Association between effector-type regulatory T cells and immune checkpoint expression on CD8+ T cells in malignant ascites from epithelial ovarian cancer.

BACKGROUND: Regulatory T cells (Tregs) play an important role in the antitumor immune response in epithelial ovarian cancer (EOC). To understand the immune-inhibitory networks of EOC, we addressed the association between Tregs and immune checkpoint expression on T cells in the tumor microenvironment of EOC. METHODS: A total of 41 patients with stage IIIC and IV EOC were included in the analysis. We harvested cells from malignant ascites and investigated them using multi-color flow cytometry. We categorized the Tregs into 3 groups: effector-type Tregs, naïve Tregs and non-Tregs, based on the expression patterns of CD45RA and Foxp3 in CD4+ T cells. Furthermore, the relationships between the expression of various immune checkpoint molecules, such as PD-1, on CD8+ T cells and each of the Treg subtypes was also evaluated. RESULTS: The median frequency of naïve Tregs, effector-type Tregs and non-Tregs were 0.2% (0-0.8), 2.0% (0-11.4) and 1.5% (0.1-6.3) in CD4+ T cells of malignant ascites from EOC patients, respectively. A high frequency of effector-type Tregs was associated with high-grade serous carcinoma compared with the other histotypes. Patients with higher proportions of effector-type Tregs showed a trend towards increased progression-free survival. We also demonstrated a correlation between a higher proportion of effector-type Tregs and increased PD-1 expression on CD8+ T cells. In addition, C-C chemokine receptor 4 expression was also observed in effector-type Tregs. CONCLUSION: These data suggest that multiple immune-inhibitory networks exist in malignant ascites from EOC patients, suggesting an approach towards combinational immunotherapies for advanced EOC patients.

Clinical significance of metabolism-related genes and FAK activity in ovarian high-grade serous carcinoma.

BACKGROUND: Administration of poly (ADP-ribose) polymerase (PARP) inhibitors after achieving a response to platinum-containing drugs significantly prolonged relapse-free survival compared to placebo administration. PARP inhibitors have been used in clinical practice. However, patients with platinum-resistant relapsed ovarian cancer still have a poor prognosis and there is an unmet need. The purpose of this study was to examine the clinical significance of metabolic genes and focal adhesion kinase (FAK) activity in advanced ovarian high-grade serous carcinoma (HGSC). METHODS: The RNA sequencing (RNA-seq) data and clinical data of HGSC patients were obtained from the Genomic Data Commons (GDC) Data Portal and analysed ( https://portal.gdc.cancer.gov/ ). In addition, tumour tissue was sampled by laparotomy or screening laparoscopy prior to treatment initiation from patients diagnosed with stage IIIC ovarian cancer (International Federation of Gynecology and Obstetrics (FIGO) classification, 2014) at the Saitama Medical University International Medical Center, and among the patients diagnosed with HGSC, 16 cases of available cryopreserved specimens were included in this study. The present study was reviewed and approved by the Institutional Review Board of Saitama Medical University International Medical Center (Saitama, Japan). Among the 6307 variable genes detected in both The Cancer Genome Atlas-Ovarian (TCGA-OV) data and clinical specimen data, 35 genes related to metabolism and FAK activity were applied. RNA-seq data were analysed using the Subio Platform (Subio Inc, Japan). JMP 15 (SAS, USA) was used for statistical analysis and various types of machine learning. The Kaplan-Meier method was used for survival analysis, and the Wilcoxon test was used to analyse significant differences. P < 0.05 was considered significant. RESULTS: In the TCGA-OV data, patients with stage IIIC with a residual tumour diameter of 1-10 mm were selected for K means clustering and classified into groups with significant prognostic correlations (p = 0.0444). These groups were significantly associated with platinum sensitivity/resistance in clinical cases (χ2 test, p = 0.0408) and showed significant relationships with progression-free survival (p = 0.0307). CONCLUSION: In the TCGA-OV data, 2 groups classified by clustering focusing on metabolism-related genes and FAK activity were shown to be associated with platinum resistance and a poor prognosis.

Opioid withdrawal syndrome developing after long-term administration of naldemedine.

OBJECTIVE: One of the side effects of opioid administration is opioid-induced constipation (OIC). To address this side effect, the oral peripheral µ opioid receptor antagonist naldemedine was developed. As this drug does not cross the blood-brain barrier, it is thought that it does not lead to opioid withdrawal syndrome (OWS) with central nervous system symptoms. METHODS: Here, we report a cancer patient who presented with symptoms centered round anxiety and irritation 4 months after administration of naldemedine for OIC and who was diagnosed with OWS after close investigation. RESULTS: The patient was a 65-year-old female who had surgery for stage IB endometrial cancer 4 years previously, but experienced recurrence involving the pelvis 2 years later. Medical narcotics were used to control pain, but naldemedine was started to control subsequent constipation. When naldemedine-related OWS was suspected and the administration of naldemedine discontinued, the above symptoms disappeared within two days, and no recurrence was observed thereafter. SIGNIFICANCE OF THE RESULTS: For patients receiving naldemedine, it is necessary to consider the possibility of OWS regardless of the period of administration in order to maintain patient quality of life.

An international randomized phase III trial of pulse actinomycin-D versus multi-day methotrexate for the treatment of low risk gestational trophoblastic neoplasia; NRG/GOG 275.

OBJECTIVES: Methotrexate and actinomycin-D are both effective first-line drugs for low-risk (WHO score 0-6) Gestational Trophoblastic Neoplasia (GTN) with considerable debate about which is more effective, less toxic, and better tolerated. The primary trial objective was to test if treatment with multi-day methotrexate (MTX) was inferior to pulse actinomycin-D (ACT-D). Secondary objectives included evaluation of severity and frequency of adverse events, and impact on quality of life (QOL). METHODS: This was a prospective international cooperative group randomized phase III two arm non-inferiority study (Clinical Trials Identifier: (NCT01535053). The control arm was ACT-D; the experimental arm was multi-day MTX regimen (institutional preference of 5 or 8 day). Outcome measures included complete response rate, recurrence rate, toxicity, and QOL as measured by FACT-G and FACIT supplemental items. RESULTS: The complete response rates for multi-day methotrexate and pulse actinomycin-D were 88% (23/26 patients) and 79% (22/28 patients) (p = NS) respectively, there were two recurrences in each arm, and 100% of patients survived. Significant toxicity was minimal, but mouth sores (mucositis), and eye pain were significantly more common in the MTX arm (p = 0.001 and 0.01 respectively). Quality of life showed no significant difference in overall quality of life, body image, sexual function, or treatment related side effects. The study was closed for low accrual rate (target 384, actual accrual 57), precluding statistical analysis of the primary objective. CONCLUSIONS: The complete response rate for multi-day methotrexate was higher than actinomycin-D, but did not reach statistical significance. The multi-day MTX regimens were associated with significantly more mucositis and were significantly less convenient.

Tumor-related mutations in cell-free DNA in pre-operative plasma as a prognostic indicator of recurrence in endometrial cancer.

OBJECTIVES: Circulating tumor DNA (ctDNA) has potential as a basis for understanding the molecular features of a tumor non-invasively and for use as a diagnostic, prognostic, and disease-monitoring marker. The aim of this study was to evaluate the clinical roles of ctDNA in patients with endometrial cancer. METHODS: Since PIK3CA and KRAS are among the most common mutated genes in endometrial cancer, somatic mutations of these genes were investigated in tumor specimens and plasma collected before surgery, using droplet digital polymerase chain reaction (ddPCR). ctDNA was defined as positive when the corresponding mutation between somatic and plasma was also detected in plasma cell-free DNA (cfDNA). Relationships of the presence of ctDNA with clinicopathological features were examined. RESULTS: Somatic PIK3CA and/or KRAS mutations were found in 68 (34%) of 199 patients with endometrial cancer. Ten (14.7%) of 68 patients had similar mutations in cfDNA. ctDNA detected in pre-operative plasma was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.008), histology (p=0.028), and lymphovascular space invasion (p=0.002), and with shorter recurrence-free and overall survival (p=0.004 and p=0.010, respectively, by log-rank test). CONCLUSION: Tumor-related ctDNA detected in plasma before surgery was associated with poorer oncologic outcome on univariate analysis in patients with endometrial cancer harboring PIK3CA or KRAS mutations.

Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma.

Endometrial endometrioid carcinoma is usually divided into three histological subgroups: grade 1 (G1), grade 2 (G2), and grade 3 (G3). Most cases of endometrial endometrioid carcinoma G1/2 have a favorable prognosis, although some can have unfavorable outcomes, especially when they involve elderly patients, with similarities to endometrioid carcinoma G3 and serous carcinoma. This retrospective study evaluated whether TP53 abnormalities in endometrial endometrioid carcinoma could be used to supplement the current grading system and improve its ability to predict clinical outcomes. Immunohistochemical expression of TP53 was analyzed using tissue microarrays from the surgically resected specimens of 475 patients with endometrial endometrioid carcinoma. Weak or moderate expression was defined as TP53-normal expression, while absent or strongly positive expression was defined as TP53-aberrant expression. The endometrial endometrioid carcinomas had originally been diagnosed as G1 (69%), G2 (18%), and G3 (13%). Univariate analyses revealed that TP53-aberrant expression was associated with poor survival in G1 and G2 cases, but not G3 cases. In addition, age (<60 years vs. ≥60 years) was correlated with TP53-aberrant expression in G1 cases (3% vs. 16%, p = 0.001), but not in G2 or G3 cases. Based on immunohistochemical TP53 expression, the endometrial endometrioid carcinomas were reclassified using a prognostic grading system as high-grade (G1 or G2 with TP53- aberrant expression, and G3 with TP53-normal or -aberrant expression) or low-grade (G1 or G2 with TP53-normal expression). The multivariate analyses revealed that the prognostic grading system (using histological grade and TP53 expression) could independently predict poor progression-free survival (hazard ratio: 2.91, p < 0.001) and overall survival (hazard ratio: 3.62, p < 0.001). Therefore, combining immunohistochemical TP53 expression with the traditional histological grading system for endometrial endometrioid carcinoma may help improve its ability to accurately predict the patient's prognosis.

Association of statins, aspirin, and venous thromboembolism in women with endometrial cancer.

OBJECTIVE: The anti-thrombogenic effects of statins and aspirin have been reported in various malignancies but have not been well examined in endometrial cancer. This study examined the association between statin and/or aspirin use and venous thromboembolism (VTE) risk in endometrial cancer. METHODS: This is a multi-center retrospective study examining 2527 women with endometrial cancer between 2000 and 2015. Statin and aspirin use at diagnosis was correlated to VTE risk during follow-up on multivariable analysis. RESULTS: There were 132 VTE events with a 5-year cumulative incidence rate of 6.1%. There were 392 (15.5%) statin users and 219 (8.7%) aspirin users, respectively. On multivariable analysis, statin use was associated with an approximately 60% decreased risk of VTE when compared to non-users (5-year cumulative rates 2.5% versus 6.7%, adjusted-hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.19-0.92, P = 0.030) whereas aspirin did not demonstrate statistical significance (2.0% versus 6.5%, adjusted-HR 0.54, 95%CI 0.19-1.51, P = 0.24). There was a trend of joint effect between statin and aspirin although it did not demonstrate statistical significance: VTE risks for dual statin/aspirin user (adjusted-HR 0.27, 95%CI 0.04-2.07), statin alone (adjusted-HR 0.40, 95%CI 0.18-0.93), and aspirin alone (adjusted-HR 0.51, 95%CI 0.16-1.64) compared to non-use after adjusting for patient characteristics, tumor factors, treatment types, and survival events (P-interaction = 0.090). When stratified by statin type, simvastatin demonstrated the largest reduction of VTE risk (5-year cumulative rates 1.1% versus 6.7%, adjusted-HR 0.17, 95%CI 0.02-1.30, P = 0.088). Obesity, absence of diabetes mellitus, type II histology, and recurrent disease were the factors associated with decreased VTE risk with statin use (all, P-interaction<0.05). CONCLUSION: Our study suggests that statin use may be associated with decreased risk of VTE in women with endometrial cancer.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Significance of abnormal peritoneal cytology on survival of women with stage I-II endometrioid endometrial cancer.

OBJECTIVE: To examine survival of women with stage I-II endometrioid endometrial cancer whose peritoneal cytology showed malignant or atypical cells (abnormal peritoneal cytology). METHODS: This is a multi-center retrospective study examining 1668 women with stage I-II endometrioid endometrial cancer who underwent primary hysterectomy with available peritoneal cytology results between 2000 and 2015. Abnormal peritoneal cytology was correlated to clinico-pathological characteristics and oncological outcome. RESULTS: Malignant and atypical cells were seen in 125 (7.5%) and 58 (3.5%) cases, respectively. On multivariate analysis, non-obesity, non-diabetes mellitus, cigarette use, and lympho-vascular space invasion were independently associated with abnormal peritoneal cytology (all, P<0.05). Abnormal peritoneal cytology was independently associated with decreased disease-free survival (hazard ratio 3.07, P<0.001) and cause-specific survival (hazard ratio 3.42, P=0.008) on multivariate analysis. Abnormal peritoneal cytology was significantly associated with increased risks of distant-recurrence (5-year rates: 8.8% versus 3.6%, P=0.001) but not local-recurrence (5.2% versus 3.0%, P=0.32) compared to negative cytology. Among women with stage I disease, abnormal peritoneal cytology was significantly associated with an increased risk of distant-recurrence in the low risk group (5-year rates: 5.5% versus 1.0%, P<0.001) but not in the high-intermediate risk group (13.3% versus 10.8% P=0.60). Among 183 women who had abnormal peritoneal cytology, postoperative chemotherapy significantly reduced the rate of peritoneal recurrence (5-year rates: 1.3% versus 9.2%, P=0.039) whereas postoperative radiotherapy did not (7.1% versus 5.5%, P=0.63). CONCLUSION: Our study suggests that abnormal peritoneal cytology may be a prognostic factor for decreased survival in women with stage I-II endometrioid endometrial cancer, particularly for low-risk group.

[Combination Therapy of Pregabalin with Tramadol for Treatment of Peripheral Neuropathy in Patients with Gynecological Cancer Receiving Taxane Containing Chemotherapy].

Taxane-based regimens are often used in gynecologic cancer chemotherapy. Chemotherapy-induced peripheral neuropathy( CIPN)is one of the typical side effects caused by taxanes. Grade 2 or higher CIPN is observed in 5% to 30% of ovarian cancer patients who are treated with paclitaxel, which is recognized as one of the unmanageable side effects leading to treatment interruption. We retrospectively investigated the significance of combination therapy of pregabalin with tramadol for CIPN in patients with gynecological cancer. In the current study, 19 patients(19/22; 86%)were administered pregabalin with tramadol orally for at least 1week, and we observed improvement of the CIPN in 15 patients(15/19; 79%).We suggest that the combination therapy of pregabalin with tramadol has a positive impact on the CIPN in patients under a taxane-based chemotherapy.

Cervical lymphoepithelioma-like carcinoma with deficient mismatch repair and loss of SMARCA4/BRG1: a case report and five related cases.

BACKGROUND: We encountered a cervical lymphoepithelial carcinoma (LEC) possessing a predominantly solid architecture with deficient mismatch repair (dMMR) and loss of expression of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex subunit. This is the first case report of LEC with dMMR and loss of SWI/SNF complex subunit. CASE PRESENTATION: A 34-year-old woman presented at our hospital with menstrual irregularities and abnormal vaginal bleeding. Magnetic resonance imaging revealed an exophytic mass in the posterior uterine cervix. Biopsy specimens confirmed squamous cell carcinoma with a 2018 International Federation of Gynecology and Obstetrics (FIGO) uterine cervical cancer stage of IB2. In a subsequent conization specimen, the tumor appeared exophytic. Microscopically, the tumor cells formed a predominant solid architecture. Abundant lymphocytic infiltration was observed. The pathological diagnosis indicated human papillomavirus (HPV)-associated squamous cell carcinoma with LEC pattern and pT1b2. Immunohistochemically, high programmed death-ligand 1 (PD-L1) expression, dMMR, and loss of the switch/sucrose non-fermentable family-related, matrix-associated, actin-dependent regulator of chromatin subfamily member 4 (SMARCA4)/BRG1, an SWI/SNF complex subunit, were observed. The patient underwent a radical hysterectomy and is alive without disease one year and five months later. Our analysis of five additional LEC cases revealed a consistent association with high-risk HPV and elevated PD-L1 expression. In addition to the present case, another patient exhibited dMMR. The SWI/SNF complex was retained except in the present case. The prognosis was favorable in all cases. CONCLUSIONS: This unique case of LEC with dMMR suggests a distinct clinical entity with potential immunotherapy implications. Analysis of the other five LEC cases revealed that LEC was immune hot, and immune checkpoint inhibitors may be effective. The two dMMR cases showed loss of MLH1 and PMS2 expressions, and prominently high tumor PD-L1 expression. In those cases, dMMR might have contributed to the morphological characteristics of LEC.

Robot-Assisted Partial Cystectomy Using the "Double Bipolar Method".

The "double bipolar method" (DBM) in robotic surgery has been widely used in Japanese general surgery and gynecology; however, it is not commonly used in the field of urology. A 55-year-old female was diagnosed with stage IA endometrial cancer. A 2-cm cystic lesion was incidentally observed at the dome of the bladder on magnetic resonance imaging. A simultaneous robot-assisted total hysterectomy and partial cystectomy using the da Vinci Xi system was planned. The gynecological procedure was first performed with the DBM, and the DBM was also used in the partial cystectomy without additional instruments to reduce surgical costs. Maryland bipolar forceps was used to excise the peritoneum, fat, and bladder wall without bleeding, enabling delicate and precise resection using the forceps' tips. Robot-assisted partial cystectomy using the DBM was feasible. When performing combined surgeries with other departments, if the DBM is already being utilized, it is worthwhile to attempt to decrease surgical cost.

Abnormal first-trimester fetal nuchal translucency and amniotic band syndrome.

We report a case of amniotic band syndrome diagnosed prenatally by serial sonographic examinations. Our initial sonographic image showed a large fetal nuchal translucency (NT) at 12 weeks' gestation. Repeated fetal ultrasound images revealed an amniotic band and right upper limb anomaly. Fetal MRI at 19 weeks' gestation revealed right forearm hypoplasia and pseudosyndactyly. The fetus was prenatally diagnosed with amniotic band syndrome and was suspected of having severe functional impairment of the deformed limb. The parents decided to terminate the pregnancy at 21 weeks' gestation. In fetuses with aneuploidy and various structural and genetic abnormalities, the NT thickness is increased in the first trimester. As far as we are aware, this is the first case report of increased NT and limb anomaly associated with amniotic band syndrome. In chromosomally normal fetuses with increased NT, intensive sonographic follow-up should provide grounds for a precise antenatal diagnosis.

Laparoscopic cystectomy of ovarian teratoma in anti-NMDAR encephalitis: 2 case reports.

We present 2 case reports of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis that was successfully treated via laparoscopic ovarian cystectomy. In both cases, resection of an ovarian teratoma resulted in eventual full recovery. Although adnexectomy has been reported for tumor resection in anti-NMDAR encephalitis, we chose ovarian cystectomy to preserve ovarian function. The efficacy of cystectomy is equivalent to that of adnexectomy. This suggests that ovarian adnexectomy may not be necessary in anti-NMDAR encephalitis with ovarian teratoma.

A pilot study of mobile digital colposcopy in Japanese patients with cervical intraepithelial neoplasm.

Digital colposcopy built around a smartphone is becoming common, and this has advantages for telemedicine and data sharing by taking advantage of smartphone characteristics. However, digital colposcopy itself is not allowed in clinical practice in Japan. The aim of the present study was to investigate the feasibility of mobile digital colposcopy incorporating a smartphone for management of cervical screening in Japanese patients. Patients who underwent colposcopy at Saitama Medical University International Medical Center between July 2019 and February 2020 were enrolled in the present study. The inclusion criteria were women aged 21-65 years old referred for colposcopy following the Japanese standard of care. Written informed consent was obtained from all patients. A total of 40 patients (52 tests) were included in the study. Following the standard of care, acetic acid was applied to the cervix, which was then visualized using a traditional colposcope, with biopsies collected as necessary. The cervix was then visualized and an imaged was captured using a mobile digital colposcope incorporating a smartphone (EVA System; Mobile ODT). All images were collected before biopsy. Images were stored on a secure cloud portal for subsequent evaluation by the provider who performed the conventional colposcopy, and the diagnoses were compared. The present study was approved by the Institutional Review Board of Saitama Medical University International Medical Center (Hidaka, Japan). The match rates for diagnoses were 75%. The match rates for the actual (from conventional colposcopy) and assumed (from digital colposcopy) biopsy sites were 61, 16 and 23%, based on definitions of the 'same', 'almost the same' and 'different', respectively. The present results indicated that ≥75% cases were equivalent in digital colposcopy and conventional colposcopy. This suggests that digital colposcopy may not be inferior to conventional colposcopy.

Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m² versus 40 mg/m² in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial.

OBJECTIVE: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m² every 4 weeks. While 40 mg/m² has recently been used in clinical practice, evidence supporting this use remains lacking. METHODS: This phase III randomized, non-inferiority study compared progression-free survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m² PLD) and a standard arm (50 mg/m² PLD) until 10 courses, disease progression or unacceptable toxicity. Eligible patients had received ≤2 prior lines. Stratification was by performance status and PFS of prior chemotherapy (<3 months versus ≥3 months). The primary endpoint was PFS and secondary endpoints were overall survival (OS), toxicity profile, clinical response and tolerability. The total number of patients was 470. RESULTS: The trial was prematurely closed due to slow recruitment, with 272 patients randomized to the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with 234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was 4.0 months vs. 4.0 months (hazard ratio [HR]=1.065; 95% confidence interval [CI]=0.830-1.366) and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831-1.397). Hematologic toxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in the experimental arm, but no difference was seen in ≥grade 2 hand-foot skin reaction. CONCLUSION: Non-inferiority of 2 PLD dosing schedule was not confirmed because the trial was closed prematurely. However, recommendation of dose reduction of PLD should be based both on efficacy and safety. TRIAL REGISTRATION: UMIN Clinical Trials Registry Identifier: UMIN000003130.

Tolerability and Efficacy of Bevacizumab Monotherapy in Older Patients With Recurrent Ovarian Cancer.

BACKGROUND/AIM: The aim of this study was to compare the tolerability and efficacy of bevacizumab monotherapy between older and younger patients with recurrent ovarian cancer. PATIENTS AND METHODS: We enrolled 32 patients with recurrent ovarian cancer who were treated with bevacizumab monotherapy and divided them into those who were 65 years and older (n=12) and those younger than 65 years (n=20). RESULTS: Except for grade ≥3 proteinuria, incidences of adverse events did not differ significantly between the groups. Although older patients exhibited more frequently cycle delay caused by non-hematological toxicities, this difference was not significant. There was no significant difference in tumor response and survival between the groups. CONCLUSION: Bevacizumab monotherapy was tolerable and effective for older patients with recurrent ovarian cancer compared with younger patients.