bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphopenia and clinical significance associated with tyrosine kinase inhibitors in metastatic renal cell cancer in Guatemalan cohort.
Authors: Ramirez Rixci , Rosales Lopez Daniel Estuardo , Godinez Jerez Francisco , Mansilla Alfredo , Camey Carolina , Oliva Vega Gustavo 
Published: May 2019

e16117 Background: Lymphopenia is associated with toxicity and clinical outcomes in several types of cancer. Decrease in absolute lymphocyte count (ALC) has been observed in the treatment with sunitinib. Objective: characterize lymphopenia ( < 1000/µL) associated with tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma (mRCC) and its relation to progression free survival (PFS). Methods: A retrospective review of the charts was performed in patients with sunitinib and/or sorafenib between April 2000 and May 2017 in Guatemalan Social Security Institute (IGSS). The Kaplan-Meier models, the Cox regression and the log-rank test are within the groups for progression-free survival. Results: Eighty-nine patients were analyzed, 56 men and 33 women. The age groups < 50 from 51 to 75 and > 75 being these 19, 34 and 34 respectively. Regarding treatment received 56 patients received sunitinib and 47 sorafenib. Lymphopenia was found in 55% and 8% of the treated with sunitinib and sorafenib, respectively (p < 0.001). Focusing on patients treated with sunitinib for all subsequent analyzes, the median PFS was 11 months (95% CI, 6-19). The median PFS was 21 months (95% CI, 11-25) for patients who will not develop lymphopenia compared to 4 months (95% CI, 3-8) in patients with lymphopenia (p = 0, 0001). Conclusions: Lymphopenia related to sunitinib is associated with a decrease in PFS in mRCC. The decrease in lymphocytes can be used as a prognostic biomarker for patients treated with sunitinib in this context. [Table: see text]
Tumor growth rate in metastatic adrenocortical carcinoma using two-dimensional computer tomography scan.
Authors: Fuller Sarah N. , Shafiei Ahmad , Ilanchezhian Maran , Bagheri Mohammadhadi , Del Rivero Jaydira 
Published: May 2019

e16125 Background: Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of 1.5–2 per million people per year. It has a poor prognosis with an overall 5-year mortality of 75-80%. The treatment of choice for a localized primary or recurrent tumor is radical surgical resection. However, patients with recurrent or metastatic disease are infrequently cured by surgery alone and chemotherapy has limited benefits. Little is known about the growth rate of metastatic lesions or how disease burden varies among patients, which poses a considerable obstacle in patient care as 17–53% of patients present with distant metastases at the time of diagnosis. Most ACC metastases are found in the liver, lung, bone, and retroperitoneum. Methods: This study retrospectively analyzed the growth rate of metastatic ACC lesions in the lung, liver, lymph nodes, and adrenal bed using serial two-dimensional segmentation of computer tomography images from 10 patients seen at the National Institutes of Health. All patients were females (mean age of 61 years; range, 49–70 years) who had an ACC diagnosis for a mean of 7 years (range, 3–14 years). Only lesions that exhibited FGD-PET avidity were included with up to five lesions per organ recorded. Results: Of the 10 patients, 7 showed metastatic disease at primary diagnosis, although all patients developed recurrent and/or distant metastatic lesions throughout the course of their disease (3 patients had lung lesions, 6 had liver lesions, 8 had adrenal bed recurrence, and 5 had lymph node involvement). Compared over a 6-month period without treatment alteration (change in chemotherapy, surgical intervention, or ablation) lung lesions increased by 11.6%, liver lesions decreased by 17.9%, retroperitoneal lesions increased by 69.25%, and lymph node lesions increased by 9.2%. Conclusions: Treatment of metastatic lesions, particularly in the liver, can increase long-term survival. Understanding growth rates of metastatic tumors may lead to improved treatment of patients with ACC.
Safety and preliminary immunogenicity of JNJ-64041809, a live attenuated, double-deleted Listeria monocytogenes-based immunotherapy, in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Drake Charles G. , Pachynski Russell Kent , Subudhi Sumit Kumar , McNeel Douglas G. , Antonarakis Emmanuel S. , Bauer Todd Michael , Patricia Daniel , Wade Mark , Zudaire Enrique , Mason Gary , Knoblauch Roland Elmar , Stone Nicole L. , Infante Jeffrey R. , Gottardis Marco , Fong Lawrence 
Published: May 2019

e16509 Background: The safety and immunogenicity of JNJ-64041809 (JNJ-809), a live attenuated, double-deleted Listeria monocytogenes (LADD- Lm)-based immunotherapy targeting relevant prostate cancer antigens, was evaluated in a phase 1, multicenter, open-label study in patients (pts) with mCRPC. Methods: Men aged ≥18 years with progressive mCRPC who had received ≥2 prior approved therapies were included. The recommended phase 2 dose (RP2D) and the safety and immunogenicity of JNJ-809 were evaluated. Dose-limiting toxicities (DLTs), adverse events (AEs), T cell response, tumor response, and JNJ-809 bacterial shedding profile were assessed at 2 dose levels, 1 x 108 and 1 x 109 colony forming units (CFU). Results: 26 pts (median age 66.5 years, White 96%) were enrolled (1 x 108 CFU, n = 6; 1 x 109 CFU, n = 20). Median duration of treatment was 2.5 months (range 0-9.7). No DLTs occurred and 1 x 109 CFU was selected as the RP2D. Most common AEs were chills (n = 24, 92%), pyrexia (n = 21, 81%), and fatigue (n = 16, 62%). Grade ≥3 AEs were reported in 18 (69%) pts and serious AEs in 7 (27%) pts including 1 pt with investigator-assessed treatment-related grade 3 intestinal obstruction. At 1 x 108 CFU, all pts had negative blood cultures. At 1 x 109 CFU, 6 pts had LADD- Lm-positive blood cultures on day 1; blood cultures on all subsequent days were negative. JNJ-809 transiently induced peripheral cytokines including interferon-γ, interleukin-10, and tumor necrosis factor-α. Of 7 evaluable pts (1 x 109 CFU), post-treatment T cell responses were demonstrated in 6 pts to the Listeria antigen LLO and in 5 pts to ≥1 of the 4 encoded tumor antigens. Best overall response was stable disease (SD) in 13/25 evaluable pts with SD ≥16 weeks in 4 pts. The study was terminated early as the data collected from 26 pts were considered sufficient to evaluate safety and immune responses. Conclusions: JNJ-809 has a manageable safety profile consistent with that of other LADD- Lm-based therapies. Observed activation of immune responses with monotherapy did not translate into clinical activity, and further development of JNJ-809 will likely require a combination approach. Clinical trial information: NCT02625857.
Fracture risk after radium-223 (Ra-223) in metastatic castration resistant prostate cancer (mCRPC).
Authors: Alonzi Roberto , Parker Chris C. , Tunariu Nina , Koh Dow-Mu , Staffurth John , Blackledge Matthew D. , Padhani Anwar R. , Tree Alison , Stidwill Helen , Finch Jessica , Chatfield Peter , Perry Sophie , Tovey Holly , Hall Emma 
Published: May 2019

e16513 Background: Ra-223 improves overall survival in patients with mCRPC, but is associated with increased risk of fracture when used in combination with abiraterone and prednisolone. We have assessed time to first new fracture in men with mCRPC receiving Ra-223 monotherapy, imaged using whole body MRI. Methods: In a prospective phase II study, patients with chemotherapy-naïve, bone mCRPC were randomised (1:1) to receive Ra-223 at 55 or 88 kBq/kg for 6 cycles, at 4-week intervals (REASURE; ISRCTN17805587). Whole body MRI was done at baseline, at cycles 2 and 4, and 1 month post-treatment. Subsequent imaging was done as clinically indicated. All scans were centrally reviewed to describe the time to first new fracture and characteristics of fractures. Time to new fracture was analysed using Kaplan Meier methods; comparisons of time to fracture between groups were based on log-rank tests. Results: 36 evaluable patients received a median of 6 cycles of Ra-223; scans were available for 35 patients. For these 35 patients, median age was 75 years (IQR: 73-80). 3 (9%) were receiving bone health agents at trial entry; 8 (23%) had received prior abiraterone or enzalutamide. 21 (60%) patients developed new fractures between randomisation and 2 years after completing treatment with radium-223. The spine was the most common location for fractures (14 patients). Median time to new fracture from randomisation was 10.8 months (95% CI: 6.2-18.2). Freedom from new fracture at 2 years post-randomisation was 21% (95% CI: 7 – 39%). Time to first new fracture was not associated with Ra-223 dose (55 kBq/kg: 10/18 patients experienced a fracture vs 88kBq/kg: 11/17; p = 0.93) or baseline use of bone health agents (3/3 vs 18/32; p = 0.09). Patients with Extent of Disease (EOD) ≥2 (defined as ≥6 metastatic sites/superscan) had earlier time to first new fracture compared to patients with EOD 1 (defined as < 6 metastatic sites) (11/18 vs 10/17; hazard ratio = 2.7, 95% confidence interval = 1.0 – 6.8; p = 0.04). Conclusions: New fractures are commonly seen on imaging in men with mCRPC during and after treatment with Ra-223 monotherapy. This observation supports treatment guidelines that recommend the use of bone health agents in men with mCRPC. Clinical trial information: ISRCTN17805587.
Clinical efficacy of abiraterone and enzalutamide metastatic castration sensitive prostate cancer patients who progressed rapidly on docetaxel with a genomic analysis.
Authors: Chen Gang , VanderWeele David James , Karzai Fatima , Bilusic Marijo , Al Harthy Munjid , Arlen Philip M. , Theoret Marc Robert , Rosner Inger L. , Chun Guinevere , Owens Helen , Couvillon Anna , Hankin Amy , Williams Monique , Gulley James L. , Dahut William L. , Madan Ravi Amrit 
Published: May 2019

e16536 Background: Docetaxel has become a standard of care for mCSPC. Enzalutamide and abiraterone have been proven to improve survival in metastatic castration-resistant prostate cancer (mCRPC) patients. Little is known about patients who have been treated with docetaxel for mCSPC and subsequent therapeutic responses. This retrospective analysis is to evaluate the response duration of abiraterone and enzalutamide in patients who previously received docetaxel for mCSPC but developed mCRPC within 12 months. Methods: Clinical Trial NCT02649855 enrolled patients with newly diagnosed mCSPC who were treated with standard androgen deprivation therapy (ADT) and docetaxel (75 mg/m2 every 3 weeks for 6 cycles) sequenced with immunotherapy (PROSTVAC) from February 2016 to present. Patients who had progression (based on consecutive PSA rises or imaging) within 1 year of completing docetaxel and went on to subsequent abiraterone/enzalutamide were evaluated. (Note these are different PSA progression criteria than used in CHAARTED, Sweeney, NEJM, 2015). A PCR-based NGS panel (OncoMine Comprehensive Assay v3) will evaluate available tissue from these patients. Results: Of the 46 patients evaluated regardless of immunotherapy sequence, 15 (33%) went on subsequent therapy after progression on docetaxel for mCSPC, with 12 patients starting abiraterone/enzalutamide (7 with high volume disease and 5 with low volume disease). The median age was 62 (41-83) years. 6/12 patients (50%) initiated enzalutamide and 6/12 patients (50%) initiated abiraterone. The median duration of treatment for both was 7.43 (1.53 – 16.0) months, the median time to prostate-specific antigen (PSA) progression was 2 (0 – 11) months; the median duration of PSA decline was 2 months in patients with both high and low volume disease. Of note, 3/12 (25%) of patients did not have PSA response, all of them had high volume disease. Conclusions: These data from a small cohort suggest that patients who have progression within 12 months of completing docetaxel for mCSPC have limited subsequent benefit from enzalutamide or abiraterone. Additional studies are required to determine optimal timing and treatment sequence for patients with mCSPC who rapidly develop mCRPC. Clinical trial information: NCT02649855.
Comparison of enzalutamide versus abiraterone in castration-resistant prostate cancer before docetaxel: Results of a propensity score-matched analysis.
Authors: Cesca Marcelle Goldner , Silveira Maysa Tamara , Pandolfi Natasha Carvalho , Oliveira Thiago Bueno , Rinck José Augusto , Da Costa Alexandre Andre B. A. , Corassa Marcelo , Formiga Maria Nirvana , Dettino Aldo A. 
Published: May 2019

e16540 Background: Metastatic castration-resistant prostate cancer (mCRPC) phenotype involves androgen-receptor signalling mechanisms that support the use of enzalutamide (EZ) and abiraterone (Abi). These therapies improve overall survival (OS) and quality-of-life, with a favourable safety profile. There is no validated data defining the best drug or sequence to be used. Methods: A retrospective cohort of mCRPC patients (pts) was analysed at AC Camargo Cancer Center. The primary objective was to compare progression-free survival (PFS) and OS in patients treated with EZ or Abi as first line (docetaxel naïve pts). Kaplan-Meier, Log-Rank Test and Cox Regression were used for survival analysis. To address unbalanced characteristics between the two treatment groups treatment efficacy was compared in a propensity score matched cohort. Results: From May, 2002 to September, 2017, 120 pts were treated with Abi (84%) or EZ (36%). Median follow-up was 21.2 months. Median age at diagnosis was 66 (48-84), the majority were Gleason score 7 (34%) and median baseline PSA was 14. Median PFS was 17.4 months in EZ and 10.6 months in Abi group (HR = 0.65; 95%CI: 0.39-1.10; p = 0.11). Median OS was not reached and 31.6 months for EZ and Abi, respectively (HR = 0.60; 95%CI: 0.27-1.36; p = 0.22). EZ was associated with a better PSA response in the first 4 months of treatment (p < 0.001). Independent prognostic factors for worse OS and PFS were ECOG ≥ 1, treatment toxicity ≥ G1 and lower PSA doubling time before treatment and for better OS and PFS were PSA response in the first 4 months and alkaline phosphatase and lactate dehydrogenase response at any time. In the propensity score matched cohort including 72 patients PFS was better in EZ group (HR = 0.36; 95%CI: 0.20-0.64; p < 0.001) but there was no difference in OS (HR = 0.66; 95%CI: 0.27-1.63; p = 0.37). Conclusions: EZ was associated with prolonged PFS and better PSA response, with no OS improvement when compared with Abi for mCRPC before docetaxel, in a propensity score matched analysis.
An open label phase 1/2A study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of TRC253, an androgen receptor antagonist, in patients with metastatic castration-resistant prostate cancer.
Authors: Rathkopf Dana E. , Saleh Mansoor N. , Tsai Frank Yung-Chin , Bilen Mehmet Asim , Rosen Lee S. , Gottardis Marco , Infante Jeffrey R. , Adams Bonne J. , Liu Lilian , Theuer Charles P. , Freddo James L. , Agarwal Neeraj 
Published: May 2019

e16542 Background: TRC253 is a high-affinity, orally active small molecule antagonist of the androgen receptor (AR) and specific mutated variants of AR that does not possess agonist activity towards either wild type or mutated AR. TRC253 inhibits AR nuclear translocation as well as AR binding to DNA and is a transcription antagonist. TRC253 treatment is efficacious in an LNCaP xenograft model driven by F877L mutant AR. Methods: In P1 dose escalation, pts with mCRPC previously treated with an AR inhibitor were assigned to increasing TRC253 doses of 40-320 mg daily. Dose escalation followed single-pt dose escalation design for the 40, 80 mg cohorts and expanded to 3+3 design in the 160, 240, 280, and 320 mg cohorts to assess safety, determine the recommended phase 2 dose (RP2D), and evaluate prostate-specific antigen response at week 12. Toxicity and efficacy assessments used NCI-CTCAE v4.03 and PCWG3 criteria, respectively. Pts were centrally screened by circulating tumor DNA using the BEAMing digital PCR assay. Results: Twenty-two pts were enrolled in phase 1 at TRC253 doses of 40 (n = 1), 80 (n = 1), 160 (n = 2), 240 (n = 6), 280 (n = 4), and 320 mg (n = 8) daily in 28-day cycles. One DLT of G3 QTcF prolongation occurred at 320 mg. No drug-related SAEs were reported. Drug-related AEs ≥ G2 included QTcF prolongation (2 G2, 2 G3), elevated lipase (1 G3), fatigue (4 G2), arthralgia (1 G2), diarrhea (1 G2), and platelet count decrease (1 G2). One pt on study had AR F877L at baseline and remained on treatment for 49 wks with PR by RECIST. The remaining 21 pts did not have AR F877L at baseline and of these, 48% (10) remained on study > 6 cycles and one pts had a > 50% decrease in PSA. Target PK exposures were achieved consistently at 280 mg. 280 mg was selected as the RP2D based on safety and PK data. Conclusions: TRC253 daily at 280 mg was well-tolerated and selected as the RP2D. P2 dose expansion is currently enrolling 2 cohorts: 15 pts with AR F877L and 30 pts without AR F877L. The objectives of P2 include collection of additional data for safety, PK, PET and efficacy of TRC253 in mCRPC pts with specific AR mutations. Clinical trial information: NCT02987829.
A single-center retrospective analysis of the effect of Radium-223 (Xofigo) on pancytopenia in patients with metastatic castration-resistant prostate cancer.
Authors: Skelton William Paul , Dibenedetto Samantha Welniak , Pang Sarah , Pan Kelsey , Barish Jacob , Nwosu-Iheme Adaeze , Dang Long H. 
Published: May 2019

e16546 Background: Radium-223 (Xofigo) has been shown to increase overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) via the phase 3 ALSYMPCA study. The side effect of persistent pancytopenia was noted in 2% of the patients, however, the incidence seen in our institutional clinical practice is higher than reported in the literature. This analysis serves to identify predictive factors and thereby help impact future therapy directions in this patient population. Methods: A retrospective analysis was performed analyzing patients with mCRPC who received xofigo at UFHealth in a 3 year span (from January 2014 to January 2017). Data collected included CBC, ECOG functional status, kidney and liver function, evidence of bony disease on imaging, prior chemotherapy regimens, total radiation dose, and PSA. This study was IRB approved. Results: 52 patients with mCRPC were identified, 27 of which received xofigo. 23 patients received treatment at UF, and one was lost to follow-up. 16 patients (73%) completed the full course (6 doses) of xofigo, while 6 did not. 10 patients (45%) developed pancytopenia, with 2 recovering counts within eight months while the other 8 had persistent cytopenias (6 of which were transfusion-dependent). Older age (74.0 ± 8.8 vs 68.7 ± 10.2) and higher ECOG score (1.6 ± 0.7 vs 1.2 ± 0.6) correlated with increased risk of pancytopenia. In addition, a higher percentage of patients who received prior radiation therapy were more likely to develop pancytopenia (90% vs 75%). All patients studied had bony disease and received prior chemotherapy. Conclusions: Albeit with a limited sample size, we found a higher rate of xofigo-induced pancytopenia in our patient population than the 2% reported in the literature. This may influence clinical decision making in the treatment of mCRPC, as pancytopenia may preclude patients from other survival-prolonging therapies. Factors such as age, functional status, and prior radiation therapy are important to keep under consideration prior to xofigo treatment. Additional larger studies are necessary to further quantify this effect.
Classification of prostate cancer based on clinical and omics data using neural networks techniques to improve prognostic power.
Authors: Marin Laura , Casado Fanny Lys , Racoceanu Daniel , Pinto Joseph A. 
Published: May 2019

e16569 Background: In 2017, prostate cancer (PCa) was the second most common cancer in men after lung cancer. While there are different courses of action to treat the disease, its mortality in Peru is higher than 50%. Conventionally, PCa is diagnosed by evaluating tissue biopsies, and classified according to the Gleason grading system. Novel molecular classifications of PCa have been proposed for diagnostic and prognostic purposes. The main goal of this work is to implement a tool predicting the disease free time of patient according to the genomic expression and highlight the genes playing an influential role on the prediction. Methods: Modern techniques to classify data keep getting broader and more accurate, in particular with the introduction of Neural Networks(NN). We implement an Artificial Neural Network automatic genomic classification strategy based on a Local Interpretable Model-Agnostic Explanations (LIME) algorithm because it allows the network to choose the features of major discriminative significance. As a proof-of-concept, we selected a sub-set of 3530 genes related to recurrence from 499 PCa genomes to build the neural networks. Results: The resulting neural network, trained and tested on cancer cell 2010 database and validate on the MSKCC data the can predict the time of recurrence within a range of three months based on the genomic expression with an accuracy of 96,9% and a loss of less than 9%. Using the implemented LIME algorithm, our results indicate that this subset of genes is informative of recurrence and plays a substantial role in the prediction. Conclusions: Instead of using a classic fully connected layer, we implemented different types of Deep Learning networks where the final network provides the predicted survival rate or time to recurrence. This information will allow the doctors to propose the best course of treatment. Our method is able to generate an augmented score, enabling a more accurate evaluation of risk and personalized treatment strategy
Cell cycle progression score and PTEN as prognostic factors for metastasis in intermediate and high-risk prostate cancer.
Authors: Trock Bruce J. , Rajamani Saradha , Vidal Igor , Glavaris Stephanie , Jones Tracy , Han Misop , Partin Alan W. , Cohen Todd , Stone Steven , De Marzo Angelo M 
Published: May 2019

e16575 Background: To evaluate the cell cycle progression (CCP) score and PTEN as prognostic markers for risk of metastasis in a radical prostatectomy (RP) cohort of NCCN intermediate and high risk prostate cancer. Methods: This IRB-approved case-cohort study included men treated with RP at Johns Hopkins from 2007-2015. Paraffin-embedded RP tissue was analyzed blind to study outcome at Myriad Genetics, for CCP score using qRT-PCR, and PTEN by immunohistochemistry. Metastasis-free survival (MFS) was analyzed with the Cox proportional hazards model, weighted for case-cohort design. CCP and PTEN were analyzed independently, and adjusted for CAPRA-S. The CCR score, which combines CCP and CAPRA-S, was also analyzed. Data were analyzed independently by Johns Hopkins and Myriad Genetics. Results: There were 209 patients, of whom 42 were cases (metastasis). Median age was 59 years, 47% had Gleason 4+3 or higher, 48% had non-organ confined tumor, and 18% had seminal vesicle or lymph node involvement. NCCN risk was intermediate in 77% and high in 23%. Median follow-up was 4 years. Both CCP and PTEN, as well as CCR score, were statistically significant in univariate analyses, but only CCP retained statistical significance in a multivariable model of CCP, PTEN, and CAPRA-S (Table). Conclusions: This is the first comparison of the CCP score and PTEN as risk factors for metastasis in a recent RP cohort of patients at NCCN intermediate or high risk. Both CCP score and PTEN were strongly associated with MFS in univariate analyses, but only CCP score retained significance in a multivariable analysis with both biomarkers adjusted for CAPRA-S. [Table: see text]