bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between Geriatric 8 screening score and treatment selection in patients with prostate cancer.
Authors: Hatakeyama Shingo , Momota Masaki , Hamano Itsuto , Okamoto Teppei , Yamamoto Hayato , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara 
Published: February 2020

206 Background: This study aimed to evaluate the geriatric 8 (G8) screening tool for detecting frailty in patients with prostate cancer. Methods: Between January 2017 and June 2019, we prospectively evaluated the G8 in 540 prostate cancer patients, 444 with localized stage M0 and 96 with metastatic stage M1 disease. The primary endpoint was the comparison of G8 scores in patients treated with robot-assisted radical prostatectomy (RARP), radiotherapy, androgen deprivation therapy alone (ADT-alone) for localized disease, and standard care for the M1 disease. Secondary endpoint included the cutoff estimation of G8 score and the influence of G8 on prognosis. Results: The median age was 75 years. G8 scores ≤14 indicating frailty were seen in 36% of RARP (n = 214), 57% of RT (n = 209), 91% of ADT-alone (n = 21), and 70% of M1 disease (n=96). The median G8 score in M0 patients was significantly higher than that in M1 patients (14.5 vs 12.8, respectively). The median G8 score in patients treated with RARP, RT and ADT-alone was 15, 14, and 12, respectively. The patients with RARP had significantly higher G8 score than that of RT or ADT-alone. The optimal G8 cutoff score for patients with M0 and M1 disease was 13.0 (AUC: 0.681). The overall survival was significantly shorter in patients with G8 <13 than that of ≥13. Conclusions: The G8 score of patients with localized and metastatic PC was significantly different. Frailty was significantly associated with treatment selection and prognosis in patients with PC.
The role of 68Ga-DOTATATE for evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Bilen Mehmet Asim , Akintayo Akinyemi A , Abiodun-Ojo Olayinka A. , Kucuk Omer , Carthon Bradley Curtis , Schuster David M. , Parent Ephraim E 
Published: February 2020

217 Background: Neuroendocrine transformation (NE) of prostate cancer is difficult to diagnose and treat. 68Ga-DOTATATE PET is useful to detect well-differentiated neuroendocrine tumors, but its application in prostate cancer is not well understood. We evaluated DOTATATE PET in patients with mCRPC and suspected or known NE. Methods: DOTATATE PET/CT were performed in 17 patients with mCRPC. Summed SUVmax of up to 5 bone and 5 soft tissue lesions in each patient were correlated with histologic presence of NE and response to standard of care treatment and clinical outcome (NCT03448458). Results: Mean age was 62.3±9.2 years. Median PSA was 39.0 ng/ml. 2/17 patients had biopsy proven NE. 1/17 was found to have squamous cell cancer and therefore excluded from analysis. 2 patients with NE had platinum-based chemotherapy. Of the 14 patients without NE, 7/14 received enzalutamide or abiraterone, and 7/14 received taxane based chemotherapy after DOTATATE PET. On PET, all patients had at least one lesion (median 7 [interquartile range 6-9]) with uptake. 11/16 patients had bone and visceral/nodal lesions, 4/16 had only bone lesions, and 1 had only nodal disease. Summed SUVmax was significantly higher in 2/16 patients with proven NE compared to the 14/16 non-NE patients (99.1± 16.5 ng/ml vs 48.4± 40.6 ng/ml; p=0.04). There was no correlation between summed SUVmax and PSA. Follow-up was available in 15/16 patients. SUVmax was higher in patients who did not respond to treatment, however, the trend was non-significant (69.5 ± 46.6 vs 39.3 ± 29.6; p=0.20). There was no significant association between survival and DOTATATE uptake. 6/16 patients had next generation sequencing. Of these, 1 patient without NE had BRCA2 mutation, and also had the highest summed uptake in this study. Conclusions: DOTATATE uptake is higher in mCRPC patients with NE or with BRCA mutation. Uptake was higher in patients who did not respond to standard of care treatment, though this was a nonsignificant trend, possibly due to small sample size. Larger studies are therefore recommended. Clinical trial information: NCT03448458.
Radium-223 in the treatment of metastatic castrate-resistant prostate cancer: A real-world Irish experience.
Authors: Peters Niamh , Gaffney John , Connolly Emma , Bambury Richard , Power Derek Gerard , Kelly Paul J. , Jamaluddin Muhammad faisal 
Published: February 2020

228 Background: Radium 223 (Ra-223) has been successfully utilised in the trial setting for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods: From September 2016 to March 2019, data from men referred for Ra-223 treatment at our institution was retrospectively collected. We recorded patient characteristics, treatments received and outcomes. Overall Survival (OS) was analysed using the Kaplan-Meier method. Results: 81 men were referred for Ra 223. Complete data was available for 56 men. Median age was 75. 79%(45/56) had over 6 bone metastases and 21%(12/56) had lymph node involvement. The median number of prior systemic treatments for mCRPC was 2. 84%(47/56) of patients were previously treated with Androgen deprivation therapy (ADT); 48%(27/56) Abiraterone, 36%(20/56) Docetaxel, 45%(25/56) Enzalutamide and 9%(5/56) Cabazitaxel. All patients were receiving bone protection agents; 57%(32/56) Zolendronic acid and 43%(24/56) Denosumab. Median ECOG was 1 at the start of treatment and 2 at completion. The median number of treatments received was 4 with 36%(20/56) completing all 6 treatments. The most common toxicity seen was grade1 fatigue occurring in10% (6/56). 17% (10/56) required a blood transfusion during their treatment course. 53%(30/56) required opioid analgesia prior to Ra 223 treatment. 76% of these men (22/30) described improved pain following Rad-223. At a median follow up of 13 months,41%(23/56) were alive. The median OS for the entire group was 7 months. Factors associated with improved OS included ECOG 0-1,fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and no prior chemotherapy use. Median OS for those who had not received prior chemotherapy was significantly better than those who had (9 vs 5 months p=0.04). Conclusions: This real world study demonstrates Ra 223 is a well tolerated palliative treatment amongst Irish men with mCRPC. Good performance status, lower alkaline phosphatase, chemotherapy naivety and a low burden of metastatic disease are factors associated with an improved overall survival.
Impact of nadir PSA level and time to nadir during initial androgen deprivation therapy on prognosis in patients with metastatic castration-resistant prostate cancer.
Authors: Hamano Itsuto , Hatakeyama Shingo , Narita Shintaro , Takahashi Masahiro , Sakurai Toshihiko , Kawamura Sadafumi , Hoshi Senji , Kawaguchi Toshiaki , Ishidoya Shigeto , Shimoda Jiro , Sato Hiromi , Mitsuzuka Koji , Tochigi Tatsuo , Tsuchiya Norihiko , Arai Yoichi , Habuchi Tomonori , Ohyama Chikara 
Published: February 2020

241 Background: It is unknown whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factors in metastatic castration resistant prostate cancer (mCRPC) patients. Methods: We reviewed the Michinoku Urological Cancer Study Group database, including 321 mCRPC patients. Optimal cutoff values for PSA nadir and TTN on survival were calculated with the receiver operating characteristic (ROC) curve. Patients were stratified into unfavorable (higher PSA nadir and/or shorter TTN) and favorable (lower PSA nadir and longer TTN) groups. The inversed probability of treatment weighing (IPTW) adjusted Cox proportional hazard model was performed to evaluate the impact of the unfavorable group on overall survival (OS) after CRPC diagnosis. Results: Median age and follow-up period were 71 years and 35 months, respectively. ROC curve analysis demonstrated cutoffs of PSA nadir >0.64 ng/mL and TTN <7 months. The unfavorable group included 248 patients who had significantly shorter OS after mCRPC and CRPC-free survival. The Cox proportional and IPTW-adjusted multivariate analyses revealed that the unfavorable group had a negative impact on OS in mCRPC patients (hazards ratio [HR] 2.98, P < 0.001). Conclusions: Higher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC.[Table: see text]
Prostate cancer survivorship care plans: What we are failing to tell men after treatment?
Authors: Choi Youngjee , Smith Katherine C. , Shukla Aishwarya , Blackford Amanda L. , Tran Phuoc T. , Peairs Kimberly S. , DeMarco Thomas M. , Choflet Amanda , Farling Kristen , Kelso Madeline , Carducci Michael Anthony , Mayonado Nancy , Tolbert Elliott , Snyder Claire Frances 
Published: February 2020

311 Background: Survivorship care plans (SCPs) present essential information about cancer treatment and follow-up recommendations for cancer survivors. We describe the completeness of prostate cancer SCPs and evaluate guideline concordance of follow-up recommendations. Methods: We analyzed 125 prostate cancer SCPs from an academic and community cancer center, abstracting demographics, cancer/treatment details and follow-up recommendations. Follow-up recommendations were compared to national guidelines. Results: Content provided in >90% of SCPs included cancer TNM stage; PSA at diagnosis; radiation treatment details (98% of men received radiation); and PSA monitoring recommendations. Potential treatment-specific side effects were listed for 69% of men who had surgery, 78% for androgen deprivation therapy (ADT) and 97% for radiation. The presence of post-treatment symptoms were noted in 67% of plans – several ADT-related side effects (e.g., bone thinning, cognitive changes, muscle atrophy) were noted for 0/21 men who completed all ADT. Guidelines recommend an annual digital rectal exam (DRE) with no physical exam otherwise specified. No SCPs specified DRE, but all 68 SCPs at the community site recommended at least annual follow-up visits with urology, radiation oncology, and primary care. Only 5/57 SCPs at the academic site specified follow-up visits (radiation oncology every 6 months). Guidelines recommend PSA testing every 6-12 months (optional 3 months if high risk) for 5 years, then annually; while duration was not specified in any SCPs, if applied to the first 5 years, 91% of SCP recommendations were guideline concordant, 7% suggested oversurveillance, and 2% were incomplete. In men who received ADT, guidelines recommend assessing bone density (by imaging or FRAX score), and goal testosterone level. Of 80 men who completed or had ongoing ADT, 2% were recommended for bone density imaging (0 had FRAX scores) and 19% for testosterone levels. Conclusions: SCP content is more complete for demographic and treatment summary information with gaps in addressing treatment effects and follow-up recommendations beyond PSA testing. These findings highlight the need to improve the quality of information in SCPs. Clinical trial information: NCT03035773.
The intraprostatic immune balance after prostate SBRT in patients.
Authors: Nickols Nicholas George , Ganapathy Ekambaram , Nguyen Christine , Kane Nathanael , Lin Lin , Diaz-Perez Silvia , Nazarian Ramin , Kishan Amar Upadhyaya , King Christopher R. , Kupelian Patrick , Rettig Matthew , Steinberg Michael L. , Cao Minsong , Knudsen Beatrice , Chu Fang-I , Elashoff David , Reiter Robert Evan , Schaue Dörthe 
Published: February 2020

339 Background: Stereotactic Body Radiotherapy (SBRT) delivers high dose per fraction radiotherapy to targets with high precision. Such hypofractionated RT appears to act as an immune adjuvant, altering the tumor infiltrating immune landscape and enriching it for lymphocytes as numerous preclinical investigations would suggest. Based on this hypothesis, hundreds of ongoing trials listed in clinicaltrials.gov currently test the combination of RT (largely SBRT) with various immunotherapies. However, studies directly measuring the representation of infiltrating immune cells after SBRT in patients are few and far between and none exist in the context of prostate cancer. We therefore sought to interrogate the tumor-immune interface after prostate SBRT using fresh tissue in patients. Methods: Fresh prostate tissue from patients (N=10) enrolled in a clinical trial of prostate SBRT (three fractions of 8 Gy directed to the prostate and seminal vesicles) in the neoadjuvant setting two weeks prior to radical prostatectomy was subjected to multicolor flow cytometry and compared to that of Gleason Grade and T stage matched controls who did not undergo neoadjuvant therapy. Results: With a threshold of significance level of 0.05 for unadjusted p-values, using two-sided two-sample t-test, myeloid cells and particularly CD14+/hiCD16+DR+ intermediate monocytes/macrophages were enriched, while lymphocytes, including T cells and CD56+16− NK cells were decreased in SBRT-treated prostates as compared to unirradiated controls. Conclusions: The immune infiltrates in prostates two weeks after SBRT demonstrates a significant lymphoid to myeloid shift consistent with a tumor microenvironment after SBRT that is likely immunosuppressive beyond what can be targeted through the PD-1/L1 or CTLA-4 axis alone. This may have implications for the design of immunotherapy trials, especially in prostate cancer, that test SBRT in combination with immunotherapies.
Lower odds of cardiac events for gonadotropic releasing hormone antagonists versus agonists.
Authors: Cone Eugene Blanchard , Marchese Maya , Reese Stephen , Nabi Junaid , Kilbridge Kerry L. , Trinh Quoc-Dien 
Published: February 2020

34 Background: Gonadotropic releasing hormone (GnRH) agonists and antagonists are first-line for advanced prostate cancer, but may be associated with cardiac toxicity. Observational studies show a relatively lower risk for GnRH antagonists, but a randomized trial found no difference. We compared the reporting of cardiac events for GnRH agonists and antagonists. Methods: We used VigiBase, the World Health Organization global database of case safety reports, which collects data from more than 130 countries to extract drug-adverse event (AE) pairs. Using Medical Dictionary for Regulatory Activities terminology, we identified AEs related to GnRH antagonist (degarelix) or agonist (leuprolide, goserelin, triptorelin, histrelin) therapy for prostate cancer, including myocardial infarction, heart failure, cardiomyopathies, new-onset valvular dysfunction, and other major cardiac events. To explore a possible relationship we used the reporting odds ratio (ROR), a surrogate measure of association using all other reactions as non-cases. A lower bound of a 95% confidence interval of ROR > 1 reflects a disproportionality signal that more AEs are observed than expected. Results: We found 10,504 AEs for GnRH agonists, and 1,606 for GnRH antagonists; 805 (7.7%) were cardiac for agonists, and 102 for antagonists (6.4%). We found no signal for overall cardiac events or any subgrouping for GnRH antagonists, but identified a signal both for overall cardiac events (ROR 1.20, 95% CI 1.12-1.29) and myocardial infarction (1.76, 1.57-1.97) for GnRH agonists. Conclusions: Using validated pharmacovigilance methodology, we found a signal for myocardial infarction for GnRH agonists, but did not detect one for GnRH antagonists. As cardiovascular disease is the most common cause of non-cancer death in prostate cancer patients, this finding is of specific relevance in the current era of novel second-line anti-androgen therapies which may compound toxicity when added to first-line therapy. The relative cardiac toxicity of GnRH agonist therapy compared to GnRH antagonists merits renewed attention.
Rucaparib for recurrent, locally advanced, or metastatic urothelial carcinoma (mUC): Results from ATLAS, a phase II open-label trial.
Authors: Grivas Petros , Loriot Yohann , Feyerabend Susan , Morales-Barrera Rafael , Teo Min Yuen , Vogelzang Nicholas J. , Grande Enrique , Zakharia Yousef , Adra Nabil , Alva Ajjai Shivaram , Necchi Andrea , Gupta Sumati , Josephs Debra Hannah , Rodriguez-Vida Alejo , Srinivas Sandy , Wride Kenton , Thomas Daleen , Dusek Rachel , Nepert Dale L. , Chowdhury Simon 
Published: February 2020

440 Background: ATLAS (NCT03397394) evaluated the efficacy/safety of the PARP inhibitor (PARPi) rucaparib in patients (pts) with previously treated locally advanced/unresectable UC or mUC. Methods: Pts with measurable disease who had progressed after 1–2 prior regimens (ie, platinum-based chemotherapy [PBC] and/or immune checkpoint inhibitors [ICI]) were enrolled regardless of tumor homologous recombination deficiency (HRD) status. Prior PARPi was not allowed. Pts received rucaparib 600 mg PO BID. Baseline tumor tissue or archival tissue ≤6 mo without intervening therapy was required; serial circulating tumor DNA samples were collected. Primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (defined as genomic loss of heterozygosity ≥10%) populations. Key secondary endpoints: progression-free survival (PFS) and safety. Clinical benefit rate (CBR) was defined as complete or partial response or stable disease (SD) lasting ≥16 weeks. Results: As of Oct 7, 2019, 97 pts were enrolled (median age 66 y [range, 39–87]); most were men (n=76, 78.4%) and had ECOG PS 1 (n=65, 67.0%). Sixty-six pts (68.0%) had both prior PBC and ICI. Twenty pts (20.6%) were HRD-positive, 30 (30.9%) were HRD-negative and 47 (48.5%) had unknown HRD status; 4 pts had a deleterious BRCA1/2 alteration. Median time on treatment was 54 d (range, 2–224). There were no confirmed responses. Of 96 evaluable pts, 27 (28.1%) had a best response of SD; CBR was 12.5% and median PFS was 1.8 mo. No relationship was observed between HRD status and clinical activity. Treatment was discontinued by 93 pts (95.9%), mainly due to radiologic or clinical progression (73.1%). Most frequent any grade treatment-emergent (any cause) adverse events were asthenia/fatigue (n=56, 57.7%), nausea (n=40, 41.2%), and anemia (n=34, 35.1%). Conclusions: Single agent rucaparib did not show activity in pts with previously treated advanced UC and enrollment was suspended at the first interim analysis. The safety profile was consistent with that observed in pts with ovarian cancer. Next generation sequencing–based characterization of the genomic landscape of mUC will be presented. Clinical trial information: NCT03397394.
Impact of bladder cancer stage on work impairment and financial toxicity.
Authors: Filippou Pauline , McCabe Sean , McCloskey Hannah , Gessner Kathryn , Hamad Judy , Deal Allison Mary , Smith Angela , Gore John L. 
Published: February 2020

460 Background: Bladder cancer has been linked to financial toxicity with conflicting results regarding the impact of stage. Our objective was to evaluate financial toxicity and work impairment among bladder cancer patients in a large cross-sectional bladder cancer cohort. Methods: We surveyed bladder cancer patients in the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine financial toxicity and work impairment. We measured financial toxicity with the COST measure and Work Productivity and Activity Impairment General Health questionnaires. Patients were also queried regarding demographic, socioeconomic and clinical characteristics with specific attention to insurance status, income, and education. Results: 972 respondents self-identified as patients with bladder cancer. Among respondents, 41% were female and 97% were white. The mean age was 67.6 years, ranging from 29 to 93 years. Respondents were highly educated (67% completed college). Most patients identified as having non-invasive bladder cancer (NMIBC, n=578 [63%]); 30% (n=270) had MIBC, 7% (n=63) had metastatic cancer. Although patients with metastatic cancer had higher average COST scores (worse financial toxicity, Table below), stage was not significantly associated with COST on bivariable (p=0.07) or multivariable analysis (p=0.14). Patients with metastatic disease were more likely to report more work time missed and activity impairment due to health on bivariable analysis; only activity impairment was statistically associated with stage on multivariable analysis (p<0.001) when controlling for age, gender, race, comorbidity, insurance, and education. Conclusions: Bladder cancer stage significantly impacts activity impairment but not percentage work time missed due to health nor financial toxicity. [Table: see text]
Recombinant humanized anti-PD-1 monoclonal antibody toripalimab in patients with metastatic urothelial carcinoma: Preliminary results of an open-label phase II clinical study (POLARIS-03).
Authors: Sheng Xinan , Chen Haige , Hu Bin , Yao Xudong , Liu Ziling , Yao Xin , Guo Hongqian , Hu Yi , Ji Zhigang , Luo Hong , Shi Benkang , Liu Jiyan , WU Jin , Zhou Fang-Jian , He Zhisong , Huang Yiran , Guo Jun 
Published: February 2020

504 Background: Patients with advanced metastatic urothelial carcinoma (UC) who experience disease progression after standard therapy have limited treatment options. Phase I studies of toripalimab in subjects with heavily pretreated metastatic UC have demonstrated an acceptable safety profile and promising clinical activity. Here we report the preliminary safety and efficacy result of toripalimab in a Phase II clinical study in Chinese patients with refractory/metastatic UC (Clinical trial ID: NCT03113266). Methods: Metastatic UC patients received toripalimab, also known as JS001, 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease were assessed for clinical response every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression and tumor mutational burden was measured for correlation with clinical response. Results: From May 2017 to Sep 2019, 151 patients were enrolled from 15 participating centers. Patient enrollment was completed for this study. The median age was 62.0 years with 66.9% of the population being male. By the cut-off date of 21 Oct 2019, common treatment related AEs were mostly Grade 1 or 2, including anemia, blood triglycerides increased, fever, protein urine present and blood glucose increased. Among 128 efficacy evaluable patients, 4 complete responses, 25 partial responses, and 35 stable diseases were observed, for an objective response rate (ORR) of 22.7% and a disease control rate of 50.0%. 62.1% (18/29) of responses were ongoing at the cut-off date. PD-L1 expression results were obtained from 121 efficacy evaluable subjects. PD-L1+ patients (n = 39, 32.2%) had significant better ORR than PD-L1- patients (n = 82), 38.5% versus 13.4%. Conclusions: Toripalimab has demonstrated encouraging clinical activity in chemo-refractory UC patients and a manageable safety profile. Toripalimab elicited a favorable 38.5% ORR in PD-L1+ patients. Nevertheless PD-L1- patients also achieved a 13.4% ORR, including one complete response. Patients will be continuously monitored for additional safety and efficacy readouts (DOR, PFS and OS). Clinical trial information: NCT03113266.