bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma miR371 for the detection of viable germ cell tumor in testicular cancer patients with enlarging or post chemotherapy residual nodes.
Authors: Nappi Lucia , Thi Marisa , Eigl Bernhard J. , Chi Kim N. , Gleave Martin , So Alan I. , Khalaf Daniel , Black Peter C. , Nichols Craig R. , Kollmannsberger Christian K. 
Published: February 2018

569 Background: The pathological constitution of post-chemotherapy residual disease (PCRD) or enlarged nodes in clinical stage I (CSI) patients (pts) with germ cell tumor (GCT) is guesswork, especially when tumor markers (β-HCG, AFP, LDH) are negative. Currently, accurate assessment requires clinical follow-up with imaging to establish patterns of growth or pathological confirmation with RPLND. A blood-based approach reliably to identify patients with non teratoma viable GCT (NTVGCT) would be valuable. Methods: miR371 extracted from plasma of 44 pts with GCT was analyzed by RT-PCR and relative expression calculated by the 2-ΔΔCt method. Plasma from healthy male volunteers was used as negative control while miR-93-5p as internal positive control. The sensitivity and specificity of miR371 were calculated correlating miR371 overexpression to the presence of relapsed/residual NTVGCT. Results: Fifty eight samples (20 CSI, 20 metastatic, 18 PCRD) were analyzed. Ten CSI pts presented with suspicious enlarging nodes (≥ IIA) and miR371 was overexpressed in 5/6 pts with confirmed tumor relapse. Neither CSI pts with unconfirmed enlarging nodes (n = 4) or with no signs of relapse (n = 10) presented high miR371 levels. miR371 was overexpressed in all the pre-chemotherapy metastatic pts (n = 10) and negative after chemotherapy (n = 10), with 4 pts presenting PCRD. miR371 was negative in all the pts with PCRD and no residual NTVGCT was detected in those pts by either pathology (n = 10) or clinical follow-up (n = 8). Sensitivity and specificity were 93.3% and 100%, respectively. Conclusions: Elevated plasma levels of miR371 correlate with the presence of NTVGCT and may lead to biological rather than radiographic assessment of active GCT. Since chemotherapy is first line option for NTVGCT while is inactive in teratoma, miR371 status may be used to select pts for chemotherapy or surgery. These encouraging findings inform upcoming North American trials for further definition of miR371 operating characteristics in all stages, sites of origin, gender and age specific GCTs. [Table: see text]
Thromboembolic (TE) complications in germ cell tumor (GCT) patients: Should use of peripherally inserted central catheters (PICC-Line) be pursued?
Authors: Francois Louis , Gross-Goupil Marine , Robert Gregoire , Ravaud Alain 
Published: February 2018

571 Background: Patients with GCT receiving cisplatin-based chemotherapy are at high risk of TE events (TEE). Several risk factors have been reported previously, such as cisplatin, Lactate Deshydrogenase, body surf area (BSA)... Methods: we conducted a retrospective study of all patients (pts) with GCT, treated with platinum salts and followed at the university hospital and anticancer center of Bordeaux (June 2007 - January 2015). The following characteristics were recorded: age, performans status, BSA, histological type, site of primitive tumor, stage, prognosis (IGCCCG classification), size of retroperitoneal lymphnode, LDH, type of venous pathway (peripheral vein, implantable venous access port or PICC-Line), prophylaxis of anticoagulant or not, TEE and median time to onset. Results: 206 pts were selected. Thirty-six (17.4%) had one or more venous or arterial TEE during or within 3 months of the end of chemotherapy: 26 deep vein thromboses, 13 pulmonary embolisms and 4 arterial accidents (2 acute limb ischemia and 2 acute coronary syndromes). The median time between treatment initiation and occurrence of TEE was 38.5 days [7-248]. Among the 12 pts with PICC-line, 6 (50%) had a TEE, including 4 cases of pulmonary embolism. In addition to the presence of a PICC-line (OR 4.62 [1.28, 15.56]), factors associated with an increased TE risk in univariate analysis were the use of implantable venous access port (OR: 3.97 [1.81; 9.12]), size of retroperitoneal adenopathy ≥ 2 cm ([2-5 cm]: OR: 24.39 [4.50 - 454.39]; > 5cm : OR : 26.25 [5,00 - 484.5]), stage II (OR : 10.19 [1,9 - 188.96]), stage III (OR :27.2 [5.34 - 479.9]), prognosis group (good : OR : 11.16 [2.16 - 205.04]) ; intermediate : OR : 31.50 [4.81 – 624.20] ; unfavorable : OR : 33.35 [5.7 – 637.34]), VIP (etoposide-ifosfamide-cisplatin) protocol (OR :6.35 [1.51 – 28.15]) and high LDH level (OR :3.88 [1.63 – 10.34]). Conclusions: These results suggest a significant association between PICC-line and the occurrence of TEE in univariate analysis. PICC-line is not risk-free and should be used sparingly in pts with GCT whose treatment objective remains primarily a cure at the cost of less toxicity.
Tandem high-dose chemotherapy and autologous hematopoietic stem cell transplantation (SCT) compared to single SCT for relapsed/refractory germ cell tumors (GCT).
Authors: Kilari Deepak , Hari Parameswaran , Qayed Muna , Fraser Raphael , Davila Omar , Kumar Shaji , Mark Tomer Martin , Nieto Yago , D'Souza Anita 
Published: February 2018

572 Background: Single-center observational studies have established the use of single or tandem SCT to salvage relapsed GCT but randomized trials are lacking. We analyzed outcomes and prognostic factors in 2,395 male SCT recipients for relapsed GCT between 1990 and 2015. Methods: Recipients of single or tandem SCT reported to the Center for International Blood and Marrow Transplant Research were identified. Outcomes were compared by SCT year: 1990-94 (N = 288), 1995-99 (N = 351), 2000-04 (N = 376), 2005-09 (N = 509) and 2010-15 (N = 871). A recent subset (n = 267, 2000-2015) with detailed disease- and transplant-related data was further analyzed with a multivariate (MVA) Cox proportional hazards model. Results: Median age at SCT was 31 (11-76) years and 49% received SCT within 12 months of diagnosis consistent with early relapse/primary refractory GCT. 26% had primary extragonadal GCT; 1,167 (49%) had intent to tandem transplant (TT). The median follow up was 51 (3-313) months. Day 100 non-relapse mortality was statistically similar at 8% in 1990-94 (vs. 4% in 2010-15) but 3-year progression-free survival (PFS) improved from 24 (18-31)% in 1990-94 to 47 (43-50)% in 2010-15 (p < 0.0001) and 3-year survival (OS) from 35 (29-40)% to 54 (50-57)% in 2010-15 (p < 0.0001). Compared with single SCT, TT recipients were younger 31 (16-62) vs 34 (13-76), with lower Hematopoietic Cell Transplantation-Comorbidity Index, more likely to undergo SCT after 1 line of chemotherapy (28% vs 9%), and within 1 year of diagnosis (51% vs 38%). TT was preferred over single SCT over time (48% of SCT were TT in 2000-04 vs. 81% in 2010-15). In MVA, non-seminoma histology, residual tumor at SCT, receipt of > 1 line of pre-SCT chemotherapy and single SCT (vs. TT), were associated with worse PFS and OS. Year of SCT was not significant when adjusted for these covariates. Conclusions: In this large longitudinal cohort, improvements in PFS and OS were observed in recent years. SCT earlier in disease course and tandem SCT were associated with superior outcomes. These data involving a large cohort reported from 225 centers confirm specialized centers’ date in a real-world setting.
Dissecting the expression landscape of genitourinary cancers.
Authors: Jeldres Claudio , Bouchard Sabrina , Richard Patrick O , Carmel Michel , Sabbagh Robert , Bisaillon Martin 
Published: February 2018

573 Background: Genitourinary (GU) cancers include bladder urothelial carcinoma (BCa), prostate cancer, kidney clear cell or papillary carcinoma, uterus endometrial carcinoma, ovarian cystadenocarcinoma and testicular germ cell tumors. Clinical data show a higher prevalence of GU cancers for men than women, suggesting significant molecular differences depending on sex regarding cancer development. This project aims at dissecting the expression landscape for all GU cancers and identify significant dysregulated genes between cancer and normal tissues specific either for men and women. The resulting data will serve a clinical application consisting in targeting novel molecular biomarkers detected in urine for GU cancers early diagnosis. Methods: Based on RNAseq data provided by The Cancer Genome Atlas, gene expression fold-change for 19,123 genes from cancer tissues and normal tissues was initially compared for each GU cancer. To ensure significant gene dysregulation, only genes showing a fold-change ≤ -log2(2) or ≥ log2(2) and a p-value < 0.05 were retained. Next, a comparison in gene expression modification between men and women for each cancer was made to identify the most significant molecular differences between both sexes. Unique dysregulated genes for each cancer were then identified and their presence or absence in urine was confirmed. From the pool of genes expressing proteins in urine, non-parametric tests for paired and unpaired values were used to determine the statistical difference between cancer and normal tissues in terms of gene expression. Results: Among 2880 genes significantly dysregulated for all five GU cancers, more than half of them were unique to BCa. Among these, 129 gene products (proteins) were ultimately detected in urine of patients. Seven up-regulated and ten down-regulated genes have shown high statistical differences between cancer and normal tissues in the Mann-Whitney U test for unpaired values. CEACAM6, S100A8 and S100A9 have shown significant differences in the Wilcoxon test for paired values which make them potential biomarkers ready for validation by LC-MS/MS. Conclusions: This present study shows the relevance to pursue research in gene expression modification in cancer to improve early diagnosis.
Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma: Exploratory pharmacogenomic analysis.
Authors: George Daniel J. , Martini Jean-Francois , Staehler Michael D. , Chang Yen-Hwa , Breza Jan , Patard Jean-Jacques , Motzer Robert J. , Magheli Ahmed , Carteni Giacomo , Donskov Frede , Escudier Bernard , Li Sherry , Casey Michelle , Valota Olga , Laguerre Brigitte , Pantuck Allan J. , Pandha Hardev S. , Patel Anup , Lechuga Mariajose , Ravaud Alain 
Published: February 2018

576 Background: In the phase III S-TRAC trial, adjuvant sunitinib (SU) prolonged disease-free survival (DFS) vs placebo (PBO) in patients with locoregional renal cell carcinoma at high risk of recurrence after nephrectomy (median 6.8 vs 5.6 y; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59–0.98; P= 0.03). An exploratory analysis evaluated associations between single nucleotide polymorphisms (SNPs) in angiogenesis-related genes and clinical outcomes in S-TRAC. Methods: Prospectively collected blood samples were genotyped for 10 SNPs and 1 insertion/deletion mutation with TaqMan assays. DFS was compared with a log-rank test for each SNP genotype in SU vs PBO arms and between SNP genotypes within each arm. P-values are unadjusted for multiplicity comparison. Results: Of 615 patients, 286 (142 SU; 144 PBO) were analyzed. There were generally no genotype frequency deviations from the Hardy-Weinberg equilibrium, but linkage disequilibrium was seen between VEGFA rs699947 and rs833061 on chromosome 6 (D′ = 1.000, r2 = 0.979). Longer DFS was observed with SU vs PBO for VEGFR1 rs9554320 C/C (median: not reached [NR] vs 5.56 y; HR 0.44, 95% CI 0.21–0.91; P= 0.023), VEGFR2 rs2071559 T/T (median: NR vs 4.47 y; HR 0.46, 95% CI 0.23–0.90; P= 0.020), and eNOS rs2070744 T/T (median: 7.07 vs 3.44 y; HR 0.53, 95% CI 0.30–0.94; P= 0.028), with a trend for VEGFR1 rs9582036 A/A (median: NR in both arms; P= 0.054) and SH3GL2 rs10963287 C/T (median: NR vs 5.35 y; P= 0.088). Shorter DFS was observed for VEGFR1 rs9582036 C/A vs C/C in the SU, PBO, and combined arms ( P< 0.05); for A/A vs common, the association was only seen in the SU arm ( P= 0.022). VEGFR1 rs9554320 A/C was associated with shorter DFS vs A/A in the PBO ( P= 0.038) and combined arm ( P= 0.006), with a trend in the SU arm ( P= 0.051). VEGFR2 rs1870377 T/T was associated with longer DFS vs A/A in the combined arms, but not in the PBO arm (n = 7 with A/A genotype in the SU arm precluded statistical tests). Conclusions: Correlations between common VEGFR1 and VEGFR2 SNPs and longer DFS with SU suggest germline SNPs are predictive of improved outcomes with adjuvant SU. Due to the exploratory nature of this analysis, prospective validation studies are needed to confirm these findings. Clinical trial information: NCT00375674.
Clinical validation of single nucleotide polymorphisms (SNPs) as predictive biomarkers in localized and metastatic renal cell cancer (RCC).
Authors: Garrigos Carmen , Salinas Ana , Melendez Ricardo , Espinosa Marta , Sánchez Iván , Osman Ignacio , Medina Rafael , Taron Miquel , Duran Ignacio 
Published: February 2018

588 Background: SNPs predictive of survival outcomes in patients (pts) with localized and metastatic RCC have been identified previously by us [Garrigós C et al, 2017]. Fifteen SNPs in 9 genes involved in angiogenesis and metabolism of antiangiogenics were recognized as predictive/prognostic in a cohort of 102 pts. The aim of the present study is to validate these associations in an independent cohort of RCC pts Methods: Genotyping was performed in DNA isolated from paraffin-embedded tumor samples from 87 pts with localized and metastatic RCC. DNA was extracted by a commercial kit (QiAGEN) and amplified with a specific primers pool for each SNP as determined by the manufacturer (Lifetech). The 15 SNPs were individually genotyped by Real time quantitative PCR with specific primers and Taqman probes (Lifetech). The presence of the selected SNPs was correlated with clinical features such as disease free survival (DFS), progression free survival (PFS) and overall survival (OS). SPSS v24 was used for statistical analysis. Results: In the localized pts (n = 66), Fuhrman grades 3-4 and stage T3-T4 significantly associated with DFS (p = 0.025 and p = 0.004, respectively). The presence of allele C of rs307826 (FLT4 gene) correlated with a greater chance of relapse (p = 0.025) and also with a shorter DFS (21 vs 35 months, p = 0.007). For the metastatic pts (n = 21), allele C of rs307826 (FLT4 gene) and allele A of rs9800958 (PRKAR1B) were linked with a shorter PFS [(8 vs 18 months, p = 0.036) and (8 vs 17 months, p = 0.043) respectively]. In the localized cohort, allele T of rs2227543 (IL8 gene) was associated with longer OS (14 vs 3 months, p = 0.039) while allele G of rs10013228 (KDR gene) linked with worse OS (4 vs 17 months, p = 0.063). Conclusions: This analysis comes to confirm our previous observations that certain genotypes could be used as prognostic/predictive factors in RCC. This is particularly important in an era where multiple treatment options are available for this disease.
Clinical and genomic characterization of low-prostate-specific antigen, high-grade prostate cancer.
Authors: Mahal Brandon Arvin Virgil , Yang David Dewei , Wang Natalie , Alshalalfa Mohammed , Davicioni Elai , Choeurng Voleak , Spratt Daniel Eidelberg , Martin Neil E. , Mouw Kent William , Orio Peter F , Choueiri Toni K. , Trinh Quoc-Dien , Feng Felix Y , Nguyen Paul L. 
Published: February 2018

59 Background: The consequences of a low prostate-specific antigen (PSA) in high-grade (Gleason 8-10) prostate cancer are unknown. We sought to evaluate the clinical implications and genomic features of this entity. Methods: Clinical and transcriptomic data from 626,057 patients with N0M0 prostate cancer were collected from two national cohorts and a large transcriptome database. Multivariable Fine-Gray and Cox regressions analyzed prostate-cancer specific mortality (PCSM) and all-cause mortality, respectively. GRID data were used to analyze transcriptomic features. Results: For Gleason 8-10 disease, the distribution of PCSM was U-shaped by PSA (PSA 4.1-10.0 ng/mL = referent), with adjusted hazard ratio (AHR) 2.70 for PSA ≤2.5 ng/mL (P < 0.001) versus 1.97, 1.36, and 2.56 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL, respectively. In contrast, distribution of PCSM by PSA was linear for Gleason ≤7 with AHR 0.41 for PSA ≤2.5 ng/mL (P = 0.127) versus 1.38, 2.28, and 4.61 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL, respectively (PGleason*PSA interaction< 0.001). Gleason 8-10, PSA ≤2.5 ng/mL disease had a significantly higher PCSM than standard high and very high-risk disease with PSA > 2.5 ng/mL (AHR 2.15, P = 0.009; 47-month PCSM 13.8% versus 4.9%). Among Gleason 8-10 patients treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with a survival benefit for PSA > 2.5 ng/mL (AHR 0.87, P < 0.001) but not for ≤2.5ng/mL (AHR 1.36, P = 0.084; PADT*PSA interaction= 0.021). For Gleason 8-10 tumors, PSA ≤2.5 ng/mL was associated with a higher expression of neuroendocrine markers compared to > 2.5 ng/mL (P = 0.046), with no such relationship for Gleason ≤7. Conclusions: Low-PSA, high-grade prostate cancer appears to be a unique entity that has a very high risk for PCSM, potentially responds poorly to ADT, and is associated with neuroendocrine genomic features.
The impact of facility case volume on overall survival in patients with metastatic renal cell carcinoma in the targeted therapy era.
Authors: Chen Yu-Wei , Tullio Katherine , Ornstein Moshe Chaim , Grivas Petros , Garcia Jorge A. , Rini Brian I. 
Published: February 2018

590 Background: Prognosis of metastatic renal cell carcinoma (mRCC) has significantly improved in the targeted therapy era. We aimed to investigate whether higher facility case volume (FCV) is associated with improved overall survival (OS) for mRCC. Methods: Patients diagnosed with mRCC from 2006-2012 were identified in the National Cancer Database. FCV was determined by the total cases of renal cell carcinoma (metastatic and non-metastatic) at each treating facility. Multivariable Cox regression model was used to investigate the association between FCV and OS. Covariates adjusted for were treatment modalities [targeted therapy, cytoreductive nephrectomy, and metastasectomy], tumor characteristics and patient sociodemographics. Results: There were 18,571 mRCC patients included in this study. The mean follow-up time was 13.2 months (median: 6; interquartile range: 2.3-17.9). After adjusting for baseline characteristics including treatment modalities (table), every increment of 100 FCV of the treating facility was associated with improved OS (AHR: 0.99, 95 CI: 0.98-0.99, p-value: 0.003). FCV was dichotomized at increasing percentiles (50th, 80th, 85th, 90th, and 95th). Improved OS was observed when high FCV was defined at 90th percentile (47 cases/year; AHR: 0.96, 95% CI: 0.92-0.99, p-value: 0.02) and 95th percentile (68 cases/year; AHR: 0.95, 95% CI: 0.91-0.98, p-value: 0.04) but not at 50th (8 cases/year), 80th (30 cases/year) or 85th percentile (38 cases/year). Conclusions: Our results suggest that treatment at hospitals with higher renal cell carcinoma FCV is associated with improved OS for patients diagnosed with mRCC in the targeted therapy era. Model is also adjusted for age, race, sex, insurance status, Charlson comorbidity score, tumor stage, nodal status, histology type, year of diagnosis, and zip code-level socioeconomic data (income, education level and residence type). [Table: see text]
Systemic immune inflammation index and treatment response in patients with metastatic renal cell cancer.
Authors: Bir YÃ¼cel Kadriye , Yasar Arzu , Ucar Gokhan , Utkan Gungor , Yildirim Nuriye , Urun Yuksel 
Published: February 2018

591 Background: To investigate the prognostic value of the pretreatment inflammatory characteristics on treatment response and survival. Methods: We included 151 patients with metastatic renal cell carcinoma (mRCC) Patients’ charts were retrospectively analyzed for their clinical, pathological and demographic features. Systemic immune inflammation index (SII) cut off is estimated with median value. Overall survival (OS) was estimated by Kaplan-Meier method for univariate analysis and Cox-regression for multivariate analysis. Results: In high SII group (SII > 844) overall survival is 11 months and in low SII group (SII < 844) overall survival is 22 months (p = 0,008). Median OS is lower in the hypercalcemic group (7 months vs.18 months, P = 0,013). In patients with anemia and thrombocytosis, OS is lower (41 months vs. 13 months p = 0,001 and 6 months vs. 18 months p = 0,01). In multivariate analysis, anemia, SII, and ECOG performance status were able to predict OS (HR = 2,69, HR = 2,04, HR = 2,57) Conclusions: In patients with mRCC, SII may have a prognostic value and higher score may related with decreased overall survival.
Effect of epidural block on restoration of protease inhibitors in patients with local kidney cancer.
Authors: Kit Oleg Ivanovich , Rozenko Dmitry A. , Frantsiyants Elena , Kozlova Larisa S. , Bandovkina Valeria A. , Dimitriadi Sergey N , Ushakova Natalya D. , Rozenko Ludmila Ya. , Duritskiy Maksim N. 
Published: February 2018

593 Background: The purpose of the study was to reveal the effect of the epidural block (EB) on the dynamics of the main universal inhibitors in the blood plasma and urine of patients with local kidney cancer. Methods: 58 patients aged 56.5±8.7 years underwent partial nephrectomy with warm ischemia for 15-20 minutes (EB – 35 patients, standard anesthesia (SA) - 23 patients). EB involved catheterization of the epidural space at Th10-L1 with the following infusion of a mixture of ropivacaine 2 mg/ml and epinephrine 2 μg/ml at 6-10 ml/hr using a syringe doser, intraoperatively and within the first three postoperative days. α2-Macroglobulin (α2M) and α1-proteinase inhibitor (α1PI) were studied by ELISA and spectrophotometry in the blood plasma and urine of patients before the surgery (b/s), 40 min after the start of the surgery (40' s/s) and on days 1 and 3 after the surgery (a/s). Results were compared to the levels in the blood plasma and urine of 29 healthy donors (N). Results: α2M and α1PI in the blood plasma and urine of all patients b/s were lower than N (p < 0.05). α2M in the blood plasma of all patients 40' s/s was similar to N. Normal α2M levels were maintained in the blood plasma in EB on days 1-3 a/s, while in SA they increased by 2.8 times on day 1 and decreased by 3.4 times on day 3, compared to the previous measurement results. α1PI in EB began to increase since 40' s/s with its normalization by the day 3 a/s; α1PI in SA was decreased in the blood plasma and urine during the whole study period. The urine/blood plasma ratio for α2M (α2Mu/α2Mb) was increased b/s in all patients, with its normalization on days 1-3 in EB and its decrease by 9.5-3.1 times on days 1 and 3 in SA. The α1PIu/α1PIb ratio was increased b/s on average by 2.1 times in all patients, with its normalization 40' s/s in EB, and remained similar to N by the day 3. Normalization was not observed in SA; α1PIu/α1PIb was decreased since 40' s/s to the day 3 by 1.8-1.4 times (p < 0.05), compared to N. The results showed that in SA, the proteolysis was not controlled in the kidney due to the inhibitor deficiency. Conclusions: The epidural block contributes to the restoration of the activity of α2M and α1PI universal endogenous inhibitors during and after surgery, in contrast to the standard anesthesia.