bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line PD-1/PD-L1 inhibitor monotherapy for advanced renal cell carcinoma (aRCC): A multi-institutional cohort.
Authors: Hatton Whitley , Basu Arnab , Koshkin Vadim S , Kilari Deepak , Jaeger Ellen , Ledet Elisa Marie , Cotogno Patrick , Manogue Charlotte , Lewis Brian E. , Layton Jodi Lyn , Krane Spencer , Sartor Oliver A. , Bilen Mehmet Asim , Desai Arpita , Barata Pedro C. 
Published: May 2020

e17109 Background: Combination regimens containing a programmed cell death protein 1 (PD-1) or a programmed cell death ligand 1 (PD-L1) inhibitor improve the clinical outcomes of previously untreated aRCC. These regimens are clinically active but are associated with adverse events (AEs). One prospective study (KEYNOTE-427) has shown clinical activity of pembrolizumab monotherapy in aRCC. We aimed to describe the utilization and outcomes of single-agent PD-1/PD-L1 in previously untreated aRCC patients (pts). Methods: Consecutive pts treated with front-line PD-1/PD-L1 monotherapy for aRCC were included. Descriptive statistics were used to analyze outcomes including overall response rate (ORR), progression-free survival (PFS) and safety. Results: A total of 28 pts (median age 60; 32% ECOG 2/3; intermediate/poor risk 86%/14%; 35% non-clear cell aRCC) were identified. Common sites of metastases included lung (57%), lymph nodes (39%), bone (21%) and brain (21%). Pts received pembrolizumab (n = 9), avelumab (n = 1) or nivolumab (n = 18) due to pt/physician’s decision (46%), poor performance status (29%) or clinical trial (21%). In evaluable pts (n = 24), the ORR was 33% in ccRCC and 30% in nccRCC. With a median follow up of 13 months (mo), the median PFS was 6.3 mo (CI 95%, 1.5-11.1) and 16 pts progressed on therapy. Frequent AEs (57%) included fatigue (21%), myalgias/arthralgias (11%) and hypothyroidism (7%). No significant grade AEs (G3+) were noted. After progression on PD-1/PD-L1 (n = 16), 39% received a subsequent anti-VEGF (cabozantinib n = 6; sunitinib n = 4; pazopanib n = 1), 42% went to hospice or died and 21% were lost to follow up. Conclusions: First-line single-agent treatment with PD-1/PD-L1 inhibitors showed a favorable safety profile and clinical activity in patients with clear cell and non-clear cell aRCC who were not considered for a combination regimen. [Table: see text]
A phase II study of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma.
Authors: Xu Huayan , Sheng Xinan , Yan Xieqiao , Chi Zhihong , Cui Chuanliang , Si Lu , Tang Bixia , Mao Lili , LIAN BIN , Wang Xuan , Li Siming , Zhou Li , Bai Xue , Guo Jun 
Published: May 2020

e17113 Background: RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC). A phase II clinical study showed that RC48-ADC has a good effect on locally advanced or metastatic urothelial carcinoma with HER2-positive expression that failed standard chemotherapy. In the study, some patients with HER2-postive immunohistochemistry (IHC 2+) but negative FISH test still benefit from the treatment of RC48-ADC.The study was to evaluate the activity and safety of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. Methods: This study is an open-label, single-center, one-arm, non-randomized phase II trial. Eligibility criteria include: histologically confirmed urothelial carcinoma, HER2-negasitive (IHC 0 or 1+), ECOG PS 0-1, treated with ≥1 prior systemic treatment. The patients received RC48-ADC treatment alone (2mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary objectives were activity (ORR) and safety. Progress-free survival, disease control rate and overall survival will also be assessed. Results: As of February 2020, 8 patients were enrolled in the study. The median age was 65 years old. At baseline, most patients (6/8) had visceral metastasis. 6 (75%) patients had received≥2 lines treatment and 4 (50%) patients had prior immune checkpoint inhibitor (CPI) therapy in second line treatment. The objective response rate was 25% (2/8) and the DCR was 75% (6/8). The ORR was 33.3% (2/6) in patients with visceral metastasis and was 50.0% (2/4) in liver metastasis patients. The ORR was 33.3% (2/6) in patients post to ≥ 2 lines of treatment and 25% (1/4) in patients post to immunotherapy. Common treatment-related AEs were AST increase (62.5%), ALT increase (50.0%), nausea (50.0%), leukopenia (37.5%), fatigue (37.5%), vomiting (37.5%), hypoesthesia (25.0%), alopecia (25.0%), and neutropenia (25.0%). Most of these AE were Grade 1 or 2. The AE of Grade 3 was neutropenia (12.5%). The SAE was CPK increased (12.5%). Conclusions: The study showed that RC48-ADC was safety and the ORR was 25% in HER-negative patients with locally advanced or metastatic urothelial carcinoma. Clinical trial information: NCT04073602.
Effect of androgen deprivation therapy combined with nivolumab on the systemic antitumor immune response in castration-sensitive prostate cancer.
Authors: Dallos Matthew , Chaimowitz Matthew , Stein Mark N. , Lim Emerson A. , Hawley Jessica , Tagawa Scott T. , Nanus David M. , Kelly William Kevin , Drake Charles G. 
Published: May 2020

e17503 Background: To date, immunotherapy has limited efficacy in castration-resistant prostate cancer. However, we previously reported that androgen deprivation therapy (ADT) has significant immunomodulatory effects and can induce a complex immune cell infiltrate before castration-resistance develops. Therefore, we designed an ongoing clinical trial to assess the effects of immunotherapy plus ADT in men with recurrent castration-sensitive prostate cancer (CSPC) (NCT03689699). We hypothesized that PD-1 blockade given at the time of castration could induce systemic anti-tumor immune responses with epitope spreading and modulate key circulating cytokine networks. Methods: 15 patients with recurrent CSPC were treated with nivolumab (480mg) every 4 weeks for 8 weeks followed by nivolumab plus degarelix for an additional 16 weeks. Sera was collected at 3 time points: pre-treatment, after nivolumab alone (8 weeks) and at completion of therapy with nivolumab plus degarelix (24weeks). To assess the therapeutic effects on systemic humoral immune responses and to evaluate for induction of epitope spreading, we analyzed treatment-induced serum IgGs against an array of self-antigens over time. We also performed a 44-parameter electrochemiluminescence assay to measure the effects of therapy on innate cytokines and the Th1/Th2 and Th17 pathways. Results: ADT combined with PD-1 blockade led to significant changes in systemic immunity including induction of humoral antigen spread with IgG responses to secondary tumor antigens including PSA, KLK2, K-Ras and modulation of key circulating cytokines. We observed a significant increase in mean levels of IFN-gamma (8.68 +/- 10.74 pg/ml vs 9.53 +/- 7.36 pg/ml), an increase in IL-10 (0.37 +/- 0.29 pg/ml vs 0.66 +/- 0.53 pg/ml) and a decrease in IL-8 (106.7 +/- 275.47 pg/ml vs 25.49 +/- 23.09 pg/ml) when comparing cytokine levels before and after nivolumab plus degarelix respectively. Conclusions: ADT plus nivolumab led to significant changes in systemic immunity and overall appeared to promote a pro-inflammatory state. This immune response also appeared tumor specific with induction of humoral responses against secondary tumor antigens. However we also observed changes in targetable immunosuppresive cytokines like interleukin-8 and are currently testing whether ADT plus combined PD-1 and IL-8 blockade can further promote robust anti-tumor immune responses in prostate cancer. Clinical trial information: NCT03689699 .
A novel liquid biopsy aid for identifying clinically significant prostate cancer in at-risk men: Combining artificial intelligence with flow cytometry-based immunophenotyping.
Authors: Dominguez George , Campisi Anthony J , Roop John , Kumar Amit 
Published: May 2020

e17508 Background: Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status thus warranting advancements in screening and early detection methods. The goal of this study was to design a liquid biopsy assay that uses flow cytometry-based immunophenotyping and artificial intelligence (AI) analysis to detect clinically significant PCa in at-risk men. Methods: Standard multiparametric flow cytometry techniques were used to immunophenotype 27 different MDSC, myeloid, and lymphocyte cell populations found in the peripheral blood of 114 biopsy-confirmed PCa (GS6 = 54; ≥ GS7 = 60) and 58 biopsy-confirmed benign prostatic hyperplasia (BPH) patients. Pattern recognition neural networks (PRNNs), a type of AI, were trained with flow cytometry data from two data sets: patients with confirmed clinically significant PCa (≥ GS7) versus patients with BPH or clinically insignificant PCa (GS6). Predictions were evaluated using the performance of the trained PRNNs on 37 known ≥ GS7 PCa patients and 40 known BPH/ < GS7 PCa patients not used in the PRNN training set (holdout samples). Results: In the holdout data set, 21 out of the 23 patients with clinically significant PCa were identified correctly (Sens = 91.3%, 95%CI = 72.0%-98.9%; PPV = 33.3%, 95%CI = 28.4%-38.7%) while 30 out of the 72 patients at low-risk or no-risk were identified correctly (Spec = 41.7%, 95%CI = 30.2%-53.9%; NPV = 93.8%, 95%CI = 79.5%-98.3%) for an accuracy of 53.7% (95%CI = 43.2%-64.0%). For all patients in this study, our data suggests that approximately 47 out of the 112 patients with BPH or GS6 PCa could have avoided an unnecessary prostate biopsy procedure. Conclusions: Pairing our PRNN with surface biomarker blood-based analyses of various leukocyte populations has enabled the ability to objectively identify patterns indicative for the existence of clinically significant PCa (≥ GS7). In a clinical setting, we believe that this technology, in use with other known clinical factors, would allow for clinicians to have a more informed decision when recommending their patients for a prostate biopsy procedure.
Comorbidity burden in prostate cancer patients by ESRD status.
Authors: Sarabu Nagaraju , Dong Weichuan , Fernstrum Austin , Ray Al , Ponsky Lee Evan , Koroukian Siran M. 
Published: May 2020

e17510 Background: The co-occurrence of cancer and end-stage-renal disease (ESRD) may pose significant challenge in the management of both diseases. Further complicating clinical decisions is our limited understanding of the comorbidity burden (CB), which also affects their outcomes to a considerable extent. The purpose of this study is to characterize the CB in prostate cancer patients, with and without ESRD. Methods: Using 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%, and dual Medicare-Medicaid enrollment status; chronic conditions identified in the year of cancer diagnosis; and ESRD status preceding prostate cancer diagnosis. We limited our study population to cancer patients enrolled in Medicare at the time of cancer diagnosis, and were receiving their care through the fee-for-service system. In this descriptive analysis, we compared the prevalence of these conditions between prostate cancer patients by ESRD status. Results: Our study population included 2,046 ESRD and 302,136 non-ESRD men diagnosed with incident prostate cancer during the study period. Compared to non-ESRD patients, a disproportionately higher percentage of ESRD patients were in the 40-54 and 55-64 age groups compared to non-ESRD (11.0 vs 0.95% and 32.2% vs. 8.51%, respectively). Similarly, the percentage of prostate cancer patients who were African American was 44.1% among ESRD patients, compared with 13.6% in their non-ESRD counterparts. With regard to comorbidities, several conditions were significantly higher in ESRD than non-ESRD patients, including: anemia (65.4% vs. 15.3%), congestive heart failure (31.1% vs. 8.9%), ischemic heart disease (38.9% vs. 25.2%), diabetes (40.7% vs. 17.0%), hypertension (68.0% vs. 42.6%), hypothyroidism (4.6% vs. 2.9%), hyperlipidemia (43.1% vs. 35.1%), and stroke (3.7% vs. 2.5%). Conclusions: Compared to their non-ESRD counterparts, ESRD patients present with high CB, severely compromising their physiologic reserve and tolerance for various cancer treatment modalities, and affecting outcomes. Future studies should compare the prevalence of specific combinations of conditions constituting multimorbidity between ESRD and non-ESRD patients, and identify multimorbidity profiles associated with a lower likelihood to receive standard treatment. Such detailed analysis will be foundational to clinical management and outcome studies.
Colina 111 PET results in a nonmetastatic castration-resistant cancer (nmCRPC) in population that is negative by conventional imaging: True incidence from real-world evidence data.
Authors: Pitzzu Martin , Gennari Luciana , Olguin Norberto , Jankilevich Gustavo 
Published: May 2020

e17522 Background: Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC) is characterized by a rising prostate-specifing antigen (PSA) level, castrate testosterone levels,and no evidence of distant metastases by conventional bone scan and croos-sectional image of the chest,abdomen and pelvis. SPARTAN and PROSPER trials recently demonstrated metastasis free survival in patients with nmCPRC treated with apalutamide with androgen blockade therapy and enzalutamide respectively, Real incidence of nmCPRC in latinoamerican population is unknown. Therefore, patients with negative conventional imaging could be metastatic with PET use, fall the percentage of non metastatic setting PET Colina demonstrated improved sensitivity and specificity used for biochemically recurrent hormone – sensitive patients and staging advanced disease. Colina – PET performance in nmCPRC remain largely unknown and requires evaluation. In this study we examined the incidence of nmCPRC in an Argentinian population by conventional imaging studies and the impact of use of Colina Pet. Methods: Overall 300 patients from public and private insitutions were assessed. Real World Evidence Prostate cancer database were retrospectively screened for records of patients with nmCPRC. Results: Three hundred medical records of consecutive patients with prostate cancer were assessed. All patients were evaluated by multidisciplinary team Localized disease 214 patients and metastatic Prostate Cancer Castration Sensitive 86 patients. With a median a six years of median follow up, 43 patients developed Prostate Cancer Castration Resistant. Six patients showed nmCPRC criteria, in all of them Colina Pet was indicated. After PET colina 5 cases were positives and only one patient were negative. Conclusions: The incidence or nmCPRC is 0,02% in argentine cohort and drop out to 0,003% with PET use. Colina-PET detected loco-regional of M1 disease in nearly all patients with CPRC and no detectable metastasis by conventional imaging. Further epidemiologic with real world evidence data studies with cost-efective evaluations should be launched to put in context the rol of PET in this setting.
Prevalence and genetic features of TMPRSS2-ERG fusion in Chinese patients with prostate cancer.
Authors: He Wei , Sun Fukang , Zhao Juping , Jun Dai , Xu Le , Wang Chenghe , Fang Chen , Huang Xin , Chen Shiqing , Zhao Xiaochen , Bai Yuezong 
Published: May 2020

e17529 Background: Prostate cancer (PCa) is one of the most common malignancies, with rising incidence rate in China. The Cancer Genome Atlas (TCGA) revealed 53% of patients with PCa had ETS family gene fusions. The most frequent fusion type of ETS fusions is TMPRSS2-ERG, which may predicts resistance to taxane and androgen-deprivation therapies. The prevalence of TMPRSS2-ERG fusion in Chinese PCa patients evaluated by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) varied from 7.5% to 78.0%. However, the sample sizes were small. In the present study, we investigated the prevalence and genetic features of TMPRSS2-ERG fusion by next generation sequencing (NGS) in a larger Chinese PCa cohort. Methods: Genomic profiling was performed through NGS from Chinese patients with PCa between January, 2017 and November, 2019. Formalin fixed paraffin-embedded (FFPE) tumor specimens or blood samples from participants were collected for NGS. IHC staining for PD-L1 expression was performed using PD-L1 IHC 22C3 pharmDx assay or Ventana PD-L1 SP263 assay. Data analyses were performed using SPSS and R 3.6.1. Results: A total of 526 Chinese PCa patients were included in this study. The median age was 70 (range, 29-90) years old. We observed 13.1% patients with a positive PD-L1 expression, 3.0% patients with MSI-H, and a median TMB of 4.0 muts/Mb (range: 0-72.9). TMPRSS2 fusions were detected in 47 (8.9%) PCa patients, and 6.8% of patients had TMPRSS2-ERG fusion, which is significantly lower than that of Caucasian patients. The PD-L1 expression pattern and TMB distribution of the TMPRSS2-ERG fusion-positive patients were similar with TMPRSS2-ERG fusion-negative patients, however no fusion-positive patients were identified as MSI-H. Among these 36 TMPRSS2-ERG fusion-positive patients, the most frequently somatic mutations were detected in TP53 (38.9%), AR (11.1%), ATM (11.1%), and PTEN (11.1%). 9 (22.2%) patients harbored somatic mutations in PI3K/ AKT/mTOR pathway that has been previously demonstrated to collaborate with ERG to promote prostate cancer progression. Conclusions: This study revealed the prevalence and genetic features of TMPRSS2-ERG fusion in Chinese PCa patients by NGS in the first time. Our results provide a better understanding of molecular features in Chinese TMPRSS2-ERG fusion-positive PCa patients.
Defining diagnostic criteria for ductal prostate cancer on prostatic MRI.
Authors: Ranasinghe Weranja Kalana Bodhisiri , Troncoso Patricia , Kokorovic Andrea , Elsheshtawi Mohamed A , Zhang Miao , Aparicio Ana , Chapin Brian Francis , Bathala Tharakeswara 
Published: May 2020

e17532 Background: Ductal prostate adenocarcinoma (DAC) is an aggressive histologic variant of prostate cancer (PCa) which often be missed due to their low PSA secretion. Further, a large proportion of DACs have extra-prostatic extension and nodal disease at presentation warranting accurate diagnosis and treatment planning. However studies have yet to differentiate DACs from high grade acinar PCas (PAC) on MRI. Therefore we aimed to develop MRI criteria to identify DACs and assess its diagnostic accuracy. Methods: Patients with histologically proven DAC who had MRIs prior to RP were identified from January 2011 to November 2018. Histology-based MRI diagnostic criteria were developed using RP specimens from nine patients with a pure dominant DAC focus and corresponding MRIs. Sixty-eight DAC patients were compared to a matched cohort of 70 patients with Gleason Score 8 or 9 PAC using the pre-defined MRI criteria. Chi-Squared, T tests, Mann Whitney U tests and sensitivity analyses were performed. Results: The following features of DAC were defined on MRI after correlation with histology: 1) intermediate T2 signal 2)well-circumscribed 3) lobulated tumor and 4) a dark peripheral rim. Majority of DACs were lobulated (79.4% vs 5.7%), with a dark peripheral rim on T2 weighted imaging (55.9% vs 4.3%) and had ≥3 MRI features compared to PAC (73.6% vs 7.2%) (all p < 0.001). Moreover, a higher proportion of pure DACs were lobulated (100% vs 5.7%), had a dark peripheral rim (94.7% vs 4.3%) and ≥3 MRI features (100% vs 7.2%) compared to PAC (all P < 0.001). There were no differences in median T2 contrast enhancement, ADC values or ADC ratios between the groups. Using our criteria MRI demonstrated sensitivity of 73.5%, specificity of 92.9 %, PPV of 90.9%, and NPV of 78.3% in diagnosing DACs if ≥3 features were present. In the diagnosis of pure DACs, MRI demonstrated sensitivity of 100%, specificity of 92.9%, PPV of 95.2%, and NPV of 100%. The area under the curve (AUC) for the diagnosis of all DACs was 0.81 and 0.98 for pure DACs. Conclusions: The presence of ≥3 features (well-circumscribed, lobulations and a dark peripheral rim and intermediate signal on the T2 phase) on prostatic MRI can help differentiate DAC from PAC. While this is the largest cohort of DACs to be analyzed, further studies are needed to validate these findings.
Racial disparities in utilization and effectiveness of first-line therapies in metastatic castrate-resistant prostate cancer.
Authors: Marar Mallika , Mamtani Ronac , Narayan Vivek , Vapiwala Neha , Parikh Ravi Bharat 
Published: May 2020

e17541 Background: Prospective evidence suggests that abiraterone use is associated with improved progression-free survival in African-American (AA) men with metastatic castrate-resistant prostate cancer (mCRPC) compared to white men. It is unclear whether race-based differences in treatment utilization and effectiveness exist for men with newly diagnosed mCRPC treated in real-world clinical practice. Methods: In this retrospective cohort study, we used the Flatiron Health electronic health record-derived de-identified database to identify patients with mCRPC who received first-line (1L) systemic therapy between 2012 and 2018. We used multivariable logistic regression analysis to examine differences in utilization of abiraterone, enzalutamide, and docetaxel between AA and white men. We then used Fine-Gray models with death as a competing risk to assess treatment-specific associations between race and time to next therapy (TTNT) – a proxy for progression-free survival. Finally, we used multivariable Cox proportional hazards analyses to assess for treatment-specific racial disparities in all-cause mortality. All analyses were adjusted for age, Elixhauser comorbidity index, baseline steroid or opioid use (a proxy for disease aggressiveness), performance status, insurance status, and (if significant) an interaction term for race and age. Results: Of 3,808 mCRPC patients in the cohort, 2,165 (68.7%) were white and 404 (10.6%) were AA. At time of metastatic diagnosis, AA men were younger (69 vs. 75, p < 0.001) and more likely to have PSA value greater than 50 (57.9% vs. 42.6%, p < 0.001) compared to white men. Median follow up was 15 months. There were no significant racial differences in 1L utilization, TTNT, or all-cause mortality associated with abiraterone, enzalutamide, or docetaxel use (Table). Conclusions: In this large real-world analysis of men with mCRPC who received 1L therapy, we found no significant treatment-specific differences in utilization, TTNT, or all-cause mortality between AA and white men. Long-term prospective evidence is needed to justify differential treatment selection for AA men with mCRPC. [Table: see text]