bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining the real-world utility of immune checkpoint inhibitors in genitourinary oncology: A single-institution retrospective.
Authors: Glick Lydia , Clark Cassra , Han Timothy M. , Mark James Ryan , Gomella Leonard G. , Handley Nathan , Kelly William Kevin , Trabulsi Edouard John , Lallas Costas D. , Chandrasekar Thenappan 
Published: May 2020

e17112 Background: Immune Checkpoint Inhibitors (ICI) are increasingly utilized for genitourinary (GU) malignancies. However, data is lacking on the efficacy of these drugs in “real-world” populations - patients who do not fit the strict clinical trial criteria, but may still benefit from therapy. We performed a retrospective analysis of patients receiving ICI at a single tertiary-care institution, with special attention to clinical trial enrollment, adverse events, progression and survival. Methods: Patients receiving ICI for GU malignancies at Thomas Jefferson University Hospital from January 2017 to January 2019 were identified. Descriptive statistics of treatment and pathologies were performed. Progression-free survival (PFS) was calculated from start of ICI to documentation of progression or last follow-up. PFS and overall survival were assessed using Kaplan Meier log-rank test, stratified by trial enrollment. Results: 111 patients were included: 37 on ICI clinical trial, 70 received ICI “off-trial” and 4 received ICI in both settings. 11 patients (10%) underwent multiple courses of ICI throughout treatment. The number of patients initiating ICI increased annually; by 2018, the number of patients initiated on ICI “off-trial” exceeded those initiating ICI “on-trial” (79% vs 21%). Treated pathology included Urothelial Carcinoma (UC; 42%), Renal Cell Carcinoma (RCC; 28%), and Prostate Adenocarcinoma (PCa; 20%). “Off-trial” ICI was more often administered later in the disease course, compared to a more even distribution of “on-trial” ICI administration. Mean PFS and OS for both cohorts can be seen in Table. Conclusions: As seen in our single-institution referral center, the use of immune checkpoint inhibitors has significantly increased – and is now more commonly used off-trial than on-trial. As their use becomes more common, their efficacy in “off-trial” populations must be further investigated. [Table: see text]
Effect of local therapies on survival in patients with metastatic adrenocortical carcinoma.
Authors: Shetty Impana , Venzon David J. , Mauda-Havakuk Michal , Thomas Bj , Bernstein Donna , Flowers Crystal , Anderson Victoria , Raygada Margarita , Levy Elliot B , Wood Bradford J. , Widemann Brigitte C. , Reilly Karlyne , Del Rivero Jaydira 
Published: May 2020

e17114 Background: Adrenocortical carcinoma (ACC) is a rare cancer with an incidence of 0.7 – 2 cases per million persons per year, and generally has a poor prognosis with a 5-year survival rate of 20-25%. In a previous review of 330 patients with ACC, the median overall survival time of patients with Stage IV ACC was 0.9 years. Currently, complete surgical resection is the only curative treatment for ACC. Cases of recurrent or metastatic ACC are infrequently curable by surgery alone and systemic therapies have limited benefit. A previous study has suggested that local interventions to resect liver metastases improve survival. We hypothesize that local therapies increase survival of patients with metastatic ACC and here we describe the characteristics of various types of regional therapies. Methods: We conducted a retrospective chart review of 26 patients with ACC who were seen at the National Institutes of Health (NIH) between 2002 and 2019 and who are currently alive. These patients had multiple interventions that were performed including surgeries, radiofrequency ablations/embolizations/cryoablations and systemic therapies. Results: The group of patients we studied were 92% female and 8% male. The ages ranged from 23 to 77, with an average age of 57. Out of the 26 patients, 11 (42%) patients had liver metastases, 17 (65%) patients had lung metastases, 4 (15%) patients had retroperitoneal recurrence, and 5 (19%) patients had lymph node involvement. All patients with lung, retroperitoneum, liver, and lymph node metastases underwent surgical intervention. In patients with liver metastases, 73% underwent liver-directed therapies and 91% received systemic therapy. In patients with lung metastases, 59% underwent radiofrequency ablation or cryoablation and 94% had systemic therapy. Among the systemic therapies, 15% of patients received zero lines of treatment, 50% of patients received one line, 12% of patients received two lines, 19% of patients received three lines, and 4% of patients received more than three lines of treatment. Conclusions: The analysis of this cohort indicates that multiple local therapies could increase patient survival. ACC metastases are most common in the liver, followed by the lungs. Patients with recurrent/metastatic ACC should be considered for regional therapies such as metastasectomy/ablation in experienced hands which can increase long-term survival in selected patients.
Intratumoural (IT) evolutionary landscape of high-risk prostate cancer and outcome: The PROGENY (PROstate cancer GENomic heterogeneitY) study of genomic and immune parameters.
Authors: Jayaram Anuradha , Goh Gerald , Kularatne Bihani Yoshana , Waterhouse Jasmin , Shanmugabavan Yaalini , Rowan Andrew , Wong Yien Ning Sophia , Freeman Alex , Akarca Ayse , Herrero Javier , Rosenthal Rachel , McGranahan Nicholas , Hung Michelle , Emberton Mark , Attard Gerhardt , Quezada Sergio A. , Marafioti Teresa , Ahmed Hashim Uddin , Swanton Charles , Linch Mark David 
Published: May 2020

e17500 Background: IT heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease and patient outcomes are uncertain. Methods: This was a prospective, single-arm, translational study using targeted multi-region prostate biopsies to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. A pre-defined exploratory objective was to evaluate the association of ITH, median inflammatory infiltrate (MII), total, clonal and neoantigens, with overall survival (OS) and time-to-next-line of therapy (TTNL). Results: 49 men with elevated prostate-specific antigen (PSA) and multiparametric-magnetic resonance imaging (MRI) detected PC underwent image-guided multiregion transperineal biopsy. 79 tumour regions from 25 patients (pts) with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification. The median follow-up was 60 months (m) with 10 death events. For %ITH, MII, total, clonal and subclonal neoantigens, patients were split by the median. Conclusions: The PROGENY study provides a diagnostic platform suitable for studying tumour ITH and has the potential to identify poor outcome subgroups in PC. Larger sample numbers in prospective trials are warranted to further investigate this hypothesis. [Table: see text]
Prostate cancer outcomes by ESRD status.
Authors: Sarabu Nagaraju , Dong Weichuan , Ray Al , Fernstrum Austin , Ponsky Lee Evan , Koroukian Siran M. 
Published: May 2020

e17513 Background: Persons with end-stage renal disease (ESRD) comprise a vulnerable subgroup of the population. Yet, rarely have studies on cancer disparities accounted for ESRD status. We sought to compare prostate cancer stage at diagnosis, treatment, and outcomes among men with and without ESRD. Methods: Utilizing SEER-Medicare database between years 2000-2016, we retrieved sociodemographic variables, including age (40-54, 55-64, 65-74, and 75+), race (African American vs. all others), marital status (married/partnered vs. all others), residence in a census tract with poverty rate > 20%; cancer stage at diagnosis (local, regional, distant, and unknown); treatment (surgery and radiation therapy); and overall and cancer specific survival (OS and CSS) from the SEER, and ESRD status preceding prostate cancer diagnosis from the Medicare portion of the file. In addition to descriptive analysis, multivariable survival analysis was utilized to evaluate the association of ESRD status with OS and CSS after adjusting for patient covariates. Results: Our study population included 2,922 ESRD and 600,848 non-ESRD men diagnosed with incident prostate cancer during the study period. A disproportionately higher percentage of ESRD patients were in the 40-54 age group compared to non-ESRD (9.7 vs 3.6%). Similarly, the percentage of prostate cancer patients who were African American was 41.5% among ESRD patients, compared with 14.4% in their non-ESRD counterparts. In addition, more ESRD than non-ESRD patients lived in census tracts with poverty rates greater than 20% (31.2% vs. 18.0%). With regard to stage, 10.6% of ESRD patients but only 4.5% of non-ESRD patients were diagnosed with distant-stage disease; and while only 24.8% of ESRD patients underwent surgery, 36.9% of non-ESRD patients did so. The rate of radiation therapy was similar across the two groups. Multivariable survival models showed that, adjusting for patient covariates, ESRD status was associated with unfavorable OS and CSS (adjusted hazard ratio (AHR): 4.00 (95% confidence interval: 3.82, 4.18), and AHR: 1.54 (1.37, 1.73), respectively). Median follow up was 3.35 and 7.13 years between the ESRD and non-ESRD cohorts. Conclusions: ESRD status in prostate cancer patients is associated with marked sociodemographic and economic disparities. Compared to their non-ESRD counterparts, more ESRD patients are diagnosed with advanced-stage disease, are less likely to undergo surgery, and experience shorter overall and cancer-specific survival. Future studies should be directed to gain insight into factors contributing to unfavorable cancer-specific outcomes.
Long-term prospective health related quality of life (HRQoL) outcomes: Impact of active surveillance before treatment of low risk prostate cancer (PCa).
Authors: Jung Nathan , Frankel Jason , Conti Galen , Porter Christopher , Flores John Paul 
Published: May 2020

e17518 Background: The treatment options for low risk PCa are active surveillance (AS), radiation therapy (RT), and radical prostatectomy (RP). HRQoL studies with long term follow up are lacking. We evaluated HRQoL of initial active surveillance vs initial treatment. Methods: The Center for Prostate Disease Research (CPDR) database was used. HRQoL data was collected for 5 years with the Expanded Prostate Cancer Index Composite (EPIC) and the 36-item Medical Outcomes Study Short Form (SF-36). Patients had low risk PCa, age less than 75, and follow up data of at least 1 year. AS was defined as no definitive treatment within 12 months of diagnosis and repeat biopsy or PSA within 18 months of diagnosis. Results: Patient characteristics are located in the table. Baseline HRQoL scores were comparable across treatment groups for all HRQoL domains, except for sexual function and bother, and physical health where RT were worse than RP. Of the 68 patients classified as AS, 4 had brachytherapy, 9 had hormone therapy, 38 had RP, and 17 had XRT as a first treatment after terminating their AS. In the Generalized Estimating Equations (GEE) model, the HRQoL scores were compared. Multivariate analysis was done accounting for baseline differences. Urinary function (p = 0.0017), urinary bother (p = 0.0028), hormone function (p = 0.035), bowel bother (p = 0.0122), sexual function (p < 0.01), sexual bother (p < 0.01), and physical health (p = 0.0457) were significantly different. For urinary function and bother, XRT had the best HRQoL scores at most time points, with AS getting worse over time as patients went on to receive treatment. AS had worse scores with hormone function and sexual function. RP had the best scores for bowel bother over the course of the study, but had the worst initial scores in sexual bother, which got better over time. Hormone bother (p = 0.5574), Bowel function (p = 0.098), mental health (p = 0.7231) were not statistically different between groups. Conclusions: Initially AS results in improved HRQoL. For those patients who undergo treatment after AS, HRQoL is no worse than those who got treatment initially. [Table: see text]
Clinicopathological predictors of bone metastases in prostate cancer patients.
Authors: Portilla Ingreed , Pinto Joseph , Flores Claudio J. , Araujo Jhajaira M , Villalobos Johanna A , Aguilar Alfredo 
Published: May 2020

e17520 Background: To determine if there is association between the clinical-pathological characteristics and the development of bone metastases in patients with prostate cancer treated in Oncosalud during the period 2016-2018. Methods: An observational, analytical, cross-sectional and retrospective study was conducted in 386 men diagnosed with prostate cancer in a Private Clinic in Peru. We presented descriptive and analytic analysis to identify variables associated with bone metastases; in addition, odds ratios were estimated. Results: In reference to the PSA groups, those patients with PSA values higher than 20 ng / ml presented a risk 9.69 times higher to develop bone metastases (95% CI: 5.08-18.45). In regard to Gleason groups, those with a 9-10 score presented a risk of bone metastasis 2.67 times higher than patients with lower Gleason score (95% CI: 1.31-5.45). In regard to the clinical stage, those patients with a T3 stage had a 6.77 higher risk than those with lower clinical stages (95% CI: 3.79-12.09). Conclusions: Clinical-pathological characteristics associated with bone metastasis were identified in patients with prostate cancer, including age, Gleason scale, PSA value and clinical T stage.
A prospective observational study of combinatorial abiraterone (AA) and radical radiotherapy (RT) in node-positive (N+) prostate cancer (PCa).
Authors: Tan Mark Ting Le , Woo Wai Yee , Sim Yen Ling Adelene , Tuan Jeffrey , Tan Terence Wee Kiat , Li Youquan , Khor Li Yan , Yeong Joe Poh Sheng , Tan Chien sheng , Tay Kae-Jack , Lee Lui Shiong , Kanesvaran Ravindran , Chua Melvin Lee Kiang 
Published: May 2020

e17555 Background: The conventional treatment backbone of N+ PCa has been hormonal therapy (HT) alone. Nonetheless, evidence from the STAMPEDE trial suggests that there could be survival benefit with the addition of local RT or AA, and there may be synergy between RT and AA in these advanced patients. We therefore conducted a prospective observational study to evaluate the efficacy of combination AA+HT+RT in patients with N+ PCa. Here, we report the preliminary biochemical response and toxicity data. Methods: Patients with N+M0/N+M1a, biopsy-proven adenocarcinoma of the prostate were enrolled. Patients were staged by 68Ga-PSMA-PET or whole body MRI. Exclusion criteria were i) ECOG ≥2; ii) cardiac event of < 6 mo interval; iii) bone and visceral metastasis. Treatment protocol entailed 18 mo of combination AA (1000 mg plus 5 mg prednisolone once daily) and HT (LHRH agonist/antagonist); RT was delivered to the prostate (78 Gy) +/- pelvis (54 Gy with simultaneous boost of 60-66 Gy to grossly involved lymph nodes in M0 patients). This was matched against a control group that received long-term HT +/- RT (N = 38). Primary endpoint of this analysis was PSA ≤0.1 ng/ml at 6 mo; secondary endpoints were PSA ≤0.1 ng/ml, testosterone ≤0.7 nmol/l at 12 mo, and toxicity outcomes. Germline genetic profiling was performed in all patients. Results: From Feb 2017 to Aug 2019, 18 men were recruited to this study, with a median fu of 15 mo (range 6.0-35.0 mo). Median age was 66.0 y (IQR 62.0-71.0y); median baseline PSA was 18.2 ng/ml (range 3.0-272); 66.7% had GS 8-10 disease; and 22.2% had M1a disease. Combination AA+HT+RT achieved PSA of ≤0.1 ng/ml in 80.0% (N = 12) and 93.3% (N = 14) of patients at 6 mo and 12 mo, respectively, in contrast to 29.4% and 25.0% of patients who were treated with HT+RT and HT alone, respectively. We observed profound castration of 87.5% (N = 14) at 6 mo, and 91.7% (N = 11) at 12 mo. Four and 6 patients experienced acute G2 genitourinary and gastrointestinal toxicities during RT, respectively; 2 patients reported late G2 GU. One patient experienced G2 fatigue and G1 liver enzyme dysfunction, resulting in dose reduction of AA. Genetic testing revealed a patient with BRCA2 frameshift mutation; interestingly, this patient failed to achieve a PSA of ≤0.1 ng/ml at 12 mo. Conclusions: We demonstrate that combinatorial AA+HT and definitive RT is well tolerated, and yield a pronounced early PSA response in N+ PCa. Long-term data will inform if this early efficacy signal leads to improved survival in these patients.
Evaluating biomarkers in metastatic castration-resistant prostate cancer patients treated with enzalutamide: PSA, circulating tumor cell counts, AR-V7 status and radiographic progression.
Authors: Gandhy Shruti U. , Karzai Fatima , Marte Jennifer L. , Bilusic Marijo , McMahon Sheri , Strauss Julius , Couvillon Anna , Williams Monique , Hankin Amy , Steinberg Seth M. , Gill Audrey , Tubbs Alisa , Schonhoft Joseph , Figg William Douglas , Arlen Philip M. , Dahut William L. , Gulley James L. , Madan Ravi Amrit 
Published: May 2020

e17569 Background: Enzalutamideis ahighly effective treatment in metastatic castration resistant prostate cancer (mCRPC). Although Prostate Cancer Working Group (PCWG) guidelines recommend continuing treatment until radiographic/clinical progression (rPD/cPD), many patients discontinue therapy for rising PSA alone. Methods: We conducted an open label, randomized phase 2 trial in mCRPC patients untreated with docetaxel, abiraterone, or enzalutamide, comparing enzalutamide alone or in combination with PROSTVAC, a therapeutic cancer vaccine designed to induce an anti-tumor immune response. The study discontinued accrual after planned interim analysis indicated no difference in progression between the two arms. Patients were followed beyond 1st of 3 confirmed PSA rises until rPD. 49 patients were analyzed for Circulating Tumor Cell (CTC) count and AR-V7 status at 1st PSA rise and at rPD/cPD or last follow up. Results: 57 patients were enrolled with median follow up time of 55.4 mo. 49/57 (86%) patients had rising PSA; median time to 1st PSA rise for all patients was 6.4 mo (95% CI: 3.7-11.0 mo) after starting enzalutamide. 38/57 (67%) patients had progressive disease (majority with rPD; 1/38 (3%) with cPD); median time to progression for all patients was 23.3 mo (95% CI: 16.1-27.8 mo). 5 patients tested positive for AR-V7 within 30 days of rPD. In patients who experienced rPD/cPD, CTCs were detected in 11/24 (46%) samples taken at rPD vs. in only 3/24 (13%) samples taken at rising PSA. CTC counts were higher at rPD compared to samples taken at rising PSA (P = 0.004, Wilcoxon unpaired test). Of the 7 patients still being treated (median time on drug = 4.2 yrs), 2 experienced rising PSA; however none of the patients had detectable CTCs at a median of 30 days from last follow up. Conclusions: These data suggest that a rising PSA may not be a warning of near-term clinically significant disease progression in mCRPC patients treated with enzalutamide, given the 17-month difference between the first rise in PSA and ultimate rPD/cPD seen in this analysis. Further, CTCs and AR-V7 status associate strongly with rPD but not with rising PSA, adding biological rationale to the hypothesis that CTC counts and AR-V7 status are associated with disease progression. Collectively, these data highlight the need to continue to educate patients and providers on PCWG criteria for progression and appropriately-timed utilization of both therapies and diagnostic tests to maximize drug efficacy in mCRPC. Clinical trial information: NCT01867333 .
Outcomes of patients with metastatic castration resistant prostate cancer according to somatic sequencing of domage DNA repair genes.
Authors: Neviere Zoé , Ricou Agathe , Vaur Dominique , Muller Etienne , Krieger Sophie , Boulouard Flavie , Castera Laurent , Leconte Alexandra , Bonnet Isabelle , Moise Laura , Coquan Elodie , Meriaux Emeline , Brachet Pierre-Emmanuel , Licaj Idlir , Lequesne Justine , Joly Florence 
Published: May 2020

e17595 Background: More than 20% of mCRPC present somatic DNA damage repair gene mutation (DDR). If some data are available for germline mutations, there are few studies describing the relation between somatic alterations and response to standard therapies in mCRPC. Methods: To describe outcomes of mCRPC patients treated with standard therapies according to somatic DDR status.A retrospective somatic analysis on a 69-gene panel was conducted among mCRPC patients. Progression-free survival (PFS) of first-line treatment was analyzed according to somatic DDR mutation as primary endpoint. First exposition to taxanes chemotherapy and PFS2 (time to the second event of disease progression) depending on therapeutic sequences (new-generation hormonotherapy [NGHT]/taxanes chemotherapy) were also analyzed. Results: Among 83 patients tested, 33 (40%) had a somatic DDR mutation, including 10 ATM, 5 BRCA2, 4 CHEK2, 3 CDK12, 3 FANCG, 1 BLM, 1 CHEK1, 1 FANCF, 1 FANCI, 1 FANCM, 1 MDC1, 1 MRE11A and 1 PALB2. In first-line treatment, 20 patients received taxanes and 63 NGHT. Median PFS was 9.8 months for mutated patients and 8.4 months for non-mutated patients (p = 0.9). For mutated patients, median PFS was 12.3 months in taxanes group and 9.8 months in NGHT group, (p = 0.74). One BRCA2-mutated patient treated by docetaxel was particularly long responder (PFS = 39.2 months). PFS of first exposition to taxanes was 8.2 months among mutated patients and 5.7 months among non-mutated patients (p = 0.31). Patients with BRCA1/BRCA2/ATM mutations had longer PFS compared to the others patients (10.6 months versus 5.5 months, p = 0.04). Ten patients received the chemotherapy-NGHT sequence (CHS) and 28 the NGHT-chemotherapy sequence (HCS). PFS2 were 16.5 months for mutated patients, whatever the sequence, and 11.7 months among non-mutated patients (p = 0.07). The 3 mutated patients (1 BRCA1, 1 BRCA2, 1 ATM mutation) had long PFS2 in the CHS (49.8 months). PFS2 of mutated patients in HCS was 15.6 months. Conclusions: Mutated mCRPC patients benefit from standard therapies, with long responders to taxanes among patients with BRCA1/2 and ATM mutations.