bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of primary tumor location in advanced urothelial carcinoma: The EORTC series.
Authors: Moschini Marco , Shariat Shahrokh F. , De Santis Maria , Bellmunt Joaquim , Sternberg Cora N. , Tombal Bertrand F. , Collette Laurence , Roupret Morgan 
Published: September 2018

e16034 Background: The prognostic relevance of the primary location of urothelial cell carcinoma (UCC) on outcomes is poorly documented. This parameter has been studied in 3 EORTC trials in advanced UCC that included patients with different initial primary tumor locations. Methods: We used the data prospectively collected in three EORTC advanced UCC studies 30924 (M-VAC versus High dose M-VAC), 30986 (MCAVI versus GC, among patients unfit for CDDP), 30987 (GC-Paclitaxel versus GC, among patients fit for CDDP). Ineligible patients and other tumor locations were excluded. Patients all had measureable distant metastases or unresectable UCC and WHO performance status 0-2. Patients were grouped by primary tumor location as bladder (BCa) versus upper urinary tract (UTUC). PFS and OS by tumor location was tested in Cox proportional hazard regression stratified by study and treatment using at 2-sided α of 0.05. Results: Of the 1,039 patients, 85.3% and 14.7% patients had BCa and UTUC, respectively. Patient and disease characteristics (Table) suggested better performance status and slightly more males among patients with GCa. With a median follow up of 4.8 years (IQR:4.0-6.7), 733 deaths were recorded and 925 had progressed or died. OS and PFS did not differ significantly by tumor location overall (P=0.317 and P=0.685 respectively, Table 1), but there is significant heterogeneity across treatments (heterogeneity P=0.0450 for OS and P=0.0121 for PFS) with a suggestion of differential results in the M-CAVI arm for unfit patients. Conclusions: Primary UTUC location is uncommon in advanced UCC and did not seem to markedly impact PFS or OS. However, the findings may vary according to treatment. [Table: see text]
Endoglin (CD105) expression in non-seminomatous germ cell tumors.
Authors: Sikaria Swati , Chopra Shefali , Xiong Shigang , Yang Dongyun , Theuer Charles P. , Hu James 
Published: September 2018

e16036 Background: Nonseminomatous germ cell tumors are known for hematogenous spread and new therapeutics are needed. Endoglin (CD105) is a cell-surface protein that is overexpressed on endothelial cells and a potential target for anti-angiogenic therapy. Preclinical studies demonstrate overexpression of CD105 in tumor vasculature and targeting CD105 in murine models have resulted in tumor regression. We examine CD105 expression in tumor cells and tumor vasculature of patients with non-seminomatous germ cell tumor. Methods: Slides of NSGCT were incubated with rabbit anti-human CD105 followed by horseradish peroxidase-labeled anti-rabbit IgG and then with substrate chromogen followed by hematoxylin counterstaining. Human kidney served as positive internal control. Endoglin positivity was assessed in tumor cells and vasculature and graded (0-3+). Results: 37 total samples were obtained, 4 were excluded (3 seminoma, 1 pure teratoma) All 37 specimens had positive endoglin staining in tumor vasculature. Of 33 specimens, 79% (26/33) had positive staining for endgolin, whereas 21% did not (7/33). (Table 1)Of patients with relapsed or refractory disease, 83% (5/6) stained positively for CD105. While this is a small sample size, 3+ staining was seen in 50% of patients (n=6) with relapsed or refractory disease, but vs 18.5% of patients (n=27) in 1stremission (Fisher’s exact test p =0.14). Conclusions: Endoglin was highly expressed in tumor and tumor vasculature of NSGCT. This small pilot study suggests high (>50%) expression correlating with relapsed or refractory disease. Further samples from patients with relapsed or refractory disease are being collected and analyzed. Endoglin is a potential target for study in non-seminomatous germ cell tumors. [Table: see text]
Germ cell tumors: Survival analysis and experience from a low- to middle-income country.
Authors: Yasmeen Samia , Hannan Abdul 
Published: September 2018

e16044 Background: We performed a retrospective analysis of Germ-Cell Tumor patients presenting to Shaukat Khanum Cancer Hospital, Pakistan to have a greater understanding of the presentation & outcomes in South-east Asia. Methods: A search of hospital registry identified 105 patients between Jan-Dec 2013, out of which survival data was available for 99. Final cut off for data collection: Sept 2016. Electronic records were reviewed & analyzed for outcomes, survival & relapse. Results: Median age: 29(18-66) years. Median Follow-up: 33(6-46) months. Testicular primary 96(91.4%). Retroperitoneal 5(4.76%). Mediastinal GCT 4(3.8%). 87(82.85%) underwent orchiectomy while upfront chemotherapy was started in 9(9.45%). Pure Seminoma 46(43.8%). Non-Seminoma 59(56%). Highest level of B-hCG for seminoma: 3607IU/L (Minimum 2.9). Highest level of AFP for Non-Seminoma: 30000IU/L (Range 0.35-30000). Median LDH: 533IU/L (Range 253-23760). Most common Non-Seminoma components: embryonal and yolk-sac tumors. Chemotherapy regimen: Etoposide/Carboplatin 39(37.1%), Bleomycin/Etoposide/Cisplatin 29(27.6%). Carboplatin for Stage-I Seminoma: 17(16.1%). 11(11.5%) patients expired due to advanced disease. Lost to follow up 14(14.7%). 76(79.8%) were alive without any disease while 4(4.02%) were alive with PD. One stage-I seminoma relapse was successfully cured with EP, while 14 Non-seminoma relapses were retreated with VeIP. Eight relapses achieved cure, while 6 had refractory disease. Off total 11 deaths, five had PD, Cisplatin induced stroke: 1, Bleomycin toxicity: 3, Neutropenic sepsis: 1. One relapse as melanoma. Median survival: yet not reached. Conclusions: Our data suggest almost same results corresponding to international literature. Most of our patients present with huge disease burden, which may not change the risk stratification, but alters prognosis. [Table: see text]
Pre-treatment neutrophil to lymphocyte ratio (NLR) association with curative intent metastasectomy (MSX) in metastatic renal cell carcinoma (RCC).
Authors: Fares Aline Fusco , Araujo Daniel Vilarim , Ricardo Eliza Dalsasso , Corassa Marcelo , Formiga Maria Nirvana Cruz , Costa Walter Henriques , Guimaraes Gustavo Cardoso , Zequi Stenio C. , Cunha Isabela 
Published: September 2018

e16051 Background: NLR is a marker of inflammation and when elevated is associated with poor outcome in many tumors, including RCC. Hereby we evaluate the association of NLR with the likelihood of curative intent MSX. Methods: We retrospectively studied 846 patients diagnosed with metastatic RCC between 2007 and 2016. 116 patients fulfilled inclusion criteria: previous nephrectomy, no sarcomatoid features and available tumor specimens from metastatic site. Regression tree for censored data method was used to find the best NLR cut-off value. NLR was examined baseline – prior to MSX or targeted therapy. Chi-square test was used to evaluate associations between variables. We estimated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards regression models were fitted to evaluate the prognostic significance of NLR in univariable and multivariable analysis. Results: The median OS for the whole cohort was 45 months (95% CI, 27.6 to 62.4 months), and the median follow-up was 78.2 months. The best cut-off NLR value was 4.07. Higher NLR was associated with shorter OS when compared to the lower NLR cohort (11.5 months vs 68.3 months HR = 0.26, 95% CI: 0.15 – 0.97, p ≤ 0.0001, respectively). Univariate analysis revealed that bone metastasis and poor IMDC criteria were associated with worse OS and that MSX and lower NLR were associated with better OS. On multivariate analysis MSX, lower NLR and favourable/intermediate group on IMDC criteria were associated with a decreased risk of death (HR = 0.41, 95% CI 0.19-0.85, p = 0.018 and HR = 0.45, 95% CI 0.22-0.90, p = 0.025, HR = 0.35, 95% CI 0.16-0.79, p = 0.012, respectively). We found a positive association of lower NLR and curative intent MSX (p = 0.002). Conclusions: NLR is a prognostic marker in metastatic RCC and a ratio ≤ 4,07 is associated with a higher likelihood of curative intent MSX.
Prognostic value and optimal cut off of neutrophil/lymphocyte ratio (NLR) in patients with metastatic renal cell cancer (mRCC).
Authors: Jankilevich Gustavo , Salazar Matias , Nacuzzi Gabriela , Chirino Daniel , Gennari Luciana 
Published: September 2018

e16059 Background: Several biomarkers were tested in mRCC but only outcome scores showed prognostic significance. Neutrophil-to-lymphocyte ratio (NLR) has shown prognostic significance for OS in a number of cancer types but value and cutoff in mRCC is unknown. Methods: The aim of this study was to evaluate NLR as prognostic factor and find a cutoff in mRCC pts. The medical records of 103 pts with mRCC were reviewed. Analysis included adjusting for baseline disease and patient characteristics and investigating potential interaction effects between NLR status and significant BL predictors of outcome. Overal Survivall (OS) was estimated by the Kaplan-Meier method.Univariate and multivariate analysis was performed by Cox regression. Results: Total pts reviewed were 103, MSKCC risk groups (37% Good, 47% Intermediate,16% Poor).Median follow up were 50 months and median OS 29 months. Nephrectomy was performed in 81% of cases.Ninety six percent received treatment (tki – mTor inhibitors). The optimal cutoff was 4, pts with NLR ≤4 vs ≥4 have higher OS 32m vs 10m HR 3,38 (IC95%: 2,60- 4,50 p:0,0001) univariate and HR: 4,32 (IC 95%: 3,35-5,4 p:0,003) in the multivariate analysis. Conclusions: Our series show MSKCC score and RLN were prognostic factors in univariable and multivariable analisys. NRL ≥ 4 identify a group of patients with poor overall survival. The NLR provides independent prognostic information for patients with mRCC and could be useful in academic and community setting. [Table: see text]
MicroRNAs (miRNAs) as predictors of extreme response to tyrosine kinase inhibitors in renal cell cancer (RCC).
Authors: Garrigos Carmen , Molina-Pinelo Sonia , Espinosa Marta , Lerma Antonio , Ávila Rainiero , Medina Rafael , Salinas Ana , Melendez Ricardo , Garcia-Donas Jesus , Rodriguez-Antona Cristina , Duran Ignacio 
Published: September 2018

e16076 Background: A number of different drugs are approved for the 1stline treatment of mRCC and provide a median PFS of ≈ 11 months. Yet, a small subset of pts will present an unusually either short or prolong response [extreme responders]. MiRNAs are small fragments of RNA that modulate gene expression controlling cell development and differentiation. Promising results about their value as predictors of drug response have been published in lung and colorectal cancer [Molina-Pinelo]. This study aims to define miRNA profiles in RCC and determine whether they can predict “extreme responses”. Methods: The expression of 754 miRNAs was analyzed with TaqMan Low Density Array Human MicroRNA Panel (TLDA) (ThermoFisher). QPCR was carried out in the System of Gene Expression and Genotyping Arrays module ViiA7. We defined long-term response pts (LR) (PFS˃11 months, n = 7) and primary refractory pts (PR) (progression as best response, n = 8). MiRNAs differentially expressed were independently analyzed by individual qPCR assays in the study cohort and in an external validation cohort of pts (n = 35). Statistical analysis was performed with SPSSv20. Results: Four miRNAs were significantly associated with patient response and differentially expressed in PR vs LR (up-regulated in PR: miR-425-5p, down-regulated in PR: miR-139-3p, let-7d and let-7e). Let-7d and let-7e were validated internally (p < 0.05) and all of them showed the same tendency but without statistically significance in the external validation cohort. Fourteen miRNAs had differential expression in tumor vs healthy tissue and seven were validated in the study cohort (tumor up-regulated: miR-146b, miR-21, miR-155, miR-122; tumor down-regulated: miR-135a, miR-200c and miR-187). When externally validated four (miR-135a, miR-200c, miR-187 and miR-21) (p < 0.05) were confirmed. Conclusions: MiRNAs could represent a valid predictive biomarker in the development of RCC and its treatment. These results have been validated in an independent cohort. MiRNAs regulation in PR vs LR patients need to continue being validated in a more extensive cohort of pts.
Temsirolimus-induced interstitial lung disease as an on-target effect in patients with metastatic renal cell carcinoma.
Authors: Eto Masatoshi , Motoshima Takanobu , Sugiyama Yutaka , Fujimoto Kiyohide , Ohyama Chikara , Mita Koji , Masumori Naoya , Kamoto Toshiyuki , Matsumoto Koichiro 
Published: September 2018

e16086 Background: An inhibitor for mammalian target of rapamycin (mTORi), temsirolimus, has been used for metastatic renal cell carcinoma (mRCC) pts with poor risk. mTOR is known to regulate proliferation of lymphocytes, which has been rationale of applying mTORi for preventing graft rejection in transplantation. However, nobody knows the immune status of mRCC pts treated with temsirolimus. In addition, accumulation of clinical practices of temsirolimus has revealed a variety of AEs including interstitial lung disease (ILD). The underlying mechanisms of ILD by mTORi remain uncertain. Moreover, the clinical impact of ILD on the clinical response to mTORi remains unknown. So, we have conducted a prospective clinical trial investigating immune parameters in mRCC pts treated with temsirolimus. This project was denominated in Japanese m-TOR Immune Modulation trial (J-TORIM) (UMIN000009662). Methods: J-TORIM was a prospective observational study recruited pts at 25 hospitals in Japan with a targeted sample size of 30. The primary objective was to evaluate whether administration of temsilorimus has consistent effects on immune parameters collected from the peripheral blood before and 3-to-5 weeks after the beginning of temsirolimus therapy. The secondary objectives were to evaluate the associations of immune parameters or ILD with ORR, PFS, and OS, and the associations of immune parameters with ILD. Immune parameters include PBMC culture with con A or lipopolysaccharide (LPS), PBMC flow cytometry with anti- CD4, CD8, CD3, PD-1, PD-L1, CD25, Foxp3 mAbs. Results: Twenty-eight patients were enrolled in the study. ORR of temsirolimus was 10.7% (1 CR and 2 PR). The most commonly reported treatment-related AEs were ILD (28.5%) and stomatitis (28.5%). There were no significant changes after temsirolimus therapy for any immunological parameters. Interestingly, a significant correlation between ILD development and ORR was observed (p < 0.01). In addition, a significant increase of regulatory T cells was also observed after the recovery of ILD (p < 0.05). Conclusions: This is the first prospective study demonstrating that ILD development can be predictive for response to temsirolimus in mRCC pts. Clinical trial information: 000009662.
Association of prostate specific-antigen doubling time (PSADT) with metastasis-free survival (MFS) and overall survival (OS) in non-metastatic castration-resistant prostate cancer (nmCRPC).
Authors: Lin Jennifer H , Macomson Brian , Tunceli Ozgur , Pericone Chris , Behl Ajay S. , Deshmukh Siddhant , Shore Neal D. 
Published: September 2018

e16525 Background: For optimal nmCRPC management, it is important to assess the rate of disease progression and its predictors. MFS and OS endpoints are likely to be important determinants in evaluating the relative impact of treatments in nmCRPC patients. This study assessed the association of PSADT with MFS and OS in real world practice. Methods: A retrospective cohort study of men ≥18 years old was conducted using the Optum electronic health record (EHR) database (2007-2016). nmCRPC was defined as a prostate cancer diagnosis, no ICD-9/10 code or therapy indicating metastatic disease, a testosterone (T) level < 50 ng/dL (castrate level) and 2 rising PSAs (relative rise ≥25%; absolute rise ≥2 ng/mL above nadir) ≥1 week apart. Baseline PSADT, calculated from the PSA nadir until 2nd rise of PSA, was grouped into < 6, 6-18 or > 18 months. A Cox proportional hazard model was used to assess the association of baseline PSADT with MFS and OS, comparing PSADT < 6 and 6-18 months against PSADT > 18 months. Multivariable analysis was adjusted for age, race, comorbidity index score, T levels, therapy and bone scans before nmCRPC. A linear trend was tested by taking PSADT as a continuous variable (median value in each group) in the model. Results: A total of 901 patients were identified. Mean nmCRPC onset age was 76 years and mean follow-up time was 2 years. The median PSADT was 7 months, ranging from 0.5 to 267 months. During follow-up, 477 patients developed metastasis and 384 died. MFS was 89%, 60%, and 47% at year 1, 3 and 5, respectively. Men with PSADT < 6 and 6-18 months had ≥50% increased risk of shorter MFS than men with PSADT > 18 months; hazard ratios (HR) were 1.87 (95% confidence interval [CI]: 1.39-2.54) and 1.50 (95%CI: 1.11-2.04), respectively. OS was 87%, 64% and 57% at year 1, 3 and 5, respectively. Shorter PSADT was associated with shorter OS (p for trend < 0.001). Men with a PSADT < 6 months had a 2-fold increased risk for decreased OS (HR = 2.04, 95% CI: 1.44-2.90). Conclusions: Patients with nmCPRC with shorter PSADT had significantly shorter MFS and OS compared to those with longer PSADT. Baseline PSADT may serve as a predictor for nmCRPC progression.
Differences in the expression of PTP-1B phosphatase in prostate cancer (PC) patients with and without adverse pathologic features (APF).
Authors: Bourlon Maria Teresa , Pineda Mauricio Mora , Urbina Ramírez Shaddai , Leon Rodriguez Eucario , Atisha-Fregoso Yemil , De Anda Gonzalez Jazmin 
Published: September 2018

e16543 Background: Localized PC is a heterogeneous disease. Currently, clinical markers are insufficient to predict the presence of APF before prostatectomy. PTP-1B phosphatase is implicated in insulin/leptin receptor activity and in cancer cells migration and invasion. PTP-1B could be a predictor marker of APF in PC. The aim was to compare the expression of PTP-1B in PC patients with vs without APF. The secondary aim was to evaluate PTP-1B as an independent predictive factor. Methods: Radical prostatectomy samples of patients with localized PC performed in a single center were identified (1990-2015). Pathologic features were re-evaluated by an expert pathologist. APF was defined as: seminal vesicle invasion or extra-capsular invasion or positive surgical margins. Tissue microarrays (TMA) immunohistochemistry for PTP-1B was done and evaluated in a 0-9 score. Statistics: Mann Whitney U-test was used to compare variables, and Spearman´s rho for correlation. To evaluate the association of PTP-1B score with the outcome of APF, a logistic regression analysis with two models was performed. The first, included biologically associated variables (metformin use, T2DM), and the second, stablished risk factors (PSA, Gleason score (GS)). Results: We identified 352 PC cases. In 190 a TMA was done, and 73 were optimal for PTP-1B expression evaluation and were included for analysis. Patient´s mean age was 62 ± 7 yo. Twenty nine (40%) without APF, and 44 (60%) with APF. Median PTP-1B score was 5 [3-8] in patients without APF vs 8 [5-9] in patients with APF (p = 0.026). PTP-1B score correlated with GS (r = 0.24, p = 0.042) and PSA (r = 0.24, p = 0.046). PTP-1B was a risk factor for the presence of APF even adjusted for the presence of metformin use and T2DM (OR 1.21; 95% CI 1.01-1.45; p = 0.037). However, PTP-1B score was not an independent risk factor for APF when PSA and GS were included (OR 1.68; 95% CI 0.97-1.41; p = 0.11). The addition of PTP-1B score to the prediction model for APF, which includes GS and PSA, only provided a slight increase in accuracy (AUC 0.73; 95% CI 0.61-0.84 vs AUC 0.71; 95% CI 0.59-0.82). Conclusions: Patients with PC and APF have an increased expression of PTP-1B.
A combination of computer extracted measurements of prostate capsule shape and tumor texture on MRI to predict biochemical recurrence post treatment.
Authors: Shiradkar Rakesh , Ghose Soumya , Purysko Andrei , Madabhushi Anant 
Published: September 2018

e16554 Background: Prostate cancer (PCa) biochemical recurrence (BCR) occurs in a significant proportion of men after treatment and is associated with increased mortality. Identifying PCa patients at risk of BCR following definitive therapy may help identify patients who might benefit from adjuvant therapy. Multi-parametric MRI (mpMRI) is being increasingly used in pre-treatment staging and risk stratification of PCa. In this work, we sought to explore whether a combination of computer extracted features relating to prostate capsule shape and tumor texture from pre-treatment mpMRI is predictive of BCR post treatment. Methods: This single center and retrospective study included 80 men with PCa who underwent pre-treatment 3T mpMRI and were followed for > 3 years post treatment. These men were grouped into a training set D1 (N = 50, 25 each of BCR+ and BCR-) and an independent validation set D2 (N = 30, 10 BCR+ and 20 BCR-). The prostate capsule and cancer region of interest (ROI) were annotated on mpMRI by a single experienced radiologist. Shape features (curvature and orientation) were extracted from a surface of interest where statistically significant differences were observed between BCR+ and BCR- patients in the training set. Radiomic features for capturing tumor textural patterns (including 1st and 2nd order statistics, Gabor and Haralick) were extracted from within the radiologist annotated cancer ROIs. Features from D1 were used to train random forest classifiers, one each with shape (Cs) and radiomic (CR) features. A fused Bayesian classifier (CR+S) was created by integrating decisions from both Cs and CR. Results: The classifiers Cs, CR and CR+S were evaluated on independent validation set D2, resulting in area under the curve (AUCs) of 0.71, 0.81 and 0.84 respectively. Cs added value in patients who had extra prostatic spread of PCa, but suffered from mpMRI intensity artefacts that affected performance of CR. Conclusions: Integrating prostate capsule shape and tumor radiomic features from pre-treatment mpMRI enabled prediction of PCa BCR after treatment. Multi-site validation is needed to establish the robustness of the approach.