bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab beyond progression: Impact of subsequent bevacizumab retreatment in patients with ovarian, fallopian tube, and peritoneal cancer after progression.
Authors: Previs Rebecca Ann , Spinosa Daniel , Fellman Bryan M. , Lorenzo Amelia , Mulder Isabelle , Mahmoud May , Enbaya Ahmed , Hansen Jean M. , Cobb Lauren Patterson , Soliman Pamela T. , Coleman Robert L. , Secord Angeles Alvarez , Westin Shannon Neville 
Published: May 2019

5557 Background: The Food and Drug Administration approved the use of bevacizumab for treatment of recurrent epithelial ovarian, fallopian tube, and primary peritoneal carcinoma (OC) in combination with chemotherapy. This study evaluates whether patients immediately retreated with bevacizumab derive benefit after progressing on a bevacizumab-containing regimen. Methods: This multi-institutional, retrospective study compared patients with high grade non-mucinous epithelial OC who received bevacizumab followed directly by another bevacizumab-containing treatment regimen to patients who received bevacizumab followed by a regimen that did not contain bevacizumab (or received no further treatment). All patient retreated with bevacizumab had stable or progressive disease on prior bevacizumab containing regimen. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan and Meier product-limit estimator and modeled via Cox proportional hazards regression. PFS was measured from the date of first bevacizumab treatment to the date of first progression, date of death or date of last clinic visit. OS was measured from the date of first bevacizumab treatment after progression to the date of death or date of last contact/clinic visit. Statistical significance was defined at the 0.05 level. Results: 275 patients received bevacizumab, of which 226 were evaluable; 102 received sequential treatment with bevacizumab and 124 received a bevacizumab containing regimen followed by a non-bevacizumab containing regimen at the time of progression. There was no significant difference between tumor grade, stage, or BRCA mutation. Median follow-up for all subjects was 17 months (range: 1.2-138.2 months). Median PFS was 10.21 months (95%CI: 8.05 - 11.79) and median OS was 22.14 months (95%CI: 17.1 – 27.4). Median PFS for patients who received bevacizumab without retreatment was 5.1 months (95%CI: 4.3 – 6.3) and 17.6 months (95%CI: 14.3 – 21.3) for patients who received sequential bevacizumab retreatment (p < 0.001). Median OS for patients who received bevacizumab without retreatment was 12.9 months (95%CI: 9.3 – 16.7) and 30.1 months (95%CI: 26.1 – 35.4) for patients who received sequential bevacizumab retreatment (p < 0.001). Conclusions: Our study shows OC patients treated with bevacizumab-containing regimens sequentially at the time of progression have significantly prolonged survival outcomes compared to those patients who received no re-treatment with bevacizumab.
Real-life data: Women with recurrent platinum-sensitive ovarian cancer and BCARGEM treatment.
Authors: van der Scheun Frederique C. , Bruijnen Cheryl P. , Witteveen Petronella , Suelmann Britt B.M. 
Published: May 2019

5566 Background: Ovarian cancer is still the most mortal gynaecological cancer in the world. Even after achieving a good clinical response after initial treatment, the cancer will relapse in 80% of the patients. Treatments that improves progression-free survival (PFS) are necessary. In 2012, the OCEANS trial showed an improved PFS (12.4 months) for patients with platinum-sensitive recurrent ovarian, primary peritoneal, or fallopian cancer (ROC) treated with carboplatin, gemcitabine plus the monoclonal antibody bevacuzimab followed by maintenance therapy of bevacuzimab (BV) till progression (BCARGEM). Based on this trial, bevacizumab was incorporated in the second line treatment protocol of various European countries for patients with platinum-sensitive ROC. However, there is no real life information yet available on the effectivity and tolerance of this one randomized clinical trial (RCT) in clinical practise. Therefore, the aim of this study was to assess what the real time efficacy and tolerance of treatment with BCARGEM was in patients with platinum-sensitive ROC. Methods: All patients with platinum-sensitive ROC and treated with BCARGEM in the UMC Utrecht Cancer Center were retrospectively selected for analysis. All data such as baseline information, assessments and adverse events during cycles were obtained from medical records. The primary outcome was PFS; secondary outcomes were relative dose intensity (RDI), adverse events (AE) leading to dose modifications, and overall survival (OS). Results: Overall, the median PFS of the 39 patients with platinum-sensitive ROC and treated with BCARGEM was 9.4 months (95% CI 4.6 - 14.2). The median OS was 20.9 months (95% CI 15.0-26.7). The average RDI for BCARGEM was 67%. None of the patients reached a RDI of 100%. In most patients (69%) neutropenia grade ≥ 3 led to dose modifications or discontinuance of BCARGEM. After treatment with BCARGEM, 34 patients started treatment with BV till progression. The median number of cycles of BV was 5. In 26 of the cases the BV was ended due to progression. Conclusions: In our retrospective study, the PFS of real life patients treated with BCARGEM is lower compared to the study patients in the OCEANS trial; 9.4 versus 12.4 months. In addition, the RDI of BCARGEM is very low reflecting the many AEs leading to dose modifications or discontinuation. Therefore, this study underlines the fact that results of RCTs with strict in- and exclusion criteria do not represent actual outcomes in clinical care, because the selected study patient does not match the patient we face in real time.
Association of Ki67 expression levels and therapy outcome in low-grade serous ovarian cancer.
Authors: Grabowski J.P. P. , Martinez-Vila Clara , Richter Rolf , Taube Eliane T , Braicu Elena Ioana , Sehouli Jalid 
Published: May 2019

5577 Background: Low-grade serous ovarian cancers (LGSOC) characterize different clinical pattern and lower chemotherapy responsiveness. The expression level of Ki67 is associated with prognosis differences in this patient group. However, Ki67 has not been evaluated as prognostic marker and a predictor of therapy outcome until now. Methods: Patients with LGSOC and Ki67 expression results were identified in institutional database. Receiver-operator characteristics (ROC) curve analysis was performed to find cut off values of Ki67% to discriminate patients with residual tumor mass after surgery from maximal debulked patients, and platinum sensitive patients from platinum resistant patients. Odd ratios (OR) and 95% confidence intervals (95% CI) were calculated using univariate and multivariate logistic regression analysis. Two-sided tests p < 0.05 and are considered statistically significant at a 95% confidence interval. The statistical analysis was performed with the IBM SPSS Statistics 25.0. Results: A total of 68 patients with LGSOC were included. All patients underwent surgery and 15 (22.1%) patients had residual mass ( > 0 mm) after cytoreduction. Sixty-one (89.7%) patients received platinum based first-line chemotherapy. Forty-three patients revealed a recurrence ≥6 months and eleven < 6 months. Patients with Ki67 < 3.6% had significantly higher therapy-free interval (TFI≥6 months), (OR = 13.9, 95%CI 1.62-118.40, p = 0.016). In the multivariate analysis of TFI over 6 months including CA 125, age at diagnosis, peritoneal carcinomatosis and ascites ( > 500ml) Ki67 < 3.6% remained significant (OR = 17.6, 95%CI 1.56-197.52, p = 0.020). Moreover, Ki67% > 3.6% were associated with higher risk of residual mass after surgery (OR = 6.75, 95%CI 1.39-32.87, p = 0.018). Conclusions: It is the first study showing association between Ki67% expression and duration of TFI to platinum-based chemotherapy as well as outcome of the surgery in LGSOC. Further prospective trials should be planned to develop predictive models in this patients.
Glutaminase (GLS) expression in primary breast cancer (BC): Correlations with clinical and tumor characteristics.
Authors: Vidula Neelima , Yau Christina , Rugo Hope S. 
Published: May 2019

558 Background: Tumor cells rely on glutamine for growth. GLS is a mitochondrial enzyme that is necessary for glutamine catabolism, and is present as isoforms GLS1 and GLS2. A GLS1 inhibitor is being studied in triple-negative (TN) BC. We studied GLS1 expression in primary BC to understand associations with clinical and tumor characteristics in publically available databases. Methods: GLS1 mRNA levels were evaluated using expression data from the TCGA (n = 817) dataset, with confirmation in METABRIC (n = 1992). Associations between GLS1 levels and tumor subtype were assessed using ANOVA, followed by the post-hoc Tukey test for pairwise comparisons. Pearson correlations were used to study associations between GLS1 and selected genes. Correlations with overall survival (OS) were studied with Cox proportional hazard model. For all analyses, p < 0.05 was considered significant. Results: In TCGA, the expression of GLS1 and its isoform GLS2 were significantly inversely correlated (r = -0.32). GLS1 expression was highest in TN compared to hormone receptor (HR)+ and HER2+ BC (p < 0.001). In addition, GLS1 expression was higher in basal vs luminal A, luminal B, and HER2 enriched BC (p < 0.001). GLS1 expression was significantly inversely correlated with ER (r = -0.45), PR (r = -0.34), and AR (r = -0.34), and these inverse correlations remained significant when restricted to TNBC (ER: r = -0.25, PR: r = -0.25, AR: r = -0.30). Consistent with previous reports of MYC upregulation of GLS1, GLS1 expression was significantly positively correlated with MYC (r = 0.26). Similarly, in METABRIC, GLS1 was most highly expressed in basal and TNBC, significantly inversely correlated with the expression of GLS2, ER, PR, and AR, and positively correlated with MYC expression. In METABRIC, higher GLS1 expression was associated with better OS (HR 0.91, p = 0.005); this association remained significant in the TN subset (HR 0.83, p = 0.03). Correlations between GLS1 and genes involved in metabolism and immune activation will be presented at the meeting. Conclusions: GLS1 expression is highest in basal and TNBC, is associated with MYC expression, and may have prognostic implications. These findings support ongoing trials of GLS1 inhibition in TNBC.
Tumor stroma proportion to predict platinum chemoresistance in primary ovarian carcinomas: A prospective study.
Authors: Lou Emil , Vogel Rachel Isaksson , Hoostal Spencer , Grad Aaron , Monu Minnu , Lukaszewski Tomasz , Deshpande Jaai , Linden Michael , Klein Molly , Teoh Deanna Gek Koon , Geller Melissa Ann 
Published: May 2019

5581 Background: Platinum chemotherapy resistance occurs in approximately 25% of patients with ovarian carcinoma and represents a major barrier to effective care of this patient population. To date there are no effective nor validate predictive biomarkers of chemoresistance of ovarian carcinomas. We performed a prospective trial designed to enroll patients with ovarian masses suspicious for ovarian cancer, with the goal of identifying tumor-based predictive biomarkers of platinum resistance. Methods: 60 women were enrolled on the study. Tumor specimens were collected from 49 of these women with newly diagnosed pelvic masses, of which 29 were found to have histopathologically proven primary ovarian carcinoma. Of these primary malignant cases, 24 had specimens accessible for assessment of tumor-stroma proportion and data available regarding chemosensitive vs chemoresistance status via review of the medical record using a UMN IRB-approved protocol. Tumor slices were stained with H&E and also for antibodies against two microRNAs (29b and 199a) differentially expressed in ovarian cancer cell lines. Tumor-stroma proportions were assessed by two experienced pathologists blinded to chemoresistance status, with <50% stroma scored as low proportion, >50% scored as high proportion. Results: The average age of assessed patients with malignant tumors was 62. 87.5% had high-grade epithelial carcinomas. Baseline median CA-125 was 416 (range 32-2782). 80% of ovarian cancer patients with chemoresistance had tumor stroma proportions >50%; 73.7% of cancer patients with chemosensitive tumors had proportions <50% (p-value: 0.047). Expression of miR29b or 199a did not significantly correlate with chemoresistance. Conclusions: Tumor-stroma proportion is a useful predictive biomarker of platinum chemoresistance. If validated in larger datasets, it would be a relatively inexpensive and helpful tool for tailoring treatment strategies and clinical decision-making in women with ovarian cancer.
Association of total hysterectomy with survival among newly diagnosed uterine cancer patients with distant organ metastasis.
Authors: Wang Yuefeng , Tillmanns Todd D. , Farmer Michael , Rinker Lillian , Somer Bradley G. , Ballo Matthew T. 
Published: May 2019

5583 Background: There is growing evidence that definitive local therapies (surgery or radiotherapy) may increase patient’s survival for some types of metastatic cancers. However, the role of total abdominal hysterectomy (TAH) for newly diagnosed uterine cancer with distant organ metastasis has not been established. The objective of this study is to determine the potential overall survival (OS) benefit associated with TAH for distant metastatic uterine cancer. Methods: The National Cancer Database was analyzed to evaluate OS for newly diagnosed uterine cancer patients with metastasis to brain, lung, liver, bone or distant lymph node, treated with chemotherapy with or without TAH. Those without treatment, treated with definitive pelvic radiotherapy, or without baseline variables were excluded. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. In order to control the selection biases, we performed Landmark analysis, and survival analysis by the sequence of chemotherapy and TAH. Separate survival analysis was performed for patients who received chemotherapy plus definitive pelvic radiotherapy (RT) or chemotherapy plus TAH and definitive pelvic RT. Results: From 2010 to 2014, 1,809 uterine cancer patients with distant organ metastasis received chemotherapy alone and 1,388 patients received chemotherapy plus TAH. At a median follow-up of 13.4 months, addition of TAH to chemotherapy was associated with improved survival on univariate (HR 0.57; P < 0.001) and multivariate analysis (HR 0.59; P < 0.001) compared to chemotherapy alone. Propensity score-matched analysis demonstrated superior median survival (19.8 vs 11.0 months) and 2-year OS (44% vs 28%) with TAH (multivariate HR 0.59; P < 0.001). Landmark analyses limited to long-term survivors of ≥0.5, ≥1, and ≥2 years showed improved OS with TAH in all subsets (all P < 0.05). The benefit of TAH was present among not only those involving one metastatic site (HR 0.59; P < 0.001), but also those involving multiple metastatic sites (HR 0.60; P < 0.001). Separate survival analyses showed chemotherapy plus definitive pelvic RT or chemotherapy plus TAH and RT were both superior to chemotherapy alone. Conclusions: In this large contemporary analysis, uterine cancer patients with distant organ metastasis receiving TAH and chemotherapy had substantial longer survival than patients treated with chemotherapy alone. Prospective trials evaluating TAH for metastatic uterine cancer are warranted.
Trends of endometrial cancer incidence from 2000 to 2015 in the United States.
Authors: Mukthinuthalapati V V Pavan Kedar , Farooq Muhammad Zain , Gupta Shweta 
Published: May 2019

5591 Background: Recent studies have shown that obesity related cancers are increasing in incidence in the US as the rates of obesity rise and some cancers, like colorectal cancer, are occurring in younger age groups. We studied trends in incidence of endometrial cancer (EC), one of the obesity related cancers, in a population wide analysis. Methods: We analyzed data from all cases of EC between 2000 and 2015 from 18 US cancer registries using the National Cancer Institute’s Surveillance, Epidemiology and End Results Program. SEER*Stat was used to query the database for annual percent changes (APC), incidence ratios and percent change in incidence across different age groups, years of diagnosis, histologic subtypes, grade and race. We also studied the reported rates and trends of obesity in the US. Results: APC of age-adjusted EC incidence between 2000 and 2015 was +0.9% (95% confidence interval (CI) 1.1-0.6, p value<0.05). Incidence of EC rose from 17.8 per 100,000 to 19.7 per 100,000 during the same duration. APC for EC incidence for age groups 20-39 and >40 were +3.2% (p-value <0.05) and +0.8% (p value <0.05), respectively. For the age-group 20-39, endometrioid EC was the only histologic subtype that rose in incidence, with an APC of +5.5% and absolute percentage change of 156%. The APC of EC in 20-39 age group was more for whites (3.5%, p-value<0.05) and Asians (2.2%, p-value<0.05) than blacks (1.8, p-value <0.05). CDC reported an increase in obesity rates in adults from 30.5% in 2000 to 37.7% in 2014. Table shows trends of EC incidence in age groups 20-39 and >40 years across various histologic subtypes. (Abbreviations: S significant, NS not significant, NC non-calculable). Conclusions: Endometrial cancer, especially of endometrioid histology, is increasing in incidence and is occurring more often in the younger population. The concomitant rise in obesity rates during the same period point towards a possible causality of the increased in incidence of EC. Population based strategies are needed to decrease the trends in obesity so as to decrease the risk of endometrial cancer in younger women. [Table: see text]
Genomic-based predictive biomarkers to anti-HER2 therapies: A combined analysis of CALGB 40601 (Alliance) and PAMELA clinical trials.
Authors: Fernandez-Martinez Aranzazu , Tanioka Maki , Fan Cheng , Parker Joel S. , Hoadley Katherine A. , Krop Ian E. , Cortes Javier , Llombart Cussac Antonio , Nuciforo Paolo , Galván Patricia , Pascual Tomas , Partridge Ann H. , Prat Aleix , Carey Lisa A. , Perou Charles M. 
Published: May 2019

571 Background: In HER2-positive breast cancer, new biomarkers of response are needed in order to direct multi-agent anti-HER2 combinations towards patients in whom they are truly needed. CALGB 40601 and PAMELA trials tested neoadjuvant dual HER2 blockade and included gene expression analysis aimed to evaluate different genomic biomarkers of trastuzumab and/or lapatinib benefit. Methods: Gene expression by mRNA sequencing (RNAseq) was performed on 265 and 142 pre-treatment tumors of the CALGB 40601 and the PAMELA clinical trials respectively. Intrinsic subtypes were determined by nCounter PAM50-predictor on the PAMELA samples. A new HER2-positive specific gene-centering method was trained on the PAMELA RNAseq data, and showed a higher concordance with PAM50 predictions obtained from nCounter platform. This method was then applied to CALGB 40601 samples. Results: In the combined cohort, the subtype distribution was 10% Luminal A, 8% Luminal B, 62% HER2-enriched (HER2-E), 10% Basal and 10% Normal-like. The pCR rate was significantly higher in HER2-E vs. not HER2-E subtypes (48.6% vs. 20.7%; P < 0.001). HER2-E subtype correlation, ERBB2 amplicon and B-cell genomic signatures were associated with pCR, while luminal signatures were associated with non-responders. In multivariate analysis HER2-E subtype, ERBB2 mRNA and IgG signature expression were independent predictors of response to paclitaxel + trastuzumab +/-lapatinib (OR = 1.98, OR = 1.51, OR = 1.48, respectively, P <0.05). The event free survival analysis at 5 years in the CALGB 40601 cohort showed a benefit of dual vs single anti-HER2-blockade (HR 0.35, P <0.05). Within the HER2-E, ERBB2-high and IgG–high subpopulations, there were also a benefit of dual vs. single anti-HER2 treatment (HR = 0.32, HR = 0.15, HR =0.15, respectively, P <0.05). Conclusions: Intrinsic subtype, ERBB2 mRNA levels, and IgG genomic signature are independent predictive biomarkers of response in the combined cohort. The clinical implementation of these biomarkers could help to design future escalation/de-escalation clinical trials in the HER2-positive neoadjuvant setting. Support: U10CA180821, U10CA180882, U24CA196171, P50-CA58223, GSK, SPORE, BCRF and SEOM. https://acknowledgments.alliancefound.org .
Germline mutation status and therapy response in high-risk early breast cancer: Results of the GeparOcto study (NCT02125344).
Authors: Pohl-Rescigno Esther , Hauke Jan , Rhiem Kerstin , Möbus Volker , Furlanetto Jenny , Denkert Carsten , Fasching Peter A. , Hanusch Claus , Tesch Hans , Weber-Lassalle Nana , Müller Volkmar , Untch Michael , Luebbe Kristina , Lederer Bianca , Jackisch Christian , Nekljudova Valentina , Schmutzler Rita K. , Loibl Sibylle , Schneeweiss Andreas , Hahnen Eric 
Published: May 2019

573 Background: GeparOcto compared the efficacy of two neoadjuvant treatment (NAT) regimens in high-risk early breast cancer (BC): Sequential intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly paclitaxel plus non-pegylated liposomal doxorubicin (PM), plus carboplatin (PMCb) in triple-negative BC (TNBC). There was no difference in pathologic complete response (pCR) rates (Schneeweiss et al. Eur J Cancer 2019). Here, we stratified pCR rates according to germline mutation status. Methods: Germline (g) mutation analysis of BRCA1/2 and 16 further BC predisposition genes in 914 patients (pts) enrolled (393 pts with TNBC, iddEPC n = 194, PMCb n = 199; 156 pts with HER2-/HR+ BC, iddEPC n = 75, PM n = 81; and 365 pts with HER2+ BC, iddEPC n = 182, PM n = 183). Results: The gBRCA1/2 mutation prevalence was 17.6% in TNBC, 14.1% in HER2-/HR+ BC and 1.4% in HER2+ BC. Overall, pts with gBRCA1/2 mutations achieved higher pCR rates than gBRCA1/2 wildtype pts (60.4% vs 46.7%, OR 1.74, P = 0.012), with more pronounced effects in the PM(Cb) arm (68.1% vs 45.7%, OR 2.53, P = 0.005). Among gBRCA1/2 wildtype pts, 76 carried mutations in non- BRCA1/2 predisposition genes. pCR rates were similar to those observed in pts without any mutation. Conclusions: Pts with gBRCA1/2 mutations benefitted most from NAT with highest pCR rates achieved in the gBRCA1/2 TNBC / PMCb group. The role of Cb for NAT of gBRCA1/2 TNBC should be further explored. Clinical trial information: NCT02125344. [Table: see text]