bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sorafenib or placebo in combination with transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEBDOX) for intermediate-stage hepatocellular carcinoma (HCC): Phase II, randomized, double-blind SPACE trial.
Authors: Lencioni Riccardo , Llovet Josep M. , Han Guohong , Tak Won-Young , Yang Jiamei , Leberre Marie-Aude , Niu Woody , Nicholson Kate , Meinhardt Gerold , Bruix Jordi 
Published: February 2017

LBA154^ Background: The global SPACE trial was conducted to evaluate the efficacy and safety of S in combination with TACE with DEBDOX in patients (pts) with intermediate-stage HCC (BCLC B). Methods: Pts were eligible if they had asymptomatic, unresectable, multinodular tumors without vascular invasion (VI) or extrahepatic spread (EHS); Child-Pugh A liver functional status; and ECOG PS 0. Pts were randomized to receive S 400 mg bid or matching P continuously (1 cycle = 4 wks) until progression. All pts received TACE with DEBDOX (150 mg doxorubicin; Biocompatibles UK Ltd) 3-7d after first dose of study drug, and then on d1 (±4d) of months 3, 7, and 13, and q6 months thereafter. The primary endpoint was time to radiologic progression (TTP) by independent review (predefined alpha = 0.15). Secondary endpoints were overall survival (OS), time to VI/EHS, time to untreatable progression (TTUP), and safety. Results: Of 452 pts screened, 307 were randomized to S (n=154) or P (n=153). The HR for TTP was 0.797 (95% CI, 0.588, 1.080; p=0.072). Median TTP (50th percentile) was 169d/166d in the S and P groups, respectively; TTP at the 25th and 75th percentiles (preplanned) was 112/88d and 285/224d in the S and P groups, respectively. There were no unexpected safety findings. Median treatment duration in the S and P groups was 4.8 and 6.3 months, respectively, and median daily dose of study drug was 566 mg and 791 mg, respectively. Conclusions: The study met its primary endpoint of improving TTP when S was added to a regimen of TACE with DEBDOX, compared with TACE with DEBDOX alone. The combination was well tolerated; no new safety findings that would preclude use of the combination were observed. The encouraging efficacy signal requires confirmation with data from ongoing phase III trials evaluating the combination of S plus TACE. [Table: see text]
Prognostic factors for survival in the phase III TROPIC trial.
Authors: Sartor A. Oliver , Oudard Stéphane , Ozguroglu Mustafa , Hansen Steinbjorn , Machiels Jean-Pascal H. , Kocak Ivo , Gravis Gwenaelle , Bodrogi Istvan , MacKenzie Mary J. , Orlandi Francisco Jorquera , Shen Liji , De Bono Johann Sebastian 
Published: February 2017

102 Background: In TROPIC ( NCT00417079 ) 755 men were randomized (378 cabazitaxel/prednisone [CbzP]; 377 mitoxantrone/prednisone [MP]). Treatment arms were well balanced; ECOG PS 0–1 (93% CbzP vs 91% MP), measurable disease (53% vs 54%), baseline pain (46% vs 45%) and ≤ 6 months from last dose of docetaxel (D) to randomization (62% vs 72%). CbzP significantly improved overall survival (OS) in mCRPC pts who progressed on or after D treatment compared with MP (HR 0.70; CI 0.59–0.83; P < 0.0001). We investigated overall prognosis and performed a multivariate analysis of factors implicated in OS from this robust dataset. Methods: A univariate analysis of a variety of factors followed by a multivariate analysis of all factors was conducted. Interactions with treatment arms were explored. Cox proportional hazard models were used to examine the effect of treatment and prognostic factors on OS. Results: In addition to the significant effect of treatment received, the univariate analysis identified ECOG PS and measurable disease at baseline, time from last dose of D to randomization, time of progression after last D treatment and pain scores at baseline as significant prognostic factors for OS. Interactions of each of these factors with the treatment were not statistically distinct, suggesting that CbzP survival benefit was consistent among the subgroups defined by these factors. After adjustments for all prognostic factors, multivariate analysis identified ECOG PS 2, measurable disease, time of last dose of D to randomization (≤ 6 months vs > 6 months) and presence of baseline pain as statistically significant prognostic factors. Following adjustments, the treatment effect on survival (CbzP vs MP) remained statistically significant (Table). Conclusions: ECOG PS, measurable disease at baseline, time from last D dose to randomization, baseline pain and CbzP treatment predicted OS in patients in the TROPIC study in a multivariate analysis. [Table: see text]
A multicenter, randomized phase II study of rilotumumab (R) (AMG 102) or placebo (Pbo) plus mitoxantrone (M) and prednisone (P) in patients (pts) with previously treated castrate-resistant prostate cancer (CRPC).
Authors: Ryan Charles J. , Rosenthal Mark , Ng Siobhan , Alumkal Joshi J. , Picus Joel , Gravis Gwenaelle , Fizazi Karim , Forget Frederic , Machiels Jean-Pascal H. , Zhu Min , Jiang Joe , Dubey Sarita , Loh Elwyn , Gerritsen Winald R. 
Published: February 2017

115 Background: R is an investigational, fully human monoclonal antibody to hepatocyte growth factor (HGF) that prevents HGF binding to the c-Met receptor. We conducted a 3-arm, double-blind, randomized phase 2 study to examine the safety and estimate the efficacy of adding R to MP in CRPC pts. Methods: Eligible pts (≥ 18 years) had progressive CRPC, prior taxane-based chemotherapy, and ECOG PS ≤ 1. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), PSA response, pharmacokinetics (PK), and safety. Pts were randomized 1:1:1 to R (15 mg/kg IV Q3W) + MP (12 mg/m2 IV Q3W, 5 mg BID orally) [Arm A]; R (7.5 mg/kg IV Q3W) + MP [Arm B]; or Pbo + MP [Arm C] for up to 12 cycles. Results: 142 pts (Arms A/B/C: 45/48/49 pts) were enrolled between March 10, 2009 and December 2, 2009. Median age: 67/67/69 yrs; ECOG PS 1: 69/71/61%; progression during prior taxane therapy: 51/54/47%. Most common reason for discontinuation was disease progression (60/58/69%). Efficacy is shown in the table. R + MP showed no statistically significant difference in OS. Adverse events (AE) with ≥ 5% difference in Arms A + B vs C included peripheral edema, 24/8%; nausea, 44/35%; mucosal inflammation, 8/0%; rash, 8/0%; arthralgia, 16/8%; neutropenia, 16/8%. Grade 5 AE: cardiac arrest, pulmonary embolism, septic shock (1 each in Arm B). R showed linear PK with mean (SD) steady state Cmin of 251 (100) and 127 (35) μg/mL and Cmax of 609 (126) and 297 (75) μg/mL in Arms A and B. R did not affect PK of M. Conclusions: R + MP was well tolerated with no unexpected toxicities. R + MP showed no significant improvements in OS, PFS, and PSA response. [Table: see text]
A phase I study of TRC105 (anti-CD105 [endoglin] antibody) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Karzai Fatima H , Apolo Andrea Borghese , Adelberg David E. , Madan Ravi Amrit , Gulley James L. , Arlen Philip M. , Parnes Howard L. , Pierpoint Ann , Kohler David R. , Price Douglas K. , Steinberg Seth M , Trepel Jane B. , Figg William Douglas , Dahut William L. 
Published: February 2017

117 Background: Preclinical and clinical evidence demonstrates an important role for angiogenesis in mCRPC biology. CD105 (endoglin) is a transmembrane protein expressed on the surface of proliferating vascular endothelial cells. The expression of CD105 is required for the formation of new blood vessels. TRC105 is a human/murine chimeric IgG1 kappa monoclonal antibody that binds to human CD105 (endoglin). It inhibits angiogenesis and tumor growth through inhibition of endothelial cell proliferation, antibody-dependent cellular cytotoxicity, and induction of apoptosis. The primary objective is to evaluate safety and identify the maximum tolerable dose (MTD) of TRC105. Secondary objectives include the assessment of TRC105 pharmacokinetics, PSA response rate, evaluation of progression free survival (PFS), overall response rate (ORR) and overall survival (OS). Methods: Patients with an ECOG performance status (PS) ≤ 2, progressive mCRPC and either chemotherapy-naïve or post-docetaxel treatment were eligible. Five cohorts of patients, on escalating dose levels, receive TRC105 intravenously at doses of 1, 3, 10 or 15 mg/kg IV every 2 weeks (cohorts 1, 2, 3, and 5) or 10 mg/kg IV weekly (cohort 4) on a 4 week cycle. Response is assessed with imaging studies every 2 months for the first four months and then every 3 months thereafter. Results: Seventeen patients are enrolled in cohorts 1-5. Median age is 65 (range 48-87), median ECOG PS is 1 (range 0−2), median Gleason score is 8 (range 6−10), median on−study PSA is 147.5 (range 0.1-3373), and median number of prior (non-hormonal) therapies is 3 (range 0−6). Median time on study is 16 weeks (range 8-28 weeks). One patient experienced a dose limiting toxicity (grade 4 vasovagal episode) in cohort 5. PSA declines were seen in 6 patients ranging from 20% to 57% from baseline. Ten out of 12 patients with measurable soft tissue disease achieved stable disease for at least two cycles. Two patients remain on study (in cohort 5). Conclusions: TRC105 is tolerated up to 15 mg/kg every two weeks with early evidence of clinical activity in mCRPC. Accrual is ongoing to evaluate ORR, PFS, and OS in the phase II portion of this study.
Is clinical stage T2c prostate cancer intermediate- or high-risk disease? Results from the SEARCH database.
Authors: Singh Abhay A , Gerber Leah , Freedland Stephen J. , Aronson William J , Terris Martha K. , Presti Joseph C. , Amling Christopher L , Banez Lionel Lloyds ,   Shared Equal-Access Regional Cancer Hospital
Published: February 2017

123 Background: Clinical stage T2c is a nebulous factor in the algorithm for prostate cancer risk stratification. According to D’Amico risk stratification cT2c is high-risk category where NCCN guidelines place this stage in intermediate-risk. As diagnostic work up with the use of MRI continues to escalate clinical staging may become more important. As cT2c represents a possible decision fork in treatment decisions we sought to investigate which risk group the clinical behavior of cT2c tumors more closely resembles. Methods: We retrospectively analyzed data from 1089 men who underwent radical prostatectomy (RP) from 1988 to 2009 who did not have low-risk CaP from the SEARCH database. We compared time to BCR between men with cT2c disease, those with intermediate-risk (PSA 10-20 ng/ml or Gleason sum (GS) =7), and those with high-risk (PSA>20 ng/ml, GS 8-10, cT3) using Cox regression models adjusting for age, race, year of RP, center, and percent cores positive. We also compared predictive accuracy of two Cox models wherein cT2c was considered either intermediate- or high-risk by calculating concordance index c. Results: A total of 68 men (3.4%) had cT2c tumors. After a median follow-up of 47.5 months, there was no difference in BCR risk between men with intermediate-risk CaP and those with cT2c tumors (HR=0.90; p=0.60). In contrast, there was a trend for men with high-risk CaP to have nearly 50% increased BCR risk compared to men with cT2c tumors (HR=1.50; 95% CI=0.97-2.30; p=0.07) which did not reach statistical significance. Concordance index c was higher in the Cox model wherein cT2c tumors were considered intermediate-risk (c=0.6147) as opposed to high-risk (c=0.6106). Conclusions: BCR risk for patients with clinical stage T2c was more comparable to men who had intermediate-risk CaP than men with high-risk. In addition, a model which incorporates cT2c disease as intermediate-risk has better predictive accuracy. These findings suggest men with cT2c disease should be offered treatment options for men with intermediate-risk CaP. As clinical staging more routinely incorporates MRI there is the potential to better identify bilateral organ-confined CaP and further establish risk classification.
Effect of lenalidomide (LEN) on biochemical responses and clinical benefit (CB) as a single agent in chemotherapy-naive castration-resistant prostate cancer (CRPC).
Authors: Nabhan Chadi , Patel Anand , Villines Dana , Tolzien Kathy , Kelby Susan K. , Lestingi Timothy M. 
Published: February 2017

128 Background: LEN has anti-angiogenesis and immunomodulatory properties making it ideal to investigate in CRPC. We report on a phase II study investigating LEN in chemotherapy-naïve CRPC patients (pts) Methods: Eligible pts received LEN at 25 mg daily on days 1 – 21 every 28-days until progression. Daily aspirin or coumadin were required. Responses were assessed every 2 cycles. Toxicity was assessed every cycle. Primary end point: The CB of LEN [Sum of complete response (CR), partial response (PR) and stable disease (SD)]. Secondary end points: Toxicity, time to radiographic and PSA progression (TTP and TTP-PSA), time to next treatment (TTNT), overall survival (OS), and LEN’s impact on quality of life (QOL). Results: 31 pts were enrolled; 27 response-evaluable (1 withdrew consent, 3 off per choice after adverse events). Median age is 74 (range 58-89) with 24 (77%) having Gleason ≥ 7 disease. Median PSA is 66 (2.1-918.6). Six pts (19%) had liver/lung involvement. Fourteen pts (51%) showed biochemical response with 4 (15%) having >50% PSA drop. TTP-PSA is 4 months (2-11). No radiographic responses seen but 17 pts had SD for a median of 4 months (2-16) (CB=55%). Median number of LEN cycles was 3 (2-15). With a median follow-up of 18 months (5-38), 17 patients (55%) remain alive; median OS of 18 months. Grade 3/4 hematologic toxicities were most common (neutropenia 41%, leukopenia 12%, anemia 9%, thrombocytopenia 9%). Other grade 3/4 toxicities: venothromboembolism, atrial fibrillation, and dehydration (6% each). Serious adverse events (SAEs) were witnessed in 10 pts (32%) with only 1 (3%, rash) definitely related to LEN. Others were not related or possibly related. Of 27 pts, 7 (26%) had a dose reduction and 2 (7%) required two dose reductions. Dose reductions occurred after cycle 3. QOL scales suggested no adverse impact. Median TTNT is 2 months (9 pts received chemotherapy, 10 pts went onto studies, 3 pts received hormonal therapies, 4 pts received radiation, 3 pts had no therapy yet, and 2 pts remain on LEN). Conclusions: LEN is active as monotherapy in CRPC. Biochemical responses are witnessed and clinical benefit is observed. Myelosuppression is the most common toxicity.
High-risk prostate cancer treated with I-125 brachytherapy.
Authors: Stockham Abigail Lauren , Reddy Chandana A. , Stephans Kevin L. , Ciezki Jay P. , Tendulkar Rahul D. 
Published: February 2017

134 Background: High-risk prostate cancer (HRPC) is commonly defined as Gleason score (GS) ≥ 8, PSA ≥ 20 ng/ml, and/or T3-T4 disease, or having a combination of two intermediate risk factors. Multimodality therapy is commonly utilized for HRPC due to concerns of extra-prostatic extension or seminal vesicle invasion. The purpose of this study was to examine the outcomes of HRPC patients treated with wide brachytherapy implant alone. Methods: From our IRB-approved registry, we performed a retrospective review of all patients with HRPC and no radiographic evidence of metastatic disease who were treated with I-125 prostate brachytherapy at Cleveland Clinic. Patients who received supplemental external beam radiation were excluded. Characteristics analyzed on univariate analysis included initial PSA, GS, clinical stage, use of androgen deprivation (AD), dose to 90% of the prostate (D90), and volume of the gland receiving 100% of the prescribed dose (V100) of 144 Gy. Endpoints included biochemical relapse free survival (bRFS) defined by nadir PSA + 2 ng/ml, and distant metastases. Results: From 7/1997- 6/2011, 389 patients with HRPC were treated with I-125 prostate brachytherapy. Median age was 70 years. Patients with GS 8-10 accounted for 40% of cases, 72% were clinical stage T1c, and the median initial PSA was 11.3 ng/ml. Concurrent AD was utilized in 67% of patients and the median D90 was 144.8 Gy (range 75.7 – 248.33 Gy). At a median follow-up of 27 months, the 5-year bRFS was 75.7% and the 5-year distant metastases-free survival was 93.1%. Nine patients died of prostate cancer (crude rate 2.3%). No clinical or treatment factors were identified that correlated with the development of biochemical failure, including the use of AD (p = 0.19, HR 0.612). Conclusions: Brachytherapy for patients with HRPC yields favorable outcomes at early follow up time. Longer follow-up and prospective studies are needed for further analysis.
Role of 5-alpha-reductase inhibitors in active surveillance of patients with low-risk prostate cancer.
Authors: Chiang Andrew Szehsun , Loblaw D. Andrew , Jethava Vibhuti , Sethukavalan Perakaa , Zhang Liying , Vesprini Danny , Mamedov Alexandre , Nam Robert , Klotz Laurence 
Published: February 2017

14 Background: Active surveillance (AS) is a recognized management option for low-risk prostate cancer. Many institutions use serial PSA values to determine when to reclassify patients into higher risk categories. The impact of 5-alpha-reductase inhibitors (5-ARIs) in this setting has not been well studied. The purpose of this retrospective review was to compare PSA doubling time prior to the initiation of a 5-ARI (pre-5-ARI) to that after the PSA nadir (post-nadir) has been reached. Methods: Between 1996 and 2010, a total of 100 patients with a history of 5-ARI use were captured from our AS database. Of these, twenty-nine had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir doubling times. The majority had stage T1c disease (89.7%) and Gleason scores of six or lower (93.1%). The average PSA at presentation was 6.93 µg/L. More patients were prescribed dutasteride (79.3%) than finasteride (20.7%). PSA doubling time was calculated using the general linear mixed-model method. Statistical analysis was performed using the non-parametric sign test. Results: Median follow-up was 69.5 months (mo). For the twenty-nine patients analyzed, the median pre-5-ARI PSA doubling time was 55.8 mo (6-556.8 mo), while that for the post-nadir values was 25.2 mo (6-231 mo) (p=0.0081). Six patients were ultimately reclassified after an average of 67.7 mo (59-95 mo), due to progression in either PSA doubling time (n=2) or Gleason score (n=4). The median pre-5-ARI and post-nadir doubling times for this group were 48.2 mo (32.4-91.1 mo) and 23.3 mo (6-44.3 mo), respectively. Five of the patients underwent radical prostatectomy, while one underwent radiotherapy with androgen deprivation. Of the six patients, one had biochemical failure after an average post-treatment follow-up of 21.3 mo (0-52 mo). Conclusions: In AS for low-risk prostate cancer, it was found that 5-ARIs significantly decreased PSA doubling time. This effect may be related to preferential suppression of benign prostatic tissue, thereby providing a more accurate depiction of the true cancer-related doubling time. If validated with a larger cohort, 5-ARIs may enhance the utility of PSA doubling time as a biomarker of disease progression in AS.
Patterns of referral for adjuvant radiotherapy after radical prostatectomy in men with prostate cancer: A population-based analysis.
Authors: Quon Harvey , Suderman Derek , Guilbert Kimi , Lambert Pascal 
Published: February 2017

140 Background: Randomized trials have shown improved biochemical disease free survival after adjuvant radiotherapy (ART) in patients with pT3 or margin positive disease after radical prostatectomy for prostate cancer. This study examines the rates of referral to a radiation oncologist for patients with high risk pathologic features after prostatectomy. Also, the impact of the presentation of these randomized trials will be examined. Methods: All men diagnosed in the province of Manitoba with prostate adenocarcinoma between 2003 and 2008 who underwent radical prostatectomy were identified through a central cancer registry database. Manual chart review was performed and detailed demographic and clinico-pathologic data were analyzed to determine their influence on referral to a radiation oncologist within 6 months of surgery. Analysis of referral rates before and after the presentation of 2 randomized trials were also examined. Results: A total of 1080 patient records of men undergoing prostatectomy for prostate cancer were reviewed. Of these, 546 (50.6%) men had at least one high risk pathologic feature. This includes pT2 margin positive disease in 298/546 (54.6%), pT3a in 154/546 (28.2%), and pT3b in 94/546 (17.2%). Multivariable logistic regression was performed adjusting for age, distance from cancer centre, Gleason score, T stage, perineural invasion, and margin status. Gleason score 8-10 (p<0.0001), higher pathologic T stage (p<0.0001), and farther distance (p=0.0028) were associated with referral for ART. Age and margin status were not significantly associated. Men with pT3a (odds ratio 3.35) and pT3b disease (odds ratio 5.32) were more likely to be referred than pT2 margin positive disease (p<0.0001). There were 78/546 (14.3%) patients with a high risk factor who were referred for ART within 6 months of surgery. The rates of referral were not significantly different before and after the presentation of randomized trials (p=0.60). Conclusions: Men with higher pathologic stage (pT3) and grade (Gleason 8-10) are more likely to receive ART. However, referral for ART did not increase significantly after presentation of the randomized trials and remains underutilized.
The effects of body mass index on pretreatment characteristics, treatment choice, and response to treatment of intermediate- and high-grade prostate cancer.
Authors: Ansley Katherine Cox , Ramahi Emma Holliday , Swanson Gregory P. , Basler Joseph W. , Du Fei 
Published: February 2017

142 Background: The relationship between obesity and prostate cancer outcomes remains unclear. A retrospective cohort study was performed to determine the effect of body mass index (BMI) on patients with intermediate to high-grade prostate cancer. Methods: Our retrospective study cohort included 1077 men from the South Texas Veteran’s Healthcare System Tumor Registry diagnosed with Gleason 7-10 prostate cancer in 1998-2008 and treated with either radical prostatectomy (RP), radiation therapy (RT) or hormone therapy (HT). Mean follow up was 4.6 ± 2.7 years. Patients were stratified into four groups on the basis of their BMI at the time of prostate cancer diagnosis (<25, 25-30, 30-35 or >35). Statistical analysis included Kruskal-wallis test and Pearson’s Chi-square test. Results: There was an inverse relationship between PSA and BMI at diagnosis; however, we found no difference in Gleason score at diagnosis. There was a difference in the primary treatment modality chosen between the BMI groups. Primary treatment modality decision was likely influenced by PSA at diagnosis, among other pre-treatment characteristics. Patients with a BMI >35 were significantly less likely to undergo RP. However, after controlling for age, primary treatment modality, Gleason score, pre-treatment PSA and diabetes diagnosis, there was no difference in overall mortality. Conclusions: Patients with an increasing BMI have a lower PSA at diagnosis, are less likely to receive RP but do not have significantly worse overall survival.