bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic and imaging biomarkers associated with cabozantinib therapy in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Vaishampayan Ulka N. , Podgorski Izabela , Heilbrun Lance K. , Smith Daryn W. , Lawhorn-Crews Jawana , Dobson Kimberlee , Fontana Joseph A. , Heath Elisabeth I. , Shields Anthony Frank 
Published: February 2017

212 Background: Cabozantinib (C) is a c-met and vascular endothelial growth factor receptor inhibitor that demonstrated remarkable responses on bone scan, but failed to demonstrate overall survival benefit. We studied the dynamics of biomarker changes with imaging and biopsies pre- and post-therapy with C to explore predictors of efficacy. Methods: Eligibility included mCRPC patients (pts) with normal organ function and performance status 0-2. C 60 mg orally was administered daily. Pretherapy and 2 weeks post, 99mTc-labeled bone scans (BS), positron emission tomography with 18F-sodium fluoride (NaF-PET) and 18F-(1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) thymine (FMAU-PET) scans were conducted. The maximum tumor standardized uptake values (SUVmax) were measured for the 5 most active lesions in at least 3 skeletal areas with each tracer. Tumor biopsies were conducted, and bone markers were measured. Results: 20 evaluable pts, 5 African American and 15 Caucasian were enrolled. Median age was 69 years, 11 had received prior chemotherapy. 16 had received prior abiraterone/enzalutamide or both.5 pts had visceral disease. 11 and 6 pts required dose reduction to the 40 mg and 20 mg daily dose respectively.8 patients had a PSA decline, of which 2 had a decline > 50%. Median PFS and OS for all 20 pts were 4.1 and 11.2 months, respectively and 3 pts were on therapy for 8, 10 and 13 months. Circulating tumor cell count changes did not correlate with PFS or OS. The NaF-PET demonstrated a median change in SUVmax of -56% (range -85 to -5%, n = 11) and -41% (range -60 to -25%, n = 9) for the pts who were clinically stable and remained on therapy for ≥ 4 or < 4 cycles, respectively. The FMAU-PET demonstrated a median change in SUVmax of -44% (-60 to -14%) and -42% (-63 to -23%) for these groups. A 50% decrease in serum BSAP was associated with a hazard ratio (HR) for progression of 0.91 (90% confidence interval [CI]: 0.71 – 1.16). For serum NTx and urine NTx, the analogous HR’s were 0.79 (90% CI: 0.61 – 1.01) and 1.07 (90% CI: 0.66 – 1.73), respectively. Conclusions: Early changes in imaging and bone markers were not predictive of clinical benefit with C. Tissue C-met testing is in process and will be correlated with PFS and OS.
Clinical accuracy of detecting recurrent prostate cancer lesions with F-18-Fluoroethylcholine or Ga-68-PSMA-HBED-CC PET/CT.
Authors: Pfister David J. K. P. , Porres Daniel , Heidenreich Axel , Behrendt Florian , Verburg Frederik 
Published: February 2017

218 Background: Ga-68-PSMA-HBED-CC (PSMA) is a novel and promising tracer for highly sensitive PET/CT diagnosis in recurrent prostate cancer (PCA). The aim of the present work was to assess the sensitivity, specificity, positive and negative predictive value (PPV/NPV) per lesion as well as the positive predictive value per patient of PSMA PET/CT in patients with recurrent prostate cancer referred for surgery after a positive PET/CT and to compare this with a collective of patients scanned using the current de-facto PET/CT standard tracer F-18-Fluoroethylcholine (FEC). Methods: In this retrospective study results of PET/CTs and post-surgical histological analysis were compared. 38 patients had FEC and 27 patients had PSMA. We performed a pelvic and/or retroperitoneal lymphadenectomy, if necessary supplemented by resection of locally recurrent lesions in accordance with imaging results. Results: In 30/38 FEC and 22/27 PSMA patients at least one focus of PCA was identified in postsurgical histology, leading to a PPV of 78.9% for FEC and 81.5% for PSMA. In FEC and PSMA patients a total of 378 and 308 lymph nodes and local lesions were removed, respectively. For FEC and PSMA the respective sensitivity was 71.2% and 86.9%, specificity 86.9% and 93.1%, PPV 67.3% and 75.7% and NPV 88.8% and 96.6%. Conclusions: In the present series PSMA PET/CT shows a somewhat better performance than the current de-facto PET/CT standard tracer FEC. Due to the very high NPV of PSMA PET/CT a selective locoregional lymphadenectomy involving only the regions affected on imaging can be discussed.
Very early PSA response to abiraterone in mCRPC patients: A novel prognostic factor to predict overall survival.
Authors: Cavaliere Carla , Caffo Orazio , Ortega Cinzia , D'aniello Carmine , Cecere Sabrina Chiara , Di Napoli Marilena , Della Pepa Chiara , Crispo Anna , Maines Francesca , Ruatta Fiorella , Iovane Gelsomina , Montella Maurizio , Pignata Sandro , Facchini Gaetano 
Published: February 2017

219 Background: In the last years the therapeutic scenario of mCRPC has undergone a radical change with the approval of new drugs. AA is approved for the treatment of mCRPC after failure of ADT in whom chemotherapy (CT) is not yet clinically indicated and for treatment of mCRPC progressed on or after docetaxel (DTX) based chemotherapy. The aim of this study is to evaluate the role of early PSA decline as a marker of response for an early detection of therapy success in mCRPC patients treated with AA. Methods: We retrospectively evaluated 87 pts with mCRPC treated with AA in compassionate use in Napoli, Trento, and Candiolo, Italy. Serum PSA levels were performed after 15, 90 days and then monthly, a time course of serum PSA was obtained. The PSA flare phenomenon was evaluated, according to a confirmation value at least one week apart. The Cox proportional hazards model was used to test the effect of several variables on survival outcomes in multivariate analyses. Results: We have collected data of 87 patients between Sep 2011 and Sep 2014; 75/87 were eligible for correlation analysis. PSA decline was observed in 78.6 % (59/75) of pts. Early PSA response ( ≥ 50% from baseline at 15 days) was found in 56%(42/75) evaluated patients and confirmed in 29 of them after 90 days. In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28,95% CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The median OS was 17,1 months(8,8-25,2). PFS at 1 year and OS reached statistical significance also in the evaluation at 90 days, HR: 0.23 95% CI 0.07-0.77, p = 0.02 and HR: 0.14 95% CI 0.03-0.70, p = 0.02 respectively. Our analysis showed a positive correlation between OS and duration of AA treatment, previous chemotherapy treatment, cumulative dose of docetaxel ≤ 675 mg/m² and previous hormonal therapy duration ( ≥ 2.5 months) for metastatic setting in early responders group. Conclusions: A significant proportion (78.6%) of patients achieved a rapid response in terms of decline of PSA. Early PSA RR ( ≥ 50% at 15 days after start of AA) can provide clinically meaningful information and could be considered a surrogate of longer PFS and OS.
EORTC trial 22991: Results of a phase III study comparing 6 months of androgen suppression and irradiation versus irradiation alone for localized T1b-cT2aN0M0 prostate cancer.
Authors: Bolla Michel , Van Den Bergh Alphonsus C.M. , Carrie Christian , Villà Salvador , Kitsios Petros , Poortmans Philip M. , Sundar Santhanam , van der Steen-Banasik Elzbieta M. , Armstrong John , Bosset Jean-Francois , Herrera Fernanda , Pieters Bradley , Slot Annerie , Bahl Amit , Collette Laurence , Maingon Philippe 
Published: February 2017

22 Background: Up to 30% patients irradiated for intermediate- or high-risk localized prostate cancer experience relapse biochemically within 5 years. We assessed if biochemical disease-free survival (BDFS) is improved by adding 6 months of androgen suppression (AS) – twice 3-month depot LHRH-agonist to primary irradiation (RT) for intermediate or high risk localized T1b-cT2a N0M0 prostate cancer. Methods: 819 patients staged cT1b-c with PSA ≥ 10 ng/ml or Gleason ≥ 7 or cT2a (UICC TNM 1997) N0 M0 with PSA ≤ 50 ng/ml were randomized between RT or RT+ADT. Centers elected one dose of prostate irradiation: 70, 74, or 78 Gy. Irradiation of pelvic nodes was left to the discretion of each institution. The trial aimed to show an increase of +7.5% in 5-year BPFS (HR=0.714) with 80% power. This requires 274 events in intent-to-treat analysis. HRQoL was assessed by EORTC QLQ-C30+PR25 (ClinicalTrials.gov NCT00021450). Results: Patients were 70 y old in median, 88% had WHO PS 0, 74.8% were intermediate risk, and 24.8% high risk. In the RT arm, 407/409 received RT, in the RT+ADT, 403/410 received RT+ AS and 3 RT. Six patients refused treatment. After a median follow-up of 7.2 years, 201 and 118 events for BPFS were observed in the RT and RT+ AS arm. RT+ AS improved BPFS compared to RT (HR=0.53, CI: 0.42-0.67, P<0.001) irrespective of the radiation dose (heterogeneity P>0.1). The 5-y BPFS increased from 69.3% to 82.5%. Clinical PFS was also statistically significantly improved (205 events, HR=0.63, CI: 0.48-0.84, P=0.001, +7.9% at 5 years). Late genitourinary toxicity was reported by 5.9% vs. 3.6% of the patients, on RT+ AS and RT, respectively (p=0.14), whereas 27.0% vs 19.4% reported severe impairment of sexual function (p=0.010). Overall HRQoL did not differ between the groups. Hormonal treatment symptoms, sexual activity and functioning scales are clinically significantly impaired by AS at month 6 and year 1; from year 2 no marked difference is seen. Conclusions: The addition of 6 months of medical castration to primary irradiation improves BPFS and PFS in intermediate- and high-risk localized T1b-cT2a N0M0 prostatic carcinoma with no persistent detriment on HRQoL or sexual function. Clinical trial information: NCT00021450.
Association of single nucleotide polymorphisms (SNPs) in SULT1E1 with response to treatment with abiraterone acetate (AA) in men with metastatic castration refractory prostate cancer (mCRPC).
Authors: Buckley Tyler Howard , Alex Anitha , Farnham James M. , Gill David , Patel Shiven B. , Teerlink Craig , Albright Frederick S. , Stephenson Robert A , Cannon-Albright Lisa A , Agarwal Neeraj 
Published: February 2017

222 Background: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict response to AA in men with mCRPC, serve as prognostic and predictive biomarkers, and guide towards more individualized therapy. Methods: 836 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 61 genes reported to be involved in the androgen metabolic pathway were investigated for association with time to treatment failure (TTF) in 68 Caucasian men with mCRPC undergoing treatment with AA. Cox proportional hazard analysis was employed using Gleason score as a covariate and assessing each SNP under an additive genetic model in which the number of minor alleles contributes increasing risk (or protection). Results: Three SNPs in SULT1E1 were associated with TTF on AA therapy after correcting for multiple testing (p < .00007) while controlling for Gleason Score (Table). Conclusions: SNPs in SULT1E1(estrogen sulfotransferase gene) were significantly associated with TTF on AA therapy, and may serve as predictive markers to treatment with AA. Further validation is being performed in a larger cohort of men with mCRPC. [Table: see text]
Association of single nucleotide polymorphism in four genes and response to androgen deprivation therapy (ADT) in men with advanced hormone sensitive prostate cancer (aHSPC).
Authors: Gill David , Alex Anitha , Farnham James M. , Buckley Tyler Howard , Patel Shiven B. , Agarwal Archana M. , Teerlink Craig , Albright Frederick S. , Stephenson Robert A , Cannon-Albright Lisa A , Agarwal Neeraj 
Published: February 2017

224 Background: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict time to response to androgen deprivation therapy (ADT) in aHSPC, serve as prognostic and predictive biomarkers, and guide towards more individualized upfront therapy. Methods: 706 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 59 genes reported to be involved in the androgen metabolic pathway were investigated for association with time to onset of castration resistance prostate cancer (CRPC) in 171 Caucasian men with aHSPC, i.e. those progressing after definitive treatment (biochemical recurrence alone, or onset of metastatic disease), undergoing treatment with ADT. Cox proportional hazard analysis was employed using Gleason score as a covariate and assessing each SNP under an additive genetic model in which the number of minor alleles contributes increasing risk (or protection). Results: Five SNPs in four genes showed evidence of association with time to CRPC on ADT while controlling for Gleason Score (p < .0002) (Table). Each of these genes had other nearby SNPs with at least nominal (p < 0.05) significance and so, don’t appear to be false positives. Conclusions: Although none of these SNPs exceeded a strict Bonferoni multiple testing correction (p < 0.00007), that threshold is almost certainly conservative as the SNPs and tests are correlated. These results are being validated in a larger cohort and may serve as predictive markers to ADT in this setting. [Table: see text]
Predictive value of bone scan index using computer-aided diagnosis system for bone scans in patients receiving first-line hormone therapy for metastatic hormone-sensitive prostate cancer.
Authors: Miyoshi Yasuhide , Yasui Masato , Yoneyama Shuko , Uemura Koichi , Kawahara Takashi , Hattori Yusuke , Teranishi Jun-ichi , Ohta Jun-ichi , Yokomizo Yumiko , Taguri Masataka , Uemura Hiroji , Yao Masahiro 
Published: February 2017

225 Background: Recently, the CHAARTED and STAMPEDE studies showed a survival benefit for docetaxel when started with androgen deprivation therapy (ADT) in men with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). While GETUG-AFU 15 failed to demonstrate a survival benefit of early chemotherapy. New biomarker for select the candidate for early chemotherapy in mHSPC is warranted. The objective of this study is to evaluate the bone scan index (BSI) using computer-aided diagnosis system for bone scans for predictive factor in patients receiving ADT as first-line hormone therapy for mHSPC. Methods: We identified consecutive 85 mHSPC patients treated with maximum androgen blockade (MAB) as first-line hormone therapy. We analyzed the correlations between progression-free survival (PFS) of MAB and clinicopathological characteristics, including patients’ age, initial PSA levels, Gleason scores, clinical TNM stage, hemoglobin (Hb), lactase dehydrogenase (LDH), c-reactive protein (CRP), and bone scan index (BSI). Statistical analyses were assessed using cox proportional hazards regression models. Results: The median patients’ age was 73 and the median follow-up duration was 11.3months. The median initial PSA value was 270 ng/ml. Median BSI was 2.7 % (range: 0.0-14.6). Clinical or PSA progression occurred in 55 (64.7%) patients. The median time to progression was 12.9 months. In multivariate analysis, three significant risk factors for PFS were identified; patients’ age ( > 73 years old vs ≤ 73; HR 0.53, p = 0.038), initial PSA levels ( > 270 ng/mL vs ≤ 270; HR 0.53, p = 0.038), and BSI ( > 2.7 vs ≤ 2.7; HR 3.0, p < 0.000). We stratified the patients into two cohorts with low risk (0-1 risk factor present) and high risk (2-3 risk factors present). We found a significant difference in PFS among risk groups (median PFS 15.3 months vs 8.5, p < 0.000). Conclusions: Patients’ age, initial PSA levels, and bone scan index were the significant predictive factors for MAB as first-line hormone therapy in patients with mHSPC. These findings might support the decision-making of induction of early chemotherapy for mHSPC.
Association between early PSA increase and clinical outcome in patients treated with enzalutamide for metastatic castration resistant prostate cancer.
Authors: Conteduca Vincenza , Crabb Simon J. , Scarpi Emanuela , Hanna Catherine , Maines Francesca , Joyce Helen , Fabbri Paolo , Derosa Lisa , Massari Francesco , Lolli Cristian , Zarif Sunnya , Jones Robert J. , Caffo Orazio , Elliott Tony , De Giorgi Ugo 
Published: February 2017

231 Background: Prostate specific antigen (PSA) decline by 50% from the baseline to 12 weeks (PSA50w12) is currently used to predict response to treatment and clinical outcome of patients with metastatic castration resistant prostate cancer (mCRPC). However, in clinical practice, PSA changes are monitored monthly in several centers. We evaluated the association between PSA changes at 4 weeks and clinical outcome. Methods: We retrospectively evaluated mCRPC patients treated with enzalutamide after docetaxel. Early PSA increase was defined as a PSA level at 4 weeks ≥ 20% (PSA+20w4) from baseline. Early PSA decline was defined as a PSA response at 4 weeks ≥ 30% (PSA30w4) and ≥ 50% (PSA50w4) from baseline.Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Interval (95% CI) were evaluated by the Kaplan-Meier method and compared with the log-rank test. A multivariate analysis was performed including the following variables: PSA+20w4, PSA30w4, PSA50w4 and PSA50w12, baseline PSA, performance status, LDH values, sites of metastases, age. Results: We assessed 193 patients with median age of 73.1 years (range, 42.8 to 90.7). The median follow-up was 11.7 months. PSA+20w4 was associated with shorter PFS (median PFS 2.0 vs. 6.1 months; HR 4.03; 95% CI 2.62-6.19; p < 0.0001) and shorter OS (median OS 5.9 vs. 15.6 months; HR 3.48; 95% CI 2.12-5.69; p < 0.0001). At multivariate analysis, PSA+20w4 remained predictive of both PFS and OS [HR 4.03 (95% CI 0.2.62-6.19; p < 0.0001) and HR 3.48 (95% CI 2.12-5.69; p < 0.0001), respectively], whereas PSA30w4 and PSA50w4 predicted only PFS [HR 0.37 (95% CI 0.21-0.67; p = 0.0009) and HR 0.34 (95% CI 0.19-0.60; p = 0.0003), respectively]. No cases of PSA flare were reported. Conclusions: An early PSA increase, defined as a PSA level at 4 weeks ≥ 20% (PSA+20w4), could be useful to identify patients unlikely to benefit from enzalutamide. Larger studies are needed to confirm PSA+20W4 as an early and cheap biomarker of primary resistance to enzalutamide.
Cardiovascular events in prostate cancer patients: A comparative analysis of German claims data.
Authors: Ruessel Christoph , Walker Jochen , Jacob Josephine , Gedamke Michael , Vosgerau Sebastian 
Published: February 2017

232 Background: In addition to the radical prostatectomy and radiotherapy, androgen deprivation therapies (ADT) have been established as a therapy option in patients with high-risk localized and metastatic prostate cancer (PCa). ADT was found to be associated with a higher risk for cardiovascular (CV) events. This retrospective claims-based study investigated whether CV event rates differ following initiation of ADT with gonadotropin-releasing hormone (GnRH) agonists or antagonists and PCa patients not treated with ADT. Methods: Analyses were based on claims data from the research database of the Health Risk Institute. Eligibility criteria included a PCa diagnosis between 2009 and 2013 and the initiation of ADT with GnRH agonists or antagonists or no ADT during follow up. Outcomes of interest included a composite endpoint of myocardial infarction (MI) or ischemic stroke (IS) as well as the occurrence of a CV event. The latter included MI, sequelae of cerebrovascular disease, IS, intracerebral hemorrhage, pulmonary embolism, phlebitis/thrombophlebitis, transient cerebral ischemic attacks and occlusion/stenosis of cerebral arteries. Results: ADT patients suffered from more comorbidities, were older, and were more likely to suffer from CV conditions than patients with no ADT during baseline. Patients treated with GnRH agonists and antagonists were comparable in terms of mean age and burden of comorbidities. The raw event rates for MI/IS and for CV events during follow up were higher in ADT patients than in patients without ADT (Table 1). Patients treated with GnRH agonists suffered more often from a CV event during follow-up than patients treated with antagonists. Conclusions: Our results indicate that ADT with GnRH antagonists is associated with fewer CV events in PCa patients than treatment with GnRH agonists. The results confirm findings from a pooled analysis of six phase III randomized controlled trials (Albertsen P. et al: Eur Urol 65 (2014) 565-573.). [Table: see text]
Impact of pelvic lymph node dissection during radical prostatectomy on 30-day post operative complications: Results from a large national database.
Authors: Pavan Nicola , Rai Samarpit , Soodana-Prakash Nachiketh , Balise Raymond R , Mir Maria Carmen , Nahar Bruno , Ritch Chad , Parekh Dipen , Gonzalgo Mark L. 
Published: February 2017

238 Background: Pelvic lymph node dissection (PLND) during radical prostatectomy (RP) is the most effective method for detecting lymph node metastases in patients with prostate cancer. The association between PLND during RP and morbidity, especially thromboembolic adverse events (AEs), remains unclear. We assessed the effect of PLND on 30−day postoperative AEs in patients undergoing RP using the American College of Surgeons’ National Surgical Quality Improvement Program database (NSQIP). Methods: A total of 21,895 men undergoing RP between 2006 and 2013 were classified into two groups according to surgical approach (MIS−RP vs. ORP) and whether PLND was performed. Multivariate logistic regression adjusting for approach and demographic features was performed to assess the impact of PLND for predicting two primary endpoints (overall complications and major complications defined as Clavien−Dindo ≥ 3) and for 17 types of complications. P−values were adjusted to maintain an experiment−wise p < 0.05. Results: MIS−RP and ORP was performed in 17,354 (79.3%) and 4,541 (20.7%) patients, respectively. PLND was performed in 7,579 (43.7%) and 3,597 (79.2%) patients in the MIS−RP and ORP groups, respectively. The overall postoperative complication rate was 8.7% (5.5% for MIS−RP and 21.0% for ORP). PLND was not associated with a higher risk of DVT (OR 0.99; p= 0.98) or PE (OR 1.02; p= 0.91). However, PLND was associated with a higher risk of superficial surgical site infection (OR 1.68; p = 0.013), organ space surgical site infection (OR 1.77; p = 0.02), and perioperative transfusion (OR 1.32; p = 0.002) regardless of surgical approach. PLND was not associated with overall or major AEs on multivariable analysis. ORP was associated with a significantly higher risk of overall (OR 4.64, p < 0.0001) and major (OR 1.6, p = 0.0004) AEs compared to MIS−RP. Conclusions: PLND during RP is associated with a significantly increased risk of certain types of AEs within the 30−day post−operative period. However, there appears to be no significant association between PLND and thromboembolic AEs.