bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, phase III study of carboplatin plus paclitaxel for 8 cycles (CP8) versus carboplatin x 8 cycles plus paclitaxel x 4 cycles (C8P4) in advanced ovarian, fallopian, or primary peritoneal carcinoma.
Authors: Bamias Aristotelis , Timotheadou Eleni , Aravantinos Gerasimos , Pectasides Dimitrios G. , Papadimitriou Christos A. , Klouvas George , Xanthakis Ioannis , Eleftheraki Anastasia G , Soupos Nikolaos , Makatsoris Thomas , Rodolakis Alexandros , Vlachos George , Pentheroudakis George E. , Papanikolaou Alexandros , Tsiatas Marinos , Antsaklis Aris , Fountzilas George , Dimopoulos Meletios A. 
Published: March 2020

5033 Background: The combination of carboplatin/paclitaxel represents the standard 1st-line chemotherapy in advanced OC, FC, and PPC. The optimal duration of paclitaxel treatment has not been defined, while its use is associated with cumulative neurotoxicity in about 50% of patients, which becomes long-term in 15-20% of cases. We, therefore, designed a randomized study to investigate the effect of administering 4 instead of 8 cycles of paclitaxel in the combination carboplatin/paclitaxel on efficacy and tolerability of this treatment. Methods: Patients with FIGO stages IIC-IV OC, FC, PPC were included. Carboplatin AUC 6 and paclitaxel at 175 mg/m2 were used. Both agents were administered for 8 cycles in the CP8 arm, while paclitaxel was administered only for 4 cycles in the C8P4. The study was powered to detect a ± 15% difference in survival rate to a baseline rate of 50 % at the 3-year time point. Results: 389 pts were randomized (2/2004-1/2008) and 380 were eligible for analysis (CP8: 192, C8P4:188). The distribution (CP8 vs C8P4) of baseline characteristics were: stage III: 78% vs. 76%; IV: 12% vs. 15%, residual disease 0 cm: 25% vs. 22%, ECOG PS 0: 68% vs. 64%, serous carcinomas: 79% vs. 68%, tumor grade III: 56% vs. 63%. During a median follow up of 72.3 months 231 patients (111 [58%] in CP8 arm and 120 [64%] in the C8P4 arm) have died. Median PFS was significantly shorter in the C8P4 arm (21.41 vs. 16.46 months, HR [95% CI]: 1.36 [1.07-1.71], Wald’s p=0.011), while OS was similar between the two arms (53.41 vs. 46.59 months, HR [95% CI]: 1.18 [0.91-1.53], Wald’s p=0.211). Lower grade 3 or 4 neurotoxicity (1.9% vs. 10.8%, p< 0.001) but higher myelotoxicity (neutropenia 38.8% vs. 28.8%, p=0.031; thrombocytopenia 20% vs. 8.3%, p=0.004) was observed in the C8P4 arm. Conclusions: Lowering the total number of cycles of paclitaxel in 1st-line chemotherapy of advanced OC, FC, PPC resulted in similar OS but shorter median PFS and is not recommended in this setting. The reduction of neurotoxicity by limiting the total paclitaxel cycles to 4 is achieved at the expense of higher myelotoxicity.
13-gene signature to predict rapid development of brain metastases in patients with HER2-positive advanced breast cancer.
Authors: Duchnowska Renata , Jassem Jacek , Goswami Chirayu Pankaj , Gokmen-Polar Yesim , Li Lang , Thorat Mangesh A. , Flores Natasha , Hua Emily , Woditschka Stephan , Palmieri Diane , Steinberg Seth M. , Biernat Wojciech , Sosinska-Mielcarek Katarzyna , Szostakiewicz Barbara , Czartoryska-Arlukowicz Bogumila , Radecka Barbara , Tomasevic Zorica , Sledge George W. , Steeg Patricia Schriver , Badve Sunil S. ,   Polish Brain Metastasis Consortium
Published: March 2020

505 Background: Brain metastases (BM) of breast cancer constitute an important part of therapeutic failures and are associated with severe morbidity and mortality. The risk of BM is particularly high in HER2+ advanced breast cancer pts. We earlier developed in this group a 13-gene signature strongly predicting for rapid development of BM (J Clin Oncol 2008; 26: 45s). Now, we validated these results in an independent group of pts and on culture model system. Methods: Discovery group included 87 samples analyzed using cDNA synthesis, annealing, selection, extension, ligation and array hybridization (DASL). Independent validation group included 75 samples analyzed using quantitative reverse-transcriptase PCR. 3D culture validation model system used immortal, non-tumorigenic human MCF10A breast epithelial cells with and without ectopic expression of HER-2 and RAD51, a DNA double strand break repair gene (one of the three genes of this group overexpressed in 13-gene signature). The number and morphology of breast acini were scored using indirect immunoflourescence and confocal microscopy. Results: Median brain metastasis-free survival (BMFS) in the discovery group for ‘high’ vs. ‘low’ expression signature tumors was 36 months and 66 months, respectively (P=0.0068), and in the validation group 54 and 86 months, respectively (P=0.032). Short BMFS was also associated with ER-negativity; BMFS in the cohort of ‘high’ 13-gene signature and ER- tumors vs. other 3 groups was 31 months and 66 months in discovery group, and 41 and 77 months in validation group (P<0.0001 and P=0.02, respectively). Overexpression of RAD51 in MCF-10A breast cells altered their three-dimensional acinar morphology and increased the percentage of invasive structures by 6.5 fold, both in the presence and absence of HER2 overexpression. Conclusions: 13-gene signature and ER-negativity predict rapid development of BM in HER+ advanced breast cancer pts. RAD51 may promote aggressiveness in breast epithelial cells. These data may be useful in the design of BM preventive trials and may prompt new treatment strategies.
The impact of interval from surgery to chemotherapy and age in advanced-stage ovarian cancer: A GOG ancillary study.
Authors: Menzin Andrew , Java James , Lovecchio John L. , Chi Dennis , Tew William P. , Bookman Michael A. , Lichtman Stuart M. 
Published: March 2020

5057 Background: To determine if an age group exists for which the interval from surgery to the initiation of chemotherapy influences progression free survival (PFS) and overall survival (OS) among women with advanced ovarian cancer treated on GOG 182. Methods: GOG 182 was a prospective, randomized trial of first-line chemotherapy in patients with advanced ovarian cancer, including those with optimal and suboptimal residual disease. Patients were randomized to one of five chemotherapy arms, employing combinations of either two or three agents delivered intravenously, with a control arm of paclitaxel and carboplatin. Chemotherapy was to be initiated within 12 weeks of primary surgery. A retrospective analysis was approved by the GOG Ancillary Study Committee to investigate the influence of age on treatment and outcomes. In that analysis, Cox regression was used to identify independent prognostic factors and estimate their covariate effects on the adjusted PFS and OS of the study population. Statistical significance was set at p<0.05. Results: The primary analysis of GOG 182 showed no differences in PFS or OS for any of the experimental arms when compared to the control regimen, and it was felt that the data from all arms could be aggregated for this analysis. Data for all regimens was pooled, and the time interval from surgery to chemotherapy was examined as a prognostic factor of survival. The interval had no statistically significant association with PFS (p=0.105). In the OS model, though, the functional form of the log interval was both significantly linear and nonlinear (p<0.001). After being flat until about 20 days (21.2 days; 95% CI, 15.0–28.2 days), the plot of log interval against log hazard increases, suggesting a changepoint time after which the associated risk of death increases. Conclusions: In this study, time interval from surgery to chemotherapy had no impact on PFS, but there was evidence of a potential time-dependent relationship with OS, which might be elucidated with a meta-analysis incorporating data from other prospective trials. Our observations did not appear to be influenced by patient age. Overall, these findings can reassure patients who are recuperating from extensive cancer surgery.
Phase I safety study of farletuzumab, carboplatin, and pegylated liposomal doxorubicin (PLD) in patients with platinum-sensitive epithelial ovarian cancer (EOC).
Authors: Kim Kenneth H. , Jelovac Danijela , Armstrong Deborah Kay , Weil Susan , Phillips Martin , Schwartz Benjamin M , Estes Jacob Michael , Alvarez Ronald David 
Published: March 2020

5062^ Background: Farletuzumab (FAR) is a humanized monoclonal antibody that binds to folate receptor-α, a target which is largely absent in normal epithelium and over-expressed in EOC. A phase I and a phase II study indicate potential utility of FAR in combination with carboplatin/paclitaxel in recurrent platinum sensitive EOC. This study assessed safety and efficacy of FAR in combination with PLD/carboplatin, which has been demonstrated to have greater efficacy than carboplatin/paclitaxel in women with platinum-sensitive EOC. Methods: A multicenter, single-arm study enrolled 15 patients with platinum-sensitive EOC in first or second relapse defined by either CA-125 or RECIST. The primary endpoint is to assess safety of FAR plus PLD/carboplatin in this population. Patients were treated with weekly FAR 2.5 mg/kg plus carboplatin AUC 4-5 and PLD 30 mg/m2 every 4 weeks for 6 cycles, followed by maintenance treatment with single agent FAR until disease progression. Initial dosing of weekly 2.5 mg/kg was later amended to 7.5 mg/kg every 3 weeks. Results: 13 of 15 patients completed 6 cycles of combination therapy; one received a total of 12 cycles of chemotherapy. Two patients progressed during combination therapy: one received 3 cycles, the other 5 cycles. The median number of subsequent single agent maintenance cycles was 8 (range 0-13). No grade 4 toxicities were observed. Of 20 grade 3 toxicities in 14 patients, 3 (1 fatigue; 2 small bowel obstructions in the same patient) were deemed by the investigator to be possibly related to FAR. These events were seen during the combination phase and were deemed by the investigator to be also possibly related to chemotherapy. All patients demonstrated clinical benefit: 1 complete response, 10 partial response and 4 stable disease. 7 patients have come off study, all for disease progression; a median PFS of 11 months was noted. 8 patients remain on study. Conclusions: These preliminary data indicate that the safety profile of FAR in combination with carboplatin and PLD is consistent with that historically recorded for carboplatin and PLD alone. Complete safety profile will be assessed; PK data and final results will be presented.
Management of antiangiogenics’ renovascular safety in ovarian cancer subgroup and intermediate results of the MARS study.
Authors: Launay-Vacher Vincent , Janus Nicolas , Gligorov Joseph , Selle Frédéric , Goldwasser Francois , Mir Olivier , Spano Jean-Philippe , Thery Jean Christophe , Beuzeboc Philippe , Daniel Catherine , Rey Jean-Baptiste , Jouannaud Christelle , Morere Jean F. , Oudard Stephane , Azizi Michel , Dorent Richard , Deray Gilbert , Ray-Coquard Isabelle 
Published: March 2020

5067 Background: Anti-VEGF drugs (AVD) are widely used in cancer patients (pts). Hypertension (HTN) and proteinuria (Pu) are class-side-effects of AVD, related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: Hypertension (HTN) and proteinuria (Pu) are class-side-effects of anti-VEGF drugs (AVD), related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Results: Among 77 OC pts been included, 38 completed the study to date (1-year follow-up (f/u)). Median age at inclusion (introduction of the AVD) was 62 years. Diabetes and HTN prevalences were 5.2% and 7.9%, respectively. Baseline renal assessment retrieved: Pu 13.2%, Hu 7.9%, mean aMDRD 80.9 ml/min/1.73m2 and 3 pts with aMDRD<60. The incidence of de novo Pu during f/u was 36.4% (Table). All pts with Pu at inclusion improved, except one. Among pts with de novo Pu, 58.3% afterwards improved/normalized. No Grade 3/4 Pu has been reported (at inclusion or during f/u) and no Hu. 17.1% developed HTN. In addition, a mean renal function decrease of -2.7 ml/min/1.73m2/year was observed and 4 pts had aMDRD<60 at the end of f/u. 36.4% had grade 1 SCr increase (median increase of 15.9%) No thrombotic micro-angiopathy (TMA) has been reported. Conclusions: The results of the MARS subgroup of OC pts shows that 1) TMA remains rare, 2) Pu develops in 36.4% of the pts, however with no Grade 3/4, 3) less than 20% developed HTN, and 4) renal function was not especially impaired. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM et Al. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. [Table: see text]
A phase II study of pazopanib in recurrent or persistent ovarian (EOC), peritoneal (PPC), or Fallopian tube cancer (FTC): A Spanish Ovarian Cancer Group (GEICO) study.
Authors: Oaknin Ana , Gonzalez-Martin Antonio , García Yolanda , Catot Silvia , Caballero Cristina , Garcia-Donas Jesus , Bover Isabel , Santaballa Ana , Guerra Eva , Pardo Beatriz , Vidal Laura , Marquez Raul , Rodriguez-Freixinos Victor , Romero Ignacio , Poveda Andres 
Published: March 2020

5068 Background: Pazopanib (P) is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit that inhibits angiogenesis. Signaling blockade of these pathways is associated with anti-tumor and anti- angiogenesis activity. Methods: Eligible patients (pts) had persistent or recurrent EOC/PPC /FTC up to 2 prior cytotoxic regimens. They had to have received at least a platinum–based line and fulfill platinum resistant criteria. Treatment consisted of P 800 mg orally QD until disease progression or prohibitive toxicity. The primary endpoint was Clinical Benefit Rate (CBR) defined as Complete Response (CR) plus Partial Response (PR) plus Stable Disease (SD) ≥ 8 weeks by RECIST v1.1.An optimal two-stage Simon design was utilized with H1and H0set at 60%and 40% respectively; Power =90% significance level of 5% (Stage 1: = 25pts; total=66). Correlative studies to identify angiogenic biomarkers to predict response to P were performed. Results: From 12/10 to 7/11, 25 pts were enrolled, 21 pts had EOC, 2PPT, and 2FTC. Median age: 64 years (range 43-81), ECOG 0/1/2:12/11/2 pts. Prior chemotherapy regimens 1/2:10/15 pts. Median weeks on treatment: 8 (range 4-25). Most frequent adverse events (AEs) were asthenia (56%), hypertension (36%) and diarrhea, nausea and anorexia (20% each).Grade 3 toxicities: Hypertension (6pts), ALT/AST elevations (3 pts), asthenia (2 pts), DVT (1pt), Fistula (1 pt), Anemia (1 pt). Six pts required dose reduction to 600 mg due to toxicity.Reasons for stopping study treatment: PD (18pts), AEs (3pts) and investigator decision (2pts). First stage analysis showed: PR:1/25, SD: 9/25, CBR:10/25; 40% (95% CI 21.1%-61.3%).No correlation between GCIG CA-125 response and RECIST criteria was established, 8 versus 1 response respectively. Median PFS was 1.83 months (95% CI 1.67-2). Conclusions: The CBR observed at the first stage did not reach the planned statistical hypothesis (CBR:12 pts). Therefore, the lack of activity of P in platinum resistant EOC/PPT/FT led to discontinuation of the study. Translational study results will be presented in an additional abstract.
Inflammatory and nutritional markers as predictors of longer hospital stay and suboptimal residual disease (RD) in ovarian cancer (OVCA).
Authors: Torres Michelle , Hartmann Lynn C. , Cliby William , Kalli Kimberly , Jatoi Aminah , Weaver Amy , Block Matthew Stephen , Mariani Andrea 
Published: March 2020

5076 Background: Advanced OVCA should be managed aggressively, and extensive surgery has been the most accepted initial treatment. Medically unfit patients or those with extensive disease, in which complete cytoreduction is unlikely, may not benefit from upfront radical surgery, and neoadjuvant chemotherapy might be an appropriate alternative. Thus, reliable preoperative indicators of surgical outcome are necessary for considering primary surgery vs. neoadjuvant chemotherapy. Our aim is to determine if C-reactive protein (CRP), IL-6, albumin and Glasgow Prognostic Score (GPS – score based on CRP and albumin) correlate with overall survival (OS), length of hospital stay (LOS), surgical morbidity, and suboptimal cytoreduction. Methods: We randomly selected 50 stages III/IV OVCA who underwent surgery as a primary treatment between July 2002 and June 2009 at Mayo Clinic with serum albumin levels and frozen serum available. CRP and IL-6 were measured in stored serum. Univariate and multivariate regression models were fit to evaluate associations with each of the outcomes. Results: Among the 50 patients, the mean age was 67.7 years. 34% had pretreatment albumin <3.5 g/ml, 22.4% had CRP level ≥10 mg/l, 26.5% had IL-6 ≥24 pg/ml and 45% had abnormal GPS score. At 1, 3 and 5 years following surgery, the OS was 75.6%, 49.8% and 36.9%, respectively. RD (0, <1, ≥1cm; p<0.001) was the only independent predictor of OS. Also, IL-6 (p=0.028) and stage (p=0.046) were independently associated with LOS, but no inflammatory or nutritional markers were significant associated with post surgical complications. Stage IV (p=0.019) and elevated CRP (p=0.044) were independent predictors of suboptimal surgery (RD ≥ 1cm). Conclusions: One-third of the patients in our series had low serum albumin at the time of the OVCA diagnosis, and at least one-fourth had elevated inflammatory markers. Advanced stage and elevated inflammatory markers (CRP and IL-6) were independent predictors of longer hospital stay and suboptimal debulking. These pilot data, if confirmed in a larger population, may help in the selection of candidates for neoadjuvant chemotherapy.
Progression-free survival (PFS) as a surrogate end point for overall survival (OS) in first-line treatment of advanced epithelial ovarian cancer (EOC).
Authors: Sjoquist Katrin Marie , Lee Chee , Lord Sally , Chatfield Mark D. , Friedlander Michael , Simes John , Marschner Ian 
Published: March 2020

5081 Background: The duration and cost of clinical trials of first-line chemotherapy in advanced EOC could be reduced if a surrogate endpoint were used in place of OS. The consensus of the Gynecological Cancer Intergroup was that PFS is the preferred primary end point for these trials due to potential confounding of post-progression therapy on OS. We performed a systematic review to assess the extent to which treatment effect on PFS is predictive of OS in this patient population. Methods: Randomised trials of first-line chemotherapy comparing platinum containing regimens in advanced EOC were identified; trials with non-platinum backbone, maintenance strategies or biological containing therapies were excluded. Summary data (hazard ratios (HR), median PFS and OS and the ratios of medians between treatment arms) were extracted. Weighted least-square (WLS) R2 by trial sample size derived using linear regression was used to report correlation. Results: 15 eligible trials with 19 treatment comparisons were identified comprising a total of 16,598 patients. There was a good correlation between treatment effect on PFS and OS (correlation of HR: r, 0.88, WLS R2, 0.71; correlation of ratios of medians: r, 0.84, WLS R2, 0.72). Good correlation between treatment effect on PFS and OS was also observed in various prognostic subgroups (Table). Conclusions: In clinical trials of first-line platinum based chemotherapy without biological agents in advanced EOC, treatment effect on PFS and OS is highly correlated. PFS could be considered as a primary end point when evaluating future first line strategies in advanced EOC. [Table: see text]
Prevalence of high-risk human papillomavirus in uterine cervical lesions among older Japanese women.
Authors: Takehara Kazuhiro , Nakamura Hiroko , Samura Osamu , Mizunoe Tomoya , Saito Akihisa , Kuraoka Kazuya , Nishiwaki Morie , Taniyama Kiyomi 
Published: March 2020

5084 Background: To estimate the prevalence and genotypes of high-risk human papillomavirus (HPV) among older Japanese women, using liquid-based cytology (LBC). Methods: ThinPrep LBC specimens were collected from 11,039 Japanese women (age range, 14-98 years). After classifying cytodiagnosis, specimens were analyzed for HPV DNA using the multiplex polymerase chain reaction method. Cervical smear specimens from 1,302 women showed positive results. To examine the prevalence of HPV in women defined as negative for intraepithelial lesion or malignancy (NILM), 2,563 samples were randomly selected from the remaining 9,737 women. Comparisons were made between women ≥50 years of age (older age group) and women <50 years of age (younger age group). Written informed consent was obtained from all patients. In this study, the high-risk HPV genotypes encountered were 16, 18, 31, 33, 35, 45, 52, and 58. Results: In the older age group with abnormal smear findings, HPV genotypes were detected in 49.7% (148/298), including high-risk HPV genotypes in 40.9% (122/298). In the younger age group with abnormal smear findings, HPV genotypes were detected in 71.7% (720/1004), including high-risk HPV genotypes in 58.1% (583/1,004). In NILM, HPV-positive rates were 4.5% (39/873) in the older age group and 11.8% (199/1,690) in the younger age group. In high-grade squamous intraepithelial lesion (HSIL) or more severe cytological findings, HPV genotypes of each group (older age group/younger age group) were detected in 61.7%/83.1%, and high-risk HPV genotypes were detected in 56.4%/74.7% of women. In positive cervical smears, HPV 16 was the most frequently detected (28.5%) in the younger age group, while HPV 52 (31.3%) and 58 (27.2%) were detected more frequently than HPV 16 (18.4%) in the older age group. Conclusions: In Japan, although HPV infection as a cause of abnormal cervical cytology is more frequent among younger age groups than in older age groups, high-risk HPV infection was more highly associated with older individuals (older age group/younger age group: abnormal smear findings, 82.4%/81.0%; HSIL or more severe cytological findings, 91.3%/89.9%). In older age groups, HPV 52 and 58 were more frequent than HPV 16.
Nuclear Y-box binding protein-1 expression as a prognostic marker and correlation with epidermal growth factor receptor expression in cervical cancer.
Authors: Nishio Shin , Ushijima Kimio , Takemoto Shuji , Sasajima Yuko , Tsuda Hitoshi , Kasamatsu Takahiro , Kamura Toshiharu 
Published: March 2020

5085 Background: Y-box binding protein-1 (YB-1) is a member of the cold shock protein family and functions in transcription and translation. Many reports indicate that YB-1 is highly expressed in tumor cells and is a marker of tumor aggressiveness and clinical prognosis. Overexpression of epidermal growth factor receptor (EGFR) has been associated with poor outcomes in cervical cancer (CC). Clinical trials have shown that EGFR inhibitors are effective against CC (JCO 2011). Nuclear YB-1 expression correlates with EGFR expression in various types of cancer. Methods: Nuclear YB-1 expression was immunohistochemically analyzed in tissue specimens obtained from 204 CC patients who underwent surgery. Associations of nuclear YB-1 expression with clinicopathological factors such as survival and EGFR (HER1 and HER2) expression were investigated. Results: Nuclear YB-1 expression was observed in 41 (20%) of 204 cases and correlated with stage, tumor diameter, stromal invasion, and lymph-node metastasis. Nuclear YB-1 expression also correlated with both HER1 expression (p=0.0114) and HER2 expression (p=0.0053). Kaplan-Meier survival analysis showed that nuclear YB-1 expression was significantly associated with poor outcomes in terms of progression-free survival (p=0.0033) and overall survival (p=0.0003). On multivariate analysis, stromal invasion, parametrial invasion, and nuclear YB-1 expression were independent predictors of survival. Conclusions: Nuclear YB-1 expression is a prognostic marker and correlates with EGFR expression in CC.