rates for patients with endometrial cancer were 94.6%, 89.4%, 78.3%, and 25.0%, respectively; and those for patients with ovarian cancer (surface epithelial-stromal tumors) were 90.5%, 78.8%, 46.0%, and 25.1%, respectively.

Optimal cytoreductive surgery in patients with advanced uterine carcinosarcoma: A multi-institutional retrospective study from the Japanese gynecologic oncology group.

BACKGROUND: The benefits of cytoreductive surgery for uterine carcinosarcoma (UCS) are unknown. The objective of this study was to determine the impact of optimal surgery on advanced UCS patient survival. METHODS: We performed a multi-institutional, retrospective study of women diagnosed with stage IIIIV UCS between 2007 and 2012. Data were obtained retrospectively from medical records, including demographic, clinicopathologic, treatment, and outcome information. Optimal cytoreductive surgery was defined as surgery resulting in a maximum residual tumor of ≤1cm. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS), and the Cox regression model was used to examine the impact of selected factors on survival. RESULTS: A total of 225 UCS patients (median age, 63years) were identified, including 136 (60%) with stage III and 89 (40%) with stage IV disease. Among these patients, 170 (76%) received optimal cytoreductive surgery. The median follow-up time was 19months. The median PFS was 11.5months (95% confidence interval [CI], 10.6-13.4) and 8.1months (95% CI, 5.1-9.5) for patients who received optimal and suboptimal cytoreductive surgery, respectively (P<0.0001). The median OS was 37.9months (95% CI, 28.3-not reached) and 18months (95% CI, 9.6-21) for patients who received optimal and suboptimal cytoreductive surgery, respectively (P<0.0001). Residual tumor >1cm was associated with worse OS while pelvic lymph node dissection was associated with improved OS. CONCLUSION: Optimal cytoreductive surgery and pelvic lymph node dissection are associated with improved OS in advanced UCS patients.

Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin.

BACKGROUND: Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy. METHODS: We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with "no vomiting", "no significant nausea", and complete response, respectively. RESULTS: Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of "no vomiting" patients (78.2 vs. 54.8 %; P < 0.0001), "no significant nausea" patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group. CONCLUSION: The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy.

Prognostic factors in patients with uterine carcinosarcoma: a multi-institutional retrospective study from the Japanese Gynecologic Oncology Group.

BACKGROUND: Uterine carcinosarcomas (UCSs) are rare and aggressive tumors. The prognostic factors are not sufficiently known. METHODS: We performed a multi-institutional, retrospective study of women with stage I-IV UCS, diagnosed between 2007 and 2012. Data obtained from medical records included demographic, clinicopathological, treatment, and outcome information. RESULTS: A total of 486 patients (median age 65 years) were identified-224 (46 %) were stage I, 32 (7 %) were stage II, 139 (28 %) were stage III, and 91 (19 %) were stage IV. Among them, 277 (57 %) had disease recurrence. Median disease-free survival (DFS) was 16.4 months [95 % confidence interval (CI) 15.7-27.2], and median overall survival (OS) was 72.0 months (95 % CI 43.0-not reached). In total, 454 (94 %) patients received adjuvant treatment, and 440 (91 %) received adjuvant chemotherapy. In multivariate analysis, stage III-IV disease, CA-125 level, and lymphovascular space invasion (LVSI) were significantly associated with shorter median DFS. Stage III-IV disease, performance status 2-4, ≥50 % myometrial invasion depth, and postsurgical residual tumor size >1 cm were significantly associated with shorter median OS. Conversely, pelvic lymph node lymphadenectomy was associated with improved DFS and OS. CONCLUSIONS: Stage, performance status, CA-125 level, LVSI, and myometrial invasion were associated with poor prognoses. Pelvic lymphadenectomy was associated with improved survival, and may be necessary for the surgical management of UCS.