Artificial Intelligence-Based Histopathological Subtyping of High-Grade Serous Ovarian Cancer.

Four subtypes of ovarian high-grade serous carcinoma (HGSC) have previously been identified, each with different prognoses and drug sensitivities. However, the accuracy of classification depended on the assessor's experience. This study aimed to develop a universal algorithm for HGSC-subtype classification using deep learning techniques. An artificial intelligence (AI)-based classification algorithm, which replicates the consensus diagnosis of pathologists, was formulated to analyze the morphological patterns and tumor-infiltrating lymphocyte counts for each tile extracted from whole slide images of ovarian HGSC available in The Cancer Genome Atlas (TCGA) data set. The accuracy of the algorithm was determined using the validation set from the Japanese Gynecologic Oncology Group 3022A1 (JGOG3022A1) and Kindai and Kyoto University (Kindai/Kyoto) cohorts. The algorithm classified the four HGSC-subtypes with mean accuracies of 0.933, 0.910, and 0.862 for the TCGA, JGOG3022A1, and Kindai/Kyoto cohorts, respectively. To compare mesenchymal transition (MT) with non-MT groups, overall survival analysis was performed in the TCGA data set. The AI-based prediction of HGSC-subtype classification in TCGA cases showed that the MT group had a worse prognosis than the non-MT group (P = 0.017). Furthermore, Cox proportional hazard regression analysis identified AI-based MT subtype classification prediction as a contributing factor along with residual disease after surgery, stage, and age. In conclusion, a robust AI-based HGSC-subtype classification algorithm was established using virtual slides of ovarian HGSC.

Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023.

We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m2 administered intravenously], topotecan [1.25 mg/m2 intravenously], paclitaxel [80 mg/m2 intravenously], or gemcitabine [1000 mg/m2 intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m2 intravenously). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator-assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32-0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38-1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment-related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification.

Metastasis to para-aortic lymph nodes cephalad to the renal veins in patients with ovarian cancer.

BACKGROUND: In patients with epithelial ovarian cancer, whether metastasis to para-aortic lymph nodes located cephalad to the renal veins (supra-renal PAN) should be classified as regional lymph node metastasis or distant metastasis remains controversial. This study was a preliminary retrospective evaluation of the pattern of supra-renal PAN metastasis in patients with epithelial ovarian cancer. METHODS: The subjects were 25 patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer who underwent systematic dissection of the para-aortic nodes, including the supra-renal PAN, and pelvic lymph nodes (PLN). Patient factors, perioperative factors, the number of dissected lymph nodes, and pathological lymph node metastasis were investigated. RESULTS: Supra-renal PAN metastasis was found in 4/25 patients (16.0%). None of the 14 patients with pT1 or pT2 disease had supra-renal PAN metastasis, while 4/11 patients (36.4%) with pT3 or ypT3 disease had such metastases. None of the patients had isolated supra-renal PAN metastasis, while patients with supra-renal PAN metastasis also had multiple metastases to the infra-renal PAN and PLN. CONCLUSIONS: In patients with epithelial ovarian cancer, supra-renal PAN metastases might be considered to be distant rather than regional metastases. Further studies are needed to better define the clinical significance of supra-renal PAN metastasis.

Conservative management of uterine artery pseudoaneurysm occurring during treatment of gestational trophoblastic disease: A case report.

Uterine artery pseudoaneurysm (UAP) is a rare disease that causes genital bleeding during the postpartum period after cesarean section. Uterine artery embolization (UAE) is an effective procedure for UAP. UAP was unexpectedly encountered in a patient with gestational trophoblastic disease; however, this patient was conservatively managed without UAE. UAP can occur during treatment for gestational trophoblastic disease. Since asymptomatic UAP may spontaneously disappear, in the selection of conservative treatment, it is important to carefully monitor patients using transvaginal ultrasonography focusing on the size of the UAP and the speed of internal blood flow.

Bevacizumab combined with platinum-taxane chemotherapy as first-line treatment for advanced ovarian cancer: a prospective observational study of safety and efficacy in Japanese patients (JGOG3022 trial).

BACKGROUND: This was the first large-scale prospective observational Japanese study evaluating the safety and efficacy of bevacizumab combined with paclitaxel and carboplatin for newly diagnosed advanced ovarian cancer. METHODS: Patients were prospectively enrolled in the primary analysis cohort if they had Stage III or IV epithelial ovarian/fallopian tube/primary peritoneal cancer and were scheduled to receive paclitaxel plus carboplatin every 3 weeks in Cycles 1-6 and bevacizumab every 3 weeks in Cycles 2-22. Primary endpoints were bevacizumab-specific adverse events and adverse events ≥ Grade 3. Secondary endpoints were progression-free survival (PFS) and the response rate. RESULTS: Among 346 patients enrolled, 293 patients formed the primary analysis cohort. Regarding bevacizumab-specific adverse events ≥ grade 3, incidence rates of thromboembolic events (1.4%), gastrointestinal perforation (0.3%), fistula (0.7%), wound dehiscence (0%), and bleeding (0%) were very low. While incidence rates of hypertension (23.2%) and proteinuria (12.6%) were high, all such events were tolerable. No patient with prior bowel resection developed perforation or fistula. Median PFS was 16.3 months (95% CI 14.5-18.9). The response rate was 77.5% (95% CI 67.4-85.7). The response rate was 63.6% in patients with clear cell carcinoma, which tended to be better than previously reported. The median platinum-free interval was 11.5 months, and the platinum-resistant recurrence rate was 24.5%. CONCLUSIONS: Combining bevacizumab with chemotherapy was tolerable and efficacy was acceptable in Japanese patients with advanced epithelial ovarian cancer. Bevacizumab seems to reduce platinum-resistant recurrence and is promising for clear cell carcinoma.

Ovarian Clear Cell Carcinoma Detected During Long-Term Management of Endometriotic Cysts in Young Patients: Possible Heterogeneity of this Tumor.

Ovarian endometriotic cysts have been identified as the possible origin of ovarian clear cell carcinoma (OCCC), so predicting or preventing future transformation is important. Early detection of clear cell carcinoma is important because it shows low sensitivity to chemotherapy and the prognosis is worse than for other histologic types. We recently treated 2 patients with OCCC. They were both young women with no family history of cancer who received long-term oral contraceptive therapy for endometriotic cysts, and the histologic diagnosis was typical clear cell carcinoma in both patients. However, in Case 1, the tumor was detected by periodic examination, tumor expression of WT1 was positive, and the stage was IA. On the other hand, Case 2 presented with fever of unknown origin, her tumor showed expression of p53, and the stage was IVB. Case 1 is alive with no evidence of disease at 38 months after surgery, while Case 2 died after 19 months despite intensive treatment. These contrasting cases suggest that we need to be aware of the risk of cancer in young women receiving long-term hormone therapy for endometriotic cysts and that OCCC may show greater heterogeneity than what has been reported previously.

An open-label, randomized, phase II trial evaluating the efficacy and safety of standard of care with or without bevacizumab in platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer patients previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer: rationale, design, and methods of the Japanese Gynecologic Oncology Group study JGOG3023.

BACKGROUND: We present the study rationale and design of the JGOG3023 study, an open-label, parallel-arm, randomized, phase II trial that aimed to assess the efficacy and safety of chemotherapy with or without bevacizumab in patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were previously treated with bevacizumab for front-line or platinum-sensitive ovarian cancer. We hypothesize that patients treated with a combination of single-agent chemotherapy and bevacizumab will show improved progression-free survival (PFS) compared with those treated with single-agent chemotherapy alone, in the setting beyond disease progression following prior bevacizumab treatment. METHODS/DESIGN: A total of 106 patients who have recurrence or progression of ovarian cancer, while receiving chemotherapy or within 6 months after the final dose of platinum, after completing at least three cycles of bevacizumab plus platinum chemotherapy will be randomized in a 1:1 ratio to treatment with single-agent chemotherapy or single-agent chemotherapy combined with bevacizumab. For chemotherapy, one of the following four drugs will be chosen by an investigator: pegylated liposomal doxorubicin, topotecan, paclitaxel, or gemcitabine. The primary endpoint is investigator-assessed PFS. The secondary endpoints are overall survival, objective response rate, number of paracentesis, and response rate by CA125. Safety will be evaluated by the incidence of adverse events. DISCUSSION: This study will assess the efficacy and safety of bevacizumab in combination with single-agent chemotherapy, which could be used continuously after disease progression following standard platinum-based chemotherapy with bevacizumab. TRIAL REGISTRATION: UMIN000017247 (registered April 22, 2015).

Safety and efficacy of neoadjuvant chemotherapy containing bevacizumab and interval debulking surgery for advanced epithelial ovarian cancer: A feasibility study.

BACKGROUND AND OBJECTIVES: The optimum treatment strategy for patients with unresectable advanced epithelial ovarian cancer is controversial. This study examined bevacizumab combined with neoadjuvant chemotherapy (NAC; paclitaxel plus carboplatin), followed by interval debulking surgery (IDS), for these patients. METHODS: In a prospective nonrandomized study, newly diagnosed patients received four cycles of NAC (three cycles combined with bevacizumab), followed by IDS. The primary endpoint was the complete resection rate at IDS. Secondary endpoints were the NAC response rate, adverse events during NAC, and perioperative complications. RESULTS: Twenty-three patients were enrolled. The complete resection rate at IDS was 60.9% (95% confidence intervals [CI]: 38.5% to 80.3%). The NAC response rate was 86.9% (95% CI: 66.4% to 97.2%). Adverse events ≥ grade 3 during NAC were neutropenia (78.3%), anemia (52.2%), hypertension (17.4%), and proteinuria (8.7%). There was no thromboembolism or gastrointestinal perforation. Grade 2 complications of IDS included lymphatic complications (13.6%), infections (9.1%), ileus (4.5%), and wound dehiscence (4.5%). There were no thromboembolic complications, fistula/abscess, or perforation/anastomotic leak, and no complications ≥ grade 3. CONCLUSIONS: In Japanese patients with advanced ovarian cancer, bevacizumab + NAC followed by IDS is an acceptable strategy. Further investigation of its prognostic effect is warranted.

Multicenter Clinicopathological Study of High-Grade Serous Carcinoma Presenting as Primary Peritoneal Carcinoma.

OBJECTIVE: We conducted a multicenter clinicopathological study to characterize patients with high-grade serous carcinoma presenting as primary peritoneal carcinoma (clinical PPC). METHODS: At 9 sites in Japan, patients with clinical PPC diagnosed according to Gynecologic Oncology Group criteria were enrolled retrospectively. The Gynecologic Oncology Group criteria allow for minor ovarian involvement by high-grade serous carcinoma. There was no systematic detailed histopathological review of the fallopian tubes to determine whether they were involved by serous carcinoma. RESULTS: There were 139 patients and 64% were aged 60 years or older. Median pretreatment serum CA-125 was 1653.5 IU/mL. Pretreatment performance status was poor in more than 50%, endometrial cytology was positive in 40.3%, and the preoperative clinical diagnosis was correct in 72.7%. Primary debulking surgery was performed in 36% of patients, whereas 64% underwent neoadjuvant chemotherapy (NAC) with interval debulking surgery (IDS). The main tumor sites were the upper abdomen (greater omentum), extrapelvic peritoneum, mesentery, and diaphragm. Lymph node metastasis was found in 46.8% of patients undergoing systematic retroperitoneal node dissection. The optimal surgery rate was 32.0% with primary debulking surgery versus 53.9% with NAC and IDS (P = 0.0139). The response rate was 82.0% with NAC and 80.6% with postoperative chemotherapy. Median progression-free survival was 19.0 months and median overall survival was 41.0 months. Multivariate analysis showed that prognostic factors for progression-free survival were NAC and residual tumor diameter after debulking surgery, whereas the only prognostic factor for overall survival was the residual tumor diameter. CONCLUSIONS: This study identified various characteristics of clinical PPC. Neoadjuvant chemotherapy with IDS is a reasonable treatment strategy, and complete debulking surgery is optimum.

Platinum-resistant recurrent ovarian cancer with long survival on bevacizumab and gemcitabine.

Platinum-resistant recurrent ovarian cancer has a poor prognosis, but combined therapy with bevacizumab and anticancer agents may be useful. We report a patient with long-term disease control by the combination of bevacizumab and gemcitabine (BEV + GEM). The patient was a 77-year-old woman with high-grade Stage IIIC serous ovarian carcinoma. In 2012, a complete response (CR) was obtained by neoadjuvant and adjuvant chemotherapy using paclitaxel plus carboplatin and tumor debulking surgery. After recurrence in 2013, CR was achieved again with gemcitabine plus carboplatin. In 2014, recurrence was detected again, but CR was achieved by third-line combination therapy with gemcitabine, carboplatin and bevacizumab. In 2015, the third recurrence was found during bevacizumab maintenance therapy. Fourth-line treatment was initiated with BEV + GEM, which has maintained stable disease for 29 months. This is the first report about marked prolongation of survival by BEV + GEM in a patient with platinum-resistant recurrent ovarian cancer.

Safe dissection of high paraaortic lymph nodes superior to the renal vein in ovarian, primary peritoneal, or fallopian tube cancer by the "Komiyama's maneuver", a modification of Kocher's maneuver.

OBJECTIVE: High paraaortic lymph nodes superior to the renal vein are often involved by metastasis from advanced ovarian cancer, but are difficult to dissect. We developed a novel surgical technique for removing these nodes. METHODS: The ascending colon is displaced from the right paracolic gutter. A retroperitoneal incision is made cranially from the ileocecal region along Monk's white line (fusion fascia) dorsal to the ascending colon. Incising the fusion fascia toward the root of the right renal vein from inside Gerota's fascia allows separation of the right kidney and mobilization of the ascending colon, partly exposing the inferior vena cava. Then the inferior vena cava below the renal vein is exposed by dissecting the right ovarian vein. Next, Kocher's maneuver is performed [1,2]. After mobilizing the duodenum, the inferior vena cava can be fully exposed below the left hepatic lobe. Then the peritoneum is incised from near the aortic bifurcation along the inferior mesenteric vein toward the ligament of Treitz, allowing complete mobilization of the small intestine and right hemicolon. Placing these viscera extra-abdominally in isolation bags provides excellent visualization of the entire aorta from the superior mesenteric artery to common iliac artery. RESULTS: This method can completely remove the high paraaortic nodes, followed by the paraaortic nodes inferior to the renal vein, without complications. CONCLUSIONS: This surgical technique for dissection of the high paraaortic lymph nodes is convenient, safe, and easy to learn. It is considered to be advantageous for management of ovarian, primary peritoneal, or fallopian tube cancer.

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer.

The fourth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer was published in 2015. The guidelines contain seven chapters and six flow charts. The major changes in this new edition are as follows-(1) the format has been changed from reviews to clinical questions (CQ), and the guidelines for optimal clinical practice in Japan are now shown as 41 CQs and answers; (2) the 'flow charts' have been improved and placed near the beginning of the guidelines; (3) the 'basic points', including tumor staging, histological classification, surgical procedures, chemotherapy, and palliative care, are described before the chapter; (4) the FIGO surgical staging of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was revised in 2014 and the guideline has been revised accordingly to take the updated version of this classification into account; (5) the procedures for examination and management of hereditary breast and ovarian cancer are described; (6) information on molecular targeting therapy has been added; (7) guidelines for the treatment of recurrent cancer based on tumor markers alone are described, as well as guidelines for providing hormone replacement therapy after treatment.

Feasibility study on the effectiveness of Goreisan-based Kampo therapy for lower abdominal lymphedema after retroperitoneal lymphadenectomy via extraperitoneal approach.

AIM: To evaluate the efficacy and safety of Kampo therapy based on Goreisan for lower abdominal lymphedema after surgical treatment of endometrial cancer or cervical cancer. METHODS: Radical surgery, including retroperitoneal lymphadenectomy, was performed for endometrial cancer and cervical cancer. After surgery, Kampo therapy based on Goreisan and integrated physical therapy were provided for patients with lower abdominal lymphedema, especially lymphedema affecting the pubic-inguinal-vulval region. Goreisan (7.5 g/day) was given orally three times a day (tds). If a significant response was not observed, Saireito (9 g/day; 3 g tds) or Gosyajinkigan (7.5 g/day; 2.5 g tds) was administered concomitantly. RESULTS: A total of 21 patients received treatment. The response rate to Goreisan monotherapy was 78%, with 22% being non-responders. Median reduction of abdominal circumference was 2.1cm (95% CI 1.3-2.85). When Goreisan was combined with another Kampo agent, the response rate was 92% and the non-response rate was 8%. The median reduction of the abdominal circumference was 2.85 cm (95% CI: 2.25-3.3). In particular, concomitant Goreisan and Saireito therapy achieved satisfactory results. No severe adverse reactions occurred. CONCLUSIONS: Goreisan-based Kampo therapy might be effective and safe for lower abdominal lymphedema after retroperitoneal lymphadenectomy. We will perform a prospective control study in the near future.

Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study.

OBJECTIVE: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. METHODS: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). RESULTS: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. CONCLUSION: The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759600.

Asymptomatic synchronous quintuple primary cancers.

We encountered a 46-year-old woman with synchronous quintuple primary cancers. She did not present with any symptoms, and her tumors were discovered at a gynecological screening. She had clear cell adenocarcinoma of the right ovary, moderately differentiated endometrioid adenocarcinoma of the endometrium, moderately differentiated adenocarcinoma of the ascending colon, well-differentiated adenocarcinoma of the rectum, and poorly differentiated papillary adenocarcinoma of the left lung. A fluorodeoxyglucose-positron emission tomography and other imaging techniques were extremely useful for the diagnosis of multiple primary cancers. Moreover, MSH2 protein expression was absent in the tumors of the ovary, endometrium, ascending colon, and rectum, while the rectal cancer also lacked MLH1 protein. These findings suggested that an abnormality of DNA mismatch repair genes was responsible for carcinogenesis.

The effects of the selective cyclooxygenase-2 inhibitor on endometrial cytological findings in uterine endometrial cancer patients.

OBJECTIVE: We previously reported that oral administration of the selective cyclooxygenase-2 (COX-2) inhibitor etodolac results in antitumor effects in endometrial cancer tissue. Herein, we investigated whether these antitumor effects could be assessed using endometrial cytological findings. STUDY DESIGN: Etodolac (400 mg b.i.d. for 2 weeks) was administered preoperatively to 21 endometrial cancer patients: 16 had COX-2-positive disease and 5 had COX-2-negative disease. Twenty-one pairs of pre- and post-etodolac-treatment endometrial cytological samples were collected to review changes in the cytological features. RESULTS: In the COX-2-positive patients, nuclear atypia was slightly decreased in 3 of the 16 cases, while the mitotic index was decreased in all cases. Cellular overlapping and tumor cell cluster outlines were somewhat affected in 6 and 8 cases, respectively. Nuclear/cytoplasmic ratio, anisokaryosis and hyperchromasia were also reduced in 6, 4, and 2 cases, respectively; however, tumor diathesis and nucleoli features were unchanged. In contrast, endometrial cytological features did not appear to be affected in the 5 COX-2-negative patients. CONCLUSIONS: We conclude that the antitumor effects observed in endometrial cancer tissues following oral administration of etodolac are reflected in and can be easily assessed by evaluating endometrial cytological features.

A case of primary uterine cervical neuroendocrine tumor with meningeal carcinomatosis confirmed by diagnostic imaging and autopsy.

Primary uterine cervical neuroendocrine tumors are rare, but affect relatively young women and the prognosis is poor despite multidisciplinary treatment. The incidence of meningeal carcinomatosis arising from malignant tumors of the uterine cervix is extremely low, only two patients with meningeal carcinomatosis arising from a uterine cervical neuroendocrine tumor have been reported in the English literature. Moreover, there have been no reports in which this was confirmed at autopsy. We encountered a pregnant woman aged 33 years who was diagnosed as having atypical carcinoid of the uterine cervix after radical surgery. Despite multidrug chemotherapy (paclitaxel + etoposide + cisplatin and irinotecan + carboplatin), the patient developed multiple organ metastases. Although there was no metastasis to the brain parenchyma or the spinal cord parenchyma, the patient also developed meningeal carcinomatosis. Whole-brain radiation therapy was performed, but was ineffective. The patient died at 19 months after her initial operation and 10 days after diagnosis of meningeal carcinomatosis. The presence of meningeal carcinomatosis was confirmed at autopsy.

[Treatment outcomes for advanced ovarian cancers with peritoneal dissemination].

PURPOSE: The prognosis of advanced ovarian cancer primarily depends on maximal surgical debulking and chemosensitivity of the tumor. Neo-adjuvant chemotherapy(NAC), maintenance chemotherapy, and interval debulking surgery(IDS)are sometimes used to improve the prognosis of advanced ovarian cancer patients. In this study, we evaluated the outcomes of these therapeutic options in the treatment of FIGO stage III and IV ovarian cancers with intraperitoneal dissemination. METHODS: Fifty patients with FIGO stage IIIc and IV ovarian cancer were evaluated. Progression-free survival(PFS)and overall survival(OS)were compared between different patient groups, including patients who underwent optimal surgery versus suboptimal surgery, patients who received NAC versus those who did not, patients who received 6 cycles of postoperative adjuvant chemotherapy versus those who received more than 7 cycles, and patients who underwent IDS versus those who did not. RESULTS: 1 ) The 5- and 10-year OS rates were 52% and 21%, respectively. 2 ) Patients in the optimal surgery group experienced significantly longer PFS than patients in the suboptimal surgery group(p=0. 04). 3) Although NAC increased the possible rate of optimal surgery from 31. 2% to 66. 7%, no significant differences in PFS or OS were observed between patients who did and did not receive NAC. 4 ) Patients who underwent more than 7 cycles of adjuvant chemotherapy after suboptimal surgery experienced significantly longer OS(p=0. 001)and a tendency toward longer PFS(p=0. 07)compared to patients who received 6 cycles of adjuvant chemotherapy. 5 ) Patients who achieved a complete response(CR)following adjuvant chemotherapy after suboptimal surgery experienced significantly longer PFS(p=0. 001)and OS(p=0. 001) compared to patients who did not obtain CR. Moreover, patients who underwent IDS and who did not obtain a CR after adjuvant chemotherapy tended to experience longer PFS than patients who did not undergo IDS(p=0. 07). CONCLUSIONS: The results of this study are essentially compatible with those of recent randomized controlled trials(RCTs) evaluating NAC, maintenance chemotherapy, and IDS in advanced ovarian cancer. We hope to obtain additional RCT results that will allow improvement of the prognosis of advanced ovarian cancer patients.

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer.

OBJECTIVE: To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. METHODS: This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs. RESULTS: Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%. CONCLUSION: Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759600.

Evidence-based guidelines for treatment of uterine body neoplasm in Japan: Japan Society of Gynecologic Oncology (JSGO) 2009 edition.

Endometrial carcinoma is one of the most common gynecologic malignancies in Japan and its incidence has increased recently. Although surgery is the cornerstone of the management of patients with endometrial cancer, there is significant variation in Japan with regard to the type of hysterectomy employed. Additionally, it remains controversial whether full nodal staging is required in all patients. Furthermore, adjuvant therapy differs between Japan and Western countries. To delineate clearly the standard of care for endometrial cancer treatment in Japan, the guidelines for the treatment of endometrial cancer were published in 2006 and revised in 2009. The 2009 edition included topics not addressed in the previous edition including the treatment of mesenchymal tumors, for example leiomyosarcoma, and sections covering the treatment of serous and clear-cell adenocarcinoma. These guidelines are composed of nine chapters and include nine algorithms. The guidelines also contain fifty-one clinical questions (CQs) and each CQ consists of recommendations, background, explanations, and references. The treatment recommendations herein are tailored to reflect current Japanese clinical practice and ensure equitable care for all Japanese women diagnosed with endometrial cancer.