bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive profiling of genomic in 80 Chinese patients with bladder cancer.
Authors: Yuan Zengjin , Yang Chunhe , Chen Jie , Zhu Yanhua , Xu Xiaohong , Wang Lingyu , Lin Rongbo , Yang Yining 
Published: May 2020

e17024 Background: Bladder cancer (BLCA) is the ninth most common malignant disease and the thirteenth most common cause of cancer death worldwide, To understand the genomic landscape of Chinese BLCA patients, 80 cases were analyzed by comprehensive genomic profiling (CGP) for genomic alterations and genome wide signatures. Methods: Formalin Fixed Paraffin Embedded (FFPE) tumor and matched blood samples of 80 Chinese BLCA patients were obtained for next-generation sequencing (NGS)-based 642 cancer genes panel assay and bladder cancer genomic profiling was evaluated. Results: Collectively, in our Chinese BLCA cohort, multiple histological subtypes, including Non-muscle invasive bladder cancer (NMIBC) (20/80, 25%), muscle invasive bladder cancer (MIBC) (49/80, 61.25%), and other subtypes (11/80, 13.75%). The top ranked somatic gene alterations in Chinese BLCA patients were TP53 (49%), TERT (34%), KMT2D (33%), KMD6A (25%), CDKN2A (23%), FGFR3 (23%), FLG (19%), PIK3CA (19%), CCDN1 (18%), RB1 (18%). Some FGFR2/3 gene fusions were detected such as FGFR2-WDR11 and FGFR3-TACC3. Interestingly, some co-mutations were identified in our cohort, such as ERBB3 was co-mutated with MUC17, FAT1 was co-mutated with RB1 etc. (p < 0.01). Out of 15 most common canonical pathways, potentially targetable genomic alterations were mainly identified in RTK-RAS (74.68%), DNA damage response (53.16%), TP53 (53.16%),chromatin remodeling (51.90%), PI3K (44.30%), NOTCH (41.77%), Cell Cycle(32.91%), Hippo (29.11%) and WNT (29.1%) pathway. Additionally, chromatin remodeling and NOTCH pathways were commonly co-altered with MYC pathway, TP53、Hippo and NOTCH pathways were significantly co-altered with DNA damage response pathway. Across samples, 33 Chinese BLCA patients had high tumor mutational burden (TMB-H) ( > 10 mutations/Mb). Only 2 Chinese patients had high microsatellite instability (MSI-H). Conclusions: Our results displayed the landscape of genomic alterations in 80 Chinese BLCA patients. The genomic alterations identified in our study may provide an opportunity to discover potential strategies for targeted and immunotherapy in BLCA. Future studies should account for these genomic alterations.
Racial and gender disparities in stage at diagnosis for bladder cancer: Results from the surveillance, epidemiology, and end results (SEER) program, 2007 to 2016.
Authors: Gupta Sachin , Joshi Monika , Weng Xingran , Wang Li 
Published: May 2020

e17032 Background: Little is known about the patterns of racial and gender disparities in bladder cancer (BC). This study will use national large database to explore those disparities. Methods: Data from the National Cancer Institute’sSurveillance, Epidemiology, and End Results (SEER) Program for cancer registries was used. Patients > = 18 years diagnosed with BC in the years 2007-2016 were identified from SEER 18 database. We used the data year 2007 because that was the year when insurance status was first collected in SEER. Chi-square tests and multinomial logistic regression were used. Results: A total of 78,151 (females: 25.58%) patients were included, with 82.74% being non-Hispanic whites, 5.83% non-Hispanic blacks, 6.69 % Hispanics and 4.74% others. Distribution of stage 0 through stage IV at diagnosis was 51.97%, 23.21%, 12.11%, 4.10% and 8.61% respectively. Blacks (P < 0.0001) and females (P < 0.0001) were diagnosed at later stages as in Table. e.g., 14.54% of blacks were diagnosed at stage IV, compared to 7.97% of whites; and 11.03% of females at stage IV vs. 7.77% of males. Racial disparity exists for any given insurance status. Within every age group, gender disparity exists. For example, for those under 50 years of age, 12.81% of women vs. 8.16% of men were diagnosed at stage IV. After controlling for age, marital status and insurance type, both gender (P < 0.0001) and race (P < 0.0001) were statistically significant in predicting stage at diagnosis. Conclusions: Racial disparity in stage at BC diagnosis was strong, with blacks suffering most from the disparity. Females were more likely to be diagnosed at later stages, and this gender disparity exists in all age groups and was not due to women living longer. The existence of both racial and gender disparities in BC makes black women most vulnerable to late diagnosis than any other racial/gender group. Oncologists treating BC patients should be aware of the racial and gender disparity. More research needs to be done to help improve early access to health care amongst female and minority BC patients. [Table: see text]
Neoadjuvant chemotherapy in muscle invasive bladder cancer: Real world data on safety and outcome.
Authors: Panthula Sree Vamsee Chetana , Philip Arun , Keechilat Pavithran , Jose Wesley Mannirathil 
Published: May 2020

e17036 Background: The standard treatment for Muscle Invasive bladder cancer (MIBC),Radical Cystectomy and Neoadjuvant chemotherapy (NACT) has shown to improve survival. Data from Indian population is scarce, and we sought to explore the efficacy, tolerability and factors affecting the outcome of Neoadjuvant chemotherapy in our population. Methods: This was a Retrospective Observational study conducted at a tertiary care centre. Patients of MIBC treated between 2008 and 2019 were included in the analysis. The NACT consisted of Gemcitabine + Cisplatin (GC) or Gemcitabine + Carboplatin (GCa). The prognostic significance of the various clinico-laboratory parameters was assessed by the log rank test. The survival analysis was done by the Kaplan Meier method. Results: Total of 40 patients received NACT from 2008-2019. The median age of study group was 62 years. Male to Female ratio was 5:1. Out of 40 patients, 26 were treated with GC and the remaining 14 received GCa. Majority (80%) patients were administered either 3 or 4 cycles of NACT. Among 18 patients who demonstrated good radiological response after NACT completion, 13 had received Cisplatin. After NACT, 32 (80%) underwent Radical Cystectomy and 3 were treated with CTRT. The remaining 5 did not receive definitive treatment. Pathological complete response (PCR) was achieved in 10 out of 32 patients (31%). Out of 10 patients with PCR, 9 belonged to Cisplatin group and only 1 in Carboplatin group. In patients with PCR, 80% remained progression free at last follow up. Grade 3/4 toxicities were minimal. However, achieving a pathological CR did not translate into significant survival benefit in our study (p value 0.10). Median follow up time and overall survival for the cohort was 29.5 and 54 months respectively. Conclusions: Gemcitabine/Cisplatin as NACT resulted in superior radiological response, PCR, PFS and OS when compared to Gemcitabine/Carboplatin in MIBC. This regimen is well tolerated and we advocate for further prospective studies with GC in this setting. [Table: see text]
Retrospective analysis of an alternative immuno-score in clinical management of patients with pT2 urothelial carcinoma.
Authors: Colombo Piergiuseppe , Zucali Paolo Andrea , De Carlo Camilla , Giordano Laura , Hurle Rodolfo , Lazzeri Massimo , Elefante Grazia Maria , D'Antonio Federica , Regis Federica , Guazzoni Giorgio Ferruccio , Santoro Armando , Roncalli Massimo 
Published: May 2020

e17038 Background: Within the mapping of the genome through the TCGA collaborative project, the urothelial carcinoma (UC) has recently revealed major intrinsic molecular subtypes, Basal, Luminal and Neural muscle-invasive UC. Here we propose a fast and standardized immuno-phenotypical score classification (Piescore), as a surrogate, which may discriminate Luminal, Basal or Neural UC and may correlate with histological and clinical variables in a mono-institutional cohort of patients treated with trans-urethral resection (TURB) and radical cystectomy (RC). Methods: This is a retrospective study of TURB specimens that harbored foci of HG pT2 (MIBC) UC from 116 pts who underwent RC. All the samples were assessed for immunohistochemical pattern, using relevant gene-expression-based markers for Basal type (CD44, CK5/6) and Luminal type (CK20 and pPARg). Piescore, investigated in both superficial and muscle-invasive component of the tumors, divided Basal and Luminal UC-types when at least 3 of the 4 markers were consistent with a specific phenotype, Mixed if two luminal and two basal markers were present simultaneously, and Neural when all four markers were negative. Results: Overall in muscle-invasive component, Piescore identified Basal phenotypes in 49 pts (42,2%), Luminal in 38 pts (32,7%), and Mixed in 9 pts (7,8%). No expression was identified in 20 pts (17,2%): 7 cases with morphological neuroendocrine differentiation and 13 cases with classical urothelial histology, all consistent with Neural phenotype. In 26,7% of cases (31/116 pts) we observed an immuno-phenotypical switch from superficial to deep component: 16 of 31 (51,6%) switched to Basal, 10 (32,2%) switched to Neural, and 5 cases (16,2%) to Mixed phenotype. No cases switched to Luminal. No cases have lost Basal phenotype from superficial to deep component, with the exception of one (switched to Neural). No statistically significant differences in terms of staging, DFS, and OS were observed in the different phenotypes. The presence of phenotypical switch did not affect angioinvasion, staging, DFS, and OS compared to non-switched cases. Conclusions: Piescore immunophenotyping (CD44, CK5/6, CK20 and pPARg) could be a simple surrogate able to stratify UC-TURB patients between Luminal vs Basal type. To our knowledge, preliminary results using the Piescore identify for the first time a phenotypical switch (to basal, Mixed or Neural) between superficial and deeper side of the same tumor, although this phenomenon did not show any prognostic implication.
Comprehensive genomic profiling (CGP) in patients with relapsed/refractory germ cell tumors (GCT).
Authors: Akel Reem , Anouti Bilal , Kern Sean , Cary Clint , Masterson Timothy A. , Jacob Joseph M , Bratslavsky Gennady , Danziger Natalie , Pavlick Dean , Hanna Nasser H. , Einhorn Lawrence H. , Ross Jeffrey S. , Adra Nabil 
Published: May 2020

e17053 Background: Understanding the genetic alterations in patients with relapsed/refractory GCT (rrGCT) could delineate the pathogenesis of cisplatin resistance. Our study uses CGP to characterize genomic alterations (GA) in refractory GCT and correlate with clinical outcomes. Methods: 432 patients with rrGCT were seen at Indiana University between Jan 2016 to Sep 2019 of whom 52 patients underwent CGP using a hybrid-capture based commercial assay to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and reported as mutations/Mb and microsatellite instability (MSI) was determined on 114 loci. PDL1 expression was determined by IHC (DAKO 22C3 antibody). Results: All patients relapsed after first-line cisplatin-based combination chemotherapy. Median age at diagnosis was 33 (range 15-68). Primary site of GCT was testicular in 85% and mediastinum in 8%. 6 patients had pure seminoma and 46 had non-seminoma. Platinum refractory disease, defined as serologic or radiographic progression within 4 weeks of first-line chemotherapy comprised 23% of patients. The primary tumor was used for sequencing in 6 cases (12%) and non-primary tumor metastatic site (lymph node, lung, liver, brain, omentum) in 46 cases (88%). The most common GA in the entire cohort were FGF6 (27%), FGF23 (27%), KDM5A (27%), CCND2 (27%), KRAS (18%), TP53 (14%), KIT (8%), APC (8%), ZNF217 (6%), MUTYH (6%), AURKA (6%), NRAS (6%), EGFR (6%), CTNNB1 (6%), GNAS (6%). Most common alterations for testicular primary tumors were FGF6, FGF23, KDM5A, CCND2, KRAS, TP53, KIT. For non-testicular primary GCT, most common GA were APC, TP53, EGFR. Most common GA for non-seminoma were FGF6, FGF23, KDM5A, CCND2, KRAS, TP53, APC. Most common GA for pure seminoma was KIT. Potentially targetable genomic alterations were found in 17 patients (33%). 10 of 17 patients (59%) tested had PDL1 score ≥1% and 3 patients had PDL1 ≥50%. Median TMB was 3.5 mutations/MB. There were 4 patients (8%) with TMB ≥ 10 mutations/Mb and 2 patients (4%) with TMB ≥ 20 mutations/Mb. 1 of 48 patients (2%) evaluated for MSI had MSI-High status. Isochromosome 12p was detected in the majority of samples where it was tested. Outcomes with GA-directed therapy will be presented at the conference. Conclusions: CGP can reveal potential therapeutic targets in patients with rrGCT including EGFR, ERBB3, KIT, and MET. Consistent with reported clinical trials in rrGCT, biomarkers predicting response to immune checkpoint blockade are uncommon with most patients having low TMB, absence of MSI-H status, and low expression of PDL1.
High-dose chemotherapy (HDCT) and peripheral-blood stem cell transplant (PBSCT) in patients age 40 or older with relapsed metastatic germ-cell tumors (mGCT).
Authors: Agrawal Vaibhav , Althouse Sandra K. , Abonour Rafat , Abu Zaid Mohammad Issam , Sullivan Cheryl K , Hanna Nasser H. , Einhorn Lawrence H. , Adra Nabil 
Published: May 2020

e17054 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity. Historically, age ≥ 40 years has been associated with greater toxicity and worse outcomes. Methods: 445 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen ( N Engl J Med 2007; 357:340-8). Kaplan-Meier methods and log-rank tests were used for progression free survival (PFS) analysis. Results: 329 pts were age < 40 while 116 pts were age≥40 and HDCT was being used as 2nd line in 85% and 79%, respectively. Median follow-up time was 42.5 months (range 0.3-173.4). Pulmonary metastasis was more frequent in the age < 40 group (66% vs. 41%, P < 0.001). Patients age≥40 were more likely to have seminoma (45% vs. 14%, P < 0.001), were more likely not platinum refractory (80% vs. 63%, P = 0.0010), and were less likely to complete 2 planned tandem cycles of HDCT (86% vs. 93%, P = 0.03). Grade 3 or higher toxicities were similar between either cohort, except for greater pulmonary toxicity in age≥40 group (8% vs. 2%, P = 0.02). Treatment-related mortality was similar between both age groups: 10 patients (3%) in age < 40 and 4 patients (3.5%) in age≥40 group died from complications of HDCT. 2-year PFS for age < 40 vs. age ≥ 40 was 58.7% vs. 59.6% (P = 0.76) and 2-year OS was 63.9% vs. 61.5% (P = 0.93). When evaluating patients with pure seminoma: 2- year OS for age < 40 vs. 40-50 vs. ≥ 50 was 100% vs 90.3%, vs 81.4%, respectively (P = 0.09). For patients with non-seminoma: 2-year OS was 58.1% vs. 37.1% vs. 54.2%, respectively (P = 0.01). In multivariable analysis for PFS: significant factors predicting worse outcomes included platinum refractory disease (HR = 1.55, P = 0.03), primary mediastinal non-seminoma (HR = 2.41, P = 0.03), not completing 2 cycles of HDCT (HR = 2.47, P = 0.01), and hCG > 1000 at initiation of HDCT (HR = 1.92, P < 0.001). Age was not a significant factor predicting worse outcomes. Conclusions: HDCT plus PBSCT is effective salvage therapy in pts age≥40 with relapsed mGCT. Patients age > 40 experience similar rates of toxicity and treatment-related mortality as those < 40 years of age.
Localized testicular germ cell tumor surveillance: A Delphi consensus study.
Authors: DA Silva Angélique , Flechon Aude , Culine Stephane , Planchamp François , Murez Thibaut , Mejean Arnaud , Pasquier David , Fizazi Karim , Joly Florence 
Published: May 2020

e17060 Background: Stage I testicular germ cell tumor (TGCT) has excellent cure rates and surveillance is fully included in patient’s management, particularly during the first years of follow-up. Surveillance guidelines differ between the scientific societies, with different recommendations concerning clinical and imaging frequency de-escalation and long term follow-up. We evaluated surveillance practice and schedules followed by French specialists and set up a DELPHI method to obtain a consensual surveillance program with an optimal schedule for patients with localized TGCT. Methods: An online survey on surveillance practice of stage I TGCT based on clinical-cases was conducted among urologists, radiotherapists and oncologists. Results were compared to AFU, ESMO and EAU guidelines. Then a panel of experts assessed surveillance proposals following a formal consensus method (DELPHI method). Statements were drafted after analysis of the previous survey and systematic literature review, with 2 successive rounds to reach a consensus. Results: Survey and DELPHI method were conducted between July 2018 and May 2019. 61 participated to the survey (69% oncologists, 15% urologists, 16% radiotherapists). About 65% of practitioners followed clinico-biological guidelines concerning 1 to 5 years of follow-up, only 25% discontinued surveillance after the 5th year, as recommended. No physician followed the ESMO guidelines of de-escalation chest imaging. A panel of 32 experts (78% oncologists, 16% urologists, 6% radiotherapists) was asked about 38 statements. Consensus was reached for 26 statements concerning clinico-biological surveillance modalities and end of surveillance after the 5th year of follow-up. For seminoma, abdominal ultrasound was proposed as an option to the abdominopelvic (AP) scan for the 4th year of follow-up. No consensus was reached regarding de-escalation of chest imaging. Conclusions: The survey proved that French TGCT specialists do not follow current guidelines. With DELPHI method, a consensus was obtained for frequency of clinico-biological surveillance, discontinuation of surveillance after the 5th year and discontinuation of AP scan on the 4th year of follow-up for seminoma. Questions remains concerning type and frequency of chest imaging.
CT abdomen only for active surveillance in patient with stage I germ cell tumor.
Authors: Ahmadi Hamed , Schuckman Anne K. , Bhanvadia Sumeet , Djaladat Hooman , Daneshmand Siamak 
Published: May 2020

e17064 Background: Surveillance of stage I GCTs includes periodic imaging of chest, abdomen and pelvis. Currently the AUA guidelines recommends CT scan of the abdomen with or without the pelvis as well as chest x ray during active surveillance for these patients. Efforts to modify the surveillance protocols aim to minimize radiation exposure in this young patient population. Per our institutional protocol, we limit cross sectional imaging to CT of the abdomen only during surveillance of stage I disease. Here we report our outcomes to determine whether any recurrence was missed or delayed based on this protocol. Methods: All patient with clinical stage I GCT who have been under active surveillance and completed at least 2 year follow up at our institution were selected using our institutional testis cancer database. Clinical and demographic information were reviewed including recurrence pattern and tumor marker status at time of recurrence. Results: A total of 89 patients who had complete follow up information in the database were included in the study. 49/89 (55%) patients had non-seminoma or mixed GCT histology. 5/89 (5%) patients had history of cryptorchidism and 16/89 (18%) patients had history of inguinal surgery. 14/89 (15%) had relapse at a median of 6.8 months. Recurrence was first detected on surveillance imaging (Imaging recurrence) in 11/14 (78%), by rising tumor markers (marker recurrence) in 2/14 (14%), and on physical exam (clinical recurrence) in 1/14 (7%) patients. Of patients with marker or clinical recurrence, only one had evidence of retroperitoneal recurrence which was detectable by CT abdomen and the other two had lung metastasis detected by chest X ray. Only one patient with imaging recurrence had pelvic lymphadenopathy which was large enough to be seen on CT abdomen. Conclusions: CT scan of the abdomen only in combination with chest imaging, tumor markers and physical exam detected 100% of recurrences in this series. CT pelvis can be safely omitted during active surveillance of stage I GCT. Future modification in guidelines for surveillance protocols of stage I GCT may be warranted with further mounting evidence.
Receptor tyrosine kinases and growth factors expression in tumor thrombus cells in patients with renal cell carcinoma (RCC).
Authors: Volkova Maria , Tsimafeyeu Ilya , Khochenkov Dmitry , Olshanskaia Anna , Vashakmadze Niko , Khochenkova Yulia , Solomko Elyso , Ashuba Saida , Matveev Vsevolod Borisovich 
Published: May 2020

e17073 Background: To our knowledge, this is a first study describing the expression of the receptor tyrosine kinases (RTKs) and growth factors (GFs) in venous tumor thrombus cells and comparing results with the expression in primary RCC. Methods: Formalin-fixed paraffin-embedded specimens of tumor thrombus and primary tumor removed from 25 untreated pT3a-T4N0-1M0-1 RCC patients were evaluated by immunohistochemistry with primary antibodies to VEGF-A, FGF2, VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRα, and PDGFRβ (Abcam/Santa Cruz Biotech) and REAL™ EnVision™ Detection System (Agilent). The extent of expression was compared with 25 specimens of primary tumor tissue (selected from the same patients). Significant differences in the expression among these groups were assessed by chi-squared and Fisher's exact tests using a semi-quantitative method (H-score). The analysis of the correlation between expression levels and RCC characteristics was also performed. Results: Mean age was 62.0 (35-74) years. pT3a, pT3b, pT3c and pT4 stages were detected in 4 (16.0%), 13 (52.0%), 7 (28.0%), and 1 (4.0%) patients. Lymph node metastases were found in 9 (36.0%) cases, 15 (60.0%) patients had 1 or more metastatic sites. All RTKs and GFs were heavily expressed in primary tumor cells. Tumor thrombus cells were characterized by significant lower expression levels of VEGFR1, VEGFR2, and PDGFRα (p < 0.05 for all). Tendency to lower expression of VEGF-A (p = 0.06), FGF-2 (p = 0.046), FGFR1 (p = 0.077), and FGFR2 (p = 0.09) was observed in tumor thrombus cells (Table). VEGFR2 expression levels were 2-times reduced in patients with supradiaphragmatic thrombus (H-score = 21.4±12.0) compared to infradiaphragmatic thrombus (H-score = 55.0±8.5, p = 0.042). Furman grade correlated with the expression levels of VEGFR1 (p = 0.035) and FGFR1 (p = 0.022) in primary tumor cells; tumor invasion into venous wall correlated with the expression levels of VEGFR1 (p = 0.023) and FGFR2 (p = 0.005) in thrombus cells. Conclusions: RCC invasion into veins is accompanied by a decrease in expression of RTKs and GFs. Further studies are needed to understand the biological significance. [Table: see text]