bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of bevacizumab (BEV)/high-dose chemotherapy (HDC) for refractory germ-cell tumors (GCT).
Authors: Nieto Yago , Tannir Nizar M. , Tu Shi-Ming , Jones Roy B. , Zurita Amado J. , Aparicio Ana , Bassett Roland , Margolin Kim Allyson , Holmberg Leona , Champlin Richard E. , Pagliaro Lance C. 
Published: March 2020

4533 Background: HDC is a curative therapy for relapsed GCT. However, multiple prior relapses, cisplatin refractoriness (relapse/progression (PD) within 4 weeks) or absolute refractoriness (no prior response), or very high tumor markers at relapse predict poor early event-free survival (EFS). The validated Beyer model (JCO 1996;14:2638) identifies groups with poor risk (5% EFS at 1-year post-HDC), intermediate risk (25% EFS) or good risk (≥50% EFS). Given high VEGF expression in metastatic GCT and synergy between BEV and chemotherapy, we studied concurrent BEV/HDC in refractory GCT. Methods: Eligibility includes ≥ 1st relapse/PD, poor/interm risk and no contraindications to HDC or BEV. Treatment consisted of 2 cycles of HDC with stem-cell support following BEV (5 mg/kg) 1 week before each cycle. HDC-1 consists of a novel regimen of infusional gemcitabine with docetaxel/melphalan/carboplatin (BBMT 2005;11:297). HDC-2 includes ifosfamide/carboplatin/etoposide. Target accrual is 25 pts, to distinguish a 1-yr expected EFS of 15% (median time to progression [TTP], 9 months) from 50% 1-year EFS (median TTP, 2 years). Results: 21 pts have been treated, median age 22 (range, 19-45) poor risk (N=15) or interm risk (N=6), cisplatin refractoriness (N=9) or absolute refr (N=12), median 3 prior relapses (1-4), median 3 prior regimens (2-6), PD at HDC: 11 pts. Tumor sites: lungs (N=15), liver (8), bones (5), brain (5), retroperit (15), mediast (12). Histol at Dx: embryonal ca (4), chorio (3), mixed with teratoma (14). Prior surgery for metastases: 8 pts (6 abdomen, 1 liver, 1 brain). Prior radiation: 6 pts. Toxicity of HDC-1: grade 3 mucositis in all pts, rash (8 G2, 2 G3) and transaminase elevation; 2 pts with marginal baseline renal function died from early sepsis; 1 pt died from late fungal pneumonia. After HDC-1, markers normalized in 14/17 evaluable pts. 15 pts received HDC-2 at a median 49 (38-66) days after 1st stem cell infusion, which was well tolerated. 8 pts had residual lesions resected with findings of either teratoma (N=2) or no viable tumor (N=6). With median follow-up of 23 (3-43) months, 14 pts are alive in CR (67% EFS). Conclusions: BEV with HDCx2 shows encouraging preliminary results in heavily pretreated refractory GCT.
A pre-cystectomy decision model to predict pathologic upstaging and oncologic outcomes in clinical stage T2 bladder cancer.
Authors: Daneshmand Siamak , Skinner Eila C , Miranda Gus , Mitra Anirban Pradip 
Published: March 2020

4578 Background: Neoadjuvant chemotherapy is the standard for advanced bladder cancer (BC), although its benefit in lower risk clinically organ-confined muscle-invasive (cT2N0M0) BC is uncertain. This study aimed to define pre-cystectomy factors in cT2N0M0 BC that could predict pathological upstaging at cystectomy and oncological outcomes. Methods: 1,964 institutional BC patients were reviewed. Neoadjuvant chemotherapy-naïve cT2N0M0 patients who underwent cystectomy were included. A multivariate classification and regression decision tree was used to assess hierarchical interactions of univariately significant variables, thereby identifying patients at greatest risk for upstaging and poor outcome. Results: 948 cT2N0M0 patients were identified; 512 (54%) were upstaged at cystectomy. Pathological upstaging was associated with poor RFS and overall survival (OS) (both p < 0.001). Age, lymphovascular invasion (both P = 0.01), multifocality (p = 0.004), deep muscle invasion, tumor growth pattern and hydronephrosis (all p < 0.001) were associated with upstaging. When these factors were included in a multivariate decision tree model, 71% of patients with hydronephrosis were upstaged and had the worst outcome (p < 0.001). In patients without hydronephrosis, tumor growth pattern was a second-tier discriminator; only 37% of patients with papillary tumors were upstaged. In patients with non-papillary tumors, deep muscle invasion was a third-tier discriminator; 70% of patients with invasion were upstaged. Age was a third-tier discriminator in patients with papillary + non-papillary features; 33% of patients ≤65 years were upstaged compared to 47% of patients >65 years. The decision tree was cross-validated and resulted in 3 risk groups – 5 year RFS/OS for low risk patients was 66%/48% versus 46%/27% for high risk patients (p < 0.001). Conclusions: This study identified pre-cystectomy variables that predict upstaging and poor outcomes in cT2N0M0 BC. The decision tree approach highlighted the most crucial prognostic variables, and can aid in identifying low risk patients in a stepwise fashion who have lower probability of upstaging and better outcomes.
Sorafenib treatment of Asian patients with advanced renal cell carcinoma (RCC) in daily practice: Subset analysis of the large non-interventional PREDICT study.
Authors: Ye Dingwei , Guo Jun , Lee Jae-Lyun , Zhou Ai-Ping , Huang Yiran , Hu Zhiquan , Fu Cheng , Liu Jiyan , Qi Lin , Li Hanzhong , Zou Qing , Hong Sung Joon , Stauch Kathrin , Böckenhoff Annette , Kim Gyunji , Zhang XiaoJing , Ahn Hanjong , Ma Jianhui 
Published: March 2020

4628 Background: Previous studies with sorafenib in Asian patients with advanced RCC were relatively small and used strict entry criteria. Here we investigated safety and efficacy in a large subset of Asian patients in the prospective, non-interventional PREDICT study of sorafenib in routine practice (NCT 00895674). Methods: Patients were eligible based on a diagnosis of advanced RCC and the decision by the investigator to prescribe sorafenib under compliance of the local product label. Tumor status, patients’ performance and physician assessment of efficacy and tolerability were collected up to 12 months. Results: Between Jan 2007 and June 2010, 1092 patients were enrolled in China (n=1033), South Korea (n=55), the Philippines (n=3) and Indonesia (n=1). In the efficacy population (n=909), baseline characteristics were: 71% male; 89% <70 years old; 89% clear cell histology; 78% prior nephrectomy; 56% prior systemic therapy; 16% high MSKCC risk; 35% ECOG PS ≥2; 5% brain metastases. Overall, 19% of patients had ≥1 concomitant disease at baseline; the most frequent concomitant diseases were hypertension (14%) and diabetes (6%). Initial sorafenib dose was 800 mg daily in 97% of patients, of whom 91% were also receiving 800 mg daily as last dose. Median duration of sorafenib treatment was 9.7 months (range 0.2–24.1), and in clinically relevant subgroups was as follows: treatment-naïve, 9.7 months; high MSKCC risk, 9.3 months; brain metastases, 8.4 months; age ≥70 years, 7.6 months; ECOG PS 2, 9.7 months; ECOG PS 3, 6.1 months. At last follow up, 63% of physicians reported good/very good efficacy and 59% good/very good tolerability. Sorafenib was well tolerated; <2% of the safety population (n=1022) reported serious drug-related adverse events (SDRAEs) and only 3% discontinued due to DRAEs. In all, 35% of patients reported a DRAE, with the most frequent being hand-foot skin reaction (21%), diarrhea (7%), rash (7%), alopecia (5%), hypertension (3%). Conclusions: In this large subset of Asian patients with advanced RCC treated in daily practice settings, sorafenib was well tolerated and provided benefit, including in clinically relevant patient subgroups.
Overall survival (OS) benefit with sipuleucel-T by baseline PSA: An exploratory analysis from the phase III IMPACT trial.
Authors: Chodak Gerald , Schellhammer Paul F. , Whitmore James Boyd , Sims Robert Brownell , Kantoff Philip W. 
Published: March 2020

4648 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer. In the IMPACT trial, sipuleucel-T showed a 22.5% reduction in risk of death vs the control group (hazard ratio [HR]=0.775 [95% CI 0.614, 0.979]; P=0.032). A pre-specified subgroup analysis for baseline prognostic variables showed homogeneous treatment effects consistently favoring sipuleucel-T. In patients (pts) with baseline PSA below vs above the median, there was a trend toward greater treatment effect (HR=0.685 vs. 0.865). In this exploratory analysis, we further sub-divide baseline PSA into quartiles to evaluate potential treatment effect patterns. Methods: The analysis included all randomized pts from IMPACT (n=512). Pts were categorized by baseline PSA quartile (Table), ECOG PS and by median for other baseline prognostic variables (i.e., LDH, PAP, ALP in bone-only disease, and Hgb). Median OS and HR were estimated using Kaplan-Meier and Cox models, respectively. Results: Increasing baseline PSA quartile was associated with markers of advanced disease. HRs suggest a consistent treatment effect in all subsets, although there is inadequate power to show significant results within each quartile. There was a trend toward an increased magnitude of treatment benefit in pts with a lower baseline PSA (Table). Results for other baseline prognostic variables also suggest a trend toward greater benefit in subjects with better prognostic features. However, results for baseline Hgb indicated an opposite trend. Conclusions: Although not adequately powered for significance, the results of this analysis support a consistent OS benefit with sipuleucel-T across PSA quartiles. The greater magnitude of benefit in pts with lower baseline PSA suggests that pts with less advanced disease may benefit more from treatment with sipuleucel-T. [Table: see text]
Correlation of UHRF1 expression in primary prostate cancer patients with adverse prognosis.
Authors: Roggero Enrico , Sarti Manuela , Pinton Sandra , Thalmann George , Catapano Carlo , Bonapace Ian Marc , Carbone Giuseppina 
Published: March 2020

4661 Background: Cancer of the prostate is a leading cause of cancer death in western countries. There is a great need to understand the clinical course of the disease and to distinguish the indolent tumors from those with aggressive behavior. Epigenetic mechanisms play an essential role in cancer initiation and progression. Our groups have recently provided evidence that over-expression of UHFR1 (ubiquitin-like with PHD and ring finger domain) leads to prostate cancer progression by activating a robust epigenetic switch involving silencing of a network of tumor suppressor genes. The purpose of this study was to evaluate in a clinical setting the prognostic impact of UHFR1 expression. Methods: In a series of 225 eligible patients (median age 63 years, range 44-75) with prostate cancer treated in a single institution with prostatectomy between 1990 and 1999 we evaluated the tumor nuclear expression of UHRF1 by immunohistochemistry (IHC). Clinical and histological data of the series were also reviewed. The UHFR1 expression (evaluated in tissue microarrays by immunohistochemistry) and prognostic factors were analyzed using univariate analyses and multivariate logistic regression analysis to identify association with overall survival (OS). Results: The median FU for the series was 137 months (range 1-229), eighty-one patients died (median FU 85 months). In Ninety-seven patients (43%) the UHRF1 expression was positive. In univariate analyses Gleason Score (<7 vs 7-9), Stage Risk Group (TNM Stage <III vs Stage III and/or N+) and UHFR1 expression (negative vs positive) were significant prognostic factors for OS with p-value <0.0001. In multivariate analyses Gleason Score, Stage Risk Group and UHFR1 expression were independent predictors for OS with respectively HRs of 2.77 (95% CI 1.72-4.46) p<0.0001, HRs of 1.96 (95% CI 1.14-3.37) p=0.014 and Hrs 1.35 (95% CI 1.02-1.78) p=0.030. Conclusions: Our results indicate that expression of UHFR1 protein, independently from historical prognostic factors, is linked with adverse prognosis for overall survival in a homogeneous primary prostate cancer treated group with long-term follow-up.
Detection of disseminated tumor cells in bone marrow as an independent prognostic factor in primary ovarian cancer patients.
Authors: Wimberger Pauline , Banys Malgorzata , Kasimir-Bauer Sabine , Hartkopf Andreas D. , Krawczyk Natalia , Marth Christian , Kimmig Rainer , Neubauer Hans , Wallwiener Diethelm , Fehm Tanja N. 
Published: March 2020

5042 Background: Detection of disseminated tumor cells (DTC) in the bone marrow (BM)of breast cancer patients is associated with poor outcome. Recent studies demonstratedthat DTC may serve as a prognostic factor in ovarian cancer.The aim of our study was to evaluate the impact of BM status on survival in a large cohort of ovarian cancer patients. Methods: 365 patients with primary ovarian cancer were included into this three-center prospective study. BM aspirates were collected preoperatively from iliac crest. Disseminatedtumor cells were identified by immunocytochemistry using the pancytokeratin antibodyA45B/B3 and by cytomorphology. Patient outcomes were evaluated using a multivariable Cox regression model. Results: Disseminated tumor cells were detected in 28% of all BM aspirates. The number of CK-positive cells ranged from 1 to 42 per 2x106 mononuclear cells. DTC status did not correlate with any of the established clinicopathogical factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 mo, 95% CI: 35 – 67 mo versus 32 mo, 95% CI: 22 – 42 mo; p = 0.003). However, disease-free survival was not related to DTC-positivity. In the multivariable analysis, BM status, FIGO stage, nodal status, resection status and age were independent predictors of reduced overall survival. Interestingly, a subset of DTCs may have stem cell properties since a subset of these cells (128 out of 228 cases) were SOX2 positive, which is an embryonic stem cell marker. Conclusions: Tumor cell dissemination into bone marrow is a common phenomenon in ovarian cancer. DTC detection has the potential to become an important biomarker for prognostication and may be included as a therapeutic target in future concepts.
Effect of BRCA mutation on prognosis in patients with ovarian cancer: A systematic review and meta-analysis.
Authors: Valachis Antonis , Polyzos Nikolaos P. , Zavos Apostolos , Mauri Davide , Lind Pehr A. 
Published: March 2020

5066 Background: To investigate whether the germ-line mutations of BRCA 1 and 2 in patients with ovarian cancer are associated with disease outcome. Methods: A systematic search of the literature was performed using search terms related to BRCA, ovarian cancer and prognosis. Studies were considered eligible if they reported the outcome of ovarian cancer in patients with BRCA 1 and/or 2 mutations compared with patients with sporadic ovarian cancer or / and no BRCA mutation. Cohort and case-control designs were included. Pooled Hazard Ratios (HR) were estimated with fixed or random effects models, depending on between-studies heterogeneity. Results: Of 2,340 titles identified, 26 articles met the inclusion criteria. Of these, 6 studies were excluded from the analysis due to duplication of results (n=1) and lack of data to calculate HR (n=5). Patients with BRCA 1 or 2 mutations had better survival compared with control group both in cohort (HR: 0.58, 95% Confidence Interval (CI) 0.42-0.79, p-value 0.0005) and in case-control (HR: 0.65, 95% CI 0.45-0.93, p-value = 0.02) studies. When only patients with BRCA 1 mutation were analyzed, the survival benefit remained significant (HR: 0.67, 95% CI 0.53-0.85, p-value = 0.001). Furthermore, the differential survival benefit of the mutation groups was even more evident among patients with BRCA 2 mutation (HR: 0.43, 95% CI: 0.30-0.63, p-value < 0.0001). A direct comparison of patients with BRCA 1 vs. BRCA 2 mutations (4 studies) revealed a significantly better survival for BRCA 2 mutation carriers (HR: 0.53, 95% CI: 0.33-0.85, p-value = 0.009). Conclusions: Our results confirm the hypothesis that BRCA status is a prognostic factor in patients with ovarian cancer. Based on these results, the use of BRCA status as a stratifying factor in therapeutic ovarian cancer trials seems to be fully justifiable. The stronger association between survival and BRCA 2 mutation, compared with BRCA 1, suggests a different nature of the dysfunction of these 2 genes.
Association of SNP genotype in ABCB1 with completion of intraperitoneal chemotherapy in ovarian and primary peritoneal cancer.
Authors: Enderica Gonzalez Sergio , Weroha Saravut John , Maurer Matthew J. , Moyer Ann M. , Goode Ellen L. , Rider David N. , Qin Rui , Haluska Paul , Costello Brian Addis 
Published: March 2020

5077 Background: A standard of care (SOC) for the adjuvant treatment of ovarian and primary peritoneal cancer is a platinum-based intravenous (IV) chemotherapy doublet. Intraperitoneal (IP) chemotherapy is also a SOC, but the high incidence of grade 3/4 adverse events has limited its acceptance among clinicians. To identify genetic markers for completion of IP chemotherapy, we analyzed SNPs in four genes known to play a role in metabolism of platinum or taxane drugs. Methods: Patients diagnosed with primary or recurrent stage III or IV epithelial ovarian or primary peritoneal cancer who had primary or secondary debulking surgery at Mayo Clinic (Rochester, MN) between January 2007 and February 2009 followed by IP chemotherapy were included in this study. A cycle was defined as IV paclitaxel (135mg/m2) on day one, IP cisplatin (100mg/ m2) on day two, and IP paclitaxel (60mg/ m2) on day eight. With prior consent from the patient, peripheral blood was obtained before treatment for extraction of germline DNA. Using a custom Illumina BeadXpress 96-plex panel, SNPs in GSTM1 (N=7), ABCB1 (N=57), CYP3A4 (N=7), and CYP2C8 (N=25) were genotyped. The association between SNPs in these subsets of genes and completion of IP chemotherapy was analyzed using linear regression. Results: Thirty-seven patients were included in this study and 16 (43.2%) completed IP chemotherapy. Twenty-two out of the fifty-seven ABCB1 SNP’s were associated with the number of cycles (p<0.15). There were no significant associations for GSTM1, CYP3A4 and CYP2C8 SNP’s. The minor A allele at missense SNP rs2229109 in the ABCB1 gene was present in five (31.2%) who completed treatment and only one (4.8%) who did not (p<0.007). However, the later was due to catheter complication. There was no association between rs2229109 and overall or progression-free survival. Conclusions: Our findings suggest that SNP rs2229109 in ABCB1 gene is associated with completion of IP chemotherapy, and potentially, less toxicity from chemotherapy. Thus, these patients may be optimal candidates for IP chemotherapy. Further studies in a larger population are needed.
Pair box (PAX8) protein to predict disease recurrence and its association with outcome in women with endometrial cancer: A retrospective study of 229 patients.
Authors: Samrao Damanzoopinder , Wang Dan , Mhawech-fauceglia Paulette 
Published: March 2020

5091 Background: Pax-8 is a member of the pair-box (PAX) family of transcription factor genes and it has been found to be overexpressed in numerous cancer cell lines including ovarian and endometrial. Possibly, inhibition of Pax8 activity may even have an impact on cancer treatment. However the role of Pax8 in human endometrial cancer has not yet been explored. Thus, the aim of this study is to determine its predictive value in disease outcome of endometrial cancer. Methods: 229 patients with available clinical data and paraffin-embedded tissue were available for review and analysis. The clinical parameters used for modeling were age, histologic subtypes, myometrial depth of invasion, lympho-vascular invasion (LVI), FIGO grade, lymph nodes positive, recurrence, disease status, recurrence time and survival time. To test the association between Pax8 and the clinical parameters, Fisher’s exact test was performed. For survival analysis, Kaplan-Meier method was performed. Results: We found a strong association between PAX8+ and high tumor grade (p=0.002), LVI + (p<0.018), and type II tumor subtype. Patients with tumor expressing Pax8 were more likely to present with shorter OS and DFS p= 0.00096 and p=0.018 respectively. There was an association of PAX8 with OS (p=0.01486) with 5-years OS probability of 80.04% for patients with Pax8- and 55.9% for patients with Pax8+. There was also an association of PAX8 and DFS probability (p=0.02028) with 5-years DFS probability was of 72.12% for patients with Pax8- versus 49.88% for patients with Pax8+ expression. Conclusions: Pax8 is a reliable marker in endometrial cancer and its overexpression can predict poor outcome.
Gene methylation in random FNA samples as biomarkers for breast cancer.
Authors: Stearns Vered , Khan Seema Ahsan , Fackler Mary Jo , Chatterton Robert T. , Jacobs Lisa K. , Khouri Nagi , Kenney Kara , Shehata Christina , Jeter Stacie , Ivancic David , Wolfman Judith , Zalles Carola M. , Huang Peng , Sukumar Saraswati 
Published: March 2020

518 Background: Current methods to determine breast cancer risk are insufficiently sensitive to select women most likely to benefit from preventive strategies. We hypothesized that candidate gene promoter hypermethylation may provide an individualized risk profile. We performed a prospective study to determine whether DNA cumulative methylation index (CMI) varies by menstrual phase or menopausal status, and to correlate CMI with established risk factors. Methods: We obtained random fine needle aspiration (rFNA) samples from healthy women age 35-60 and determined their menopausal and menstrual status, lifetime Gail risk, mammographic breast density, and cytologic atypia assessed as the Masood score. We evaluated CMI of 11 candidate genes in rFNA cells using the Quantitative Multiplex Methylation-Specific PCR (QM-MSP) technique. We used Wilcoxon test and ANOVA model to compare CMI across menopausal and menstrual (follicular, mid-cycle, luteal) categories, respectively. We used linear regression model to adjust for age and BMI. Methylation scores were log-transformed in the analysis. Results: We enrolled 390 women at the Avon Breast Centers at Johns Hopkins and Northwestern, the majority through the Love/Avon Army of Women, and 380 completed study procedures. Median age 50 (36-60), mean BMI 28 (18.7-50.8), 52% were postmenopausal. Mean life-time Gail risk 14.6 (5.6-54.1), mean percent mammographic density 19.6 (2.5-72.8), and mean Masood score (N=354) 13.6 (7-18). QM-MSP analysis was completed on 229 samples. We did not observe differences in CMI among menopausal (P=0.4895) or menstrual categories (P=0.2333). There was no association between CMI and life-time Gail risk (P=0.706) or breast density (P=0.4116). We observed a significant correlation between CMI and Masood score (P=0.0167). Conclusions: CMI correlates with degree of cytologic atypia and is potentially a robust indicator of breast cancer risk since it does not vary with menstrual or menopausal status. Next, we will select genes that best reflect changes in the clinical parameters to create a gene methylation signature that will be validated in other studies and correlated with breast cancer risk.