bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience of a Brazilian oncological center using abiraterone acetate in metastatic castration-resistant prostate cancer patients.
Authors: Preto Daniel D`Almeida , Zucca Luis Eduardo , Carcano Flavio Mavignier , Zylberberg Ricardo , Neif Joao Antonio Junior , Fruet Filho Carlos Alberto 
Published: February 2018

364 Background: Abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients. In Brazil, despite this medication has been approved by health regulatory agency since 2013, due to the high cost, few public services release to their patients. It's interesting to note that this drug configures the eighth most judicial request medication in the country, as the way brazilian constitution ensures equal treatment for all patients. Methods: We performed a unicenter retrospective cohort study of 45 patients with mCRPC, receiving AA after chemotherapy with docetaxel, in the period from 2014 to 2016. The primary end point was OS. The secondary end points included the epidemiological profile, assessing the type of access to medication (judicial request, health insurance and patient's resource) and PSA response rate. Results: The median OS was 15 months. The mean duration use of AA was 10.87 months (± 6.8). Most patients (75.6%) have filed a lawsuit to get the medication and the average time between the request and the application of AA was bigger in this judicial request group (2.7 vs 1.4 months). Biochemical response was evidenced in 39% of patients. Conclusions: Our unicenter data on post-Docetaxel use of AA improved overall survival in a select group of mCRPC patients, and it is in line with the COU-AA-301 trial. Cost effectiveness evaluations combining with a patient`s protocol should be performed in order to incorporate this medication into the brazilian public health system. Characteristics of the patients. [Table: see text]
Survival after sipuleucel-T (SIP-T) and low-dose ipilimumab (IPI) in men with metastatic, progressive, castrate-resistant prostate cancer (M-CRPC).
Authors: Ku Justine , Wilenius Kirk , Larsen Claire , De Guzman Kyle , Yoshinaga Steven , Turner Jeffrey S. , Lam Richard Y. , Scholz Mark C. 
Published: February 2018

368 Background: Phase III trials evaluating enzalutamide or abiraterone in MP-CRPC prior to docetaxel report a median survival of 35 months. SIP-T functions by stimulating cancer-specific dendritic cells and prolongs survival. IPI showed a borderline survival advantage in a large randomized trial. Thus, there may be potential synergy with SIP-T and IPI (SIPIPI) in combination. Methods: Between April 2013 and April 2014, 9 docetaxel-naive men with MP-CRPC were treated prospectively with SIP-T followed immediately by low-dose IPI 1 mg/kg given for a total of 1 to 3 doses every three weeks. As has been previously published (Immuno Targets and Therapy, March 2017), cancer-specific immunoglobulins (IGS) directed at PA2024 and PAP showed a statistically-significant increase after SIP-T and a further statistically-significant increase, above the level achieved with SIP-T, after IPI. Three patients died from progressive disease after 9, 18, and 20 months. This abstract updates the outcome and survival of the remaining 6 patients. Results: Adverse events from SIPIPI were negligible. For the 9 men, the median age, Gleason score, and number of previous hormonal interventions were 77 years, 8, and 3, respectively. Median baseline PSA and Gleason score were 1.7 and 8, respectively. Eight men had bone metastases and 1 had lymph node metastasis. For the 6 surviving men, median follow-up since SIPIPI is 50.5 months (40-53). Their median PSA as of September 2017 is 5.5 (range: 0.27–18.10). Further treatment since SIPIPI includes abiraterone (4) enzalutamide (5) radium-223 (3) docetaxel (2) cabazitaxel (1) carboplatin (1) pembrolizumab (2) and Olaparib (1). One patient continues with a stable PSA of 0.27 without any further treatment post SIPIPI except SBRT. Conclusions: In this small trial of SIPIPI performed in men with docetaxel-naive MP-CRPC, median survival has now surpassed 4 years and the 6 surviving men still maintain a relatively low median PSA of 5.5. One man continues in durable remission without any further therapy except SBRT administered immediately post IPI.
Impact of 2012 USPSTF prostate cancer screening recommendations on prostate cancer detection and presentation at Kaiser Permanente Northern California (KPNC).
Authors: Presti Joe , Horton Brandon , Alexeeff Stacey , Prausnitz Stephanie , Avins Andy 
Published: February 2018

37 Background: In 2012, the USPSTF gave a “D” grade to PSA-based prostate cancer screening stating “the benefits of PSA-based screening for prostate cancer do not outweigh the harms”. The impact on prostate cancer screening, detection and presentation are unknown. Methods: A retrospective cohort design encompassing the years 2010 to 2015. In screen-eligible, KPNC members (African American men ages 45-69 and all other men ages 50-69), the annual rates of PSA testing, prostate biopsy and the grade and stage of all prostate cancers at presentation were compared between the pre-guideline period, 2010/2011; and the post-guideline period , 2014/2015. Results: The rate of screening declined substantially from the pre-guideline period to the post-guideline period, from a rate of 42.7% of eligible men screened per year during 2010/2011 to a rate of 32.5% of eligible men screened per year during 2014/2015; the relative rate and 95% confidence interval (CI) was 0.762 (0.759-0.765). Comparing the same time periods, the rates of prostate biopsy and overall prostate cancer detection declined even more sharply, with relative rates of 0.391 (95%CI 0.375-0.407) and 0.455 (95%CI 0.436-0.475) respectively. There was a modest increase in the rate of metastatic disease between these two time periods, with a relative rate of 1.29 (95%CI 1.11-1.48). Conclusions: Following the 2012 USPSTF statement, significant declines in PSA testing, prostate biopsy and overall cancer detection rates were seen along with a significant increase in the rate of patients presenting with metastatic disease. [Table: see text]
Retrospective analysis of fatigue in men with metastatic castration-resistant prostate cancer treated with enzalutamide.
Authors: Sridhar Srikala S. , Smith Alan D. , Fallah-Rad Nazanin , Hansen Aaron Richard 
Published: February 2018

374 Background: Enzalutamide (E) improves survival in men with metastatic castration-resistant prostate cancer (mCRPC). Fatigue (F) while taking E is poorly understood and may limit the use of this life-prolonging drug. Methods: All men treated with E for mCRPC at Princess Margaret Cancer Centre from August 2010 and July 2016 were included. Relevant factors collected, include age, ECOG, Charleston Comorbidity Index, disease characteristics, prior therapies, concomitant medications, and details regarding E treatment and response. Univariate (UVA) and multivariate (MVA) analysis were performed using logistic regression. Results: 415 men started E for mCRPC during this period. Median age at diagnosis was 66 years (range 42-94) and median time to castration-resistance (TTCR) was 113 days. Prior therapies included docetaxel (21%) and abiraterone (26%). Bone was the most common site of metastasis (76%) followed by lymph nodes (45%) and visceral (20%). Concurrent corticosteroid use was 18% and PSA response (≥50%) rate was 55%. Median duration on E was 224 days. F on E occurred in 178 patients (43%) and 56 (13%) men required a dose-reduction due to F. 26 men (6%) stopped E due to F (Table). Conclusions: F is an important and common side effect of E in men with mCRPC. Duration of exposure to androgen deprivation, markers of systemic inflammation (such as increased NLR and platelets) and advanced age appear to be associated with E-related F and difficulty administering drug. There was no association between corticosteroid use and E-related F and difficulty administering drug. [Table: see text]
68-Ga prostate-specific membrane antigen-PET as a diagnostic and clinical decision making tool in biochemical recurrences post-radical prostatectomy.
Authors: Tan Janice Ser Huey , Goh Charles Xian-Yang , Li Youquan , Tuan Jeffrey , Chua Eu Tiong , Tan Terence , Wang Michael L. , Lee Lui Shiong , Tay Kae Jack , Lam Winnie Wing Chuen , Chua Melvin 
Published: February 2018

377 Background: In patients with biochemical relapse (BCR) following radical prostatectomy (RadP), risk stratification by clinical indices alone is suboptimal for identifying subgroups likely to benefit from salvage radiotherapy (RT). It is also recommended that combination hormonal therapy (HT)-RT improves rates of salvage and survival, hence the need for a clinical tool to better stratify patients for RT and HT-RT; the latter approach for patients at risk of occult metastases. Herein, we investigated the role of 68Ga-Prostate-specific Membrane Antigen (PSMA)-PET in the detection of regional and distal recurrences, and for clinical decision making in a prospective cohort of patients with BCR post-RadP. Methods: 68Ga-PSMA-PET and CT were performed in a cohort of 50 RadP patients with BCR. Radiological interpretation was independently performed by two assessors, who were blinded to the patient identifiers. PSMA+ lesions were considered as true positives; negative-PSMA in the presence of continued PSA rise defined false negative. Impact on clinical decision making was reviewed by comparison of PSMA-PET and CT findings in the post-RadP PSA 0.5-2.0 ng/ml subgroup. Results: Overall detection rate for 68Ga-PSMA/PET was 74% (37 of 50) in our cohort with a median post-RadP PSA level of 2.19 (IQR = 0.45-4.26). Detection rates were significantly increased at a PSA cut-off > 1.0; 96% (25 of 26) at > 2.0 and 100% (5 of 5) at 1.0-2.0 compared to 67% (4 of 6) at 0.5-1.0, and 23% (3 of 13) at < 0.5 (P < 0.001). In 0.5-2.0 PSA subgroup, 3 regional nodes and 11 distal (6 nodes, 4 bones, 1 lung) lesions were detected. This altered treatment in 5 of the 11 (46%) cases; 3 N+ cases would have been recommended for HT-RT and pelvic nodal RT, while RT would be omitted in 2 patients due to low volume systemic disease. Conclusions: Our findings support the existing data for PSMA-PET as a sensitive diagnostic tool for clinical recurrences post-RadP. Additionally, the detection of small volume nodal and distal lesions at post-RadP PSA levels of < 2.0 ng/ml highlights the potential utility of PSMA-PET for selecting patients to treatment intensification with HT-RT or omission of RT in cases of distal relapse.
Predictors of improved biochemical progression free survival for salvage prostate bed radiotherapy after radical prostatectomy.
Authors: Wright Emma Grace , Challapalli Amarnath , White Paul , Persad Rajendra , Masson Susan , Kirk Hannah , Hilman Serena , Koupparis Anthony , Rowe Edward , Bahl Amit 
Published: February 2018

38 Predictors of improved biochemical progression free survival for salvage prostate bed radiotherapy after radical prostatectomy Background: About a third of patients undergoing radical prostatectomy (RP) develop biochemical recurrence, the rate of which increases to ~50% in high risk patients, with adverse features such as positive margins & seminal vesicle invasion. Postop salvage radiotherapy (SRT) to the prostate bed improves biochemical progression free survival (bPFS). We sought to evaluate the benefit of SRT and predictors of bPFS. Methods: Patients who received SRT from Jan11 to Dec15 were retrospectively analysed. All patients had prostate bed radiotherapy (66Gy/33#/6.5wks). Hormone therapy (HT), when used was for a short duration of 3-6 months. PSA relapse after SRT was defined as serum PSA rising above the posttreatment nadir to a level of ≥0.2 ng/mL or by the initiation of HT after completion of SRT. The bPFS was calculated as the time from start of SRT till date of undetectable PSA, analysed by Kaplan-Meier estimates and log-rank test. Results: Overall, 111 patients were analysed. Median follow-up was 46 (range; 6-80) months. 46% (51/111) patients received HT. The median pre-SRT PSA was 0.4 ng/mL (range, 0.07 to 4.9). The bPFS rate was 60.4% overall, 65%for those with a pre-SRT PSA (ng/mL) level of ≤0.5 (n = 74), 53.6% for those with a PSA of > 0.5 to ≤1.5 (n = 28), 44.4% for those with a PSA of > 1.5 (n = 9); (p = 0.33). There was no significant difference in bPFS rates for pre-SRT PSA of ≤0.2 compared to PSA ≤0.5. Significantly improved bPFS rates were seen with an interval of > 6m from detectable PSA to start of SRT (69% vs. 46.5%: p = 0.026), and a trend towards better bPFS rates when the time interval was > 24m from RP to first detectable PSA (73% vs. 53%: p = 0.08). However, bPFS was similar in the proportion of patients (46%) who had HT compared to those (54%) who did not have HT. Conclusions: We have shown that there was no significant difference in bPFS rates between early (detectable PSA at 0.2) and deferred SRT and our data supports the practice of deferred SRT prior to PSA going above 0.5. Short course of HT was not shown to improve bPFS. The ongoing RADICALS and RAVE trials will further clarify these aspects.
Daily versus weekly prostate cancer image-guided radiotherapy: A phase 3, multicenter, randomized trial.
Authors: de Crevoisier Renaud , Bayar Mohamed-Amine , Pommier Pascal , Muracciole Xavier , Pene Francoise , Dudouet Philippe , Latorzeff Igor , Beckendorf Veronique , Bachaud Jean-Marc , Laplanche Agnes , Supiot Stephane , Chauvet Bruno , N'Guyen TD , Bossi Alberto , Crehange Gilles , Lagrange Jean-Leon 
Published: February 2018

4 Background: The optimal frequency of prostate cancer image-guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT. Methods: This Phase III randomized trial recruited 470 patients with N0 localized prostate cancer, from 21 centers between June 2007 and November 2012. Total IGRT doses ranged from 70 to 80 Gy. Patients were randomly assigned (1:1) to two prostate IGRT control frequency groups: daily or weekly (Days 1, 2, and 3, then weekly). The primary outcome was 5-year recurrence-free survival (RFS). Secondary outcomes included overall survival (OS) and toxicity (CTCAE V.3.0). Post-hoc analyses included biochemical progression-free interval (BPFI), clinical progression-free interval (CPFI) and second cancer-free interval (SCFI). Results: Median follow-up was 4.1 years (Q1 – Q3 = 3.1 – 5.1).There was no statistically-significant difference in RFS between the groups (hazard ratio [HR] = 0.81 [95% CI: 0.52 – 1.25]; p = 0.330). OS was worse in the daily control group versus the weekly control group (HR = 2.12 [95% CI: 1.03 – 4.37]; p = 0.042). Late rectal toxicity (Grade ≥1) incidence was significantly lower in the daily control group (HR = 0.71 [95% CI: 0.53 – 0.96]; p = 0.027). BPFI was better in the daily control group versus the weekly control group (HR = 0.45 [95% CI: 0.25 – 0.80]; p = 0.007). CPFI was better in the daily control group (HR = 0.50 [95% CI: 0.24 – 1.02]; p = 0.057). SCFI was worse in the daily control group versus the weekly control group (HR = 2.21 [95% CI: 1.10 – 4.44]; p = 0.026). Conclusions: Compared to weekly control, daily IGRT control in prostate cancer significantly decreases the risks of recurrence and late rectal toxicity but is associated with an increased risk of second cancer. Clinical trial information: NCT00433706.
Two-year follow-up from the phase 3 KEYNOTE-045 trial of pembrolizumab (pembro) vs investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC).
Authors: Bellmunt Joaquim , De Wit Ronald , Vaughn David J. , Fradet Yves , Lee Jae-Lyun , Fong Lawrence , Vogelzang Nicholas J. , Climent Miguel A. , Petrylak Daniel Peter , Choueiri Toni K. , Necchi Andrea , Gerritsen Winald , Gurney Howard , Quinn David I. , Culine Stephane , Sternberg Cora N. , Nam Kijoeng , Frenkl Tara L. , Perini Rodolfo F. , Bajorin Dean F. 
Published: February 2018

410 Background: Based on interim results from the phase 3 KEYNOTE-045 (NCT02256436) study comparing pembro v investigator’s choice of chemotherapy (chemo), pembro was approved for the treatment of locally advanced or metastatic UC that has progressed during or after a platinum-containing regimen. Updated results after 2 years of follow-up are presented. Methods: Eligible patients (histologically or cytologically confirmed UC, progression after platinum, ECOG PS 0-2, measurable disease per RECIST v1.1, ≤2 lines of systemic therapy) were randomly assigned 1:1 to pembro 200 mg Q3W or investigator’s choice of paclitaxel 175 mg/m2 Q3W, docetaxel 75 mg/m2 Q3W, or vinflunine 320 mg/m2 Q3W. Primary efficacy end points were OS and PFS (RECIST v1.1, blinded central review). ORR (RECIST v1.1, blinded central review) was a secondary end point. Results: As of Oct 26, 2017, among the 542 enrolled patients (pembro, 270; chemo, 272), median follow-up was 27.7 mo. Median OS was significantly longer with pembro v chemo (10.3 v 7.3 mo; HR, 0.70; P < 0.0002). OS benefit with pembro v chemo was seen in all PD-L1 expression subgroups (HR: combined positive score [CPS] < 1, 0.82; CPS ≥1, 0.58; CPS < 10, 0.75; CPS ≥10, 0.56) and was maintained regardless of age, ECOG PS, prior therapy, liver metastases, baseline hemoglobin, time from last chemo, histology, risk factor group, and choice of chemo. PFS was not different between arms (2.1 v 3.3 mo; HR, 0.96; P = 0.32). ORR was higher with pembro v chemo (21.1% v 11.0%). Median duration of response was longer with pembro (not reached [1.6+–30.3+ mo] v 4.4 mo [1.4+–29.9+ mo]), and a greater proportion of responses lasted ≥12 mo (68% v 35%) as assessed by Kaplan-Meier method. Fewer patients with pembro v chemo experienced a treatment-related adverse event of any grade (62.0% v 90.6%) and a grade ≥3 adverse event (16.5% v 50.2%). Conclusions: Results observed over 2 years of follow-up, including OS benefit and superior safety with pembro v chemo, were consistent with the interim analyses that led to the approval of pembro in locally advanced or metastatic UC that progressed during or after platinum-based chemotherapy. Clinical trial information: NCT02256436.
Nivolumab monotherapy in metastatic urothelial carcinoma: Longer-term efficacy and safety results from the CheckMate 032 study.
Authors: Sharma Padmanee , Callahan Margaret K. , Bono Petri , Kim Joseph W. , Spiliopoulou Pavlina , Calvo Emiliano , Pillai Rathi Narayana , Ott Patrick Alexander , De Braud Filippo G. , Morse Michael , Le Dung T , Taylor Matthew H. , Bendell Johanna C. , Jäger Dirk , Chism David D. , Antonia Scott Joseph , Aanur Nivedita , Yang Lingfeng , Rosenberg Jonathan E. 
Published: February 2018

414 Background: Nivolumab has shown efficacy and acceptable safety in 2 open-label, multicenter studies (CheckMate 032 and 275) and is approved for patients (pts) with metastatic urothelial carcinoma (mUC) after ≥1 platinum-based therapy. Here we report longer-term efficacy and safety results for pts with mUC in the phase 1/2 CheckMate 032 study who received nivolumab monotherapy based on > 2 years of follow-up. Methods: Pts with mUC, regardless of programmed death-1 ligand 1 (PD-L1) expression status, received nivolumab 3 mg/kg intravenously every 2 weeks until progression or discontinuation. Tumor PD-L1 membrane expression was assessed with Dako PD-L1 immunohistochemical staining. Primary endpoint: objective response rate (ORR; RECIST 1.1); other endpoints: safety, progression-free survival (PFS), overall survival (OS), and duration of response. Results: Of 78 treated pts (median age 65.5 years; range, 31-85), 52 (66.7%) had received ≥2 prior therapies. At a minimum follow-up of 24 months, 11 pts (14.1%) remain on treatment. Treatment discontinuation was mainly due to disease progression (52 pts [66.7%]). Tumor PD-L1 expression was evaluable in 68 pts (87.2%); 26 (38.2%) pts had ≥1% and 42 (61.8%) had < 1% expression. The table shows overall efficacy. Updated ORR was 25.6%, with 1 additional complete response (CR) achieved for a CR rate of 8%. Median duration of response was not reached. ORR, 1- and 2-year PFS and OS rates were similar between the PD-L1 < 1% and > 1% subsets. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 22 pts (28.2%); most frequent were ↑lipase (6.4%), ↑amylase (5.1%), and maculopapular rash (3.8%). One pt had a grade 5 TRAE (pneumonitis). Conclusions: Nivolumab showed clinically meaningful, durable efficacy with promising long-term survival regardless of PD-L1 expression, and no new toxicity signals with longer-term follow-up in previously treated pts with mUC. Clinical trial information: NCT01928394. [Table: see text]
Correlation of MECA-79-positive high endothelial venule density with clinical outcomes in upper tract urothelial carcinoma patients treated with radical nephroureterectomy.
Authors: Hashimoto Yasuhiro , Yamamoto Hayato , Yoneyama Tohru , Imai Atsushi , Hatakeyama Shingo , Yoneyama Takahiro , Koie Takuya , Ohyama Chikara 
Published: February 2018

417 Background: High endothelial venules (HEVs) are present in lymph nodes and tertiary lymphoid organs. It has been reported that low HEV density is associated with the poor prognosis of several carcinomas. MECA-79 antibody recognizes L-selectin ligand (6-sulfosialyl Lewis X glycan) expressed in HEV. In the present study, we examined whether MECA-79 positive HEV density was associated with clinical outcomes of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Methods: Eighty-eight patients with UTUC who underwent RNU at the Hirosaki University hospital between January 2008 and December 2016 were enrolled. Tissue microarray for MECA-79 was performed, and HEV densities were calculated. HEV density < 1.5/mm2 was defined as HEV (−); HEV density ≥1.5/mm2 was defined as HEV(+). Results: Of 88 patients, 64 (72.7%) were male and 24 (27.2%) were female. The average age was 68.5 years (range, 36–84 years). Fifty-three patients (60.2%) had previously undergone neoadjuvant chemotherapy. The mean observation period was 39.0 months. Twenty-one (23.8%) patients developed recurrence, whereas 16 (33.3%) patients died during follow-up. Five-year cause-specific survival (CSS) rate was 66.1%, and five-year disease-free survival (DFS) rate was 70.7%. In our cohort, 25 (28.4%) patients were found to be HEV(−), whereas 63 (71.5%) were found to be HEV(+). The mean HEV density was 6.3/mm2(0-41.6). The 5-year DFS rates for HEV (+) and HEV (−) patients were 78.0% and 53.9%, respectively, with a statistically significant difference between the groups. (log-rank, p = 0.042). Moreover, the 5-year CSS rates for HEV (+) and HEV (−) patients were 72.5% and 53.4%, respectively, with a statistically significant difference between the groups. (log-rank, p = 0.0036). Conclusions: Low MECA-79-positive HEV density may be associated with poor prognosis of patients with UTUC treated with RNU. Despite the small sample size and preliminary nature of our study, our study provides valuable insights to guide future research.