bluuebunny/crossref_metadata_2025_split huggingface dataset:
An estimate of premature deaths averted with immunotherapy in treating Brazilian patients with advanced clear cell renal cell carcinoma.
Authors: Lenz Gabriel , Peruzzo Nicolas , Arraes Cecília , Lopes Gilberto 
Published: May 2019

e16114 Background: Clear cell renal cell carcinoma (RCC) accounts for 3% of all cancers in Brazil, and the majority of these patients (pts) are treated in our public health system, SUS. Sunitinib and Pazopanib were incorporated into SUS in early 2019 for use in metastatic RCC (mRCC). Although Nivolumab plus Ipilimumab (NI) is the standard first-line systemic therapy for intermediate- and poor-risk pts with mRCC, these drugs are not yet available. We aimed to estimate the number of premature deaths that could be averted with incorporation of NI for mRCC pts treated in SUS. Methods: We used incidence rates reported by GLOBOCAN to estimate the annual number of pts with mRCC due to receive first-line systemic therapy in Brazil. Privately insured patients were excluded. A review (Lalani et al., 2018) and CheckMate 214 Trial were used to estimate stage distribution at diagnosis and overall survival (OS) in 12 months, respectively. We explored differences in the number of deaths between different therapeutic strategies. Results: GLOBOCAN estimates 9,619 new cases of RCC per year in Brazil, of which 72.1% are to be treated in SUS. Twenty-five percent are de novo metastatic. Among patients with mRCC, 75% have intermediate- or poor-risk disease. That is, 1,300 pts with intermediate- or poor-risk mRCC are to be treated each year in SUS. We estimated that 9,360 pts are expected to be alive over a 10 year period with sunitinib and 10,400 pts with NI. Conclusions: In the Brazilian public health system, it can take more than a decade for novel therapies to be incorporated. Over a ten-year period, approximately 1,040 pts with mRCC will die prematurely due to the lack of access to immunotherapy (NI) in the public health system. Studies to evaluate the cost-effectiveness of NI for Brazilian pts with mRCC are urgently needed.
Objective response and prolonged stable disease in refractory adrenocortical carcinoma treated with cabozantinib: An international case series and protocols of phase II clinical trials.
Authors: Kroiss Matthias , Megerle Felix , Wendler Julia , Jimenez Camilo , Quinkler Marcus , Malzahn Uwe , Goebeler Maria-Elisabeth , Fassnacht Martin , Habra Mouhammed Amir 
Published: May 2019

e16118 Background: Median overall survival (OS) in advanced adrenocortical (ACC) is only 12-15 months. Previous clinical trials with oral multi-kinase inhibitors (MKI) were negative likely due to inadvertent drug interaction with mitotane. Objective: To investigate the potential of cabozantinib (CABO) monotherapy in ACC patients. Methods: Retrospective cohort study at three referral centers for ACC (U.S. and Germany). Results: Fifteen patients (13 female) with progressive disease after mitotane (14/15 patients) and three (median; range 0-8) further systemic therapies were treated with 60 mg (20-140) CABO. Mitotane had been discontinued in all patients, in 11/15 patients mitotane was stopped > 270 days before CABO treatment or plasma concentration documented to be < 2 mg/L. Adverse events (AE) of grade 1/2 and 3 were observed in 12 and 2 patients, respectively and consistent with the known safety profile of CABO. Best response was partial response in 3, stable disease in 4 and progressive disease in 8 patients. Progression-free survival (PFS) of > 4 months (PFS4) was observed in 7 patients. Median PFS and OS was 12 and 41 weeks, respectively. Two single center phase II trials of CABO in advanced ACC in the U.S. (NCT03370718) and Germany (NCT03612232) will accrue 18 and 37 patients, respectively. Mitotane discontinuation and plasma concentrations < 2 mg/L are key inclusion criteria. The primary endpoint is PFS4. Conclusions: Cabozantinib monotherapy appears to be safe and active as a monotherapy in advanced ACC. Two parallel phase II trials will investigate CABO prospectively while controlling for drug interaction with mitotane.
Study of the clinical characteristics of scrotal mesothelioma.
Authors: Zhang Chen , Goldsztajn Harry Jack 
Published: May 2019

e16122 Background: Scrotal mesothelioma (SM) is an extremely rare type of genitourinary cancer. To the best of our knowledge, no clinical trial was performed in SM. The objective of this study aims at evaluating the clinical characteristics of scrotal mesothelioma. Methods: Retrospective and comprehensive literature search was performed for SM case report/series on PUBMED/Medline. 184 articles were found through January 2019 and 81 articles were excluded due to non-English language or unavailability. A total of 124 patients in 103 articles were included. All necessary data were extracted including age, asbestos exposure history, clinical presentation, diagnostic method, tumor marker, management approach and surveillance. P < 0.05 was considered significant. Results: Out of 124 patients, the median age at diagnosis was 60 years old. 16 patients (12.9%) had a history of asbestos exposure, 58 (46.8%) without exposure and 50 (40.3%) were not mentioned. Most common initial presentation was hydrocele (n = 78, 62.9%), followed by mass (n = 38, 30.6%). 50% (n = 62) of tumors presented on the right testicle while 34.7% (n = 43) were on left side, 0.8% (n = 1) bilaterally and 14.5%(n = 18) were unclear. 40 (32.3%) patients developed metastatic disease, while 20 (16.1%) developed it at diagnosis. 102 (82.3%) patients were diagnosed by post-operative pathology, and 22 (26.7%) were diagnosed before surgery. Alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) were checked in 24 patients. AFP was uniformly negative (100%) and hCG was negative in 23 patients (95.8%). Most patients underwent surgery (n = 119, 96%), of which orchiectomy and/or hemiscrotectomy (n = 93, 78.2%) comprised the majority. For adjuvant therapy, 14 (11.3%) patients received radiotherapy and 9 (7.3%) received chemotherapy. Out of 71 patients without initial metastasis and with follow-up data, median follow-up time was 17 months, median time to recurrence was 19 months, and 5-year recurrence-free status was 11.3%. Conclusions: The most common presentation of SM is hydrocele and the most common location is the right testicle. Surgery is a common intervention, but the recurrence rate is high. Due to limited number of reports, more clinical data and further clinical studies are warranted for management guidance.
Venous thromboembolism related hospitalizations among patients with genitourinary malignancy in the United States: A nationwide analysis.
Authors: Albagoush Sara , Abushalha Kamelah , Aurit Sarah J , Baskaran Janani , Gbadamosi-Akindele Maryam 
Published: May 2019

e16126 Background: Cancer Patients are at high risk of developing venous thromboembolism (VTE), pulmonary embolism (PE), and deep venous thrombosis (DVT). In this study, we aim to get an estimate of the incidence of VTE as a primary admission diagnosis among patients with genitourinary malignancies. Methods: We utilized ICD-9-CM and ICD-10-CM codes to identify patients with malignant neoplasms of the prostate, bladder, kidney, and testis who are older than 18 years and admitted with a primary diagnosis of DVT, PE within the NIS database during 2007-2016. Unadjusted incidence of DVT and PE was analyzed for each cancer site with the Rao-Scott chi-square test; multivariable logistic regression was employed to adjust for age, biological sex ( not for prostate/ testicular cancer), race, insurance, year of admission, and use of chemotherapy to further examine incidence. Results: We identified 3,339,985 admissions affiliated with genitourinary malignancies of whom 0.59% experienced DVT and 0.13% experienced PE with bladder cancer patients have the highest risk of hospitalization for VTE ( 79/1000). Within bladder cancer population; insurance ( p < 0.001) and hospital location and teaching status ( p < 0.001) were associated with DVT incidence; and biological sex ( p = 0.040) and race and ethnicity ( p = 0.026) with PE incidence. For all sites combined and after adjusting for all else, it was found that every year increase in age was associated with 1.2% increased odds of DVT or PE incidence (OR 95% CI: 1.01-1.02; p < 0.001). Further, rural vs. urban teaching hospitals had 41.2% increased odds (95% CI: 1.26-1.58; p < 0.001), and urban non teaching vs. urban teaching hospitals had 35.1% increased odds (95% CI: 1.26-1.45) of DVT or PE incidence. African Americans vs. whites had 46.8% increased odds of DVT or PE incidence (95% CI: 1.35-1.60; p < 0.001). Conclusions: Within the population of genitourinary malignancies who admitted with a primary diagnosis of VTE; the incidence was higher with older age, African Americans, uninsured population, in rural and urban non teaching facilities, bladder cancer population.
Antigen (Ag) spread after sipuleucel-T and correlation with overall survival (OS): A real-world experience.
Authors: Berry William R. , Pieczonka Christopher Michael , Vogelzang Nicholas J. , Karsh Lawrence Ivan , Bailen James L. , Van Velzen Krista , Kandadi Harini , Sheikh Nadeem Anwar , Dakhil Shaker R. 
Published: May 2019

e16504 Background: Sipuleucel-T is an autologous cellular immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. In IMPACT (NCT00065442), a phase 3 trial, sipuleucel-T-induced immune responses against target Ag prostatic acid phosphatase (PAP) or PA2024, a recombinant protein consisting of PAP and granulocyte macrophage colony stimulating factor, correlated with OS (Sheikh 2013). Additionally, sipuleucel-T-induced immunoglobulin G (IgG) responses against secondary, non-target Ag (i.e. Ag spread) and the breadth of Ag spread also correlated with improved OS (GuhaThakurta 2015). Here we assessed Ag spread and OS in real-world patients from PRIME (NCT01727154), an immune monitoring sub-study of sipuleucel-T trials Methods: IgG levels in pre and wk 6 (2 wk post sipuleucel-T completion) sera from PRIME (n = 100) were quantified using Luminex xMAP. IgG responses to secondary Ag (LGALS3, PSA, KLK2, LGALS8, K-Ras, E-Ras) were defined as ≥ 1.5-fold increase over baseline. OS associations with individual Ag responses and total number of Ag per patient were assessed using the Kaplan-Meier method. Hazard ratios (HR) were estimated using a Cox Proportional Hazard Model. Results: IgG responses to ≥1 secondary Ag were observed in ≥72% of patients. Individual IgG responses to LGALS3, K-Ras, and LGALS8 at wk 6 were significantly associated with OS. Furthermore, breadth of Ag spread positively correlated with OS (Table); as the total number of Ag responses per patient increased, OS improved compared to patients with no secondary IgG responses. Conclusions: The results presented are consistent with findings from the prior phase 3 trial IMPACT. Secondary Ag responses were generated in real-world patients treated with sipuleucel-T, and these responses correlated with OS. Furthermore, breadth of Ag spread also correlated with improved OS. Clinical trial information: NCT01727154. [Table: see text]
Targeting differential response using molecular guided biopsies in bone-metastatic prostate cancer.
Authors: Roth Alison , Tomlins Scott A. , Tuite Michael , Liu Glenn , Jeraj Robert 
Published: May 2019

e16516 Background: Methods for molecular image-guided biopsies have been limited to targeting lesions with high radiotracer uptake. The purpose of this study is to determine the value of using molecular imaging response to select lesions for biopsy. Methods: 7 metastatic prostate cancer patients received 18F-NaF PET/CT scans at baseline and after 12 weeks of enzalutamide therapy. Lesion uptake was quantified semi-automatically. Lesions were classified as partially responding (PR, significantly decreased uptake), stable disease (SD, no significant change), and progressing disease (PD, significantly increased uptake) using test-retest limits of agreement for the relative change in SUVtotal. In the case that response was stable by SUVtotal, the relative change of SUVmax (and corresponding limits of agreement) were used to reclassify response. 3 candidate lesions from each response category (PR, PD) were selected, including SD lesions if needed. Interventional radiologists biopsied two lesions from different response categories per patient within 7 days of the week 12 scan. Up to 3 needle cores and aspirate were taken per biopsy. Core and aspirate samples were subjected to multiplexed PCR using custom Ampliseq panels targeted to common mutations (DNA) and alterations (RNA) in prostate cancer. The presence of androgen receptor splice variant 7 (AR-V7) was determined for each sample. Results: 8/13 lesions biopsied contained tumor, but one patient’s samples were not tracked (one lesion contained tumor). 7/11 tracked lesions contained tumor including 2/3 PR lesions, 1/4 SD lesions, and 4/4 PD lesions. The average tumor content in successful needle passes was 30.0% for PR (3/6 passes), 20.0% for SD (1/8 passes), and 35.7% for PD lesions (7/8 passes). Aspirate samples were acquired for 1 PR and 3 PD lesions; all 4 contained tumor. AR-V7 was identified in 0/2 PR, 0/1 SD, and 3/4 PD lesions. 3/7 patients had two biopsy lesions that contained tumor. Two patients had PR and PD biopsies and one patient had SD and PD biopsies). AR-V7 was identified in the PD lesions of one of the PR/PD patients and the SD/PD patient. Conclusions: Molecular imaging response has the potential to increase the success of difficult biopsy scenarios. Additional information about developing therapy resistance can be gathered by preferentially sampling PD lesions. Clinical trial information: NCT02677376.
Adherence enhancing program for patients with metastatic, castration-resistant prostate carcinoma treated with abiraterone acetate plus prednisone: A cluster randomized trial.
Authors: Suttmann Henrik , Feyerabend Susan , Gleissner Jochen , Hübner Andreas , Mathes Tim , Baurecht Werner , Krützfeldt Katrin , Sweiti Hussein 
Published: May 2019

e16520 Background: Abiraterone acetate plus prednisone (AA+P) is an effective treatment for patients (pts) with metastatic, castration-resistant prostate carcinoma (mCRPC). Adherence is an important factor for the success of AA+P treatment. Research has shown that adherence in pts taking oral anti-cancer agents is often lower than required. The objective of this cluster randomized trial (CRT) was to assess the influence of an adherence enhancing program (AP) for AA+P in pts with mCRPC. Methods: This was a pragmatic parallel CRT of pts with mCRPC performed under real-world conditions. The study sites were randomly assigned to AP or no-AP (1:1) using a computer generated random schedule. The AP consisted of an educational video and reminder telephone calls. The primary endpoint was “rate of therapy discontinuation after 3 months for reasons other than disease progression or start of a new cancer therapy” (discontinuation). A secondary outcome was medication adherence (Morisky Scale; MMAS-4). Results: In the final intention-to-treat analysis, 47 sites comprising 360 men were allocated to AP and 40 sites comprising 315 men to no-AP. Baseline characteristics and results for each group are presented in the table. The odds ratio (OR) for discontinuation, adjusted for baseline adherence was 1.16 (95%CI: 0.63 to 2.11) and 1.21 (95%CI: 0.74 to 1.97) for 3 and 6 months, respectively. The OR for medium/low medication adherence, adjusted for baseline adherence, was 0.56 (95%CI: 0.26 to 1.21) and 0.84 (95%CI: 0.36 to 1.97) for 3 and 6 months, respectively. Conclusions: The rate of treatment discontinuation in the first 3 and 6 months was low and similar in both study arms. Medication adherence at baseline was generally high, but with some difference between both arms. The adjusted OR for medication adherence at 3 and 6 months revealed a trend towards a slower drop in medication adherence for the AP arm, compared to the no-AP arm, but with a wide confidence interval. Table Clinical trial information: 284. [Table: see text]
Safety and clinical outcomes of GT0918 (Proxalutamide), a potent androgen receptor (AR) blocker, in patients with mCRPC progressing on standard (SoC) and experimental therapies: Phase I/II trial.
Authors: Vogelzang Nicholas J. , Levin Richard , Chu David , Gabrail Nashat Y. , Nordquist Luke T. , Stein Mark N. , Dave Harish P. , Zhang Phoebe , Zhou Karl 
Published: May 2019

e16527 Background: GT0918 is a new chemical entity of AR blocker. A phase I dose escalation study was planned for 6 dose cohorts in pts with mCRPC who have progressed on SoC and experimental therapies. No DLT or major toxicity was found in planned doses, therefore a cohort of 600 mg daily was added in December 2018. Methods: Patients (pts) with histologically confirmed mCRPC who progressed on enzalutamide +/- abiraterone and docetaxel were eligible. GT0918 was administered once daily orally for 28 consecutive days for DLT assessment. Pts could continue on GT0918 until they experienced intolerable toxicity, disease progression or withdrew consent. All pts consented for exploratory biomarker studies of CTC and cf-DNA/RNA. Results: 40 pts were treated with GT0918 in 7 cohorts. Pts had metastatic disease to bone only (44%), and lymph node +/-visceral +/- bone (56%), who progressed on multiple lines of therapies including but not limited to abiraterone, enzalutamide, docetaxel, cabazitaxel. GT0918 related adverse events (AEs) were grade 1 or 2 as per CTCAE v4.03. including fatigue, anemia, nausea, loss of appetite, hot flushing, depression, etc. The most common TEAE is fatigue and all pts at 500 mg dose reported having fatigue and one pt required dose reduction. Toxicity at the 600mg is still being analyzed but at least 2 pts had tremor. Treatment duration showed more pts in the treatment of 400 mg and 500 mg with SD in this heavily pretreated group (see Table). Exploratory biomarkers of CTCs also suggested higher dose of GT0918 resulted in better clinical outcomes. Conclusions: GT0918 administrated orally once daily was well tolerated. Better clinical outcomes were shown in dose cohorts of 400 mg and 500 mg without major toxicities. Thus these 2 doses were selected for dose expansion. Table. Clinical outcomes of GT0918 in heavily pretreated mCRPC pts Clinical trial information: NCT02826772. [Table: see text]
Prediction of metastatic castrate-resistant prostate cancer response to abiraterone or enzalutamide by a baseline blood-based CTC gene expression signature.
Authors: Lariviere Michael Joseph , Haas Naomi B. , Cherkas Yauheniya , Nielsen Karl , Foulk Brad , Patel Jaymala , Smirnov Denis , Vaughn David J. , Amaravadi Ravi K. , Savitch Samantha L. , Majmundar Krishna , Buckingham Thomas H. , Yee Stephanie S. , Jones Jeremy , Pal Sumanta K. , Carpenter Erica L. 
Published: May 2019

e16529 Background: Prostate cancer is the most common cancer in men in the U.S., with 30% 5-year overall survival (OS) for patients (pts) with metastases. To take a precision medicine approach to the management of metastatic castrate-resistant prostate cancer (mCRPC), we developed a blood circulating tumor cell (CTC)-based test to identify mCRPC pts most likely to benefit from abiraterone (abi) or enzalutamide (enza). Methods: In this multi-institution prospective study, men with mCRPC were enrolled prior to starting abi (1,000 mg/d plus prednisone 10 mg/d) or enza (160 mg/d). At baseline (BL), 12 w, and progression, blood samples were collected for CellSearch-based CTC enumeration and qPCR-based gene expression analysis. Results: 69 pts (median age 68 y [50-82]) received abi (n = 25) or enza (n = 44) and had evaluable blood samples. Consistent with prior publications, among 43 pts with BL CTC > 0, clearance of detectable CTCs (BL CTCs > 0 and 12 w CTCs = 0), was achieved in 24 patients (55.8%), and was associated with greater median OS (31 mo vs. 18 mo, log-rank p = 0.03). The 43 pts with BL CTC > 0 were then randomly divided into training (n = 31) and validation (n = 12) sets. Baseline gene expression data for the training set was used to develop a model to predict CTC clearance, starting with a panel of 141 expressed genes/isoforms including those associated with prostate cancer. Of the models tested, random forest yielded the best performance, with respective training and validation set sensitivity of 0.7 and 1, specificity 0.75 and 0.71, AUC 0.88 and 0.91. Top genes identified include those previously associated with disease – HOXB13, ESRP2, KLK3, GRHL2, and KRT19, among others. Conclusions: A gene expression signature from a baseline blood sample with CellSearch-enriched CTCs can predict clearance of detectable CTCs in response to abi/enza with high AUC and may give insight into molecular mechanisms of response. A prospective study with a larger number of patients will be required to further validate our findings. Ultimately, this blood test has the potential to select the patients most likely to benefit from second-generation antiandrogen vs. non-hormonal systemic treatment.
DPP4 inhibitors as novel agents in improving survival in patients with prostate cancer: A SEER-Medicare study.
Authors: Shah Chintan , Hong Young-Rock , Bishnoi Rohit , ali azka , Skelton William Paul , Dang Long H. , Huo Jinhai , Dang Nam H. 
Published: May 2019

e16532 Background: Dipeptidyl peptidase-4 (DPP4) is a cell surface protein expressed in variable amounts on different tissues and plays a vital role in tumor biology as well as regulation of the immune system. In-vitro studies have shown that the DPP4 biochemical activity is twice as high in prostate cancer cells compared to benign prostate tissues. Furthermore, blocking of DPP4 activity in-vitro was demonstrated to inhibit tumor angiogenesis and tumor invasiveness through a number of cellular mechanisms. Meanwhile, DPP4 expression is modest in normal as well as cancerous pancreatic cells. Methods: Using linked SEER and MEDICARE database, we identified patients with prostate cancer (PRC) or pancreatic cancer (PC) with coexisting type II diabetes mellitus. Furthermore, we analyzed the impact of DPP4 inhibition in the overall survival (OS) in these patients between 2001 and 2013. Analyses were performed using SAS, version 9.4. We excluded patients taking metformin. Results: We identified 7229 patients with PRC and 2401 patients with PC. OS was significantly better in PRC patients taking DPP4 inhibitors (262 patients) with HR 0.75 (95% CI: 0.59-0.97; P = 0.02) compared to those not on DPP4 inhibitors. Meanwhile, for patients with PC, OS was not significantly different between patients taking DPP4 inhibitors (177 patients) compared to those who were not (HR 1.03; 95% CI: 0.88-1.21; P = 0.7). Subgroup analyses of PRC patients demonstrated a trend toward a beneficial effect of DPP4 inhibitors, irrespective of stage (stage I, NR; stage II, HR 0.81; stage III, NR; stage IV, 0.76),use of chemotherapy (HR 0.83 with chemotherapy and HR 0.70 without chemotherapy) or hormonal use (ADT) (HR 0.87 with ADT and HR 0.71 without ADT), prostatectomy (HR 0.50 with prostatectomy and HR 0.77 with no prostatectomy) or radiation (HR 0.89 with radiation and HR 0.64 without radiation). Conclusions: This is the first population-based analysis showing the OS benefit of DPP4 inhibitors in PRC patients. On the other hand, OS was not improved in PC patients taking DPP4 inhibitors likely due to low levels of expression of DPP4 cell surface protein on pancreatic tissues. A prospective trial would help confirm our findings.