bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation and implementation of a mobile app decision support system for quality assurance of tumor boards: Analyzing the concordance rates for testis cancer at a multidisciplinary tumor board of a tertiary referral center.
Authors: Ural Yasemin , Heidenreich Axel , Elter Thomas , Yilmaz Yasemin , Pfister David A. 
Published: February 2020

399 Background: Guideline-compliance in the management of GCT is suboptimal concerning and it results in significantly impaired long-term survival. To facilitating guideline concordant decisions even in less experienced MTD, we developed an algorithm-driven and validated mobile App to provide evidence-based recommendations. This App contains latest guideline versions and it is continuously updated to include practice changing clinical trials. It is the purpose of this study to analyse treatment decision made by MTD compared to guideline recommended therapy. Methods: 302 patients with GCT and MTD decision were randomly selected from our database. Concordance rates of MTD recommendations were compared to query results of the digital APP “Easy Oncology” performed by 2 independent, blinded reviewers. Descriptive statistics and data analysis included IBM´s statistics software SPSS Version 25. Correlation analysis of cancer case characteristics was performed by Kendalls Tau, Gamma, Pearson and Spearman tests. Results: Median age was 35 (18-82) years. Clinical stages I, IIA-C, and III were identified in 32%, 37%, and 31%, resp. According to IGCCCG 56%, 18%, and 25% demonstrated good, intermediate, and poor prognosis, resp. 56% were non-seminomas and 44% were seminomas. 60%, 16%, and 7% of MTD decisions were related to 1st-line, 2nd, and 3rd line therapy and 18% dealt with follow up. Overall concordance rate was 99% (301/302). Concordance rates in CS I, IIA-C, and III were 100%, 98% and 99%, resp. Concordance rates with regard to 1st, 2nd and 3rd line therapy were 99% (135/136), 100%, and 88% (13/14). Conclusions: Our validated expert-created mobile decision support system demonstrates easy and reliable application in daily routine in an expert tertiary referral centre. The APP relies on guideline and trial based information and avoids MTD decisions by expert opinions. It might improve the MTD decision in less experienced MTDs which is currently evaluated in a prospective study.
Effect of increasing Medicaid coverage in Medicaid expansion states on stage at presentation for urologic malignancies.
Authors: Meng Xiaosong , Trivedi Hersh , Kenigsberg Alexander P. , Ghandour Rashed , Margulis Vitaly , Bagrodia Aditya , Lotan Yair , Woldu Solomon L. 
Published: February 2020

400 Background: Medicaid Expansion (ME) was introduced by the Affordable Care Act to improve access to care for low income individuals by increasing the annual income limits to 138% of the poverty line. However, not all states have elected to participate in ME. Using the National Cancer Database (NCDB), we sought to assess the effects of participation in ME on the four most common urologic malignancies. Methods: The NCDB was queried for bladder, prostate, kidney and testis cancer from 2012-2016, to span the time period two years before and two years after the main ME which took place in 2014. Trends in insurance status at time of diagnosis and effects on stage at presentation before and after ME were analyzed. Results: The percentage of patients with Medicaid coverage at the time of diagnosis for all four urologic malignancies increased significantly after 2014, with a commiserate decrease in the percentage of uninsured patients (Table). By 2016, significantly more patients had Medicaid coverage at diagnosis in ME states compared to those in Non-ME states (bladder 5.0% vs 2.5%, prostate 5.9% vs 2.2%, kidney 9.7% vs 4.1%, 19.5% vs 7.2%, all p < 0.01). However, the stage at presentation for all four urologic malignancies did not significantly differ for patients in ME versus non-ME states. Conclusions: Despite an increase in the proportion of patients with Medicaid coverage after 2014, surprisingly, there was not an associated change in stage at presentation for urologic malignancies in ME states. Further long-term analysis is necessary to evaluate if expanded Medicaid coverage impacts overall survival in this patient population.[Table: see text]
High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) for relapsed metastatic germ cell tumors (mGCTs): The Alberta experience from 2001 to 2018.
Authors: Zhang Hanbo , Alimohamed Nimira S. , Basappa Naveen S. , Cheng Tina , Chu Michael , Cox-Kennett Nanette , Ernst D. Scott , Fontaine Amelie , Ghosh Sunita , Heng Daniel Yick Chin , Littleton Richard , North Scott A. , Railton Cindy , Sandhu Irwindeep , Stewart Douglas Allan , Venner Chris , Venner Peter M. , Kolinsky Michael Paul 
Published: February 2020

406 Background: HDC-ASCT is a standard therapy for patients (pts) with mGCTs whose disease progresses on or after conventional dose chemotherapy. We conducted a retrospective review of HDC-ASCT in pts with relapsed mCGT in Alberta over the past two decades. Methods: Pts with mGCTs who received HDC-ASCT at two provincial referral cancer centers in Alberta, Canada from 2001-2018 were identified. Baseline clinical and treatment characteristics were collected as well as overall survival (OS) and disease-free survival (DFS). Relevant prognostic variables were analyzed. Results: Forty three pts were identified. Median age was 28 years (range 19 – 56). Majority (95%) had non-seminoma histology and testis/retroperitoneal primary (84%). Twenty pts (47%) had poor risk disease as per IGCCC at start of first-line chemotherapy. HDC-ASCT was used as second-line therapy in 65% and 58% received tandem HDC-ASCT. Median follow-up from ASCT was 22 months (range 2 – 181). At last follow-up, 42% of pts are alive without disease, including 3/7 (43%) of pts with primary mediastinal disease. Two-year and 5-year DFS/OS were 44%/51% and 41%/43%, respectively. Median OS and DFS for all pts were 27.9 months (10.2 – NR) and 9.3 months (4.2 – 124), respectively. Conclusions: We found that HDC-ASCT is an effective salvage therapy in mGCT, consistent with existing literature. Pts appeared to benefit regardless of primary site. Though limited by small sample size, we found a numerical difference in DFS and OS between 2nd and 3rd line HDC-ASCT and single vs. tandem ASCT.[Table: see text]
Genomic analysis for potential targetable mutations in relapsed and refractory germ cell tumors.
Authors: Kern Sean Q. , Einhorn Lawrence H. , Adra Nabil 
Published: February 2020

407 Background: A large number of metastatic germ cell tumors (GCTs) are cured with platinum-based chemotherapy. Patients that have relapsed or refractory disease can be cured with salvage therapy including salvage surgery, standard dose or high-dose chemotherapy with stem-cell transplant. However, 15-20% of patients with metastatic GCT are incurable with current therapeutic options. We sought to perform a genetic analysis on a cohort of these incurable patients to determine the presence of therapeutically targetable genetic mutations. Methods: After obtaining IRB approval, patients treated at Indiana University for refractory or relapsed GCT from 2016-2019 were analyzed with a next-generation sequencing (NGS) platform. Clinically relevant genomic alterations were reviewed to determine the potential for targeted therapies. Results: 10 patients with testicular (9) or ovarian (1) GCT underwent an analysis of tissue (7), blood (1), or both (2) with a mean 2.9 potential targetable mutations per patient. Four patients had NGS from preserved gonadal tissue removed prior to chemotherapy while 6/10 sample specimens were obtained post standard (1) or high-dose (5) chemotherapy. Potential known therapeutic targets were found in 80% (8/10). Of the platforms that tested biomarkers, high microsatellite instability (MSI) (1/5), intermediate tumor mutational burden (1/4), and high PD-L1 expression of 90% (1/3) was appreciated. The MSI-high patient did not respond to pembrolizumab. A patient with a KIT only mutation did not achieve a response to imatinib. One patient with KRAS, KIT, RAF1, CCND2, MET, AR, CDK6, PDGFRA, EGFR, and BRAF mutations was treated with brentuximab and was progression free for 2.5 months. Common mutations were CCND2 (4/10), RAF1 (2/10), KIT (2/10), and KRAS (2/10). Other mutations actionable in non-GCT tumors included ERCC1, TUBB3, RRMI, PIK3CA, TOPO1 and TP53. Conclusions: NGS identifies potential clinically relevant genomic alterations. Genetic mutations may enable future effective therapies as our understanding of platinum-resistant disease evolves. To our knowledge, this is among the first reports utilizing next-generation sequencing in GCT to direct potential therapeutic agents.
A phase I study of guadecitabine (SGI-110) plus cisplatin in patients with platinum refractory germ cell tumors.
Authors: Albany Costantine , Spinella Michael J. , Adra Nabil , Hanna Nasser H. , Einhorn Lawrence 
Published: February 2020

408 Background: Guadecitabine (SGI-110) is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine resistant to degradation by cytidine deaminase. Platinum-refractory germ cell tumors (GCT) showed significant DNA hypermethylation compared to platinum sensitive tumors. In preclinical studies, GCT were extremely sensitive to low dose decitabine which restored sensitivity to cisplatin in cell lines. We aimed to assess the safety and clinical activity of guadecitabine in combination with cisplatin in patients with platinum-refractory GCT. Methods: In this open-label, phase 1 study, patients with GCT refractory to or had relapsed after platinum-based treatment were treated with subcutaneous (SQ) guadecitabine, once-daily for 5 consecutive days, followed by cisplatin on day 8 with growth factor support (GFS) in a 28-day treatment cycle. A modified toxicity probability interval (mTPI) dose-escalation design was used in which we treated patients with guadecitabine doses of 30-45 mg/m2 plus cisplatin 100 mg/m2 up to 6 cycles until progression or intolerable toxicity. The primary objective was to assess safety and tolerability of the combination, determine the maximum tolerated dose (MTD). Secondary objective was objective response rate (ORR). Results: Fourteen patients with incurable disease were enrolled. Primary site were testis 11, mediastinum 2, and ovarian 1. All progressed after at least 2 lines of standard of care chemotherapy including HDCT. Dose-limiting toxicities were neutropenic fever. Most common toxicities were neutropenia (82% any grade), thrombocytopenia (42%), anemia (33%), neutropenic fever (8%), and diarrhea (8%). The maximum tolerated dose of guadecitabine was 30 mg/m2 x 5 days and cisplatin 100 mg/m2. We observed 2/14 complete response lasting more than 6 months, 2 partial response and 1 stable disease. ORR 28.5%. Conclusions: We report the first study of chemo-priming with epigenetic therapy in GCT. Guadecitabine 30 mg/m2 x 5 days and cisplatin 100 mg/m2 with GFS was safe and tolerable and showed promising activity with 4/14 responses in this highly treatment refractory patient population. Clinical trial information: NCT02429466.
Origin of somatic transformation in germ cell tumor of testis (TGCT): Role of differentiation versus dedifferentiation in a mature teratoma.
Authors: Umbreit Eric , Joon Aron , Westerman Mary E. , Vyas Shikhar Gautam , Maity Tapati , Uthup Joma , Hofstetter Wayne Lewis , Ward John Francis , Karam Jose A. , Zhang Miao , Pisters Louis L. , Wood Christopher G. , Tu Shi-Ming 
Published: February 2020

410 Background: TGCT is a prototype stem-cell malignancy recapitulating the ontogeny of solid tumors. We studied the roles of differentiation versus dedifferentiation in a bona fide well-differentiated tumor, namely mature teratomas, associated with or without somatic transformation. Methods: Between 2001 and 2013, we identified 7 out of 13 cases in which teratoma and somatic transformation were present within the same residual tumor after chemotherapy and resected at our institution with sufficient quantity and quality for DNA and RNA analysis. We performed primary cell culture, flow cytometry, and xenografts to evaluate stem-ness biomarkers and tumor phenotypes of freshly resected mature teratomas. Results: We detected very few mutations within a preselected gene pool (T200) in all tumor samples. The "within patient mutation agreement" from a mutation matrix of 57 genes, in which at least one mutation occurred between teratoma and somatic transformation, was 86.2 to 94.8%. There was disparity in gene expression, including miR7-3HG, ARHGEF35, and DLX6, between the 7 matched tumor pairs (log2 fold change of about 2). Prospective primary cell culture studies using cell surface stem-ness markers (SSEA3, TRA1-60, Cripto-1, CD90, CD133, CD44) indicate presence of stem cells embedded within residual mature teratomas (n = 3) after chemotherapy. Conclusions: Molecular profiling confirms a common clonal origin between teratoma and somatic transformation but refutes the idea of dedifferentiation of teratoma to somatic transformation. Presence of stem cells embedded within mature teratomas and capable of differentiation into separate ontogenetic lineages could account for the origin of somatic transformation in TGCT.[Table: see text]
Expression of circulating miR375 and miR371 to differentiate teratoma and viable germ cell tumor in patients with post-chemotherapy residual disease.
Authors: Nappi Lucia , Thi Marisa , Adra Nabil , Leao Ricardo Romao Nazario , Eigl Bernhard J. , Chi Kim N. , Gleave Martin , So Alan , Black Peter C. , Hamilton Robert James , Daneshmand Siamak , Cary Clint , Masterson Timothy A. , Einhorn Lawrence H. , Nichols Craig R. , Kollmannsberger Christian K. 
Published: February 2020

414 Background: Viable germ cell tumors (vGCT) express high levels of certain circulating microRNAs, including miR-371a-3p (miR371) that has shown high specificity and sensitivity. However, neither tissue nor serum/plasma from patients with only teratoma are miR371 positive. miR375 is overexpressed in teratoma tissue, but detectability in blood is unknown. Methods: miR371 and miR375 expression was analyzed in 100 patients with various stages and histology of GCT. miR375 expression in teratoma was validated in patients with post-chemotherapy pathologically confirmed teratoma (PCPCT). The miRNAs expression was assessed by RT-PCR and quantified by ΔΔCT method. The optimal cut-off for miR375 expression was estimated by Youden index ( > 20). Spike-in cel-miR-39-3p, miR-451 and miR-30b-5p were used as internal controls. Sensitivity, specificity, AUC of the ROC of miR375 in detecting teratoma was analyzed. Results: In the discovery cohort miR371 and miR375 were measured in 62 pts: 27 CSI NED, 15 chemo-naïve metastatic seminoma and 20 with PCPCT. miR375 was over-expressed in pts with teratoma compared to CSI and seminoma pts (p = 0.002), while miR371 was expressed in the seminoma pts and undetectable in the PCPCT and CSI pts (p < 0.001). In the post-chemotherapy setting, 38 pts were analyzed: 21 PCPCT, 6 vGCT and 11 complete remission (CR). Also in this cohort, miR375 was over-expressed in pts with teratoma compared to the pts presenting vGCT and post-chemotherapy CR (p = 0.01), while miR371 was detectable only in the pts with vGCT (p < 0.001). Overall, sensitivity and specificity of miR375 in identifying teratoma were 78% and 80%, respectively; the AUC was 0.7 (95% CI: 0.5490-0.8186; p < 0.01). Conclusions: Pts with residual post-chemotherapy teratoma present higher plasma levels of miR375 compared to pts with vGCT in whom miR375 is low but miR371 is expressed at high levels. The simultaneous evaluation of miR371 and miR375 may be clinically useful to predict the histology of the GCT components in pts with post-chemotherapy residual disease to inform the best therapeutic options (surgery or chemotherapy). Further validation within larger studies is warranted.
Predictive capacity of miRNA-375 in identifying teratoma in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND).
Authors: Kenigsberg Alexander P. , Lafin John T. , Meng Xiaosong , Abe Dreaux , Savalyeva Anna , Singla Nirmish , Woldu Solomon L. , Lotan Yair , Kapur Payal , Margulis Vitaly , Amatruda James F. , Bagrodia Aditya 
Published: February 2020

416 Background: Traditional tumor markers for testicular germ cell tumor (TGCT), lactate dehydrogenase (LDH), beta-human chorionic gonadotropin (hCG), and alpha-fetoprotein (AFP), have limited sensitivity in detecting residual tumor on PC-RPLND. Micro-RNAs (miRNA) have emerged as a promising serum markers to predict residual TGCT on RPLND. Previous reports have suggested high levels of miRNA-375 in teratoma. The purpose of this study was to evaluate serum miRNA-375 as a tumor marker for PC-RPLND teratoma. Methods: We prospectively collected pre-surgical serum samples from consecutive GCT patients undergoing PC-RPLND. Serum miRNA-375-3p and -5p expression was validated and quantified by qPCR. Receiver operating characteristic (ROC) analysis and logistic regression were utilized to evaluate test characteristics and predictors of teratoma. Results: 40 patients underwent PC-RPLND. 18 had benign pathology, 2 viable TGCT, 19 teratoma, and 1 embryonal rhabdomyosarcoma. 3 miRNA specimens were excluded as outliers. miRNA-375-5p was undetectable in all samples examined. ROC analysis of miRNA-375-3p revealed an area under the curve of 0.503. Of 19 patients with teratoma, 16 had elevated miRNA-375-3p (84.2% sensitivity). 6/17 with benign pathology had normal mi-RNA-375-3p (35.3% specificity). 16/27 with positive tests harbored teratoma (59.3% positive predictive value). 6/9 with negative miRNA-375-3p had benign disease (66.7% negative predictive value). Univariate analysis demonstrated that clinical stage, pre-RPLND LDH, AFP, hCG, N/L ratio, and miRNA-375-3p were not significant predictors of teratoma. Conclusions: miRNA-375 does not predict teratoma on PC-RPLND. Tissue expression of miRNA-375 did not translate to serum expression in our study. Reliable predictors of teratoma on PC-RPLND remain elusive.
Health-related quality of life in Japanese patients with bladder cancer according to a newly developed Japanese version of the Bladder Cancer Index.
Authors: Osawa Takahiro , Wei John , Abe Takashige , Yamada Shuhei , Frumido Jun , Miyata Haruka , Kikuchi Hiroshi , Matsumoto Ryuji , Sato Yasuyuki , Hirakawa Kazushi , Sasaki Yoshihiro , Tanaka Hiroshi , Kashiwagi Akira , Morita Ken , Takada Norikata , Minami Keita , Harabayashi Toru , Murai Sachiyo , Shinohara Nobuo 
Published: February 2020

427 Background: We developed a Japanese version of the Bladder Cancer Index (BCI) to measure HRQOL in Japanese patients treated with various surgical methods. In addition, we performed a cross-cultural comparison of sexual function and bother in bladder cancer patients between the United States and Japan. Methods: The Japanese version of the BCI was developed through a multistage process after a pilot study. Its reliability and validity were examined in Japanese bladder cancer patients via a cross-sectional analysis. The patients were enrolled from August 2016 to March 2018. They also completed the Japanese version of Short Form (SF)-12, the EuroQol five-dimension scale (EQ-5D), and the Functional Assessment of Cancer Therapy-Bladder (FACT-BL). We also compared the Japanese cohort with an American cohort; i.e., the validation cohort used to develop the original version of the English BCI. Results: In total, 371 patients with a median age of 72 years and a median disease duration of 29 months were enrolled. Of these patients, 221 underwent transurethral resection of the bladder tumor, and 150 underwent radical cystectomy. The internal consistency value was ≥0.7 for all subscales, except the bowel function subscale. Each BCI domain was poorly correlated with the SF-12 and EQ-5D, but moderately well correlated with the FACT-BL. The urinary function and bowel function scales exhibited minimal (2.1–9.7%) amounts of missing data, whereas relatively high (≥15%) levels of missing data were seen in items relating to urinary bother, bowel bother, sexual function, or sexual bother. A missing data value of ≥15% was correlated with higher age (p<0.05). Japanese patients were more likely than American patients to report poor sexual function. However, Japanese were less likely than American to be concerned about sexual function. Conclusions: We confirmed the reliability and validity of the Japanese version of the BCI, although it needs to be revised to make it more comprehensible for elderly patients. We found differences between American and Japanese patients with bladder cancer. The BCI can be used for cross-cultural assessments of HRQOL in bladder cancer patients.
Frailty has significant impact on treatment selection in patients with muscle-invasive bladder cancer.
Authors: Iwamura Hiromichi , Hatakeyama Shingo , Fujita Naoki , Okamoto Teppei , Suzuki Yuichiro , Saito Fumitada , Yamamoto Hayato , Imai Atsushi , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara 
Published: February 2020

429 Background: Although measuring frailty is important to estimate risks and to aid shared decision making, the impact of frailty on surgical indication in muscle-invasive bladder cancer (MIBC) remain unclear. We aimed to investigate the impact of frailty on treatment modality selection in patients with MIBC. Methods: Between October 2013 and September 2019, we underwent frailty evaluation in 149 patients with localized or locally advanced MIBC (T2-4N0-1M0). Frailty evaluation included modified Frailty index (mFI), Fried phenotype (FP), and frailty discriminant score (FDS). Primary purpose was comparison of frailty between the patients who underwent radical cystectomy (RC group) and trimodal therapy for bladder preservation (TMT group). Optimal cutoff values of frailty between the RC and non-RC groups was defined by receiver operating characteristic curve. Secondary purpose included overall survival (OS) comparison between in patients with frail and non-frail. Overall survival (OS) was compared using Kaplan-Meier method and Cox regression analysis. Results: Of 149, 88 and 61 patients were classified to RC and TMT group, respectively. The median age in the TMT group was significantly older than that in the RC group (80 vs. 68 years). A significantly higher prevalence of frailty was observed in the TMT group than that of the RC group in FP ≥3 (5.7% vs. 61%, P < 0.001), mFI ≥2 (22% vs. 61%, P < 0.001), and FDS ≥2.30 (40% vs. 72%, P < 0.001). Univariate logistic regression analysis showed that frailty was significantly associated with TMT. Frailty was significantly associated with overall survival between the RC and TMT groups in the FP and FDS, whereas it was not the case in mFI. Conclusions: Frailty was significantly associated with indication of RC in patients with MIBC. Measuring frailty is important to estimate risks and to aid shared decision making.