bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of PSA levels and survival outcomes in patients with chemotherapy-naïve, castration-resistant prostate cancer (CRPC) who were treated with androgen receptor signaling axis targeting agent (ARAT): A Japanese cohort study.
Authors: Shimomura Tatsuya , Mori Keiichiro , Yamamoto Toshihiro , Onuma Hajime , Inaba Hiroyuki , Hata Kenichi , Kimura Takahiro , Egawa Shin 
Published: March 2019

315 Background: PSA decline is used as one of the treatment outcome of androgen receptor signaling axis targeting agent (ARAT) in general. However, correlation between PSA decline and survival outcome is not discussed enough. In this study we evaluated how PSA decline influence the survival outcome of ARAT against chemo-naive castration resistant prostate cancer (CRPC). Methods: A total of 200 chemo-naïve CRPC cases treated with ARAT (abiraterone acetate or enzalutamide) were included in this study. We investigated the relationship between PSA response rate and survival outcome (PSA progression free survival (PSA-PFS), Failure free survival (FFS) and overall survival (OS)). Results: PSA response rate correlated with PSA-PFA, TFS and OS significantly (p<0.0001, <0.0001, 0.0009, respectively). And we categorized PSA decline in four groups, group 1: no PSA decline, group 2: 0-50%, group 3: 50%-90%, group 4: over 90%. Median PSA-PFS were 2M (group 1), 4M (group 2), 10M (group 3) and 16M (group 4) (p<0.0001). Median FFS were 3M (group 1), 6M (group 2), 12M (group 3) and 27M (group 4) (p<0.0001). Median OS were 28M (group 1), 36M (group 2), not reached (group 3 and 4) (p=0.0056). In terms of OS, there is a big different between PSA decline <50% and ≥50% in survival curve. And we compare the factors influencing PSA decline ≥50%. PSA and age at initiating ARAT are significant factors predicting PSA decline 50%. Lower PSA and lower age correlated PSA decline ≥50%. Conclusions: PSA decline strongly correlated with PSA-PFS, FFS and OS in this study. It would be a surrogate marker predicting survival outcomes of chemo-naïve CRPC cases treated with ARAT. Further investigation is warranted to confirm these results.
The outcome of loco-regional radiotherapy in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.
Authors: Yildirim Berna , Cem Onal , KOse Fatih , Oymak Ezgi , Sedef Ali Murat , Besen Ali Ayberk , Aksoy Sercan , Guler Ozan Cem , Sumbul Ahmet Taner , Mertsoylu Huseyin , Ozyigit Gokhan 
Published: March 2019

316 Background: To evaluate the potential benefit of curative radiotherapy (RT) to primary tumor in metastatic castration resistant prostate cancer (mCRPC) patients treated with abiraterone. Methods: The clinical parameters of 106 mCRPC patients treated with abiraterone in the either pre- or post-chemotherapy setting were retrospectively evaluated. All patients had PSA progression or radiographic progression suitable for metastasis according to the RECIST guidelines with or without PSA progression. Patients were either oligometastatic (≤5 metastases) at diagnosis or became oligometastatic after systemic treatment were analyzed. Local RT to primary tumor and pelvic lymphatics was delivered in 44 patients (41%), while 62 patients (59%) did not have RT to primary tumor. Results: Median follow-up times for patients overall and for those who survived were 14.2 months (range, 2.3–54.9 months) and median OS for entire cohort was 21.9 months. The median OS was significantly higher in patients treated with local RT to primary tumor compared to patients without local RT (p = 0.04). Local RT to prostate and pelvic lymphatics significantly diminished local recurrence rate ( p = 0.003). In univariate analysis, a decline in PSA levels ≥50% of baseline was significant prognostic factor for both OS and PFS in entire cohort and in patients receiving prostate RT. In multivariate analysis, PSA response ≥50 of baseline obtained ≥3 weeks after abiraterone therapy is the only significant prognostic factor for better OS and PFS. Additionally, local RT to prostate is nearly significant prognosticator for improved OS. Patients treated with primary RT to prostate had significantly less progression under abiraterone and longer abiraterone period compared to patients without local prostate RT. Conclusions: Local prostate RT significantly improves OS and local control but not PFS, in mCRPC treated with abiraterone. Patients treated with primary RT to prostate had significantly less progression under abiraterone and longer abiraterone period compared to patients without local prostate RT.
Regional variations in online education test performance for prostate cancer care.
Authors: Jaganathan Hamsa , Roc Anne , Turell Wendy , George Daniel J. 
Published: March 2019

317 Background: Regional variations in prostate cancer (PC) care in the US remain an issue with inconsistent clinician adherence to quality measures endorsed by national health services. To assess potential disparities in PC care among US-based healthcare providers (HCPs), we compared test performance of clinician participants in PC continuing medical education (CME) activities across 4 US regions. This would enable targeted education with region-specific strategies to effectively manage PC and promote consistent, high-quality care for all patients. Methods: PlatformQ Health developed and executed 3 online CME activities in PC (live broadcast and on-demand). The 1st 2 activities attracted 448 learners July 2016-2017. The 3rd activity attracted 319 learners to date May-Nov 2018. Self-reported US-based practicing HCPs (294) were included in this study. The percent of correct answers to CME tests pre-activity, post-activity, and at 8-weeks were collected and tested for significance (using 1 and 2 factor ANOVA tests) among 4 US regions: Northeast, Midwest, South, and West. CME test questions included case studies, new data on castration-resistant PC, and managing adverse events. Results: No significant difference was observed among the 4 regions in the pretest scores (p = 0.080, α = 0.05). While there was a significant improvement in performance among learners between pretest and posttest (p = 0.001), no significant regional variations were observed. There was also a significant improvement in performance from pretest to the follow-up test, which validates retention of knowledge 8 weeks after the education (p = 0.0016). However, learners from the South region performed significantly better than learners from the other regions (p < 0.05) when it came to 8-week retention. Conclusions: Education can improve knowledge and competence in PC management among US-based HCPs. Future studies, including post- test surveys regarding practice integration, should identify reasons for regional discrepancies in test performances among providers specializing in PC. A broader understanding towards PC care variations can help tailor CME activities specific to regional issues and identify region-specific best practices and learning gaps.
Synergistic effects of the PARP inhibitor olaparib and pharmacological ascorbate in castration-resistant prostate cancer.
Authors: Gordon Nicolas , Schiewer Matthew Joseph , Gallagher Peter , Mandigo Amy C , Dylgjeri Emanuela , McNair Christopher , De Leeuw Renee , Jones Jennifer K , Neupane Neermala Poudel , Shafi Ayesha A , Brand Lucas , Kelly William Kevin , Knudsen Karen E. 
Published: March 2019

326 Background: The administration of ascorbate has proved lethal to and highly selective for a variety of cancer cell types; however, despite an increasingly impressive body of evidence, there has not been a robust effort to translate the observed in vitro and in vivo outcomes to the clinic. This is partially due to the fact that the mechanism by which ascorbate exerts its anti-cancer effect is still under investigation. A simplified model depicts ascorbate as a pro-drug for reactive oxygen species (ROS), which accumulate intracellularly and generate DNA damage. It was therefore hypothesized that poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi), by inhibiting DNA damage repair, would augment the toxicity of ascorbate. Methods: In vitro and in vivo models systems queried for anti-tumor effects of PARP inhibitors and ascorbate. Results: Two distinct castration-resistant prostate cancer (CRPC) models were sensitive to ascorbate at physiologically attainable concentrations. These in vitro models were then subjected to treatment with three different PARP inhibitors (olaparib, niraparib, and talazoparib) alone and in combination with ascorbate. The addition of a sub-lethal dose of ascorbate significantly increased cell death across a range of doses for all three PARP inhibitors. A combination index was generated for olaparib and ascorbate in both CRPC models; the results suggest a strongly synergistic relationship between olaparib and ascorbate. Use of a CRPC in vivo model demonstrated that the combination of olaparib and ascorbate significantly increased tumor doubling time compared to vehicle controls and monotherapy. This in vivo efficacy was even more profound in an additional model using castrated mice to mimic the effect of hormone therapy. Additional mechanistic studies are in progress to further investigate the potential for ascorbate and olaparib combination therapy. Conclusions: Ultimately, these data suggest the combination of ascorbate and PARP inhibitors could be an effective treatment for CRPC.
The impact of intraductal carcinoma of the prostate on the grade group system.
Authors: Kato Masashi , Yamamoto Akiyuki , Ishida Ryo , Kimura Tohru , Sano Tomoyasu , Gotoh Momokazu , Tsuzuki Toyonori 
Published: March 2019

34 Background: The 2014 International Society of Urological Pathology (ISUP) and WHO 2016 classifications proposed a new grade group system for prostate cancer. Intraductal carcinoma of the prostate (IDC-P) is newly recognized on them and is reported to be strongly associated with high-grade and high-volume invasive prostate cancer. Although the presence of the IDC-P influences biochemical failure in radical prostatectomy patients, no data are available regarding the significance of IDC-P in integrating to the classification grade group system. The aim of this study is to enhance the utility of grade group system integrating into the presence of IDC-P. Methods: We retrospectively evaluated 1019 patients with prostate cancer who underwent radical prostatectomy without neoadjuvant or adjuvant therapy at the hospitals that the authors were affiliated with between 2005 and 2013. Data on age, PSA level at diagnosis, clinical T stage (cT), pathological T stage (pT), presence of Gleason pattern 5 (GP5), presence of IDC-P, and surgical margin status were analyzed to predict PSA recurrence after prostatectomy. Results: The median patient age was 67 (range, 45–80) years. The median initial PSA was 6.8 ng/ml (range, 0.4–82 ng/ml). The median follow-up period was 82 (range, 0.7–148) months. IDC-P was detected in 157 patients (15.4%). Among these patients, IDC-P positive rate increased correlated with upgrading. The grade group were as follows: Group 1 without IDC-P, 16.0% (n=163); Group 2 without IDC-P, 46.1% (n=470); Group 3 without IDC-P, 15.7% (n=160); Group 4 without IDC-P, 2.6% (n=27); and Group 5 without IDC-P, 4.1% (n=42); Group 2 with IDC-P, 2.9% (n=29); Group 345 with IDC-P, 12.6% [n=128; Group 3 (n=60); Group 4 (n=13); Group 5 (n=55)] Group 3, 4, and 5 with IDC-P showed a significantly worse prognosis than any other groups without IDC-P and Group 2 with IDC-P (p<.0001). In a multivariate analysis, integrating IDC-P into ISUP Grade, PSA level at diagnosis, and surgical margin status significantly predicted the prognosis (P < .0001). Conclusions: Integrating the presence of IDC-P into the grade group system will improve the accuracy of patients’ outcome prediction.
Keynote 057: Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG).
Authors: Balar Arjun Vasant , Kulkarni Girish S. , Uchio Edward M. , Boormans Joost , Mourey Loic , Krieger Laurence Eliot Miles , Singer Eric A. , Bajorin Dean F. , Kamat Ashish M. , Grivas Petros , Seo Ho Kyung , Nishiyama Hiroyuki , Konety Badrinath R. , Nam Kijoeng , Kapadia Ekta , Frenkl Tara L. , De Wit Ronald 
Published: March 2019

350 Background: The PD-1 inhibitor pembro has durable antitumor activity in pts with metastatic urothelial carcinoma. Upregulation of the PD-1 pathway has been observed in BCG-resistant NMIBC, suggesting pembro may benefit. Efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study; updated results for pts with carcinoma in situ (CIS) with or without papillary tumor (cohort A) are reported. Methods: Pts with histologically confirmed HR, BCG-unresponsive CIS with or without papillary disease, who received adequate BCG therapy and were unable/unwilling to undergo radical cystectomy received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Pts with HR NMIBC or progressive disease during treatment were required to discontinue. Primary end point: complete response rate (CRR); key secondary end points: duration of response and safety. Results: 103 pts (median age 73 years; CIS alone 71.8%; median number of prior BCG instillations 12) have enrolled in cohort A. 3-mo CRR rate was 38.8% (95% CI 29.4%-48.9%) by central assessment. Among 40 pts who achieved CR at 3 mo, 72.5% maintained CR at last follow-up (median 14.0 mo; range 4.0-26.3) and median CR duration has not been reached (range 0+ to 14.1+ mo). 80.2% of pts had a CR duration of ≥6 mo (Kaplan-Meier method). 10 (25.0%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle invasive or metastatic disease. Treatment-related adverse events (AEs) occurred in 65 (63.1%) pts; most frequent were pruritus (10.7%), fatigue (9.7%), diarrhea (8.7%), hypothyroidism (5.8%), and maculopapular rash (5.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.6%) pts; 1 death was considered treatment-related (colitis in patient inadequately treated with steroids). Immune-mediated AEs occurred in 19 (18.4%) pts. Conclusions: Pembro had encouraging activity in pts with HR, BCG-unresponsive CIS with or without papillary tumors and a safety profile consistent with that of previous experience. Updated data using additional follow-up will be presented. Clinical trial. Clinical trial information: NCT02625961.
Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study.
Authors: Tagawa Scott T. , Faltas Bishoy Morris , Lam Elaine Tat , Saylor Philip James , Bardia Aditya , Hajdenberg Julio , Morgans Alicia K. , Lim Emerson A. , Kalinsky Kevin , Simpson Pamela S. , Galsky Matt D. , Goswam Trishna , Wegener William A. , Petrylak Daniel Peter 
Published: March 2019

354 Background: Patients (pts) with mUC who progress after platinum (PLT)-based chemotherapy and immune checkpoint inhibitor (CPI) therapy have poor outcomes and limited treatment options. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate. It consists of a monoclonal antibody targeting Trop-2, an epithelial cell surface antigen overexpressed in UC, conjugated to the active metabolite of irinotecan (SN38). Methods: We performed a phase I/II basket study in pts with advanced solid tumors receiving intravenous SG administered on day 1 and 8 of 21-day cycles, until progression or unacceptable toxicity. CT/MRI scans were obtained at 8-week intervals for response assessment. We evaluated pts with mUC who progressed after ≥1 prior systemic therapy and were treated with SG at the 10 mg/kg dose level. Endpoints included safety, objective response rate (ORR) by RECIST 1.1, clinical benefit rate (CBR; complete response [CR], partial response [PR], or else SD ≥6-mo), and Kaplan-Meier estimated duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: 45 pts (41M/4F; median age 67, range 49-90; ECOG 0/1: 31%/69%) received a median of 2 (range: 1-6) prior treatment lines, including PLT-based chemotherapy (95%) and CPI (38%). 33 had visceral metastases involving liver (n=15), lung (n=27), and other organs (n=5). The ORR was 31% (14/45), with 2 CR and 12 PR. In pts with visceral involvement, the ORR was 27% (9/33). The ORR in CPI-treated pts was 23% (4/17). The median DOR was 12.6 mo (2 pts continuing >2 y), and the CBR was 47% (21/45). Median PFS and OS were 7.3 mo and 18.9 mo, respectively. The AE profile was consistent with prior reports. Grade ≥3 AEs in ≥5% of pts were neutropenia/neutrophil count decreased (38%), anemia (11%), hypophosphatemia (11%), diarrhea (9%), fatigue (9%), and febrile neutropenia (7%). Conclusions: SG demonstrated clinical activity in pts with relapsed/refractory mUC, including CPI-treated pts and pts with visceral disease. A single-arm, open-label, global phase 2 trial is underway to evaluate antitumor activity and safety of SG in advanced UC.(TROPHY-U-01; NCT03547973). Clinical trial information: NCT03547973.
BMS-986205, an indoleamine 2, 3-dioxygenase 1 inhibitor (IDO1i), in combination with nivolumab (nivo): Updated safety across all tumor cohorts and efficacy in advanced bladder cancer (advBC).
Authors: Luke Jason J. , Tabernero Josep , Joshua Anthony , Desai Jayesh , Varga Andrea I. , Moreno Victor , Gomez-Roca Carlos A. , Markman Ben , De Braud Filippo G. , Patel Sandip Pravin , Carlino Matteo S. , Siu Lillian L. , Curigliano Giuseppe , Liu Zhaohui , Ishii Yuko , Wind-Rotolo Megan , Basciano Paul Andrew , Azrilevich Alex , Gelmon Karen A. 
Published: March 2019

358 Background: Nivo (antiPD-1) has shown durable responses and manageable safety (ORR, 19.6%; grade 3‒4 treatment-related AEs [TRAEs], 18%) in advBC (Sharma et al. Lancet Oncol 2017), but prolonging survival in more pts requires additional approaches to overcome tumor evasion mechanisms. IDO1 allows tumor escape through kynurenine (KYN) production, which stimulates regulatory T cells and suppresses effector T-cell proliferation. Anti─PD-1 can upregulate IDO1, supporting the rationale for combining nivo with an IDO1i. BMS-986205 is a selective, potent, once-daily (QD) oral IDO1i that works early in the IDO1 pathway to reduce KYN production. BMS-986205 + nivo showed favorable safety and efficacy in heavily pretreated pts with select solid tumors (Luke et al. SITC 2017; NCT02658890). Updated safety across all tumor cohorts and efficacy in the immuno-oncology (I-O)naive advBC cohort are reported. Methods: Dose-escalation methods in this phase 1/2a, open-label study were previously described; during expansion, pts received BMS-986205 100 or 200 mg QD + nivo 240 mg IV Q2W or 480 mg IV Q4W. Objectives included safety and ORR by RECIST v1.1 (includes unconfirmed responses). Results: As of Mar 2018, 516 pts received BMS-986205 + nivo; 45% had ≥2 prior regimens. TRAEs occurred in 57% of pts (grade 3‒4, 12%), the most common being fatigue (15%) and nausea (12%); 19 pts (4%) discontinued due to TRAEs, and 3 pts ( < 1%) died due to a TRAE (myocarditis, Stevens-Johnson syndrome, and hepatic failure). In all treated pts and within the advBC cohort (n = 30), the frequency and severity of TRAEs and rate of discontinuation due to TRAEs was lower with the 100- vs 200-mg BMS-986205 dose. Among the 27 pts with I-Onaive advBC, with a median duration of follow-up of 24 wk, ORR was 37% (3 CRs, 7 PRs), and the DCR was 56%; ORR in pts with tumor PD-L1 ≥1% (Dako PD-L1 IHC 28-8 pharmDx assay; n = 14) vs < 1% (n = 10) was 50% vs 30%. Conclusions: BMS-986205 + nivo was well tolerated in heavily pretreated pts, and tolerability was improved with the 100-mg BMS-986205 dose. Preliminary evidence of efficacy was observed in advBC, supporting further evaluation of BMS-986205 + nivo. Clinical trial information: NCT02658890.
Role of adjuvant chemotherapy in advanced stage upper urinary tract urothelial carcinoma after radical nephroureterectomy: A competing risk analysis.
Authors: Kang Minyong , Kim Hyung Suk , Joung Jae Young , Shin Yong Ho , Jeong Byong Chang , Kim Tae Jin 
Published: March 2019

367 Background: To determine whether adjuvant chemotherapy (ACH) influences cancer-specific mortality, bladder cancer-specific mortality, and other-cause mortality in patients with locally advanced upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU) through the use of competing risk analysis. Methods: Among 785 patients with UTUC who underwent RNU from 1994 through 2015, we analyzed 338 individuals with locally advanced UTUC (pathologic T3–T4 and/or positive lymph nodes) without distant metastases. Patients were classified into two groups according to receipt of ACH. The study endpoints were UTUC-, bladder cancer- and other cause-specific survivals. The association of potential risk factors with outcome was tested with the Fine and Gray regression model. Results: Overall, 42.6% (n = 144) received ACH following RNU. During a median follow-up duration of 31.5 months, rates of UTUC-, bladder cancer-, and other cause-mortalities were 32.5% (n = 110), 5.0% (n = 17), and 4.1% (n = 14), respectively. Of note, there were no significant differences in overall survival between the observation and ACH groups according to the competing risks of death (UTUC, bladder cancer, and other causes of death). Multivariate analysis showed that only older age at surgery (≥ 65 years; hazard ratio [HR] = 1.71) and positive resection margin (HR = 7.25) remained as poor predictors of UTUC-specific and bladder cancer-specific survival, respectively. Additionally, no factors were identified as independent predictors of other causes of death. Conclusions: In summary, through competing risk analysis, we demonstrated that postoperative chemotherapy did not improve UTUC-specific and bladder-cancer specific survival, nor other cause-specific survival, in patients with locally advanced UTUC who underwent RNU. These results can offer practical information for clinicians regarding treatment decision making in these patients, who are at high risk of death due to competing causes.