bluuebunny/crossref_metadata_2025_split huggingface dataset:
Split-dose cisplatin as an alternative to every-3-week dosing when using cisplatin/gemcitabine to treat advanced urothelial cancer.
Authors: Gonzalez Cinthia Marie , Jordan Emmet , Zabor Emily C. , Kania Brooke Elizabeth , Regazzi Ashley Marie , Ostrovnaya Irina , Iyer Gopa , Bajorin Dean F. , Bambury Richard Martin , Rosenberg Jonathan E. 
Published: February 2017

373 Background: Cisplatin-based chemotherapy is the standard of care first-line therapy for locally advanced or metastatic urothelial cancer (mUC) with reported response rates (ORR) of 50%, median progression free survival (mPFS) 7 months and median overall survival (mOS) 14 months in phase III trials using cisplatin 70 mg/m2 every 3 weeks (q3wk). Many patients cannot receive cisplatin due to impaired performance status, renal dysfunction, or other co-morbidities. Carboplatin is an alternative but is associated with lower response rates and shorter survival. Administering cisplatin 35 mg/m2 day 1+8 (i.e., split dose) every 3 weeks may be associated with lower toxicity and allow more patients receive the drug. In this retrospective analysis we examined the safety and efficacy of cisplatin/gemcitabine using split dose cisplatin. Methods: Patients who received split dose cisplatin/gemcitabine between 2007-2013 were identified. We recorded baseline demographics, clinical characteristics, and number of cycles administered. Responses were determined retrospectively using RECIST v1.1; OS and PFS were assessed using the Kaplan-Meier method. Results: 50 patients were identified and baseline characteristics are outlined in Table 1. The median number of cycles administered was 4 (range 1-7). 25 patients (50%) discontinued therapy due to completion of planned course, 14 (28%) due to progressive disease and 11 (22%) due to toxicity. ORR was 54%, mPFS was 5.4 months (95% CI: 4.2 – 8.8) and mOS was 13.3 months (95% CI: 9.6 – 21.9). Conclusions: In this analysis, split-dose cisplatin was administered safely in patients who were deemed ineligible for the q3wk regimen and efficacy did not appear to be compromised. The split-dose regimen may allow more patients tolerate cisplatin, the most active FDA-approved drug in this disease. [Table: see text]
Frailty as a marker of adverse outcomes during cystectomy for urothelial cancer.
Authors: Kates Max , Patel Hiten , Sopko Nikolai , Liu Jen-Jane , Pierorazio Phillip M , Bivalacqua Trinity 
Published: February 2017

374 Background: Frailty has been identified as a marker of physiologic reserve, and a more accurate predictor of adverse postoperative outcomes compared with age. Although many definitions of frailty exist, recently a clinical predictive rule, the “modified frailty index”(mFI), has been developed utilizing administrative data to predict adverse outcomes in the lung cancer population undergoing lobectomy. Our goal was to validate this clinical rule among patients with bladder cancer undergoing cystectomy. Methods: Patients undergoing cystectomy were identified from the National Surgical Quality Improvement Program (NSQIP) participant use files (2006-2011). The mFI was defined as in prior studies with 11 variables based on mapping the Canadian Study of Health and Aging Frailty Index to NSQIP comorbidities and activities of daily living (ADL)s. These 11 variables each received 1 point, and the sum was divided by 11 for a fraction between 0 and 1. Univariate χ2, independent sample t-test, and logistic regression analyses were performed where appropriate. Results: Of the 1,302 cystectomy patients identified, 30% had mFI of 0, 40% had mFI of 0.09, 21% had mFI of 0.18, and 9% had mFI ≥0.27. Overall, 56% of patients experienced a Clavien complication. Patients with mFI ≥0.27 were older ( 72 vs 64 yrs)and more likely to be smokers (54%) compared with mFI of 0 (30%, p<0.01). Mean operative times (342-349 minutes) were similar across mFI indices. Reoperation (5% vs 8.5%) and readmission (20.5% vs 25%) were higher when mFI =0 compared with mFI≥0.27 (P<0.01). Clavien 4 and above complications occurred in 9.1% (36/396), 10.1% (53/526), 12.9 % (35/270) and 13.6% (15/110) among patients with an mFI of 0, 0.09, 0.18, and ≥0.27, respectively (p=0.05). Similarly, the overall mortality rate increased from 2.5% in the lowest frailty index group to 5.4% in the highest. Conclusions: Among patients undergoing cystectomy, the modified frailty index can identify those patients at greater risk for severe complications, readmissions, and mortality. Given that bladder cancer is increasing in prevalence particularly among the elderly, pre-operative risk stratification is crucial to inform decision-making.
Management and outcomes of clinical stage II a/b seminoma: Results from the National Cancer Database.
Authors: Paly Jonathan J. , Gray Phillip John , Lin Chun Chieh , Sineshaw Helmneh , Jemal Ahmedin , Efstathiou Jason Alexander 
Published: February 2017

378 Background: Testicular seminoma is the most common solid tumor seen in patients aged 15-35 and disease specific survival approaches 100% in controlled studies, even for those with node-positive disease. We sought to describe modern practice patterns as well as survival outcomes and factors associated with receipt of adjuvant therapy for patients presenting with initial clinical stage (CS) IIA/B disease. Methods: Data on patients diagnosed with CS IIA/B testicular seminoma from 1998-2011 were extracted from the National Cancer Data Base. Demographic, clinical, treatment, payer characteristics were evaluated using multivariate logistic regression to identify factors associated with receipt of chemotherapy or adjuvant radiation therapy (ART) within 6 months of orchiectomy. Five-year Kaplan-Meier overall survival (OS) by CS and treatment was calculated. Results: In total, 2,185 patients with CS II A/B were included. Management included orchiectomy alone (11.35%), adjuvant chemotherapy (27.46%), or ART (52.72%). In multivariate analysis, receipt of orchiectomy plus ART rather than adjuvant chemotherapy was more likely with CS IIA status (OR 2.4, p < 0.01), treatment outside of teaching or NCI network institution (OR 1.9-2.8, p < 0.02), or tumor size ≥4cm (OR 1.6, p < 0.01). Receipt of ART was less likely in Hispanic patients (OR 0.6, p=0.03) or in those diagnosed from 2006-2011 (OR 0.5, p < 0.01). Five-year OS for all patients was 97.2% for orchiectomy + ART, and 93.9% for orchiectomy + chemotherapy (log-rank p = 0.01). For CS IIA patients, 5-year OS was 98.3% for orchiectomy + ART versus 93.6% for orchiectomy + chemotherapy (log-rank p < 0.01). Differences in OS for CS IIB treated with chemotherapy or ART were not statistically significant. Conclusions: Consistent with national guideline recommendations, our analysis suggest that compared to chemotherapy, ART is associated with a survival advantage for CS IIA patients. Chemotherapy or ART showed no significant difference in effectiveness in patients with CS IIB. Disease bulk, race, treatment center type, and time period are associated with choice of adjuvant therapy. Longer follow-up and validation of these results is needed to account for late effects of treatment.
Frequent expression of PD-L1 in testicular germ cell tumors.
Authors: Fankhauser Christian Daniel , Curioni Fontecedro Alessandra , Beyer Joerg , Tischler Verena , Sulser Tullio , Moch Holger , Bode Peter Karl 
Published: February 2017

379 Background: Testicular germ-cell cancer is curable even in the presence of metastatic disease. Yet, about 10-15% of patients become cisplatin-refractory and will eventually die of their disease. Moreover, short- and long-term side effects of cisplatin make the search for less toxic treatment strategies worthwile. Programmed Death Receptor 1 (PD-1, CD279) is one member of the extended family of T cell regulators expressed on the surface of activated T cells, B cells, and macrophages. Its ligand, PD-L1 (B7-H1, CD274), is expressed on tumor cells, T cells and other tissues. The interaction of these two molecules negatively regulates immune responses. Of major interest is that inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses in vitro and mediate clinical antitumor activity . The aim of this study was to analyze the expression of PD-L1 in testicular germ-cell tumors to evaluate its potential as predictive marker for further therapeutic strategies. Methods: Immunohistochemistry was performed in 486 Formalin Fixed Paraffin Embedded (FFPE) specimens using a monoclonal rabbit antibody (E1L3N, Cell Signaling Technology, Inc. (CST) of Danvers, MA, USA). Results: PD-L1 expression was found in 171 out of 248 (69%) seminomas, 19 out of 48 (40%) yolk sac tumors, 7 out of 46 (15%) teratomas, 2 out of 10 (20%) choriocarcinomas and 53 out of 87 (61%) embryonal carcinomas. In 20 out of 20 Intratubular germ-cell neoplasia unclassified (IGCNU) and also in 20 out of 20 normal tissue specimens no single case exhibited PD-L1 expression. Conclusions: Our study describes for the first time the frequent expression of PD-L1 in a large series of human testicular germ-cell tumors, but not on normal testis tissue or IGCNU. Based on our results, checkpoint inhibition with anti-PD1 and anti-PDL1 antibodies might represent an attractive approach in germ-cell cancer, where new active agents are urgently needed.
A panel of dynamic micromechanical biomarkers in the detection and differentiation of prostate cancer.
Authors: Good Daniel W. , Hammer Steven , Scanlan Paul , Stewart Grant , Reuben Robert L , McNeill Alan S 
Published: February 2017

38 Background: Elasticity devices enable quantitative measurements and can reduce the need for operator interpretation. Our dynamic assessment enables micromechanical markers to be identified: amplitude ratio [AR], phase lag [PL] and mean ratio [MR], at specific frequencies. Aim: To assess the efficacy of a panel of dynamic micromechanical biomarkers for the detection of prostate cancer (Primary endpoint) (and differentiation of significant from insignificant disease (secondary endpoint)) in ex-vivo prostates and in patients, using a direct elasticity assessment probe (E-finger). Methods: Patients undergoing surgery for prostate cancer were enrolled into a prospective clinical study; exclusion criteria (previous TURP, 5ARI). Ex-vivo prostates were systematically assessed at multiple points on posterior surface. In-vivo testing was done using the probe attached to the index finger and assessing the prostate via DRE using 12 -16 different areas. Measurement points were marked and noted on final pathology to allow correlation with final histology. CART was used to create a model of the micromechanical markers and regression analysis used to identify histopathological parameter associations. Results: 22 patients were recruited to the study to date, mean age was 64 (55 – 73), median PSA 7.5 (5.5 – 10), over 50% were cT1c, median weight 51g (44 – 68) and over 50% were pT3 on final pathology. Over 600 measurement points were assessed. The in-vivo marker panel was made up of: 10HzARA, 10HzPLA, 1HzPLC, 15HzMRB and 1HzARA. Sensitivity was 89%, specificity 87%, PPV 86%, NPV 88% for cancer detection in-vivo. That for the ex-vivo tests were Sen 71%, Spec 81%, PPV 80%, NPV 72% (primary outcome). For differentiation of clinically significant from insignificant areas sensitivity and specificity were 81% and 75% respectively (secondary outcome). Correlation of the marker panel with underlying tumour volume was strong (R2 = 0.75). Conclusions: These results show the promise of micromechanical biomarkers in the detection of prostate cancer and in the differentiation of significant from insignificant disease. This study shows that these markers maintain their accuracy from the ex-vivo into the in-vivo environment.
Interim [18f] fluorodeoxyglucose positron emission tomography (PET) for early metabolic assessment of response to PEB chemotherapy for metastatic seminoma: Preliminary findings.
Authors: Giannatempo Patrizia , Alessi Alessandra , Raggi Daniele , Farè Elena , Tana Silvia , Nicolai Nicola , Serafini Gianluca , Padovano Barbara , Piva Luigi , Biasoni Davide , Torelli Tullio , Catanzaro Mario , Stagni Silvia , Maffezzini Massimo , Gianni Alessandro M. , Mariani Luigi , Crippa Flavio , Salvioni Roberto , Necchi Andrea 
Published: February 2017

381 Background: A risk-adapted strategy for metastatic seminoma may further refine the necessary burden of chemotherapy while sparing futile treatment. The objective of this study was to evaluate the association of the early metabolic response to cisplatin, etoposide, and bleomycin (PEB) and dimensional response. Methods: Patients (pts) with newly-diagnosed seminoma and who were candidate to PEB were staged at baseline by computed tomography (CT), PET and serum tumor markers (STM). Then, restaging with PET after 2 cycles of PEB (PET2), and with CT after treatment (3-4 cycles [CT3-4]) were provided. One (greatest) target lesion was chosen to evaluate metabolic/dimensional changes. Wilcoxon rank sum test was used to analyze the association between PET response and either the shrinkage of target lesion (primary endpoint) or baseline, or final dimensions. Results: In the time-frame 02/2009-11/2013, 37 pts have been enrolled. Two pts had CSIIA, 13 CSIIB, 13 CSIIC, and 9 CSIII. 3 had an intermediate prognosis because of liver (n=1) and bone (n=2) disease. The latter were recognized by PET while having a bone-negative CT scan. 4 had a retroperitoneal and 1 a mediastinal primary. All pts had a PET-positive target disease. After 2 cycles of PEB, 27 pts (72.9%) had a metabolic complete response (CR), 10 a partial response (PR). 12 pts had a CR at CT3-4. Median follow up was 18 months (IQR: 13-23). A significant association was found between PET2 response and baseline (p=0.003), final diameter (p<0.001), and % of tumor shrinkage (p=0.014). Pts with PET2 CR had a median residual diameter of 1.2 cm (IQR: 1-1.9) while pts with PET2 PR 3.75 cm (IQR: 2.6-6.1, p=0.002). 6 Pts received RT after PEB. 2/10 pts with PET2 PR had a relapse (0/27 CR). Conclusions: A significant association was found between PET2 response and tumor shrinkage in pts with metastatic seminoma. PET2 CR pts could be predicted not to need additional re-imaging or treatment after PEB, and simplifying the follow up should be an endpoint. PET2 PR category includes pts yielding a difficult-to-treat disease. A detailed cost-efficacy analysis of the strategy will be required further.
Complicated postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in advanced testicular germ cell tumours: Is it worth the efforts?
Authors: Heidenreich Axel , Porres Daniel , Pfister David J. K. P. 
Published: February 2017

382 Background: PC-RPLND is performed in patients with residual masses following chemotherapy for advanced testicular cancer. Complicated PC-RPLND is defined by redo, salvage or desperation procedures including the necessity to resect major adjacent vascular, skeletal or intestinal structures. We report on our single centre experience of complicated (group A) versus uncomplicated PC-RPLND (group B). Methods: A total of 138 patients underwent PC-RPLND and 24 (14.8%) patients underwent complicated RPLND: resection of major retroperitoneal vessels n=15 (9.3%), skeletal and pancreaticoduodenal structures in 5 (3.1%) and 4 (2.5%) patients, respectively. We performed a retrospective analysis of treatment-associated complications (Clavien-Dindo classification). Progression-free, cancer-specific and overall survival was calculated. Results: There were significant differences between group A and B concerning tumour diameter (5.9 vs 18.6cm, p = 0.03), intermediate/poor IGCCCG risk (39.9% vs 83.4%, p=0.02), seminomatous primary (7.9% vs 20.8%, p=0.03). Pathohistology of the residual masses was significantly different between group A and B: vital cancer was identified in 6 (4.3%) and 8/24 (33.3%, p=0.02) pts, resp., whereas teratoma was identified in 37 (26.8%) and 14/24 (58.3%, p=0.01), resp. In addition 3 pts in group B demonstrated malignant somatic transformation. After a median follow-up of 32 months for group B, 3 patients with MTS experienced recurrences, 1 patient died of the disease. The remainder survived event-free. In group A, median follow-up was 37 months and DOD was observed in 2 pts, 8 pts (5.8%) experienced recurrences. Frequency of complications grade I-IIIb did not differ significantly between group A and B with vascular or skeletal surgery (6.2 vs 13.3%), however, it increased significantly to 65% in pancreatic surgery (p < 0.001). Conclusions: Few patients with advanced NS need complex surgery in an interdisciplinary setting with good functional and oncological outcome. Despite an increased risk of short-term complications complicated PC-RPLND results in long-term survival > 90% and it is justified if performed at specialized centres.
Multiplatform comprehensive kinase analysis of penile squamous cell carcinoma (PSCC) to identify drivers and potentially actionable therapeutic targets.
Authors: Mehta Amitkumar N. , Yang Eddy Shih-Hsin , Willey Christopher Douglas , Crowley Michael , Chen Dongquan , Anderson Joshua , Naik Gurudatta , Cooper Tiffiny , Sonpavde Guru 
Published: February 2017

389 Background: PSCC is an orphan malignancy with poorly understood biology and suboptimal systemic therapy. Given that kinases may be drivers of disease and readily actionable, we performed comprehensive multiplatform analysis of kinases in PSCC tumor tissue and adjacent normal tissue. Methods: We collected fresh frozen tumors from 10 patients with PSCC, of whom 3 had adjacent normal tissue available. After macrodissection to demarcate tumor from normal tissue, the samples underwent analysis of kinases using platforms to assess DNA, RNA and kinase activity. Next Generation Sequencing of 515 kinase genes was performed using the Agilent Kinome capture and run on the Illumina HiSeq2500 at PE100bp. The Nanostring nCounter platform analyzed the expression (RNA) of 519 kinase genes. Global kinase activity of tissue lysates was measured using Pamstation@12 high-content phospho-peptide substrate microarray system (PamGene International). Upstream kinase prediction was performed and network mapping was done with GeneGo MetaCore. Ingenuity pathway analysis data was performed to integrate over-expression at the activity and gene expression level with coexisting missense mutations at DNA level. Results: Top pathways observed to be upregulated in both the kinase activity and gene expression platforms were PTEN Signaling, STAT3 Pathway, GNRH Signaling, IL8 Signaling and B Cell Receptor Signaling. Potentially relevant missense mutations were seen in 176 kinase genes, with the top altered pathways overlapping with gene overexpression being GNRH Signaling, NF-kB Signaling, and STAT3 pathways. ERBB2, ERBB3 and SYK were altered on gene sequencing and also showed elevated kinase activity. Kinases previously implicated in prostate cancer (PAK4, TNK2), breast cancer (ERBB2) and genital dysplasia (ROR2) also demonstrated mutations. Conclusions: Multiplatform comprehensive analysis of kinases at the DNA, RNA and protein activity levels discovered several potential drivers of PSCC and actionable therapeutic targets. Further validation in preclinical and translational trials is warranted to make advances in this rare malignancy with substantial unmet needs.
Bilateral testicular germ cell tumors.
Authors: Curreri Stephanie A. , Markt Sarah C. , Miller Rowan , O'Donnell Elizabeth , Bernard Brandon David , Kamran Sophia C. , Albiges Laurence , Wright Alexi A. , Sweeney Christopher , Beard Clair 
Published: February 2017

392 Background: Germ cell tumors (GCTs), both seminomatous and non-seminomatous, account for greater than 90% of testicular cancers. While bilateral testicular GCTs are rare, the incidence of bilateral tumors has increased over time. Methods: 668 cases of bilateral and 38,593 cases of unilateral testicular GCTs were reported between 1973 and 2011 by the SEER database. Patient characteristics and tumor features were analyzed. Results: The incidence of bilateral GCTs among men with testicular GCTs was 1.7% (668 of 39,261 total cases). Among the 668 men with bilateral GCTs, 53% (n=353) of second GCTs occurred within three years after the first cancer. 29% (n=196) of bilateral tumors occurred synchronously. Among patients with bilateral GCTs, 378 first GCTs and 466 second GCTs were seminomatous. 43% of bilateral cases were concordant seminomatous GCTs, 16% were concordant non-seminomas, and 41% were discordant histologies. 68% of unilateral GCTs, 70% of first GCTs, and 82% of second GCTs were staged as Localized disease. Testicular cancer was the cause of death for 4% (n=1,630) of men with a unilateral GCT and 1% (n=8) of men with bilateral GCTs. A second malignant neoplasm (SMN) was the cause of death for 2% (n=736) of men with a unilateral GCT and 2% (n=16) of men with bilateral GCTs. Conclusions: Among men with bilateral testicular GCTs, 59% had concordant histological diagnoses between their first and second tumor. Most (53%) second cancers among men with bilateral tumors occurred within three years after diagnosis of first cancers. Men who experience bilateral testicular GCTs do not appear to have an increased risk of death due to testicular cancer or a subsequent non-germ cell malignant neoplasm compared to men with a unilateral testicular GCT. [Table: see text]
Programmed death ligand-1 (PD-L1) expression in penile squamous cell carcinoma.
Authors: Wang Jennifer , Rodriguez Jaime , Rao Priya , Pettaway Curtis Alvin , Pagliaro Lance C. 
Published: February 2017

393 Background: PD-1 protein is a co-inhibitory receptor expressed on B cells, T cell, and NK cells. Its ligand PD-L1 (B7-H1) leads to inhibition of T cell proliferation and cytokine production and is not expressed on normal tissues other than macrophages, but is expressed on various human carcinomas. Expression of PD-L1 in the HPV-associated disease penile carcinoma is unknown. Methods: Formalin-fixed paraffin-embedded tumor specimens were obtained from 19 patients. PD-L1 staining was done with an E1L3N rabbit monoclonal antibody with the summary of a positive score using H-score membrane staining, which considers both intensity and percentage of cells, with >5% score as a positive. HPV status was also evaluated using FISH or p16 immunohistochemical staining to evaluate for correlation with PD-L1. Results: 23 samples between primaries and lymph nodes were collected from the 19 patients with 5/23 samples (22%) positive for anti-PDL1 staining. 6 samples (26%) were positive for HPV by at least one method of testing with 2/6 (33%) HPV positive patients having positive PD-L1 membrane staining. In both of these samples, there was equivocal peritumoral inflammatory infiltration of PD-L1 cells. Conclusions: This analysis shows that PD-L1 is expressed in penile squamous cell carcinomas and may indicate a role for future anti-PD-L1/PD-1 drugs as therapeutic options. Further analyses of correlated clinical features, survival, and separate PD-L1 staining in peritumoral inflammatory cells are underway.