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Brain metastases from ovarian cancer remain rare and the appropriate treatment is unknown. We investigated survival outcomes following salvage chemotherapy before and after bevacizumab approval to evaluate the efficacy of bevacizumab in patients with brain metastasis from ovarian cancer.We investigated 23 consecutive patients with brain metastasis from ovarian cancer at our hospital between 2001 and 2020. Bevacizumab was administered for treating ovarian cancer after approval in Japan in November 2013. Survival after brain metastasis was compared between 9 patients treated before bevacizumab approval (2000-2013) and 14 patients treated after approval (2014-2020). Seven patients treated in the latter period received bevacizumab-salvage chemotherapy for brain metastasis.Median survival in all patients was 9.1 months [95% confidence interval (CI)=4.2-33.5]. In addition, patients treated during the latter period presented better survival outcomes than those treated in the former period (former, 2.9 months vs latter, 33.5 months, log-rank test, p=0.015; Wilcoxon test, p=0.009). Multivariate analysis revealed that bevacizumab addition (p=0.020), interval to brain metastasis (p=0.005), number of brain lesions (p=0.001), number of recurrences (p=0.001), and platinum sensitivity (p=0.028) were independently associated with survival in all cohorts.Bevacizumab-based salvage chemotherapy may improve survival outcomes in patients with brain metastasis.

IntroductionChemotherapy-induced nausea and vomiting (CINV) decrease patients’ quality of life and negatively impact treatment outcomes. Although standard prophylactic antiemetic therapy for acute CINV recommended by guidelines is effective, poor guideline implementation is a worldwide problem. In Japan, prophylactic antiemetic therapy is relatively well implemented for chemotherapy associated with high emetogenic risk, while implementation gaps are observed for that with low emetogenic risk.Although most reports on factors influencing appropriate antiemetic prescription focus on physicians’ attitudes and behaviours, a more comprehensive exploration is needed since chemotherapy is expected to involve pharmacists, nurses and eventually hospital directors. The purpose of this qualitative study is to comprehensively explore the factors that influence the implementation of appropriate prophylactic antiemetic procedures at cancer care hospitals in Japan.Methods and analysisThis study is a hospital-based qualitative study using semistructured individual interviews. The target population will be hospital directors, and chiefs (including proxies) of departments of oncology and/or chemotherapy, pharmacy and nursing, working in the hospitals, selected by purposive sampling. We will obtain information on antiemetics in chemotherapy regimens, antiemetic routine use and awareness of guidelines using prequestionnaires. Interviews will then be conducted online using an interview guide. The Consolidated Framework for Implementation Research will be used to collect and analyse the interview data. We will also create new codes inductively, as required. In addition, we will refer to the aggregate results of the Quality Indicator survey to determine the implementation of recommended antiemetic prescriptions for each hospital and discuss the relationship with influencing factors.Ethics and disseminationThis study has been approved by the National Cancer Centre Ethics Approval Committee (approval number: 2020-305). The study findings will be disseminated via peer-reviewed journal publications and presentations to academics, policy-makers, and clinicians at scientific conferences.

To investigate whether rectosigmoid colectomy can improve the prognosis of patients with early-stage ovarian cancer when the ovarian tumor adheres to the rectum. We retrospectively studied 210 consecutive patients with stage I/II ovarian cancer treated between 2000 and 2016. The surgical strategy differed between the periods 2000–2007 and 2008–2016 with respect to adhesion between the ovarian tumor and rectum. In the former period, ovarian tumor was exfoliated from the rectum. Only when the residual tumor was apparently observed on the rectal surface after salpingo-oophorectomy with hysterectomy, it was subsequently removed by colorectal surgeons performing rectosigmoid colectomy. In the latter period, the ovarian tumor was resected en bloc with the rectum by performing rectosigmoid colectomy. We compared the progression-free survival (PFS) between the two treatment periods. Rectosigmoid colectomy was performed more frequently in the latter period than in the former period (43 patients, 31% vs. 6 patients, 8%, p

We investigated whether highly aggressive surgery has survival and perioperative complication benefit in patients with advanced ovarian cancer.This retrospective study included 209 patients with stage III/IV ovarian cancer who underwent aggressive surgery [surgical complexity score (SCS) ≥8] between January 2008 and December 2018. Patients were categorized into the SCS 8-12 (less aggressive surgery, 83 patients) and SCS ≥13 (highly aggressive surgery, 126 patients) groups. Survival outcomes and perioperative complications between the groups were compared. Patient suitability for primary debulking surgery or neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) was based on the evaluation of performance status, tumor load, and ascites. If patients were suitable for NACT/IDS, the residual tumor margins were marked at the initial laparotomy. The previously marked lesions were removed during IDS, even in patients with macroscopic tumor resolution.Prevalence rates of stage IV disease, poor performance status, presence of omental cake, peritoneal cancer index ≥15, and IDS performed were significantly higher in the highly aggressive surgery group than in the less aggressive surgery group. The median progression-free survival (PFS) and overall survival (OS) were not significantly different between the groups (PFS, 32 and 31 months, respectively; p=0.622; OS, 99 and 75 months, respectively; p=0.390). The incidence of severe perioperative complications was not significantly different between the less aggressive group (4.8%) and the highly aggressive surgery group (6.4%) (p=0.767).Highly aggressive surgery with appropriate selection regardless of the timing of cytoreduction benefits patients with advanced ovarian cancer.

This study investigated the pattern of first recurrence of advanced ovarian cancer before and after the introduction of aggressive surgery. We investigated 291 patients with stage III/IV epithelial ovarian, fallopian tube, and peritoneal cancer. Aggressive surgery including gastrointestinal and upper abdominal surgeries was introduced for advanced ovarian cancer in 2008. The site and time until first recurrence were compared between 70 patients treated without aggressive surgery (2000–2007) and 221 patients who underwent aggressive surgery (2008–2016). The intraperitoneal recurrence rate was significantly lower in patients treated during 2008–2016 than in patients treated during 2000–2007 (55% [82/149] vs. 81% [46/57], p

Splenectomy with or without distal pancreatectomy is occasionally performed during cytoreductive surgery for advanced ovarian cancer. We investigated pre-, intra-, postoperative risk factors and predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) in patients who underwent cytoreductive surgery for advanced ovarian cancer.We investigated 165 consecutive patients with ovarian, fallopian tube, and peritoneal carcinoma categorized as stage III/IV disease, who underwent splenectomy with or without distal pancreatectomy as a component of cytoreductive surgery performed as initial treatment at Chiba University Hospital. Patient characteristics, clinical factors, and surgical outcomes were compared between those with and without CR-POPF.CR-POPF occurred in 20 patients (12%). There were no significant intergroup differences in the characteristics between patients with CR-POPF and patients without CR-POPF except for operative time, intraoperative blood loss, amylase (AMY) levels in drain fluid on postoperative day (POD)1 and POD3, and pancreatic stump thickness. Multivariate analysis showed that the POD3 drain fluid AMY level was the only significant risk factor and predictor of CR-POPF in patients who underwent cytoreductive surgery for advanced ovarian cancer. The receiver operating characteristic curve of the POD3 drain fluid AMY level, which predicted development of CR-POPF showed an area under the curve of 0.77, and the optimal cut-off value of AMY was 808 U/L. A pancreatic fistula did not occur in patients with POD3 drain fluid AMY levels130 U/L.The POD3 drain fluid AMY level can be early diagnostic predictor CR-POPF after splenectomy with or without distal pancreatectomy for advanced ovarian cancer.

In July 2019, in accordance with the Medical Information Distribution Service Manual for Guideline Development 2014, which was based on the Grading of Recommendations Assessment, Development and Evaluation approach, the Japanese Society of Medical Oncology (JSMO) and the Japan Society of Clinical Oncology (JSCO) published clinical practice guidelines (CPGs) on chemotherapy and other drug therapies for older patients with cancer (JSMO-JSCO CPGs). In September 2020, at one year after the publication of these guidelines, a survey was conducted to determine the extent to which they had been disseminated to JSMO and JSCO members and implemented in daily practice.This nationwide, cross-sectional, web-based survey was conducted with JSMO and JSCO members. We surveyed the participants' overall awareness of the JSMO-JSCO CPGs, and their knowledge about, attitudes toward, and perceived barriers to adherence to each recommendation using validated questionnaires based on theoretical frameworks used in previous studies (Awareness to Adherence Model, Clinicians' Assessments of Practice Guidelines in Oncology questionnaires, and Knowledge-Attitudes-Behavior Framework).Among JSMO and JSCO members who had been informed of the survey, 1230 responded (response rate: 8.6% and 4.8%, respectively). From these respondents, 107 were excluded because they did not practice anticancer drug therapy at the time of the survey. Of the remaining 1123 eligible participants, 674 (60.0%) were aware of the JSMO-JSCO CPGs before the survey, 492 (73.0%) of whom had read all or part of the guidelines (publications 57.1%, JSMO website 34.8%, and JSCO website 14.0%). Knowledge about, attitudes toward, and barriers to adherence to each recommendation differed widely according to the clinical questions. The most commonly cited barriers were lack of awareness, lack of agreement, lack of evidence, lack of outcome expectancy, patient values and preferences, and patient factors.This survey identified different barriers to guideline adherence, including providers' knowledge, attitudes, and external factors, depending on each recommendation. Effective strategies to overcome these barriers can be expected to improve the implementation of the guideline recommendations. Based on the results of this survey, efforts should be made to promote further the use of the clinical guidelines in daily practice.

Background: We evaluated whether the serum hormone levels are useful in the differential diagnosis of granulosa cell tumors (GCTs), regardless of menopausal status. Methods: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, and progesterone were measured preoperatively in all patients (n = 471) who underwent surgery for ovarian tumors at Chiba University Hospital between 2009 and 2021. These were compared in two groups, a GCT group (n = 13) and a group with other histological types (non-GCT) (n = 458). Results: The GCT group had significantly lower serum LH and FSH (p = 0.03 and p < 0.001, respectively) and significantly higher testosterone, estradiol, and progesterone (p < 0.001, p < 0.001, and p = 0.045, respectively) than the non-GCT group. Multivariate analysis revealed that serum FSH and estradiol were significantly associated with GCT (FSH, odds ratio (OR) = 0.0046, 95% confidence interval (CI) = 0.0026–0.22, p = 0.004; estradiol, OR = 0.98, 95% CI = 0.96–0.998, p = 0.046). Receiver-operating characteristic curve analysis for GCTs showed that the area under the curve of serum FSH was 0.99, with a sensitivity of 100% and a specificity of 98%, when the cutoff level was set at 2.0 IU/L. Conclusions: Preoperative serum FSH level is an extremely useful marker for differentiating GCTs from all ovarian tumors.

IntroductionElderly cancer patients often have ageing-related physical and psychosocial problems that should be fully shared with their oncologists. Geriatric assessment (GA) can assess these ageing-related problems and guide management. Communication support might also facilitate implementation of GA-guided management. We will conduct a multicentre, randomised controlled trial to examine the efficacy of a programme that combines a GA summary, management recommendations and communication support to facilitate ageing-related communications between elderly Japanese patients with cancer and their oncologists, and thus to implement programme-guided management.Methods and analysisWe plan to recruit a total of 210 patients aged ≥70 years, diagnosed with incurable cancers of gastrointestinal origin, and referred for first-line or second-line chemotherapy. In the intervention arm, a summary of management recommendations based on a GA and question prompt list (QPL) will be provided to patients and shared with their oncologists at the first outpatient visit after randomisation by trained intervention providers. For 5 months after the initial intervention, implementation of GA-guided management recommendations will be reviewed monthly with the patients and their oncologists to implement management as needed. The GA and QPL will be re-evaluated at 3 months, with a summary provided to patients and their oncologists. Those participants allocated to the usual care arm will receive usual oncology care. The primary endpoint is the number of conversations about ageing-related concerns at the first outpatient visit after randomisation.Ethics and disseminationThis study was approved by the institutional review board of the National Cancer Center Japan on 15 April 2021 (ID: 2020–592). Study findings will be disseminated through peer-reviewed journals and conference presentations.Trial registration numberUMIN000045428.

Objective Metastatic lymph node resection around the porta hepatis is sometimes required to achieve complete cytoreduction for ovarian, fallopian tube, and primary peritoneal cancer. Hence, this study aimed to present the surgical approach of peripancreatic lymph node removal around the porta hepatis as part of primary debulking surgery. Methods A 75-year old woman with stage IIIC primary peritoneal serous carcinoma underwent primary debulking surgery by means of the following procedures: bilateral salpingo-oophorectomy, total hysterectomy, omentectomy, total pelvic peritonectomy, rectosigmoid colectomy with anastomosis, right hemicolectomy, right diaphragm resection, partial jejunal resection, and pelvic and para-aortic lymphadenectomy. Furthermore, she underwent enlarged peripancreatic lymph nodes resection located in the hepatoduodenal ligament and on the posterior pancreatic head. An anatomic variant of the common hepatic artery was identified to be arising from the superior mesenteric artery and not from the celiac artery. The common hepatic artery ran behind the portal vein. We resected the lymph nodes without causing injury of the hepatic artery, portal vein, and common bile duct and achieved complete cytoreduction. Results The histological examination revealed high-grade serous carcinoma in three of nine resected peripancreatic lymph nodes. In contrast, only one lymph node metastasized in the interaortocaval region among the 63 resected regional lymph nodes (paraaortic and pelvic lymph nodes). Conclusion Metastatic peripancreatic lymph nodes resection around the porta hepatis is feasible and sometimes necessary for cytoreductive surgery for advanced ovarian, fallopian tube, and primary peritoneal cancer.

Bacterial translocation, in which intestinal bacteria pass through the intestinal wall, enter the blood circulation, and spread to other sites of the body, is thought to cause bacteremia and sometimes febrile neutropenia (FN) in patients who receive cancer chemotherapy. We collected blood samples from 39 patients with various cancers at baseline and after chemotherapy began (during chemotherapy) and explored how frequently bacteria could be detected in the blood using a highly-sensitive, bacterial rRNA-targeted reverse transcription quantitative polymerase chain reaction (PCR) assay. Bacterial traces, typically Escherichia coli and Enterobacter spp., were detected in 10 patients (25.6%) at baseline and 11 patients (28.2%) during chemotherapy. The bacterial traces were positive either at baseline or during chemotherapy in 3 (60%) of 5 patients who had FN, and 6 (46%) of 13 patients aged 65 years or older. These findings support the notion that bacterial translocation occurs in patients with cancer regardless of whether they receive chemotherapy and can lead to the development of FN and other treatment-related infections.

Ovarian carcinomas sometimes grow in the pelvic cavity, adhering firmly to the pelvic sidewall. These cases are often considered as inoperable or result in the incomplete resection because the tumors are not mobile. We performed en bloc resection of the tumors along with the entire internal iliac vessel system to achieve complete resection. Twenty of 237 consecutive patients with FIGO stage II–IV ovarian, fallopian tubal, or primary peritoneal carcinoma who underwent cytoreductive surgery at Chiba University Hospital between January 2008 and December 2016 had locally advanced tumors adhered firmly to the pelvic sidewall. We performed isolation of the tumors from the pelvic sidewall using the following procedure: the trunk of internal iliac vessels, the obturator vessels, the inferior gluteal and internal pudendal vessels were isolated and divided. The tumor together with the entire internal iliac vessel system was isolated from the sacral nerve plexus and piriform muscle. We examined the surgical outcomes, perioperative complications, and prognosis for the patients who underwent this procedure. All patients successfully underwent complete resection, resulting in no gross residual disease in the pelvic cavity. There was no mortality within 90 days postoperatively. Two patients had Grade IIIb complications, comprising wound dehiscence and vesicovaginal fistula. Recurrence occurred in nine of the patients. However, no recurrence was observed in the pelvic sidewall. The median progression-free survival was 43 months. Removal of the entire internal iliac vessel system is feasible for the complete resection of locally advanced ovarian carcinomas adhered firmly to the pelvic sidewall.

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a rare tumor derived from mesenchymal tissue. Although standard chemotherapy for SHT/HPC has not been established, temozolomide plus bevacizumab (TMZ+Bev) therapy for SFT/HPC has been reported. The effectiveness and safety of TMZ+Bev (temozolomide 150 mg/m2 orally on days 1–7 and days 15–21 and bevacizumab 5 mg/kg intravenously on day 8 and day 22 on a 28-day cycle), which was administered from December 2013 until April 2019 to four patients with SFT/HPC, were retrospectively analyzed. Four patients with SFT/HPC received TMZ+Bev. The age of the patients ranged from 41 to 75 years. Two were male, and the primary tumor sites were the meninges in three patients and the pleura in one. One achieved partial response; the others, stable disease (SD). The progression-free survival time ranged from 9.4 to 29.6 months according to RECIST v1.1. One patient died 59 months after using TMZ+Bev, and the others survived for 17 to 64 months. All patients experienced Grade 3 or higher lymphopenia, and three had Grade 3 or higher leukopenia and neutropenia. One patient subsequently received doxorubicin; another, pazopanib. TMZ+Bev therapy for SFT/HPC is safe and effective for maintaining long-term SD.

The standard chemotherapy regimen for unresectable or recurrent biliary tract cancer is gemcitabine combined with cisplatin (GC). To evaluate the effectiveness and safety of chemotherapy in patients with unresectable or recurrent biliary tract cancer in the real world, we retrospectively analyzed the clinical courses of patients who underwent chemotherapy with GC from January 2015 to November 2019. Forty-eight patients underwent the GC regimen. One patient (2.1%) achieved a complete response, seven patients (14.6%) achieved a partial response, 26 patients (54.2) achieved stable disease, 11 patients (22.9%) achieved progressive disease, and 3 patients (6.3%) were not evaluable. The overall response rate was 16.7%. The median overall survival was 14.2 months (95% CI: 13.8–14.6), and the median progression-free survival was 7.7 months (95% CI: 4.2–11.2). Thirty-nine patients (81.3%) experienced grade 3 or higher severe adverse events as follows: 54.2% experienced neutropenia, 20.8% experienced anemia, 12.5% experienced thrombocytopenia and 20.8% experienced biliary tract infection. As a second-line chemotherapy, S-1 was used in seventeen patients, and stable disease was achieved in three patients (17.6%). The GC regimen for biliary tract cancer is effective and safe for unresectable or recurrent biliary tract cancer in routine clinical practice.

We examined whether the extent of initial peritoneal dissemination affected the prognosis of patients with advanced ovarian, fallopian tube, and peritoneal carcinoma when initially disseminated lesions > 1 cm in diameter were removed, regardless of the timing of aggressive cytoreductive surgery. The extent of peritoneal dissemination was assessed by the peritoneal cancer index (PCI) at initial laparotomy in 186 consecutive patients with stage IIIC/IV. Sixty patients underwent primary debulking surgery and 109 patients underwent neoadjuvant chemotherapy followed by interval debulking surgery. Seventeen patients could not undergo debulking surgery because of disease progression during neoadjuvant chemotherapy. The median initial PCI were 17. Upper abdominal surgery and bowel resection were performed in 149 (80%) and 171 patients (92%), respectively. Residual disease ≤ 1 cm after surgery was achieved in 164 patients (89%). The initial PCI was not significantly associated with progression-free survival (PFS; p = 0.13) and overall survival (OS; p = 0.09). No residual disease and a high-complexity surgery significantly prolonged PFS (p p = 0.02, respectively) and OS (p p ≤ 0.01, respectively). The extent of initial peritoneal dissemination did not affect the prognosis when initially disseminated lesions > 1 cm were resected.

Simple Summary We tried to minimize the number anastomoses, restore intestinal continuity, and avoid stoma creation for 295 patients with stage III/IV ovarian cancer who underwent low anterior rectal resection (LAR) with or without colon resection during cytoreductive surgery. When remaining colon cannot reach the rectal stump after left hemicolectomy with LAR, we used the following three techniques for tension-free anastomosis: right colonic transposition, retro-ileal anastomosis through an ileal mesenteric defect, or additional colic artery division. The rate of stoma creation and rectal anastomotic was 3% (9/295) and 6.6% (19/286), respectively. Among 21 patients in whom the remaining colon did not reach the rectal stump after left hemicolectomy with LAR, 20 underwent tension-free anastomosis, including eight, six, and six patients undergoing right colonic transposition, retro-ileal anastomosis through an ileal mesenteric defect, and an additional colic artery division, respectively. Colorectal anastomosis is feasible in patients with extended colonic resection. Abstract Extended colon resection is often performed in advanced ovarian cancer. Restoring intestinal continuity and avoiding stoma creation improve patients’ quality of life postoperatively. We tried to minimize the number of anastomoses, restore intestinal continuity, and avoid stoma creation for 295 patients with stage III/IV ovarian cancer who underwent low anterior rectal resection (LAR) with or without colon resection during cytoreductive surgery. When the remaining colon could not reach the rectal stump after left hemicolectomy with LAR, we used the following techniques for tension-free anastomosis: right colonic transposition, retro-ileal anastomosis through an ileal mesenteric defect, or an additional colic artery division. Rates of stoma creation and rectal anastomotic were 3% (9/295) and 6.6% (19/286), respectively. Among 21 patients in whom the remaining colon did not reach the rectal stump after left hemicolectomy with LAR, 20 underwent tension-free anastomosis, including eight, six, and six patients undergoing right colonic transposition, retro-ileal anastomosis through an ileal mesenteric defect, and an additional colic artery division, respectively. Colorectal anastomosis is feasible for patients with extended colonic resection. Low anastomotic leakage and stoma rates can be achieved with careful attention to colonic mobilization and tension-free anastomosis.

AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients. METHODS We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage IV gastric cancer. In particular, 30 or 40 mg/m2 of docetaxel on day 1, 60 mg/m2 of cisplatin on day 1, and 2000 mg/m2 of capecitabine for 2 wk were administered every three weeks. RESULTS Three patients were treated with modified DCX (mDCX) with 30 mg/m2 docetaxel, and five patients were treated with this regimen with 40 mg/m2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes. CONCLUSION mDCX was well tolerated by Japanese patients with stage IV gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.

Objective Ovarian carcinomas sometimes metastasize to the cardiophrenic lymph node. We present a surgical technique for metastatic cardiophrenic lymph node resection following full-thickness resection of the right diaphragm. Methods A 51-year-old woman presented with ovarian carcinoma and cardiophrenic lymph node metastasis with peritoneal dissemination. The surgical procedure for metastatic cardiophrenic lymph node resection following full-thickness resection of the right diaphragm was as follows. (1) Stripping of the right diaphragm peritoneum was started from the ventral side toward the dorsal side. At the area where stripping was ceased due to tendon or muscle invasion, the thoracic cavity was opened. Full-thickness resection of the diaphragm was proceeded in the left-right direction. (2) The bare area was exposed. Full-thickness resection of the diaphragm was continued along the bare area. (3) After the right diaphragm resection was completed, the remaining right diaphragm was cut toward the cranial side. The metastatic cardiophrenic lymph node was grasped and pulled by forceps, and subsequently resected using a vessel-sealing device. (4) After thoracic chest tube placement, the diaphragmatic defect was closed by continuous non-absorbable sutures. Results We successfully achieved metastatic cardiophrenic lymph node resection following full-thickness resection of the right diaphragm without intra- or postoperative complications. Conclusion Metastatic cardiophrenic lymph node resection is a simple procedure for gynecologic surgeons who are able to perform full-thickness resection of the diaphragm.

Objective We investigated the learning curve for a monodisciplinary surgical team consisting of gynecologic oncologists performing cytoreductive surgery for advanced ovarian cancer, involving high-complexity procedures with bowel resection and upper abdominal surgery. Methods We investigated 271 consecutive patients with ovarian, fallopian tube, and peritoneal carcinoma undergoing cytoreductive surgery for stage III/IV disease. All operations were performed by a team consisting of only gynecologic oncologists. Patients were classified into 2 groups depending on the surgical complexity score (a cumulative score based on complexity and number of procedures performed). Learning curves for patients with moderate (4–7, 63 patients) and high scores (8–18, 208 patients) were evaluated using cumulative sum (CUSUM) analysis of operative time, total blood loss, and perioperative complications. Results Operative time and total blood loss showed a learning curve. The CUSUM curve for operative time peaked at the 28th and 51st case in the moderate- and high-score groups, respectively. The CUSUM curve for total blood loss peaked at the 16th and 55th case in the moderate- and high-score groups, respectively. The CUSUM curve for complications (Clavien-Dindo ≥ IIIb) showed a downward slope after the 6th case in the high-score group and remained within the acceptable range throughout the study. Conclusion Proficiency in performing high-complexity surgery was achieved after approximately 50 cases and this number is greater than the number of cases required to perform moderate-complexity surgery. Acceptable rates of severe perioperative complications were observed even during the initial learning period in cases of high-complexity surgery.

Objective This study aimed to evaluate the presence of pathological residual tumor (pRT) in each initial disseminated site after neoadjuvant chemotherapy (NACT) to assess the appropriate surgical margins during interval debulking surgery (IDS) for a favorable prognosis. Methods This prospective descriptive study included patients with stage IIIC-IV epithelial ovarian, fallopian tubal, and peritoneal cancer. One hundred eleven patients underwent diagnostic exploratory laparotomy, and their initial intra-abdominal dissemination statuses were recorded. Any tumor >1 cm in diameter found during the exploratory laparotomy was resected during IDS even if it was macroscopically invisible after NACT. The pRT rate after NACT and negative predictive value (NPV; probability that sites with macroscopically invisible tumors have no pRT) during IDS were assessed in each disseminated site. Results A median of 5 NACT cycles were performed. Sites with a high incidence of pRT and low NPV included the rectosigmoid colon (71.4%, 38.6%), transverse mesentery (70.3%, 50.0%), greater omentum (68.3%, 51.7%), right diaphragm (61.9%, 48.1%), paracolic gutters (61.1%, 50.0%), and vesicouterine pouch (56.6%, 50.0%). Organs/tissues with a high incidence of pRT featured a low NPV. The median progression-free survival and overall survival in this cohort were 27.7 and 71.9 months, respectively. Conclusion Even if a disseminated site >1 cm in diameter before NACT is invisible during IDS, microscopic disease remains present within it. The appropriate surgical margins for IDS with a favorable prognosis could be secured by resecting a lesion of >1 cm before NACT even if it is invisible during IDS.

Resistance to anticancer drugs is a critical issue in cancer treatment. Alterations in gene expression and DNA methylation profiles that accompany the acquisition of drug resistance are associated with resistance mechanisms. To analyze chemotherapy-associated alterations in gene expression and DNA methylation in gastric cancer cells obtained from ascites, ascitic fluids were collected from a patient with gastric cancer before chemotherapy with capecitabine and oxaliplatin (CapeOX), and after the disease had progressed. The fluids were cultured for 10 days, passaged into new flasks, and cultured for an additional 2 weeks. Normal cells, including white blood cells and mesothelial cells, were removed. The expression and DNA methylation profiles of 18,185 genes were analyzed using microarray, and compared between cells in ascitic fluids collected before and after the chemotherapy with CapeOX. In addition, fluorouracil- and oxaliplatin-resistant AGS cells were established and analyzed. Pathways having genes with expression profiles altered by CapeOX included those associated with ‘signaling by G-protein-coupled receptor’ and the ‘immune system’. Genes that were commonly expressed at higher levels in CapeOX-resistant ascitic cells, fluorouracil-resistant AGS cells. and oxaliplatin-resistant AGS cells compared with those in untreated cells included telomerase reverse transcriptase (TERT), apolipoprotein C1 (APOC1) and serine/threonine/tyrosine kinase 1 (STYK1), whereas genes commonly expressed at lower levels in the three drug-resistant cell types compared with the untreated cells included defensin β4A (DEFB4A). A comparatively large number of genes exhibited altered methylation levels in drug-resistant AGS cells compared with the CapeOX-resistant cells. In addition, among the genes expressed at higher levels in decitabine-treated AGS cells, the majority were expressed at higher levels in fluorouracil-resistant AGS cells, and exhibited lower methylation levels. Taken together, the present study has demonstrated that comparing the expression profiles of gastric cancer cells obtained from ascitic fluids before and after chemotherapy with the expression profiles of drug-resistant cultured cells is a useful method for analyzing the molecular mechanisms underlying chemotherapy resistance.

12012 Background: Geriatric assessment (GA) is recommended in various guidelines for older adults with cancer, but is not widely used in daily practice. This study aims to identify multi-level barriers and facilitators of GA implementation in daily oncology practice, based on a theoretical implementation framework. Methods: We conducted 20 semi-structured interviews with healthcare providers and managers in 14 hospitals treating older adults with cancer in Japan. The Consolidated Framework for Implementation Research (CFIR) was used to guide the collection and analysis of interview data using a deductive approach. CFIR consists of 5 major domains (I. intervention characteristics, II. outer setting, inner setting,. individual characteristics, and V. process), including 39 constructs. Differences in the constructs influencing GA implementation between hospitals where GA is routinely performed (high implementation, HI) and hospitals where GA is not performed or performed only in clinical trials (low implementation, LI) were explored. Results: Among constructs identified as barriers or facilitators of GA implementation, 15 multi-level constructs greatly differed between 5HI and 5LI, including 4 constructs from intervention characteristics, 6 from inner setting, 1 from individual characteristics, and 4 from process. In HI, GA was self-administered (I. adaptability), or administered on a mobile app with interpretation (I. design quality and packaging). In HI, healthcare providers strongly perceived the need to change the practice for older adults (III. tension for change), and recognized GA as fitting in with existing workflow as part of their jobs (III. compatibility). In LI, they did not realize the need to change practice, and rejected GA as an extra burden on their heavy workload. In HI, the usefulness of GA was widely recognized by healthcare providers (IV. knowledge and beliefs about the intervention), GA was given high priority (III. relative priority), had strong support from hospital directors and nursing chiefs (V. leadership engagement), and multiple stakeholders were successfully engaged, such as healthcare providers, especially nurses (V. key stakeholders), directors and nursing chiefs (V. opinion leaders), and those who dedicated themselves to implementing GA (champions). Conclusions: This is the first study to reveal the multi-level barriers and facilitators of GA implementation in daily oncology practice. The findings highlight the need to focus not only on individual or intervention characteristics, but also on the inner setting and the process of implementing GA. Our findings suggest future strategies, such as devising the administration of GA using technology, conducting local needs assessment and consensus discussions about the usefulness and priority of GA, and engaging multiple stakeholders.

5556 Background: The recent SCORPION trial showed that aggressive primary debulking surgery (PDS) did not improve survival outcomes in patients with advanced ovarian cancer and was associated with a high incidence of perioperative morbidity. We compared survival outcomes and morbidity between patients who underwent highly aggressive and less aggressive surgery at our hospital; patients with high tumor loads were treated with neoadjuvant chemotherapy (NACT), followed by aggressive surgery. Methods: This retrospective study included 209 patients with a surgical complexity score (SCS) ≥8, who underwent aggressive surgery between January 2008 and December 2018. PDS, followed by chemotherapy was performed in this study, and NACT followed by interval debulking surgery (IDS) was performed in patients with excessively high tumor loads, a poor general condition, or unresectable lesions in whom PDS was contraindicated. Based on the median SCS, patients were categorized into highly aggressive surgery and less aggressive surgery groups, and we performed an intergroup comparison of progression-free survival (PFS), overall survival (OS), and perioperative morbidity. Results: The median SCS was 13 in all cohorts. The less aggressive surgery group (SCS < 13) and the highly aggressive surgery group (SCS≥13) included 83 and 126 patients, respectively. The peritoneal cancer index in the highly aggressive surgery group was higher than that in the less aggressive surgery group (20 vs. 9). Notably, 52 patients (63%) underwent PDS in the less aggressive surgery group, and 104 patients (83%) underwent IDS after NACT in the highly aggressive surgery group. No intergroup difference was observed in patients without any residual disease (less aggressive surgery group: 74 patients [89%] vs. highly aggressive surgery group: 118 patients [94%], p = 0.245). The median PFS in the less- and highly aggressive surgery groups was 32 months (95% confidence interval [CI] 24–45) and 31 months (95% CI 27–34) (log-rank test, p = 0.622; Wilcoxon test, p = 0.926), respectively. The median OS in the less- and highly aggressive surgery groups was 99 months (95% CI 59–not reached) and 75 months (95% CI 56–106) (log-rank test, p = 0.390; Wilcoxon test, p = 0.799), respectively. Severe perioperative complications (Clavien-Dindo grade ≥IIIb) occurred in 4 patients (4.8%) and 8 patients (6.4%) in the less- and highly aggressive surgery groups, respectively (p = 0.767). Conclusions: Aggressive surgery benefits both patients with less advanced and advanced ovarian cancer. Selection of the optimal timing of debulking surgery may lead to better survival outcomes without an increase in perioperative morbidity in patients with high tumor loads, who undergo highly aggressive surgery.

Complete resection is important to improve the prognosis of advanced ovarian cancer. The efficacy of the soft coagulation mode built into the VIO system has been reported in hepatic and pancreatic surgeries and in retroperitoneal lymphadenectomy.[1–3][1] However, there are no reports or surgical

Background: This study aimed to evaluate the safety and efficacy of weekly paclitaxel and cisplatin chemotherapy (wTP) in patients with ovarian cancer who developed carboplatin hypersensitivity reaction (HSR). Methods: We retrospectively investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed carboplatin HSR during previous chemotherapy (carboplatin and paclitaxel) at our institution between 2011 and 2019. After premedication was administered, paclitaxel was administered over 1 h, followed by cisplatin over 1 h (paclitaxel 80 mg/m2, cisplatin 25 mg/m2, 1, 8, 15 day/4 weeks). We investigated the incidence of patients who successfully received wTP for at least one cycle, treatments compliance, progression-free survival (PFS), and overall survival (OS). Results: The median number of wTP administration cycles was 4 (Interquartile Range IQR, 3–7), 71 patients (83%) successfully received wTP, and 15 patients (17%) developed cisplatin HSR. The efficacy of treatment was as follows: 55 (64%) patients completed the scheduled wTP, 9 (10%) patients discontinued due to HSR to cisplatin within 6 cycles, 1 (1%) patient discontinued due to renal toxicity (grade 2) at the 6th cycle, and 21 (24%) patients discontinued due to progressive disease within 6 cycles. The median PFS and OS after administration of wTP were 10.9 months (95% CI: 7.7–17.7) and 25.9 months (95% CI: 19.0–50.2), respectively. Conclusions: wTP was safe and well-tolerated in patients who developed carboplatin HSR.

Antiemetic recommendations during concurrent chemoradiotherapy (cisplatin-based concurrent chemoradiotherapy (CCRT)) have not been established yet. The aim of this study was to investigate whether the combination of palonosetron plus aprepitant, without routine use of dexamethasone, could alleviate chemoradiotherapy-induced nausea and vomiting (CRINV). This was a non-randomized, prospective, single-center, open phase II study. Patients with cervical cancer, who were treated with daily low-dose cisplatin (8 mg/m2/day) and concurrent radiation (2 Gy/day, 25 fractions, five times a week), were enrolled in this study. All patients received intravenous palonosetron (0.75 mg on day 1 of each week) and oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3 of each week). The primary endpoint was the percentage of patients with a complete response, defined as no emetic episodes and no use of antiemetic rescue medication during the treatment. Twenty-seven patients (median age, 50 years; range, 33–72 years) were enrolled in this study between June 2013 and April 2014. A total of 13 (48 %) patients showed a complete response to the antiemetic regimen, while 8 patients (30 %) had emetic episodes and 6 patients (22 %) used rescue medication without emetic episodes. No severe adverse effects caused by palonosetron plus aprepitant were observed. The combination of palonosetron plus aprepitant was permissive for the prevention of CRINV. This regimen should be considered for patients in whom dexamethasone is contraindicated or not well tolerated.

Objective The aim of the study was to evaluate the association between tumor histology and serum sex hormone levels in postmenopausal women with ovarian tumors. Methods We preoperatively measured serum levels of gonadotropins and sex steroids, including estradiol, progesterone, and testosterone, in 69 postmenopausal women who underwent surgical resection for ovarian tumors. Tumors were classified as surface epithelial-stromal tumors, sex cord-stromal tumors, germ cell tumors, and metastatic tumors. Surface epithelial-stromal tumors were divided into mucinous, serous, clear cell, and endometrioid tumor subgroups. Patients were divided into two groups depending on tumor type: mucinous and nonmucinous, and any association between these tumor types and serum sex hormone levels were evaluated. Results Univariate analyses revealed that serum sex steroid levels were significantly higher in women with mucinous ovarian tumors compared with women with other tumor types. Serum gonadotropin levels, age, body mass index, tumor size, and tumor malignancy status did not affect the sex steroid levels. Multivariate analysis evaluating sex steroid levels and tumor histology revealed that high serum progesterone levels were significantly and independently associated with mucinous ovarian tumors. A serum progesterone cut-off level of at least 1.3 nmol/L was the most accurate for differentiating mucinous tumors from other tumor types (area under the curve, 0.81; sensitivity, 75%; and specificity, 86%). Conclusions Serum progesterone levels were significantly elevated in postmenopausal women with mucinous ovarian tumors. In these women, serum progesterone levels may thus represent a useful biomarker for predicting tumor histology preoperatively, which would aid treatment planning.

e18086 Background: Advanced ovarian clear cell carcinoma (ACCC, stage III/IV disease) is a rare tumor characterized by chemoresistance. To evaluate the efficacy of bevacizumab (Bev) for ACCC, we investigated the survival outcome of first-line treatment before and after the approval of Bev for ovarian cancer treatment in November 2013 in Japan. Methods: We recruited 28 consecutive patients diagnosed with ACCC at our institution between 2007 and 2018. We performed cytoreductive surgery and administered paclitaxel-carboplatin chemotherapy (paclitaxel: 80 mg/m2 + carboplatin area under the curve 2.0–3.0 mg/mL/min, weekly without break) as first-line chemotherapy. Bev (15 mg/kg/3 weeks) was also administered after its approval. We compared progression-free survival (PFS) between Bev+ group (n = 18) and Bev- group (n = 10) using the Kaplan–Meier method and a Cox regression model. Results: Patients characteristics were similar between the Bev- and Bev+ groups. The median age was 54 years and 53 in the Bev- and Bev+ groups (p = 0.810), respectively. Three (30%) and 4 (22%) patients in the Bev- and Bev+ groups had stage IV disease (p = 0.674), respectively. The performance status (PS) was ≥2 in 1(10%) and 5 (28%) patients in the Bev- and Bev+ groups (p = 0.375), respectively. Peritoneal cancer index was 5.5 and 5.5 in the in Bev- and Bev+ groups (p = 0.727), respectively. Primary debulking surgery was performed in 10 (100%) and 11 (61%) patients in the Bev- and in Bev+ groups, respectively. Surgical complexity score was 9 and 9 in the Bev- and in Bev+ groups (p = 0.700), respectively. Completeness of resection was higher in the Bev- group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev+ group received ≥21 cycles of Bev. The median PFS increases from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis revealed that Bev use (p = 0.005) and PS < 2 (p = 0.035) were independent prognostic factors for PFS; however, completeness of resection was not a prognostic factor (p = 0.052). Conclusions: Bev in first-line chemotherapy improves the survival outcome of ACCC. [Table: see text]

6058 Background: Carboplatin (CBDCA) hypersensitivity reactions (HSR) often occur in patients with ovarian cancer. Once CBACA HSR occurs, it is difficult to use platinum even though the patients had platinum-sensitive disease and consequently the survival of the patients cannot be prolonged. We had administered weekly paclitaxel and cisplatin (CDDP) chemotherapy (wTP) for patients with ovarian cancer who developed CBDCA HSR in previous chemotherapy. We investigated the safety and efficacy of wTP. Methods: We investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed CBDCA HSR in previous chemotherapy (paclitaxel/CBDCA) at our institution between 2011 and 2019. After premedication was administered, paclitaxel and sequentially CDDP were administered as one hour infusion, respectively (paclitaxel 80 mg/m2, CDDP 25 mg/m2; 1, 8, 15 day/4 weeks). Results: The median cycle of the previous chemotherapy of CBDCA was 8 (interquartile range [IQR], 6–11). The grade of CBDCA HSR was 1 in 57 (66%), 2 in 26 (30%), and, 3 in 1 (1%) patient(s). WTP was administered for the first line in 21 (24%), second line in 35 (41%) and third or more line in 30 patients (34%). The median cycles of wTP administration was 4 (IQR, 3–7). We observed that severe CDDP HSR did not occur in any patients and 15 patients (17.4%, grade 1, 10 patients; grade 2, 5) developed CDDP HSR. All CDDP HSR were successfully managed with infusion interruption and Hydrocortisone Sodium Phosphate administration. There was no relation between the grade of CBDCA HSR in the previous chemotherapy and the rate of CDDP HSR (p = 0.363). Progression-free survival and overall survival after administration of wTP were 10.9 months (95% CI: 7.7–17.7) and 25.9 months (95%Ci: 19.0–50.2), respectively. Conclusions: 71 patients (82%) who developed CBDCA HSR in previous chemotherapy were able to continue administration of wTP without CDDP HSR. WTP was safe and effective for the patients who developed CBDCA HSR. [Table: see text]

Objective Advanced ovarian cancer commonly disseminates to the diaphragm. A complete removal of a bulky diaphragmatic disease is sometimes difficult. We present the surgical technique that we used for resecting a large nodular and disseminated subphrenic tumor that occupied the subphrenic space using liver mobilization and the Pringle maneuver. Methods The patient was a 78-year-old woman with FIGO IIIC left ovarian carcinosarcoma. She had a metastatic subphrenic tumor measuring 12 cm in diameter. The subphrenic tumor resection was performed as a part of cytoreductive surgery. Owing to the adherence between the right diaphragm and the liver, the diaphragm was resected in full thickness. The liver was mobilized by keeping the resected part of the diaphragm attached to the liver. The subphrenic tumor and the attached diaphragm were resected en bloc by excising the liver which was adjacent to the tumor. During the resection, the hepatoduodenal ligament was clamped with a Satinsky clamp (Pringle maneuver) to reduce blood loss from the liver. The diaphragmatic defect was closed with permanent mesh. Results We achieved complete cytoreduction with no residual tumor without ICU admission. No severe intraoperative or postoperative complications were observed. The patient was discharged on postoperative day 22 and started adjuvant chemotherapy on postoperative day 27. The histological examination revealed the carcinosarcoma in the diaphragmatic peritoneum, although the carcinosarcoma did not infiltrate the adjacent liver. Conclusion Resection of a metastatic bulky subphrenic tumor using liver mobilization and the Pringle maneuver is a feasible technique for the treatment of advanced ovarian cancer.

Dose-dense chemotherapy consisting of a combination of epirubicin and cyclophosphamide (EC) improves the survival of patients with breast cancer. Although pegfilgrastim was used at a subcutaneous dose of 6.0 mg in a pivotal study of dose-dense EC treatment, pegfilgrastim at a dose of 3.6 mg has been approved in Japan. We have assessed the feasibility of dose-dense EC treatment supported with a 3.6 mg dose of pegfilgrastim by evaluating the relative dose intensity (RDI) and safety of the treatment, together with measuring the pegfilgrastim concentrations remaining on the day of starting the next cycle of chemotherapy. Patients with primary breast cancer received a total of 4 cycles of dose-dense EC treatment every 2 weeks, together with a subcutaneous injection of 3.6 mg pegfilgrastim on the day after chemotherapy. The serum granulocyte colony-stimulating factor (G-CSF) concentrations were measured on the 15th day of every chemotherapy cycle. From March 2015 through to July 2016, a total of 51 patients (median age 51 years; range 33–73 years) were studied. The mean RDI was 95.2% (range 60.0–100%). Although most adverse events were consistent with those reported in previous studies, pneumocystis pneumonia developed in two patients during the following course of docetaxel treatment. The median serum G-CSF concentration was 92.5 (range 30.4–440) pg/ml. With support provided by pegfilgrastim injection at a dose of 3.6 mg, dose-dense EC is feasible and associated with maintenance of a high RDI. There was no clinically significant accumulation of serum G-CSF concentrations associated with the use of a 3.6 mg dose of pegfilgrastim at 2-week intervals.

Objective We evaluated the efficacy and safety of aggressive surgery for advanced ovarian cancer at a non-high-volume center. Materials and methods We evaluated consecutive patients with stage III/IV ovarian, fallopian, and peritoneal cancer undergoing elective aggressive surgery from January 2008 to December 2012, which encompassed the first 5years after implementing an aggressive surgery protocol. After receiving appropriate training for 9months, a gynecological surgical team began performing multi-visceral resections. Primary debulking surgery was chosen when the team considered that optimal surgery was achievable on the initial laparotomy, otherwise interval debulking surgery was chosen (the protocol treatments). Analysis was performed on an intention-to-treat basis (full-set analysis), and outcomes were compared to those of patients who underwent standard surgery between 2000 and 2007. Results Of 106 consecutive patients studied, 87 (82%) underwent aggressive surgery per protocol and 19 were excluded. Serous carcinoma was the most common disease (78%), followed by clear cell carcinoma (7%), and 32% of the patients had stage IV disease. The respective median progression-free and overall survival rates increased from 14.6 and 38.1months before implementation, respectively, to 25.0 and 68.5months after implementation, respectively. Complete resection was achieved in 83 of the 106 patients (78%), and the surgical complexity score was high (>8) in 61 patients (58%); although there was no mortality within 12weeks of surgery, major complications occurred in 8 patients. Conclusions We confirmed that outcomes improved after implementing aggressive surgery for advanced ovarian cancer, without causing a significant increase in mortality. Factors enhancing survival outcomes are discussed.

Cisplatin, a first-generation platinum derivative, is one of the most widely used anticancer agents and can treat a broad spectrum of malignancies. Cisplatin-induced nephrotoxicity is a major dose-limiting side effect resulting from damage to the proximal tubules of the kidney. This nephrotoxicity can be prevented by lowering the concentration of cisplatin and shortening the period of cisplatin exposure to the proximal tubules. In clinical practice, high-volume hydration(3 L intravenous isotonic saline), forced diuresis(mannitol and/or furosemide), and magnesium supplementation have been generally used to lower the risk of cisplatin-induced nephrotoxicity. Short hydration(short-term, low-volume hydration with oral fluid intake)has recently been undertaken among patients with reserved renal function and good performance status, especially in outpatient settings. Carboplatin is a second-generation platinum-based agent that is almost completely excreted from the kidneys following its administration. Its pharmacokinetics can be predicted based on the glomerular filtration rate(GFR). The area under the blood concentration-time curve(AUC), an indicator of drug exposure volume in the body, is closely correlated with hematotoxicity and antitumor effect. It is now a widespread practice to set carboplatin doses based on the GFR after establishing a target AUC. This article describes the characteristics of these 2 platinum-based drugs, focusing on the recommendations based on the recently published guidelines regarding nephropathy in patients undergoing cancer drug therapy.