bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplatform molecular analysis of biomarkers in renal cell carcinoma.
Authors: Ho Thai Huu , Millis Sherri Z. , Doll Nancy , Gatalica Zoran , Reddy Sandeep K. , Bryant David , Joseph Richard Wayne , Vogelzang Nicholas J. 
Published: February 2017

501 Background: Predictive biomarkers of response to targeted therapy are lacking in renal cell carcinoma (RCC). We evaluated a cohort of RCC patients referred for molecular profiling to identify potentially actionable recurrent molecular aberrations. Methods: 166 consecutive renal cases referred to Caris Life Sciences over 2 yrs were evaluated with central pathology review. Cases were subtyped into clear cell (ccRCC), n=100, papillary (PRCC), n=20, sarcomatoid, n=10, translocation, n=6, medullary, n=4 or unclassified, n=26. 63% of cases were metastatic. Testing included a combination of sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and/or gene amplification (CISH or FISH). Results: ccRCC had a 52% loss of PTEN, while PRCC had a 21% loss (p value=0.02). 100% of ccRCC with sarcomatoid features (4) showed aberrant expression of PD-L1 and were infiltrated with PD-1+ tumor infiltrating lymphocytes; 100% of 10 non-ccRCC sarcomatoids also had aberrant expression of PD-L1. Loss of PBRM1 expression was observed in 60% of ccRCC. Loss of histone 3 lysine 36 trimethylation (H3K36me3), which is associated with SETD2 mutations, was observed in 30% of ccRCC. TOP2A was overexpressed in ccRCC at 30% and in non-ccRCC at 50%. 100% of ccRCC and PRCC overexpressed EGFR; a single unclassified renal cell carcinoma did not overexpress EGFR. 50% of cases had cMET overexpression, amplification, or mutation. HER2 was not amplified or overexpressed in any RCC; a single rare HER2 mutation (R816H) was found in a collecting duct carcinoma. VHL mutations were identified in 50% of ccRCC tumors. We observed lower rates of TP53 (14%), ATM (6%), and PIK3CA(4% ccRCC, 7% PRCC) mutations compared to other cancers. Conclusions: Multiplatform molecular profiling of renal cell carcinoma identifies potential predictive biomarkers in ccRCC. The documented activity of everolimus in ccRCC (RECORD-1 trial) may be attributable to PIK3CA pathway alterations. RCC with sarcomatoid features may respond to PD1/PD-L1 targeted immunotherapies. The impact of molecular profiling in ccRCC to predict responses to currently available targeted therapy has important implications for trial design and patient selection.
Survival comparison analysis of two historical cohorts of metastatic renal cell carcinoma patients (cytokine therapy versus targeted agents): A European single-center experience over 26 years.
Authors: Hutterer Georg C. , Golbeck Silvia V. , Mrsic Edvin , Krieger Daniel , Bezan Angelika , Jesche Johanna , Pummer Karl , Zigeuner Richard , Pichler Martin 
Published: February 2017

513 Background: By the approval of new targeted agents in 2006, the standard of therapy in metastatic renal cell carcinoma (mRCC) changed, since they demonstrated significantly improved progression-free survival (PFS) rates compared with interferon in phase III clinical trials. Differences in overall survival (OS) could not be proven since many patients switched to another effective substance after progression of the disease. Thus, we compared two mRCC patient cohorts in order to detect OS differences between immunotherapy and targeted therapies in a real-life population outside controlled clinical trials. Methods: Clinico-pathological data from 594 mRCC patients, operated between 1984 and 2010 at a single tertiary academic center, were evaluated retrospectively with the null hypothesis, that there is no statistically significant difference in OS of patients treated either with interferon or targeted agents. Using electronical patient records, all data regarding the beginning, duration, lines, and different forms of therapies were assessed. Patients’ cancer-specific survival (CSS), as well as OS, were assessed using the Kaplan-Meier method, compared with the log-rank test. A first analysis revealed results for the entire study cohort. Subsequently, outcome analyses were restricted to mRCC patients with clear cell histology only. Results: With respect to the complete follow-up period, our results in both analyses did not show a statistically significant OS difference between the two therapy modalities. By limiting the observation period to 5 years after treatment initiation, a statistically significantly improved median five-year OS rate (26 mo.) for clear cell mRCC patients treated with targeted agents was observed, compared with 21 mo. in the interferon group (p=0.028). Conclusions: Our results confirm the presumption of an improved OS in mRCC attributable to treatments with targeted agents compared with previous cytokine therapies.
Subcapsular prostate cancer: Identification with mpMRI and MRI/TRUS fusion-guided biopsy.
Authors: Brown Anna Mary , Sankineni Sandeep , George Arvin Koruthu , Rais-Bahrami Soroush , Wood Bradford J. , Merino Maria J , Pinto Peter A. , Choyke Peter L. , Turkbey Baris 
Published: February 2017

52 Background: The subcapsular region is often under-sampled by standard 12-core transrectal ultrasound (TRUS) prostate biopsy. We retrospectively evaluated multi-parametric MRI (mpMRI) features of subcapsular prostate cancers (PCa) and their detection on MRI/TRUS fusion-guided biopsy (FgBx). Methods: All patients referred for 3T mpMRI and subsequent FgBx under an IRB-approved protocol from Jan 2010 to July 2014 were reviewed. Histologically confirmed subcapsular lesions (just inside the prostate capsule with capsular border length >> width) were identified. Impact of the FgBx on clinical management according to current National Comprehensive Cancer Network (NCCN) guidelines was evaluated, with prior status based on outside TRUS biopsy results. Results: Of 992 eligible patients, 33 had subcapsular prostate lesions on mpMRI. In this subpopulation, mean age, PSA, and prostate volume were 63 years (range 52-76), 8.4ng/mL (1.2-63), and 53 mL (12-125). The FgBx, consisting of targeted (TBx) and systematic (SBx) portions, confirmed PCa in 24 of 33 patients. Five cancers (21%) were only detected by TBx. The remaining 19 were diagnosed on both TBx and SBx, but in 5 of these 19 (26%), higher Gleason scores were found on TBx cores. The FgBx results more accurately classified patients’ NCCN risk scores, with 17 prior unknown or low risk PCa upgraded to higher risk scores (Table). Conclusions: Subcapsular lesions on mpMRI are rare but largely malignant. Most are found on 12-core SBx, but ~20% require TBx for diagnosis, and TBx more accurately grades >25% of the lesions. The FgBx may improve clinical management of patients with subcapsular PCa, since more aggressive cancer was found in 17 of 24 patients. [Table: see text] [Table: see text] [Table: see text]
Impact of timing of biochemical failure on the eventual development of clinical failure after definitive treatment with brachytherapy or external beam radiotherapy for prostate cancer.
Authors: Ciezki Jay P. , Reddy Chandana A. , Klein Eric A. , Ulchaker James , Angermeier Kenneth , Tendulkar Rahul D. , Stephans Kevin L. , Campbell Steven C. , Stephenson Andrew J. 
Published: February 2017

53 Background: Late treatment failure is often considered to be a rare event. We will assess the influence of the timing of biochemical failure (bF) after definitive brachytherapy (BT) or external beam radiotherapy (EBRT) for prostate cancer on its frequency and association with clinical failure (cF). Methods: Patients with prostate cancer treated between 1996 and 2009 with at least 5 years of follow-up (N= 2,293; 1,060 EBRT, 1,233 BT) were studied in the context of an IRB-approved inception cohort study. Those with a bF were reviewed to determine the timing of bF [< 5 years after treatment (bF<5) vs. > 5 years after treatment (bF>5)] and occurrence of cF post-bF. The bF definition used was the nadir + 2.0 ng/mL version. Results: Of the total patient population, 477 (21%) were noted to have bF- 244 (11%) bF<5 vs. 233 (10%) bF>5. The median follow-up after bF for the bF< 5 group is 41 months while in the bF> 5 group it is 22 months. In the BT group, 94 (8%) failed < 5 years and 87 (7%) failed > 5 years. In the EBRT group, 150 (14%) failed < 5 years and 146 (14%) failed > 5 years. The median PSA value (ng/mL) at the time of bF for all patients, EBRT, and BT in the bF<5 group was 3.70, 3.65, and 3.80, respectively (p=not significant). The median PSA value (ng/mL) at the time of bF for all patients, EBRT, and BT in the bF>5 group was 3.01, 3.01, and 3.04, respectively (p=not significant). Overall, 53.3% of patients in the bF<5 group developed cF while 27% of patients in the bF>5 group developed a cF. The actuarial five year rate of cF for the bF <5 group was 50% vs. 38% for the bF>5 group (p= 0.028). The detection of bF and cF was closely linked to PSA testing frequency ( p < 0.0001). Conclusions: The risk of bF does not appear to decrease >5 years post treatment. Late bF (i.e. >5 years after treatment) may still result in eventual cF. While cF is less common after bF > 5 years post definitive therapy, it still affects 27% of those with bF and is strongly associated with PSA testing frequency. The lower rate of cF after 5 years may relate to the shorter follow-up time for this group.
5α-reductase from radical prostatectomy tissue and utilization of testosterone and androstenedione to produce DHT: A dual isotope method and preliminary results.
Authors: Kovac Evan , Chang Kai-Hsiung , Klein Eric A. , Sharifi Nima 
Published: February 2017

58 Background: Previous work has shown that 5α-reductase prefers androstenedione (AD) in favor of testosterone (T) for dihydrotestosterone (DHT) synthesis in castration-resistant prostate cancer. Yet, 5α-reductase substrate preference in the setting of localized prostate tissue has yet to be fully elucidated. We propose a novel ex-vivo method for tracking steroid handling by the prostate and report our preliminary findings. Methods: Prostate tissue from the peripheral and transitional zones of patients who underwent radical prostatectomy (RP) for localized prostate cancer were incubated in media, along with (3H)-labeled AD and (14C)-labeled T. Media was collected after 7, 24 and 48 hours of incubation, treated with glucuronidase and high performance liquid chromatography (HPLC) was used to identify steroids tagged with either 3H or 14C. Results: In total, 11 patients were consented for tissue procurement at the time of RP. Qualitatively, both AD and T are utilized by the prostate to produce DHT. Over time, concentrations of tritiated AD decreased, while concentrations of tritiated T, 5α-androstanedione and DHT rose. Similarly, concentrations of 14C-T decreased over a 48-hour period, while AD, 5α-androstanedione and DHT increased. Conclusions: We describe a dual isotope method for characterizing androgen handling by prostate tissue from patients with localized prostate cancer, using 2-channel radiolabel detection. Preliminary results show that both AD and T can be utilized by localized prostate cancer tissue. Future work will focus on determining if different phenotypes of androgen handling exist among various patient genotypes and cancer risk groups.
18F-choline PET/CT for the assesment of pelvic lymph node metastases in high-risk prostate cancer patients.
Authors: Pinto Ivan Federico , Sandoval Camilo , Diaz Jorge Gonzalo , Vidal Alvaro Daniel , Altamirano Jaime Antonio , Vilches Roberto Mauricio 
Published: February 2017

61 Background: Assesment of pelvic lymph node involvement is a major dilemma due to poor diagnostic accuracy of conventional imaging such as computed tomography of the pelvis or magnetic resonance of the pelvis. Recently incorporation of new tools such as 18F-choline PET/CT address this issue, although there are few studies in this set of patients. To evaluate the 18-choline PET/CT diagnostic accuracy for staging of pelvic lymph node involvement in patients with high risk prostate cancer. Methods: Patients with diagnosis of high risk prostate cancer according to D’Amico risk assessment criteria where staged with a 18F-choline PET/CT prior to treatment with retropubic radical prostatectomy plus superextended bilateral lymph node dissection at our institution. 18F-choline PET/CT was compared with the results of pathological analisys of lymph nodes. We calculated sensitivity, specificity, positive and negative predictive value for 18F-choline PET/CT. Results: Between January 2012 and August 2014 a total of 36 patients met the following inclusion criteria: diagnosis of high prostate cancer (cT2c or more or PSA above 20 ng/ml or a gleason score 8-10), good performance status (ECOG 0-2) and a 18F-choline PET/CT as a preoperative staging procedure. Sensitivity, specificity, positive and negative predictive value were 64%, 92%, 77% and 85% respectively. Conclusions: 18F-choline PET/CT is a non invasive procedure that provides good information regarding pelvic lymph node involvement status that is better than the results of other techniques in published series, with a higher sensitivity in our group of patients. It is highly specific which means there is a very good chance that a patient with a normal study does not have lymph node metastases when analyzed.
Radical prostatectomy versus high intensity-focused ultrasound for localized prostate cancer: A matched-pair comparison.
Authors: Pasticier Gilles , Crouzet Sebastien , Colombel Marc , Rouviere Olivier , Rabilloud Muriel , Chapelon Jean-Yves , Mege-Lechevallier Florence , Tonoli-Catez Helene , Martin Xavier , Gelet Albert 
Published: February 2017

74 Background: Radical prostatectomy is the gold standard treatment for localized prostate cancer. HIFU is a treatment option with promising outcomes. No randomized study is available to compare those techniques. The goal of the study was to evaluate the oncologic outcome of patients treated with HIFU and radical prostatectomy by using a matched pair analysis to compare the 2 groups. Methods: A total of 710 patients treated between 2000 and 2005 were prospectively followed in our institutional database and matched to a 1:1 basis following know prognostic variables: prostate-specific antigen (PSA) level, Gleason score, and clinical stage. After matching, 588 patients (294 in each group) were further analysed. The starts of salvage external beam radiotherapy (S-EBRT) or definitive palliative androgen deprivation therapy (ADT) were primary endpoints. Other endpoints were overall, cancer specific and metastasis free survival rates: The survival rates were calculated with Kaplan-Meier estimate Results: The seven years S-EBRT free survival rate was significantly lower after HIFU than after RP (62% versus 78%, p=0.001). The palliative androgen deprivation free rate at nine years was not significantly different between HIFU and RP (86% versus 87%, p=0.271). At nine years the overall, cancer specific and metastasis free survival rates were similar: 89%, 97%, 94 % and 89%, 97% and 97% for HIFU and RP respectively (p=0.186, 0.312, 0.107). Conclusions: Matched pair comparison of HIFU and RP has shown a higher rate of S-EBRT for HIFU. At 9 years, the rate of patients who need palliative ADT, the overall cancer specific and metastasis free survival rates were not significantly different between HIFU and RP.
Results of an online survey of physical, emotional, and practical concerns for prostate cancer survivors in the United States.
Authors: Darwish Oussama M. , Adsul Prajakta , Siddiqui Sameer 
Published: February 2017

75 Background: Prostate cancer survivors face numerous health concerns after treatment. The type of treatment received may have a significant impact on the physical, emotional and practical concerns of the patient. Methods: We analyzed self-reported data from the 2010 LIVESTRONG survey for people affected by prostate cancer. Survey questions were divided into 3 sections including physical, emotional, and practical concerns in the survivorship period. Survey was administered online between June 20, 2010 and March 31, 2011 on the LIVESTRONG.org website. Results: Of the 12,307 respondents, 281 males were included in the analysis based on a primary diagnosis of prostate cancer and US residency status. Mean age was 60 years (range, 41-94) and the majority were white men (90%). The 3 most common physical concerns were decrease in sexual function (70%), urinary frequency (54%) and fatigue (35%). The leading emotional concerns were fear of cancer recurrence (61%), grief about death of other cancer patients (52%) and worry about cancer genes in family members (51%). Practical concerns were cost beyond insurance coverage (90%), financial debt (40%), and inability to continue previous work (6%). One way ANOVA was conducted to detect differences in number of physical, emotional and practical concerns across types of treatment received (surgery, radiation, hormonal and combination). Significant differences were seen in number of physical (p=0.02), emotional (p=0.04) and practical (p<0.001) concerns for patients receiving different treatments (Table 1). Patient concerns also varied based on length of follow-up after treatment. Conclusions: Based on treatment type, hormonal patients have the greatest physical and emotional concerns compared to other treatment options, while surgery patients demonstrate the most practical concerns. The results of the survey illuminate the principal physical, emotional and practical concerns of prostate cancer survivors, and can assist in prioritizing and addressing major patient concerns after prostate cancer treatment.
Surgical margins and biochemical recurrence risk at 2 years for robotic prostatectomy: Comprehensive evaluation and CUSUM analysis of oncological outcomes.
Authors: Sivaraman Arjun , Sanchez-Salas Rafael , Prapotnich Dominic , Yu Kaixin , Olivier Fabien , Doudeau Christian , David Stephane , Barret Eric , Secin Fernando P. , Ingels Alexandre , Rozet Francois , Galiano Marc , Mombet Annick , Cathala Nathalia , Cathelineau Xavier 
Published: February 2017

80 Background: To evaluate the learning curve of Minimally Invasive Radical Prostatectomy (MIRP) in our institution and apply the cumulative summation (CUSUM) analytical technique to identify salient learning curve transition points in terms of oncological outcomes. Methods: Clinical, pathologic, and oncological outcome data were collected from our prospectively collected MIRP database to estimate Positive Surgical margin (PSM) and Biochemical Recurrence (BCR) trends during a 15 year period from 1998 to 2013. All the RPs (laparoscopic (LRP) / Robotic Assisted [RARP]) were performed by 9 surgeons. PSM was defined as presence of cancer cells at inked margins. BCR was defined as serum Prostate Specific Antigen (PSA) >0.2 ng/ml and rising or start of secondary therapy. Surgical learning curve was assessed with the application of Kaplan-Meier curves, Cox regression model, CUSUM and logistic model in order to define the “transition point” of surgical improvement. Results: We identified 5,547 patients with localized prostate cancer treated with MIRP (3,846 - LRP and 1,701 – RARP). Patient characteristics of LRP and RARP were similar. The overall risk of PSM in LRP was 25%, 20% and 17% for the first 50, 50 to 350 and >350 cases, respectively. For the same population, the 5-year BCR rate decreased from 21.5% to 16.7%. RARP started 3 years after the LRP program (after approximately 250 LRP). The PSM rate for RARP decreased from 21.8% to 20.4% and the corresponding 5-year BCR rate decreased from 17.6% to 7.9%. The CUSUM analysis showed significantly lower PSM and BCR at 2 years occurred at the transition point of 350 cases for LRP and 100 cases for RARP. In multivariable analysis, predictors of BCR were PSA, Gleason score, extra prostatic disease, seminal vesicle invasion and number of operations (p < 0.05). Patients harboring PSM showed higher BCR risk (23% vs. 8%, p < 0.05). Conclusions: Learning curve trends of MIRP in our large, single center experience showed significant reduction in PSM and BCR risk at 2 years are noted after the initial 350 cases and 100 cases of LRP and RARP, respectively.
The association of a 17-gene genomic prostate score with adverse surgical pathology and recurrence following surgery for localized prostate cancer (PCa): A comparison of African American and Caucasian patients.
Authors: Cullen Jennifer , Rosner Inger L. , Brand Timothy C. , Ali Amina , Chen Yongmei , Zhang Nan , Tsiatis Athanasios C. , Knezevic Dejan , Maddala Tara , Lawrence H. Jeffrey , Febbo Phillip G. , Srivastava Shiv , Sesterhenn Isabell , Mcleod David G. 
Published: February 2017

86 Background: Molecular assays can improve risk assessment for newly diagnosed PCa, but it is imperative to characterize assay performance in different racial groups, since tumor biology and clinical outcomes may vary. A racially diverse cohort of men (20% AA) with PCa in the Center for Prostate Disease Research multi-center national database was used to determine the association of GPS with outcomes in men treated with radical prostatectomy (RP) for localized PCa. Methods: Biopsy specimens from 431 men treated with RP for NCCN very low, low or intermediate risk PCa at 2 U.S. military medical centers were tested with a 17-gene RT-PCR assay to validate the association between GPS (scale 0-100) and 1) biochemical recurrence (BCR) following RP, and 2) adverse pathology (AP) at RP. BCR was defined as 2 successive PSA levels > 0.2 ng/mL. AP was defined as high-grade (primary Gleason pattern 4 or any pattern 5) and/or pT3 disease. Cox proportional hazards and logistic regression models were used. Results: GPS was obtained in 402 cases (93%), including 82 AA men. A broad range of GPS results was observed in both AA and CA men; GPS distributions were similar between AA (median GPS = 30.3; inter-quartile range (IQR): 23-38) and CA (median GPS = 30.3; IQR: 23-40); no correlation was observed between GPS and race (r = -0.04, p = 0.45). No differences in expression of individual genes or gene groups in the assay were observed between the two groups. In univariable analysis, PSA, biopsy GS and NCCN risk group were associated with BCR and AP, but race was not. The associations between GPS and clinical outcomes were similarly strong and statistically significant in both AA and CA men - BCR HR/20 GPS units = 3.0 (95% CI: 2.0-4.3) for CA vs. 3.5 (95% CI: 1.0-11.7) for AA; AP OR/20 units = 4.0 (95% CI: 2.6-6.6) for CA vs. 2.9 (95% CI: 1.2-7.6) for AA (p < 0.05 for all). Conclusions: In this cohort of patients treated in a health care system with equal access, clinical outcomes and the tumor biology measured by GPS were similar between AA and CA patients. GPS is a significant predictor of BCR and AP in men treated with RP for localized PCa in both AA and CA men.