bluuebunny/crossref_metadata_2025_split huggingface dataset:
RECORD-4 multicenter phase II trial of second-line everolimus (EVE) in patients (pts) with metastatic renal cell carcinoma (mRCC): Anti-VEGF cohort subanalysis.
Authors: Cosgriff Thomas , Yang Lin , Alyasova Anna , Ye Dingwei , Karpenko Andrey , Li Hanzhong , Alekseev Boris , Xie Li-ping , Kowalyszyn Ruben Dario , Karyakin Oleg , Neron Yeni Verónica , Collins LaTonya , Brechenmacher Thomas , Lin Chinjune , Morgan Liza , Motzer Robert J. 
Published: February 2017

611 Background: RECORD-4 assessed EVE in pts with mRCC who progressed after only 1 prior therapy and enrolled pts into 3 cohorts based on first-line sunitinib (cohort 1), other anti-VEGF agents (cohort 2) or cytokines (cohort 3) (J Clin Oncol2015;abstr 4518). Median PFS in cohort 2 was 7.8 mo (95% CI, 5.7-11). This RECORD-4 subanalysis assessed EVE outcomes after individual first-line anti-VEGF agents in cohort 2. Methods: Pts received EVE 10 mg/d until progression of disease (RECIST, v1.0) or intolerance. Primary end point was PFS per investigator review. Data cutoff was Sept 1, 2014. In this analysis, efficacy and safety were analyzed for pts in cohort 2 (n=62) who received sorafenib (Sor, n=23), bevacizumab (Bev, n=16), pazopanib (Paz, n=13), tivozanib (Tiv, n=5), or axitinib (Ax, n=3); missing information for 2 pts. Results: In groups Sor/Bev/Paz/Tiv/Ax, respectively, 96/81/100/80/33% of pts had good/intermediate MSKCC prognosis, 30/94/54/100/100% were white, 70/0/38/0/0% were Asian, and 83/75/77/100/67% were <65 years of age. Median duration of exposure in groups Sor/Bev/Paz/Tiv/Ax, respectively, was 5.5/6.7/6.2/8.1/11 mo. Median PFS (95% CI) was 5.7 (3.6-11.3) mo in group Sor, 9.2 (2.2-NE) mo in group Bev, and 9.2 (1.9-18.0) mo in group Paz. Overall rate of grade 3/4 adverse events (AEs), rates of discontinuation due to AEs, and rates of dose adjustments due to AEs are presented in the table. Conclusions: Results of this RECORD-4 subanalysis demonstrated a favorable benefit-risk profile of second-line EVE in pts whose disease progressed during or after first-line anti-VEGF therapies. Results should be interpreted with caution due to small patient numbers. Clinical trial information: NCT01491672. [Table: see text]
The impact of PBRM1 and BAP1 expression on outcomes of patients with metastatic renal cell carcinoma (mRCC) treated with VEGF-targeted therapy (TT).
Authors: Fay Andre Poisl , de Velasco Guillermo , Gray Kathryn P. , Ho Thai Huu , Song Jiaxi , Kapur Payal , Albiges Laurence , McDermott David F. , Heng Daniel Yick Chin , Brugarolas James , Choueiri Toni K. , Signoretti Sabina 
Published: February 2017

616 Background: Polybromo-1 (PBRM1) and BRCA1 associated protein-1 (BAP1) are genes commonly mutated in clear cell RCC (ccRCC) and have been associated with clinical outcome. This work aims to evaluate the impact of PBRM1 and BAP1 expression by IHC in mRCC patients treated with VEGF-TT. Methods: PBRM1 and BAP1 expression was evaluated by IHC in a TMA including 146 mRCC patients. PBRM1 and BAP1 IHC scores were dichotomized as a binary variable: negative (-) or positive (+) (weak positivity was excluded). The associations of PBRM1 or BAP1 expression with baseline clinico-pathological characteristics were evaluated, as well as with overall survival (OS) and time to treatment failure (TTF) usingCox proportional hazards models. Results: Out of 146 patients, 116 and 109 samples had available results for PBRM1 and BAP1 staining, respectively. Overall, 90% (n = 131) patients had ccRCC. 70/116 samples (60%) were PBRM1- and 26/109 patients (24%) were BAP1-. Only 12% (n = 13) of patients had simultaneous negative PBRM1 and BAP1. While there was no association between PBRM1 expression status and clinical factors, BAP1- samples were associated with poor IMDC prognostic risk score (p = 0.004) and higher Fuhrman grade (p = 0.012). PBRM1+ patients showed a trend towards an increased risk of death and a shorter TTF compared to PBRM1- patients (OS: HR = 1.38, 95%CI: 0.92-2.07, p = 0.1; TTF: HR = 1.39, 95%CI: 0.94-2.06, p = 0.1). BAP1 expression was not independently associated with OS or TTF. Conclusions: Loss of PBRM1, but not BAP1 expression showed a trend towards longer TTF and OS in mRCC patients treated with VEGF-TT.
Hemorrhagic complications of robot-assisted laparoscopic partial nephrectomy for renal masses.
Authors: Franklin Andrew , Campbell Jack , Pokala Naveen 
Published: February 2017

621 Background: Partial nephrectomy is the current standard of care for T1a tumors. With advances in laparoscopy and robotic-assisted surgery, RPNx is increasingly being performed for complex renal tumors. However, significant hemorrhagic complications can occur. We review hemorrhagic complications following RPNx. Methods: At our institution 111 RPNx were performed on 110 patients (2011-2015). Demographic data and Nephrometry scores were determined. Total operating time, intraoperative blood loss, postoperative blood transfusion rate, gross hematuria, need for further procedures and mortality were collected. Pathology, including histologic diagnosis, and margin status was recorded. Results: Of 111 RPNx, 110 were done for renal masses and 112 masses were removed. Of these, 77% were malignant and most common commonly Renal Cell Carcinoma, Clear Cell pT1a (51%). Mean operative time was 245 minutes (SD 68), mean blood loss was 297 mL (SD 68), and average length of stay was 2.8 days. Hemorrhagic complications occurred in 21 patients (19%). Five had hematuria and 16 received a transfusion. Four patients required interventional radiology (IR) for angioembolization. Two patients died, one from hemorrhagic complications, and the other from septic shock related to a bowel injury. The most common Nephrometery score was 4a followed by 5a. Of those with hemorrhagic complications the most common Nephrometery score was 8, with 60% being 7 or higher. Among patients needing IR, 75% were 6 or higher and the one patient who died had a score of 11a in the setting of bilateral renal masses. Patients with hemorrhagic complications had a change in hemoglobin and hematocrit from per- to post-operation of 3.06 g/dL and 9.07% respectively compared to 2.34 g/dL and 6.28% for patients with no hemorrhagic complications. Conclusions: RPNx is a safe and nephron-sparing surgery for patients with appropriate renal masses. Significant hemorrhagic complications can occur, commonly managed with blood transfusions or angioembolization. However, catastrophic bleeding can occur in patients with high Nephrometry scores and monitoring in the ICU setting is recommended in high-risk patients.
Bladder and bowel symptoms with intensity-modulated radiation therapy (IMRT) for prostate cancer (PC).
Authors: Vapiwala Neha , Jacob Rojymon , Newman Diane , Markland Alayne , Kennedy Richard , Burgio Kathryn , Wilson Tracey , Bavaria Thomas , Wein Alan J. , Goode Patricia 
Published: February 2017

66 Background: Perioperative behavioral therapy is effective in decreasing urinary incontinence, urgency and frequency after radical prostatectomy (RP). We conducted a pilot study to determine if these symptoms occurred with sufficient frequency and impact on quality of life (QoL) to warrant behavioral therapy prior to and during PC IMRT. Methods: Expanded Prostate Cancer Index Composite Short Form (EPIC-26) is sensitive to health-related (HR) QoL effects of PC therapies. We administered EPIC-26 immediately prior to RT (baseline), and 1, 2, 6, and 12 months (mos) from baseline to PC patients undergoing IMRT at University of Alabama and University of Pennsylvania. Paired Wilcoxon’s test was used to compare rates of bladder and bowel symptoms during IMRT. Results: Of 79 men, 48% were black, with mean: age 64.6+6.9 years; BMI 28.3+5.7; Gleason Score 7.3+1.1 and baseline PSA 11.9+23.6ng/mL; 5% had prior TURP, 30% prior RP, 64% adjuvant hormonal therapy, 8% combination brachytherapy. EPIC domain scores worsened for urinary irritative/obstructive (p<.001), UI (p=0.02), and bowel (p<0.001) symptoms during therapy (at 1 month). Conclusions: Urinary and bowel symptoms were common at baseline and increased slightly during IMRT. Studies of behavioral therapy prior to and during IMRT are warranted. [Table: see text]
Phase I/II study of hypofractionated intensity modulated radiotherapy (IMRT) for prostate cancer including simultaneously integrated boost (SIB).
Authors: Chang Michael G. , Saraiya Siddharth , Mukhopadhyay Nitai , Anscher Mitchell 
Published: February 2017

67 Background: The purpose of this study is to evaluate the toxicity of hypofractionationed H- IMRT treatment including SIB IMRT when pelvic nodes were covered. Additionally, we assessed early treatment efficacy through PSA control (biochemical failure defined as PSA more than nadir + 2 ng/mL). Methods: Men with localized prostate cancer were enrolled in a phase I/II trial to receive H-IMRT to the prostate, seminal vesicles)(SV) and pelvic lymph nodes (LN) using simultaneous integrated boost (SIB) method. Low risk (LR) patients received 69.4 Gy to the prostate only in 29 fractions. The intermediate (IR) and high risk (HR) patients received 72 Gy to the prostate, 54 Gy to the proximal 1 cm SV, and 50.4 Gy to the pelvic LN when risk of LN involvement >15% by Roach formula. Treatment was given in 30 fractions using intraprostatic fiducials and daily image guidance. PTV expansion for prostate and SV was 0.3 mm posteriorly and 0.7 cm in all other directions. The IR and HR patients received androgen deprivation therapy (3 years for HR patients, and 6 months for IR patients). Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated according to CTCAE v3.0. Results: 55 men (29 African American and 26 white) were enrolled on trial with 20% LR, 41% IR and 39% HR disease (NCCN criteria). The median age was 55 with median follow-up time of 37.9 months. 26 patients received pelvic nodal SIB-IMRT. Toxicity is reported in the table. The biochemical control rate for the cohort was 91% at 3 years. Patients with pelvic LN IMRT experienced grade 2+ acute GI toxicity 38% vs 21% in the non-nodal IMRT group. (p= 0.25 by chi-square test). Conclusions: Hypofractionated SIB-IMRT can be delivered safely. Late grade III GI and GU toxicity for our cohort were 0% and 3.6% respectively. Our prospective trial shows acceptable toxicity with moderate hypofractionation in treating prostate cancer while maintaining good PSA control. Clinical trial information: NCT01117935. [Table: see text]
Trends in histology of newly diagnosed prostate cancer subsequent to USPSTF PSA screening recommendation.
Authors: Olsson Carl A. , Anderson Ann E. , Kapoor Deepak A. 
Published: February 2017

68 Background: Reports on impact of the United States Preventive Services Task Force (USPSTF) Grade D recommendation against PSA screening have been short-term and contradictory. We sought to assess whether changes in prostate biopsy (PBx) pathology reporting had occurred in our large urology practices and if such changes persisted over time. Methods: We reviewed prostate histology in the 2 years prior to the USPSTF publication in 2012, and 3 years subsequent to this recommendation. All men (3,429) undergoing PBx in years 2010/11 were combined, creating a baseline against which similar reviews of 2013-August 2015 (2,773, 2,577 and 1,767 patients, respectively) were compared. Analysis of PBx results was the same in all years; we focused only on patients with a cancer diagnosis. Each PBx core was studied for both primary Gleason pattern and score and each patient was assigned a Weighted Gleason Index (WGI) wherein each positive core was multiplied by its own Gleason score, resulting in a single number representing both score and number cores positive. Results: The percent positive PBx increased over time, from the combined rate of 39% (1,338) in 2010/11 to 41.4% (1,147) in 2013, 42.6% (1,097) in 2014 and 46% (813) in 2015 (p<.001). Of 16,271 cores in 2010/11, 5,097 or 31.3% were positive; 14.8% had Gleason 8-10 scores. Of 13,960 cores in 2013, 4,415 or 31.6% were positive; 19.7% had Gleason 8-10 scores. Of 13,577 cores in 2014, 4,694 or 34.6% were positive; 26.1% had Gleason 8-10 scores. Of 10,380 cores in 2015, 3,396 or 32.7% were positive; 25.4% had Gleason 8-10 scores. Gleason 6 scores were stable over time; Gleason 7 scores "lost" 10% over time to higher scores. WGI for 2010/11 was 25.5, compared to 26.0 in 2013 (p=.60), 29.8 in 2014 (p<.001) and 29.2 in 2015 (p=.001). There was no significant difference in WGI from 2014-15. Conclusions: The combined Gleason 6 score stability and decreased biopsies suggest that fewer low risk patients are undergoing PBx- a favorable outcome. However, there has been a persisting increase in both numbers of positive cores as well as cores found with higher Gleason scores. This increases patients presenting with higher risk disease and portends a possible reversal of gains made in reducing prostate cancer mortality.
The 4Kscore to predict the grade and stage of prostate cancer in the radical prostatectomy specimen: Results from a multi-institutional prospective trial.
Authors: Nahar Bruno , Punnen Sanoj , Sjoberg Daniel , Zappala Stephen M , Parekh Dipen 
Published: February 2017

69 Background: A recent prospective validation study confirmed the 4Kscore accurately predicted aggressive prostate cancer on prostate biopsy. We investigated the association between the 4Kscore and pathologic grade and stage at radical prostatectomy, where the entire prostate gland is sampled. Methods: Prospective enrollment of 1,312 men who were referred for prostate biopsy for clinical suspicion of prostate cancer occurred at 26 sites throughout the United States from October 2013 to April 2014. We selected men who were found to have positive prostate cancer biopsies and elected to undergo radical prostatectomy. The 4Kscore is an algorithm that incorporates a panel of 4 Kallikreins (total PSA, free PSA, intact PSA and human kallikrein-2) in addition to age, digital rectal examination, and prior biopsy status. We assessed the concordance between the 4Kscore prior to biopsy and grade of prostate cancer at radical prostatectomy. 4Kscore test results were compared for those with and without non organ-confined tumors at surgery using the Wilcoxon rank-sum. Results: Among the 1,312 men who enrolled in this validation study, 144 were found to have prostate cancer and underwent radical prostatectomy. We saw a significant association between the 4Kscore and grade at surgery with higher scores relating to worse grade. For men with Gleason 6, 7, and 8 or higher cancers in the surgical specimen the median (IQR) 4Kscore was 7% (4, 12), 25% (12, 38), and 47% (24, 66) (p<0.0001).The median 4Kscore among men with non organ-confined cancer was significantly higher then men with cancers confined to the prostate ([36% (IQR 19,58)] vs. [19% (IQR 9, 35)], p=0.002). Conclusions: In a subset of men who underwent radical prostatectomy, the 4Kscore was significantly associated with pathological grade and extracapsular extension in the surgical specimen, with higher scores being linked to higher grade and more aggressive histology. The test can be beneficial to aid in treatment decision making for men who are contemplating observation of their cancer versus immediate treatment.
Defining the optimal PSA range for the maximal predictive efficacy of PSA density to detect prostate cancer on biopsy: Results from a multi-institutional and prospective contemporary cohort.
Authors: Rai Samarpit , Pavan Nicola , Soodana-Prakash Nachiketh , Nahar Bruno , Dong Yan , Satyanarayana Ramgopal , Parekh Dipen , Punnen Sanoj 
Published: February 2017

70 Background: PSA density (PSAD) is an important predictor of prostate cancer (PCa). We assessed whether the predictive accuracy of PSAD varied based on the range of PSA or whether the patient had a previous negative prostate biopsy (PB). Methods: We assessed a prospective cohort of men who were referred for a PB due to suspicion of PCa at 26 different sites across USA. The area under the receiver operating characteristic curve (AUC) was used to assess the added predictive accuracy of PSAD versus PSA across 3 different PSA ranges ( < 4, 4 – 10, > 10 ng/mL) and in men with or without a prior negative PB for the detection of any and significant (Gleason ≥ 7) PCa. Results: Of the 1,290 men, 585 (45%) and 284 (22%) had any and significant PCa, respectively. PSAD was significantly more predictive than PSA for detecting any PCa in the PSA ranges of 4 – 10 (AUC 0.70 vs 0.53, P < 0.00001) and > 10 (AUC 0.84 vs 0.65, P < 0.00001) ng/mL. Similarly, for significant PCa, PSAD was more predictive than PSA in the PSA ranges of 4 – 10 (AUC 0.72 vs 0.57, P < 0.00001) and > 10 (AUC 0.82 vs 0.68, P = 0.0001) ng/mL. Furthermore, PSAD was significantly more predictive than PSA in detecting PCa in men that had a prior negative PB (AUC 0.69 vs 0.56, P = 0.0001 for any PCa and AUC 0.81 vs 0.70, P = 0.0042 for significant PCa), and those that didn’t (AUC 0.72 vs 0.67, P = 0.0001 for any PCa and AUC 0.77 vs 0.73, P = 0.0026 for significant PCa). However the difference between the AUC of PSAD and PSA (ΔAUC) was a lot more pronounced in men that had a prior negative PB (ΔAUC = 0.13 for any PCa and ΔAUC = 0.11 for significant PCa) as opposed to those that didn’t (ΔAUC = 0.05 for any PCa and ΔAUC = 0.04 for significant PCa), suggesting that PSAD is a much better predictor than PSA alone in men who have undergone a previous PB. Conclusions: As PSA increases, the predictive accuracy of PSAD over PSA appears to improve for the detection of any PCa and significant PCa. Additionally, PSAD has a more pronounced predictive value over PSA in detecting any and significant PCa in men who have undergone a prior negativePB. We support the use of PSAD testing to avoid unnecessary biopsies in men who have elevated PSA secondary to an enlarged prostate.
Utility of prostate multiparametric MRI (mpMRI) for recurrent prostate cancer after radiation therapy and cryotherapy.
Authors: Kovac Evan , Purysko Andrei , Jones J. Stephen , Magi-Galluzzi Cristina , Klein Eric A. , Stephenson Andrew J. 
Published: February 2017

71 Background: We evaluated the accuracy of mpMRI for identifying locally recurrent prostate cancer after primary radiotherapy and cryotherapy. Methods: Between 2009-2015, 61 patients with evidence of rising PSA after external-beam radiotherapy (EBRT) (N = 33), brachytherapy (N = 6), and cryotherapy (N = 22) were evaluated for locally recurrent prostate cancer with mpMRI and prostate biopsy. Of these patients, 6 (10%) received androgen deprivation therapy (ADT) in combination with EBRT for a median of 24 months. Three of the cryotherapy patients received prior EBRT. Patients were identified from a prospective mpMRI database. All patients with a lesion of interest (LOI) underwent a ≥ 12-core, post-mpMRI cognitive fusion prostate biopsy. We excluded 16 patients with mpMRI who did not undergo prostate biopsy (5 positive, 11 negative). Results: Median age was 70 (IQR: 64-77). The median time from primary treatment to mpMRI was 5 years (IQR: 3-9) and the median PSA at mpMRI was 3.6 ng/mL (IQR: 2.1-5.5). Median prostate volume was 18.8 cc (IQR: 11.0-28.0 cc). mpMRI revealed lesions of interest (LOI) in 39 (64%) and 41 (67%) had biopsy-proven local recurrence. Of the 22 patients with negative mpMRI, 8 (36%) had a positive biopsy, with a median prostate volume of 19 cc, median maximum cancer length of 5 mm, median PSA of 2.5 and biopsy Gleason scores 3+3 (N = 1), 4+3 (N=2), 5+4 (N = 1), 5+5 (N = 1) and ungraded due to treatment effect (N = 3). Of the 39 patients with LOI on mpMRI, 33 (85%) had a positive biopsy. Table 1 summarizes the mpMRI and biopsy results. The sensitivity, specificity, PPV and NPV of mpMRI to predict cancer diagnosis at biopsy was 80.5%, 70.0%, 84.6% and 63.6%, respectively. On univariate analysis, gland size (p=0.367), PSA (p=0.872), biopsy Gleason score (p=0.892) and primary treatment modality (p=0.177) did not significantly predict discrepancy between mpMRI and biopsy findings. Conclusions: mpMRI reliably identifies prostate cancer recurrence after primary radiation therapy and cryoablation. [Table: see text]
Predictive parameters of symptomatic haematochezia following 5-fraction gantry-based SABR in prostate cancer.
Authors: Musunuru Hima Bindu , Davidson Melanie , Cheung Patrick , Chu William , Chung Hans T. , Vesprini Danny , Liu Stanley K. , Mamedov Alexandre , Ravi Ananth , D'Alimonte Laura , Commissso Kristina , Helou Joelle Antoine , Deabreu Andrea , Zhang Liying , Loblaw Andrew 
Published: February 2017

79 Background: To identify clinical and dosimetric predictors of high-grade haematochezia (HH) following 5-fraction gantry based stereotactic ablative radiotherapy (SABR). Methods: Data about haematochezia in 258 patients who received 35-40Gy SABR in 5-fractions (weekly or alternate days) as part of sequential phase II prospective trials was retrieved. Haematochezia was graded as per the Fox Chase LENT criteria, ≥ grade 2 rectal bleeding was labeled as HH. Patients needing steroid suppositories, 4% formalin or 1-2 sessions of argon plasma coagulation (APC) were graded as grade 2 haematochezia. If a patient required >2 sessions of APC, blood transfusion or a course of hyperbaric oxygen, this was grade 3 and development of visceral fistula was grade 4. Various dosimetric and clinical factors were analyzed using univariate and multivariate (MVA) analyses. Receiver-operating characteristic (ROC) curve analysis and recursive partitioning analysis (RPA) were used to determine clinically valid cut-off points and risk groups, respectively. Results: Median follow-up was 29.7 months (IQR 20.6, 61.7). HH was observed in 19.4%. Median time to develop HH was 11.7 months (IQR 9.0, 15.2). Resolution occurred a median of 6.7 months (IQR 5.7, 12.4) later; 3% was prevalent at last follow-up. At two years, cumulative HH was 4.9%, 27.2% and 42.1% in patients who received 35Gy to prostate (4mm planning target volume-PTV margin), 40Gy to prostate (5mm PTV margin) and 40Gy to prostate/seminal vesicles (5mm PTV margin), respectively ( p-value< 0.0001). In the ROC analysis, volume of rectum receiving radiation dose of 38Gy (V38) was a strong predictor of HH with an AUC of 0.65. In MVA, rectal V38 (≥2.0cc; p-value<0.0001, OR 4.9); use of anti-coagulants (p-value<0.0002, OR 14.9) and presence of hemorrhoids (p-value<0.006, OR 3.2) were the strongest predictors. In RPA, rectal V38<2.0cc and use of anticoagulants orrectal V38 ≥2.0cc plus one other risk factor resulted in a HH risk>30%. Conclusions: Rectal V38 and two clinical factors were strong predictors of high-grade haematochezia following 5-fraction SABR. Planning constraints should aim to keep the rectal V38 below 2.0cc.