bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of oral etoposide plus IV irinotecan for patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503).
Authors: Matsumoto Koji , Katsumata Noriyuki , Shibata Taro , Takano Tadao , Nishimura Ryuichiro , Kasamatsu Takahiro , Satoh Toyomi , Saitoh Motoaki , Nishimura Sadako , Matsumura Noriomi , Kobayashi Hiroaki , Aihara Satomi , Nogawa Takayoshi , Saito Toshiaki , Ushijima Kimio , Fukuda Haruhiko , Konishi Ikuo , Kamura Toshiharu 
Published: March 2020

5537 Background: Developing effective chemotherapy for patients (pts) with platinum (Pt) resistant ovarian cancer is unmet medical needs. Topoisomerase inhibitors, such as oral etoposide and iv irinotecan, have been reported to show some efficacy for Pt - resistant ovarian cancer as monotherapy. Combining these two agents should be an intriguing idea. Following phase 1 and feasibility study reported in ASCO2002 and 2005, this study aimed to assess safety and efficacy of oral etoposide plus iv irinotecan for pts with Pt -resistant and taxane pre-treated ovarian cancer (UMIN-CTR ID: UMIN000001837). Methods: Eligible pts are given etoposide at 50 mg/m2 p.o. from day 1 to 21, and irinotecan 70 mg/m2iv, at day1 and day15, repeated every 28 days, up to 6 cycles. Primary endpoint is response rate (RR), secondary endpoints are adverse events, progression-free survival (PFS), and overall survival (OS). As a SWOG two-stage design, at least 55 pts are required with one-sided alpha of 0.05, beta of 0.2 and expected and threshold value for primary endpoint as 35% and 20%. Sixty pts are to be registered. Results: From April 2009 to January 2012, 61 pts were entered to this study. One patient was ineligible, thus 60 pts were analyzed for the study. RR was 21.7% (1 CR + 12 PR, 89% C.I. 13.5 – 31.9 %, one-sided p=0.42). At the data cut-off at November 2012, median PFS and OS were 4.1 (95% C.I. 3.5 – 5.6) and 12.4 (95% C.I. 10.1 – 14.8) months, respectively. Six months-PFS was 35.0 %. For pts with Pt --free interval (PFI) >= three months (n = 33), RR was 30.3 % (95% C.I. 15.6 -48.7 %), median PFS and OS was 5.8and 16.9 months, respectively. For safety, G3/4 neutropenia, anemia, and thrombocytopenia were 60.0 %, 36.7 % and 11.7%, respectively. G3/4 non-hematological toxicities over 10 % were febrile neutropenia (FN) (18.3%), fatigue (13.3%), nausea (11.7 %) and anorexia (11.7 %). FN was more frequent in elderly pts of 65 years or older (28.6 %). Two treatment-related deaths occurred, both in elderly. Conclusions: As a whole, this regimen did not meet primary endpoint for further phase 3 study. Elderly pts should be treated very cautiously with this regimen. However, promising efficacy could be expected for those with PFI >= 3 months. Clinical trial information: UMIN000001837.
Benefit in progression-free survival (PFS) to expect based on CA125 reduction at week 6 in recurrent ovarian cancer (ROC) patients: CALYPSO phase III trial data (a GINECO-GCIG study).
Authors: Wilbaux Melanie , Henin Emilie , Colomban Olivier , Oza Amit M. , Pujade-Lauraine Eric , Freyer Gilles , Tod Michel , You Benoit 
Published: March 2020

5547 Background: Prediction of the expected survival benefit based on CA125 change in treated recurrent ovarian cancer (ROC) patients would be very useful. It may help for early selection of the best drug candidates during drug development, and for clinical trials. We used mathematical modeling to: 1) quantify the links between CA125 kinetics and progression-free survival (PFS) benefit, and 2) to estimate the CA125 decline required to observe a 50% PFS improvement. Methods: CALYPSO randomized phase III trial database, comparing 2 platinum-based regimens in ROC patients was used. The cohort was randomly split into a “learning dataset” (N=356) to estimate model parameters and a “validation dataset” (N=178) to validate model performances. A full parametric survival model was developed to quantify the links between tumor size changes; CA125 kinetics; prognostic factors and PFS. The predictive performance of the model was evaluated with simulations on the validation dataset. Results: PFS from 534 ROC patients was properly described by a parametric model with log-logistic distribution. The factors significantly linked to PFS were fractional changes in CA125 (ΔCA125) and in tumor size (ΔTS) from baseline at week 6; baseline CA125 (CA125BL); and patient therapy free interval. By reducing this model, ΔCA125 was a better predictor of PFS than ΔTS. Simulations verified the predictive performance of this model. Patients should achieve at least 49% ΔCA125 decline induced by treatment to observe 50% PFS improvement. This effect was independent on treatment arm. Conclusions: This is the first drug-independent parametric survival model quantifying links between PFS and CA125 kinetics in ROC. The CA125 modeled decline required to observe a 50% improvement in PFS in treated ROC patients was defined. It may be a surrogate marker of PFS gain, and may embody an early predictive tool for go/no go drug development decisions and for clinical trials. Validation in other datasets is warranted.
Does alopecia predict response to chemotherapy and prognosis in patients with advanced ovarian cancer? A meta-analysis of prospective randomized phase III trials with 5,114 patients of the AGO meta data base.
Authors: Sehouli Jalid , Erol Edibe , Richter Rolf , Reuss Alexander , Fotopoulou Christina , Mahner Sven , Pfisterer Jacobus , Du Bois Andreas 
Published: March 2020

5553 Background: Alopecia is a relevant side effect of chemotherapy. Our aim was to validate and unconfirmed broad patient´s opinion that a low rate of alopecia may predict poor response to chemotherapy and poor overall survival (OS). Methods: Individual patient data analysis of 5114 patients from four prospective randomised phase III trials conducted between 1995 and 2004 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Uni- and multivariate analyses were performed adjusted for age, number of cycles, individual trial, residual mass, tumor stage and histology. Results: 5,114 patients with ovarian cancer (OC) were analyzed. Most patients presented with advanced stage FIGO III/IV (87.8%). A median of 6 cycles were applied (range 0-11). Worst alopecia grade was 0 in 2.2%, 1 in 2.7% and 2 in 87.1%. In 8% patients no data about alopecia were documented. Patients with complete alopecia were more likely to achieve remission (OR 2.83, 95% CI 1.68-4.78 for grade 2 compared to grade 0/1) and had favourable progression-free survival of 19.0 months, (95%CI 18,2-19.7) compared to patients with grade 0/1 (13.8, 95%CI 12.2-15.3 and 14.3, 95%CI 10.8-17.8). Median OS was also significantly longer after grade 2 alopecia 48.8 months (95%CI 47.0-50.5), compared to 28.1 months (95%CI 22.3-33.9) and 33.9 months (95%CI24.3-43.6) for grade 0 and 1, respectively. This prognostic impact was not reteined in multivariate analysis. However, onset of alopecia was an independent prognostic factor for OS: patients with complete alopecia after cycle 3 had a favourable outcome compared to patient who experienced alopecia later during therapy (HR 1.22, 95%CI 1.02-1.46) or no alopecia (HR 1.29, 95%CI 0.98-1.70). Conclusions: We could show for the very first time that there is no evidence that the rate of alopecia is associated with the effect of chemotherapy is of any prognostic relevance. The observation that early onset of alopecia is associated with OS should be confirmed.
Comparison of two multimarker serum tests for the prediction of ovarian cancer in women with a pelvic mass.
Authors: Grenache David G. , Vucetic Zivjena 
Published: March 2020

5555 Background: Distinguishing between benign and malignant disease in women with a pelvic mass is difficult. OVA1 and ROMA are two multi-marker serum tests that are FDA-cleared to assess risk of malignancy in individuals with a pelvic mass. This study compared the accuracy of these tests for the prediction of ovarian cancer (OCa) in women with a pelvic mass. Methods: OVA1 and ROMA risk scores were determined in a subset of 146 serum samples obtained prospectively from pelvic mass patients. Patients were categorized by an initial cancer risk assessment (ICRA) performed by a physician and true cancer status determined surgically. 31 patients with malignancy (6 with a benign ICRA) and 115 patients with benign disease (25 with a malignant ICRA) were evaluated. Quest Diagnostics performed the OVA1 tests (CA-125, prealbumin, apolipoprotein A-1, β2-microglobulin, transferrin) and calculated and interpreted the risk score. ROMA tests (CA-125 and HE-4) were determined by automated immunoassay using an Abbott Architect analyzer. ROMA risk scores were calculated using published formulas and interpreted against cutpoints previously established for automated CA-125 and HE-4 performed by manual ELISA. Results: There were 70 pre- and 76 post-menopausal subjects. Of the 31 with malignancy, 26 had OCa (54% >stage II), 5 with an ICRA of benign. ROC curve analysis of the entire cohort produced an AUC of 0.88 (95% CI 0.80-0.95) and 0.93 (95% CI 0.87-0.99) for OVA1 and ROMA, respectively. OVA1 had a sensitivity of 0.97 and a specificity of 0.55. ROMA had a sensitivity of 0.84 and a specificity of 0.83. The sensitivity of OVA1 for OCa in the ICRA benign cohort (N = 5) was 0.80 and for ROMA was 0.40. The respective specificity for benign disease in this cohort (N=90) was 0.64 and 0.90. The sensitivity of ROMA for OCa increased to 0.60 with a slight decrease in specificity (0.87) when a cutpoint determined by ROC curve analysis was used. Conclusions: Overall, OVA1 and ROMA have similar performance characteristics. In women with an ICRA of benign, OVA1 was more sensitive among those who had OCa but ROMA was more specific among those who did not. The use of a ROMA cutpoint specific for the combination of automated CA-125 and HE-4 tests improved sensitivity.
Clinical relevance of VEGF-receptor status in primary ovarian cancer: A pilot study for future biomarker analyses.
Authors: Wimberger Pauline , Chebouti Issam , Kuhlmann Jan Dominik , Kimmig Rainer , Kuhlisch Eberhart , Lachmann Robert , Kasimir-Bauer Sabine 
Published: March 2020

5556 Background: Antiangiogenic treatment in addition to platinum/taxane based chemotherapy was shown to improve progression-free survival in first- and second-line chemotherapy in ovarian cancer patients. Predictive markers for antiangiogenic treatment are of high interest. Therefore we investigated VEGF-receptor (VEGFR) expression as possible biomarker candidate in primary ovarian cancer tissue and its clinical impact. Methods: A total of 82 patients with primary ovarian cancer were enrolled into this study. Primary tumor tissue was analyzed for the expression of VEGFR1, VEGFR2 and VEGFR3 by immunhistochemistry. Moreover, the presence of circulating tumor cells (CTC) in the blood was detected by immunomagnetic enrichment and multiplex reverse transcriptase-polymerase chain reaction (Adnatest Ovarian Cancer, Adnagen). Disseminated tumor cells (DTC) in the BM were identified by immunocytochemistry using the pancytokeratin antibodyA45B/B3 and subsequent automatic detection based on staining and cytomorphology. Results: Positivity for at least one VEGFR was observed in 43% of cases. The positivity rates for VEGFR1, -2 and -3 were 34%, 17% and 27%, respectively. VEGFR-status of the primary tumor neither correlated with established clinicopathogical parameters (age, FIGO-stage, nodal status, grading, histological subtype) nor with the presence of CTC or DTC. In addition, VEGFR-status does not provide prognostic significance in regard to progression-free and overall survival (OS). Nevertheless, a trend was observed that patients, being positive for VEGFR3 at primary diagnosis, were more likely to experience suboptimal debulking (p = 0.074). CTC-positivity after adjuvant therapy significantly correlated with OS, but multivariable analysis showed only residual tumor as prognostic factor for OS. Conclusions: The VEGFR-family, albeit frequently expressed in our patient cohort, provided neither prognostic nor predictive relevance, but could probably be a predictor for debulking efficiency. The implementation of VEGFR-status into future biomarker studies should carefully be considered.
Relationship of microRNA expression profiles and recurrence in advanced serous ovarian carcinoma.
Authors: Nam Eun Ji , Yim Ga Won , Kim Jae Hoon , Kim Sunghoon , Kim Sang Wun , Kim Jae-Wook , Kim Young-Tae 
Published: March 2020

5557 Background: Most patients with epithelial ovarian cancer eventually succumb to chemo-resistant disease. Although microRNAs have been recognized as important regulators of gene expression, little is known about microRNA expression profiles in recurrent serous ovarian carcinoma. We assessed the microRNA expression profiles which contribute to recurrence in advanced serous ovarian carcinoma. Methods: Eight pairs of primary and recurrent tumor samples from 8 patients with advanced serous ovarian carcinoma and 4 normal ovarian samples from patients treated for benign uterine disease between May 2006 and Dec 2012 were examined using miRNA microarray. microRNA profiling were validated using real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: Alterations of microRNA expression profiles in primary and recurrent tumor samples have similar patterns when compared with normal ovarian tissues. Among 31 up-regulated microRNAs more than 4-fold in primary tumors, 27 microRNAs were also significantly up-regulated in recurrent tumor samples. Likewise, Among 35 down-regulated microRNAs more than 4-fold in primary tumors, 34 microRNAs were also significantly down-regulated in recurrent tumor samples. Comparing to primary tumor, we found 60 microRNAs which were significantly up-regulated, including miR-630, 370, and 575, and 52 microRNAs which were significantly down-regulated, including miR-509-3p, 514a-3p, and 506-3p in recurrent serous ovarian carcinoma. Conclusions: Our results indicate that dysregulation of microRNAs may play a role in recurrence of serous ovarian carcinoma.
Clinical study of intraperitoneal injection bevacizumab (BV) combined with intraperitoneal hyperthermic perfusion chemotherapy (CT) in treatment of malignant ascites of ovarian cancer (OC).
Authors: Zhao Hui , Du Nan , Fu Yan , Wang Haibin , Fan Zhongyi 
Published: March 2020

5558 Background: To study the efficacy and safety of intraperitoneal injection BV combined with intraperitoneal perfusion CT in treatment of malignant ascites of OC and to investigate the clinical significance of the concentration change of vascular endothelial growth factor (VEGF). Methods: Patients with malignant ascites of OC were randomly divided into treatment group (n = 31) and control group (n = 27). All enrolled patients received TC (paclitaxel 135mg/m2, iv d1+ carboplatin AUC=5, iv d1), 1 time/3 weeks for 6 weeks. Patients in the control group were treated with intraperitoneal perfusion CT combined with intraperitoneal cisplatin (40mg/m2)1 time/2 weeks for 6 weeks. Besides the treatment of the control group, patients in the treatment group received intraperitoneal injection with BV 300mg after each intraperitoneal perfusion CT for 6 weeks. The improvement of life quality, efficacy and adverse effects were evaluated. The concentrations of VEGF and CA-125 in ascites of the two groups were assayed by ELISA method. Results: No severe side effect was observed in all the patients. The response rate of the treatment group was higher than that of the control group (90.32% vs. 59.26%, p < 0.05). The improvement rate of quality of life (QOL) of the patients in the treatment group was also higher than that of the patients in the control group (93.55 % vs. 48.15%, p < 0.05). The concentration of VEGF in ascites of the treatment group after treatment was lower than that before treatment (p < 0.05). And after treatment, the concentration of VEGF in ascites of treatment group was lower than that of the control group (p < 0.05). Conclusions: Intraperitoneal injection BV combined with intraperitoneal perfusion CT in the treatment of malignant ascites of OC is effective and safe. The concentration of VEGF and CA-125 levels, in ascites may be used as monitoring index for treatment effect of malignant ascites of OC with intraperitoneal injection BV.
Prognostic impact of estrogen receptor (ER) level changes during progression for patients with both ER-positive (ER+) primary breast cancer and paired recurrence.
Authors: Dieci Maria Vittoria , Barbieri Elena , Goubar Aicha , Andre Fabrice , Omarini Claudia , Bettelli Stefania Raffaella , Piacentini Federico , Ficarra Guido , Conte Pier Franco , Guarneri Valentina 
Published: March 2020

556 Background: We have previously reported that ER+ breast cancer (BC) patients (pts) who become ER-negative at relapse have a poorer overall survival (OS) as compared to those still ER+ at relapse [Dieci et al., Ann Oncol 2013]. Our aim is to evaluate whether, among the group of patients with an ER+ status on both primary and recurrence, changes in the level of ER expression may be of prognostic value. Methods: A total of 81 pts with ER+ primary BC and ER+ paired recurrence who underwent relapse biopsy at Modena University Hospital were studied. ER status was assessed by IHC and the cutoff for ER-positivity was >=10%. Samples were defined as ER-high (>50%) and ER-low (>=10% and <=50%). HER2-status was defined according to IHC and/or FISH results. OS was calculated as the time interval between primary BC diagnosis and death or last follow up. Results: Biopsied recurrences were: distant (86%) and local relapses (14%). Fifteen percent of primary and 21% of recurrent tumors were HER2-positive. Sixty-two pts maintained the same ER level (i.e. high or low) on both primary and relapse (ER-level concordant), whereas 19 changed from ER-high to ER-low or viceversa (ER-level discordant). No difference in OS was observed between the ER-level concordant and the ER-level discordant groups (p=0.3). However, we identified those pts whose ER-high primary BC turned into ER-low as having a particularly poor outcome. Indeed, 10yrs-OS rates were 51% for the ER-level concordant group, 50% for pts changing from ER-low to ER-high and 14% for pts changing from ER-high to ER-low (p=0.0019). Finally, we focused on the subset of pts starting from an ER-high primary BC and showing an ER+/HER2-negative phenotype on both primary and relapse (n=51). The drop of ER-level expression below the 50% cut-off at relapse was confirmed as a poor prognostic factor, as compared to pts maintaining an ER-high level (10yrs-OS 53% vs 17%, p=0.0063). Conclusions: We demonstrated that, even in the case of maintenance of the same single-receptor status (ER+) and/or tumor phenotype (ER+/HER2-negative) between primary BC and recurrence, relapse biopsy may provide relevant prognostic information.
Evaluating the accuracy of frozen section in borderline ovarian tumors.
Authors: Gupta Natasha , Rajpal Tanuja , Sharma Sameer 
Published: March 2020

5564 Background: The objective of this study was to evaluate accuracy of frozen section in borderline ovarian tumors and to determine the tumor characteristics that lead to higher likelihood of inaccurate intraoperative diagnosis (IAIOD). IAIOD is a clinical problem that restricts the diagnostic accuracy of frozen section in borderline ovarian tumors. Methods: This was a retrospective chart review of 622 consecutive cases that were diagnosed with pelvic mass and underwent surgery at busy gynecology services of two institutions, between 2006-2011. Of these cases, 52 were diagnosed as borderline ovarian tumors by frozen section. Experienced pathologists performed frozen section with second opinion from specialized gynecologic pathologists as needed. Terms such as “at least borderline” were also evaluated to help stratify patients. Frozen section and final permanent histology reports were compared. Patient and tumor characteristics that may cause IAIOD such as age of patient, histological subtype, size of tumor, bilaterality, CA-125 levels were studied. Staging was performed when borderline or malignant ovarian tumors were identified by frozen section. Results: Agreement of the frozen section results with final pathology was observed in 37 out of 52 patients with a diagnostic accuracy of 71.15 %. Under diagnosis occurred in 12 out of 52 patients and over diagnosis occurred in 3 out of 52 patients. Age >40 years, size of tumor >5 cm, bilaterality of tumors and CA-125 were not found significant in causing IAIOD when chi-square analysis was performed. Characterization by “at-least” borderline terminology at the time of frozen section did not help identify patients with higher likelihood of IAIOD. Conclusions: In our study, the rate of IAIOD was high, at 23% despite experienced pathologists and using “at-least borderline” terminology. Traditionally described features leading to inaccuracy with frozen sections, such as large tumors with mucinous histology did not increase the risk of IAIOD in this study. Patients with unilateral, small tumors and non-mucinous histology had greatest risk for IAIOD. Given this information, full staging of all borderline ovarian tumors identified at time of frozen section should remain the standard of practice.
Characterization of patients who received prior chemotherapy for advanced breast cancer (ABC) in BOLERO-2.
Authors: Campone Mario , Lebrun Fabienne , Noguchi Shinzaburo , Pritchard Kathleen I. , Burris Howard A. , Beck J. Thaddeus , Ito Yoshinori , Yardley Denise Aysel , Bachelot Thomas Denis , Pistilli Barbara , Melichar Bohuslav , Petrakova Katarina , Arena Francis P. , Erdkamp Frans , Harb Wael A. , Litton Jennifer Keating , Panneerselvam Ashok , El-Hashimy Mona , Taran Tanya , Gnant Michael 
Published: March 2020

557 Background: In patients with hormone-receptor–positive (HR+) breast cancer, endocrine therapy is the standard of care both in the adjuvant setting and as first-line treatment for ABC. For selected HR+ patients with ABC, chemotherapy (CT) may be utilized if disease burden is high and rapid symptom control is required (Barrios CH. GAMO.2010). In the phase 3 BOLERO-2 study (NCT00863655), 1 line of prior CT in the ABC setting was allowed. This subset analysis examined disease characteristics and the efficacy of everolimus (EVE) plus exemestane (EXE) in patients who received CT for ABC prior to BOLERO-2 study entry. Methods: In BOLERO-2, 724 patients with HR+, human epidermal growth factor receptor-2–negative (HER2–) ABC whose disease recurred or progressed during/after a nonsteroidal aromatase inhibitor were randomized 2:1 to EVE (10 mg/d) + EXE (25 mg/d) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local investigator review and confirmed by blinded independent central review. Results: A subset of 186 patients (26%) received prior CT for ABC: 125 in the EVE + EXE group and 61 in PBO + EXE. In this subset, 54% (67 of 186) of patients received prior CT only in the advanced setting and 46% (58 of 186) of patients received prior CT in both the neoadjuvant/adjuvant and advanced settings. Incidences of visceral metastases (67% vs 56%), multiple metastases (79% vs 66%), and ≥ 4 metastatic sites (18.3% vs 15%) were higher in ABC patients with prior CT for ABC at study entry versus those with no prior CT for ABC. Disease recurrence < 6 months from initial diagnosis was recorded in 32.2% (n = 60) of prior CT patients versus 17.3% (n = 93) of patients with no prior CT. Median PFS (by local assessment) in patients who received prior CT for ABC was substantially longer with EVE + EXE versus PBO + EXE (6.1 vs 2.7 mo; HR = 0.38; 95% CI, 0.27-0.53). PFS by central review showed similar results (7.1 vs 2.8 mo, respectively; HR = 0.42; 95% CI, 0.27-0.65). Conclusions: These results demonstrate that patients with HR+, HER2– ABC who received previous CT in the advanced setting had a higher tumor burden and derived clinically significant benefit from combination treatment with EVE + EXE. Clinical trial information: NCT00863655.