bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative effectiveness of first-line VEGF TKI followed by second-line therapy with either a VEGF TKI or an mTOR inhibitor in patients with metastatic renal cell carcinoma.
Authors: Patel Shiven B. , Tantravahi Srinivas Kiran , Gill David , Poole Austin , Merriman Joseph , Batten Julia A. , Stenehjem David D. , Agarwal Neeraj 
Published: February 2017

495 Background: In the INTORSECT trial, not progression-free (PFS), but overall survival (OS) was higher with sorafenib vs. temsirolimus in 2nd setting after 1st sunitinib therapy. Here, we compare the PFS and OS between any vascular endothelial growth factor inhibitor (VEGF TKI) and mTOR inhibitors (mTORi) in 2nd setting in mRCC after progression on 1st VEGF TKI. Methods: Pts were identified from an institutional database. Survival estimates of PFS and OS were assessed from initiation of 2nd therapy by Kaplan-Meier methodology and stratified by the median PFS of the 1st therapy. Results: Of 142 pts, 66 received a VEGF TKI (n=24, 36%) or an mTORi (n=42, 64%) in 2nd setting. Pts and disease characteristics with corresponding outcomes are presented in the table. Conclusions: A trend for improved PFS and OS was found with 2nd therapy with a VEGF TKI over an mTORi. Longer OS with 2nd VEGF TKI was seen in those on 1st VEGF TKI <8 months suggesting that continued VEGF inhibition may be a reasonable strategy in these pts. Data need to be validated in a larger cohort. [Table: see text]
Concordance of Gleason score on biopsy and after prostatectomy: A SEER database analysis.
Authors: Wong Andrew Thomas , Agarwal Manuj , Navo Elliot B. , Schwartz David , Schreiber David 
Published: February 2017

50 Background: The Gleason score (GS) is a well-established prognostic factor and is used to guide clinical decision-making for patients with prostate cancer. Concordance between the clinical GS of the core biopsy and of the pathologic specimen after radical prostatectomy has ranged from 30% to 75% in prior single-institution studies. The objective of this study is to analyze biopsy concordance utilizing the population-based Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients diagnosed with localized prostate adenocarcinoma (cT1c-4 Nx-1 M0) who underwent prostatectomy from 2010-2011 were identified in the SEER database. Agreement between clinical and pathologic GS was analyzed using the kappa (k) statistic. Univariate and multivariate logistic regression was performed to identify factors which may impact concordance using SPSS v21. Results: A total of 34,195 patients were included in this analysis. Median age was 61 and median PSA was 5.9 ng/ml. The majority of patients had clinical GS of 6 or 7 (76.5 %) and PSA < 10 ng/ml (77.4%). Overall concordance was 55.4% with k of 0.36, indicating fair agreement. Results are summarized in the Table. Of patients with clinical GS 6, concordance was 55.3%, with 43.1% upgraded to pathologic GS 7. Among patients with clinical GS 7, concordance was 66.9% for GS 3+4 and 42.9% for GS 4+3. Concordance was 24.8% among patients with clinical GS 8, with 57.4% downgrade rate. On multivariate analysis, Black race, increasing age, higher PSA and SEER registries California, Connecticut, Hawaii and Iowa predicted for decreased likelihood of concordance. Conclusions: This is, to our knowledge, the largest contemporary study of prostate biopsy concordance. We found a substantial rate of upgrade from GS 6 or 7 as well as significant downgrade from GS 8. Further investigation is needed to determine other potential factors to predict biopsy concordance. [Table: see text]
Comparative effectiveness of everolimus (EVE) and axitinib (AXI) for second-line treatment of metastatic renal cell carcinoma (mRCC) in the United States: A retrospective chart review.
Authors: Vogelzang Nicholas J. , Pal Sumanta Kumar , Signorovitch James E. , Reichmann William M. , Chopra Pooja , Liu Zhimei , Perez Jose Ricardo , Jonasch Eric 
Published: February 2017

500 Background: EVE and AXI are approved as 2nd-line TTs for mRCC. This study compares OS and PFS among mRCC patients treated with EVE and AXI following 1st TKI. The extent to which the duration of 1st TKI can inform optimal selection of a 2nd-line TT is of interest. Methods: A retrospective patient chart review study was conducted. Medical oncologists or hematologists/oncologists who treated ≥3 mRCC patients in the past year were recruited from a national panel. Patient eligibility criteria included: 1) aged ≥18 years; 2) initiated and discontinued 1st TKI (sunitinib or pazopanib) for medical reasons; 3) initiated 2nd TT between 2/1/2012 and 1/31/2013. OS was defined as time from initiation of 2nd TT to death. PFS was defined as time from initiation of 2nd TT to physician/chart reported progression or death, whichever occurred first. Multivariable Cox proportional hazards models were used to estimate the hazard ratio (HR) for OS and PFS between EVE and AXI, adjusting for age, gender, type and duration of 1st TKI, response to 1st TKI, duration of mRCC at 2nd TT, disease profile, performance status, sites of metastases, and years of physician practice. Comparative effectiveness was also analyzed by the type and duration (<6, 6-12, >12 months) of 1st TKI. Results: A total of 298 and 122 patients received 2nd TT with EVE and AXI. After adjusting for baseline characteristics, there was no statistically significant difference between EVE and AXI in OS [HR (95% CI): 1.10 (0.69-1.75)] or PFS [HR (95% CI): 1.12 (0.81-1.54)]. When stratified by subgroups defined by type and duration of 1st TKI, there was no statistically significant difference in OS between EVE and AXI in all subgroups, except for patients with <6 months on sunitinib as 1st TKI in which AXI had longer OS (HR =3.95). There was no statistically significant difference in PFS between EVE and AXI in all subgroups. Conclusions: In this large, retrospective chart review study, there was no significant difference in OS or PFS between EVE and AXI. Subgroup analyses stratified by duration of 1st TKI did not suggest that longer duration of 1st TKI was associated with better efficacy for 2nd-line AXI vs. EVE.
Association of pharmacokinetics of axitinib with treatment outcome and adverse events in advanced renal cell carcinoma patients.
Authors: Tsuchiya Norihiko , Igarashi Ryoma , Suzuki-Honma Naoko , Fujiyama Nobuhiro , Narita Shintaro , Inoue Takamitsu , Saito Mitsuru , Akihama Susumu , Tsuruta Hiroshi , Miura Masatomo , Habuchi Tomonori 
Published: February 2017

506 Background: Therapeutic drug monitoring (TDM) has been recognized as a useful tool for optimizing the dose of many drugs. The effectiveness of TDM for molecular targeted agents, however, has not so far been established. In this study, we examined the associations between pharmacokinetics of axitinib (AXI) and adverse events (AEs) and clinical outcomes in patients with advanced renal cell carcinoma (aRCC). Methods: The pharmacokinetics of AXI was examined in 24 patients (18 males and 6 females) with aRCC. The plasma AXI levels were measured using high-performance liquid chromatography and a pharmacokinetic study was performed on day 7 in the first cycle. Subsequently, the associations between the pharmacokinetics of AXI and the occurrence and grade of AEs, best tumor response, and progression-free survival (PFS) were investigated. Results: All the patients were been treated with 10 mg/day of AXI at the day of pharmacokinetics and the trough levels were ranged between 1.2 and 70.97 ng/mL. The trough levels were significantly associated with the occurrence of hypertension, hyperthyroidism, and grade 1 or higher proteinuria (p=0.037, 0.024, 0.027 by Mann-Whitney test, respectively), and were associated with the best tumor response (by Mann-Whitney test, p=0.043) (Table 1). Patients with 5.0 ng/mL of higher trough levels of AXI showed a tendency toward longer PFS than those with the trough levels less than 5.0 ng/mL (Table 2). Conclusions: TDM of AXI in patients with aRCC may be useful to determine the adequate dose and prevent severe AEs. Further studies are mandatory to conclude the usefulness of TDM of AXI for the long-term clinical efficacy in patients with aRCC. [Table: see text] [Table: see text]
Outcomes and prognosticators in patients with pathologic T4 renal cell carcinoma.
Authors: Borregales Leonardo , Kim Dae Y. , Qiao Wei , Tamboli Pheroze , Jonasch Eric , Tannir Nizar M. , Matin Surena F. , Wood Christopher G. , Karam Jose A. 
Published: February 2017

514 Background: The 2010 American Joint Committee on Cancer (AJCC) TNM staging system defines pathological T4 renal cell carcinoma (RCC) as extension of tumor beyond Gerota’s fascia and/or invading contiguously into the adrenal gland. This subset of patients with the highest stage and locally advanced disease demonstrate poor outcomes with an estimated 5 year-survival rate of 20-30%. For this high-risk population, patient selection is imperative for proper patient counseling and to identify patients who would benefit from surgical intervention. Our objective was to study patient outcomes and determine prognostic variables predicting survival in pT4 RCC. Methods: From July 1992 to January 2012, we identified 64 patients at our institution who underwent radical nephrectomy and were found to have pT4 disease. The clinical and pathological variables were studied using univariate analysis to identify prognostic variables predicting survival using the Cox proportional hazards model. Survival plots were estimated using Kaplan-Meier method and survival analysis was performed using log-rank test. Results: Median patient age was 56 years (35-82), and 46 (68.7%) were male. Fifty-two (83%) patients had ECOG Performance Status 0 or 1. At diagnosis, 20 (32%) patients were M0 and 42 (68%) were M1. Median tumor size was 13 cm (5.5-25). Forty-nine (76%) patients had clear cell RCC and 26 (40%) had sarcomatoid features. Forty-seven (73.4%) patients had Fuhrman grade 3 or 4. Twenty-eight (44%) patients were pN0, 16 (25%) were pN1, and 20 (31%) were pNx. On multivariate analysis, the significant predictors of survival (p < 0.05) were M stage at time of nephrectomy, pN stage, performing LN dissection, Fuhrman grade, and presence of sarcomatoid features. Conclusions: Survival in patients with pT4 remains poor. Predictors of survival in pT4 RCC patients include M stage, N stage, LN dissection, Fuhrman grade, and sarcomatoid features. Preoperative identification of patients with pT4 needs refinement, and could help improve patient management and selection for inclusion in neoadjuvant trials.
Validation of an active surveillance threshold for the CCP score in conservatively managed men with localized prostate cancer.
Authors: Stone Steven , Cuzick Jack M. , Fisher Gabrielle , Yang Zi Hua , North Bernard , Berney Daniel M. , Beltran Luis , Greenberg David , Møller Henrik , Reid Julia E. , Gutin Alexander , Lanchbury Jerry S. , Brawer Michael K. , Scardino Peter T. 
Published: February 2017

54 Background: Active surveillance (AS) is an increasingly popular treatment modality for men with localized prostate cancer. However, better risk stratification is needed to appropriately select men for AS. The cell cycle progression (CCP) score has proven to be a robust predictor of prostate cancer outcomes in various clinical settings, including conservatively managed cohorts. Here, we present a validation of an AS threshold for a predefined score that combines CCP with CAPRA (combined clinical CCP risk (CCR) score) for predicting prostate cancer mortality (PCM) in conservatively managed patients. Methods: We determined the CCR score distribution in 505 men who were tested in our clinical laboratory and, based on their clinical characteristics, might typically be considered for AS. Specifically, the training cohort consisted of men who had Gleason score ≤ 3+4; PSA < 10 ng/ml; < 25% cores positive; and clinical stage ≤ T2a. A threshold CCR score of 0.80 was selected such that 90% of the men in the training cohort had scores below the threshold. The performance characteristics of the threshold were then evaluated in two independent cohorts of conservatively managed men (TAPG1 [N= 180] and TAPG2 [N=585]). Survival data were censored at 10 years. Results: The primary pre−planned analysis called for evaluating the CCR threshold on TAPG2. There were 60 men (of 585) below the threshold in the validation cohort and the threshold validated, dichotomizing the cohort into high and low risk groups (log rank P−value = 0.0008). There were no deaths in patients below the threshold and the Cox proportional hazard estimate of 10−year PCM associated with the CCR threshold was 3.3%. The 10−year risk of PCM associated with the threshold in the combined cohort (TAPG1 and TAPG2) was 3.2% and there were no observed prostate cancer deaths in patients below the threshold. Conclusions: For patients considering deferred treatment, the CCR score provides significant prognostic information at disease diagnosis. The threshold presented here was derived from the ‘typical’ risk of PSM for AS patients and can be used to guide patient selection for AS based on an integrated view of risk assessment.
Use of multiparametric MRI to alter management pathways: Treatment patterns of prostate cancer in the targeted biopsy era.
Authors: Chelluri Raju , Frye Thomas P , George Arvin , Fascelli Michele , Ho Richard , Abboud Steven , Walton-Diaz Annerleim , Sankineni Sandeep , Turkbey Baris , Wood Bradford J. , Pinto Peter A. 
Published: February 2017

56 Background: As the use of multiparametric MRI (mpMRI) to diagnose prostate cancer (PCa) becomes established, better knowledge of treatment patterns is needed to counsel patients. Prior studies have shown 40-55% undergo Radical Prostatectomy (RP), while only 6% prefer Active Surveillance (AS), and that stratification by risk does not greatly alter treatment pathways. We aim to delineate the distribution of PCa treatment modalities in the MRI/US fusion-guided prostate biopsy (FB) era. Methods: A retrospective review was performed of all patients who underwent FB at the NIH from 2010 to present. Demographics, Gleason scores, MRI Suspicion scores and treatment outcomes were recorded. Patients were stratified according to D’Amico Risk Criteria, and outcomes were coded into four categories: AS; RP; Radiation (XRT, Brachytherapy); and Other (Systemic or Focal therapy). Results: 839 men were reviewed. Mean age was 62.6 years old and mean PSA was 9.7 ng/mL. Total cancer detection rate was 70% (n = 589). Of FB positive men, 474 had treatment information available. Overall 225 (47.5%) entered AS, 158 (33.3%) underwent RP, 61 (12.9%) received XRT, and 30 (6.3%) received other intervention. Subgroup analysis by MRI suspicion score (Table) showed 47.4% frequency of RP in the high vs. 30.9% and 19.4% for moderate and low suspicion groups, respectively. Analysis by D’Amico Risk (Table) showed 86% of low risk men chose AS vs. 0% of high risk men. Conversely 9.7% of low, 44.5% of intermediate and 55.7% of high risk men underwent RP. Conclusions: FB was associated with a higher rate of AS choice as a treatment modality for low risk disease. However most patients with clinically significant PCa still chose RP as their treatment. FB is an additional tool that allows the urologist to better counsel patients and provides individualized treatment for PCa. [Table: see text]
Oncological outcomes in high-risk prostate cancer after radical prostatectomy based on Gleason score: USC experience with 3,755 cases.
Authors: Djaladat Hooman , Xu Weichen , Cai Jie , Lieskovsky Gary , Daneshmand Siamak 
Published: February 2017

60 Background: Gleason score is an important predictor of oncological outcomes after radical prostatectomy. However, it remains unclear whether there is a difference in outcomes between Gleason score (GS) 8 and 9-10 disease. We compare oncological outcomes after open radical prostatectomy for prostate cancer patients with GS of 8 versus 9-10. Methods: Of 3,755 radical prostatectomy patients (1987-2008), 360 patients with final pathology of GS 8, 9 or 10 and N0M0 were included. No significant differences between age, race and surgical margins between the two groups. Impact of GS on outcomes was controlled for preoperative PSA, pathological stage, use of adjuvant radiation therapy and use of neoadjuvant/adjuvant hormone deprivation therapy in multivariable analyses. Outcomes of interest were biochemical recurrence free survival (BCRFS), clinical recurrence free survival (CRFS) and overall survival (OS). Kaplan Meier plots, log rank tests and multivariable Cox regression model were used to analyze the data. Results: Median follow-up for GS 8 and GS 9-10 were 10.0 years and 8.6 years, respectively (p=0.43). Conclusions: Long term follow up after radical prostatectomy reveals significant differences in BCRFS and CRFS but not OS between patients with GS 8 vs. 9-10 prostate cancers. Further studies may examine sub-stratification of GS 8 tumors into a lower risk category than GS 9-10 tumors. [Table: see text] [Table: see text]
The association of very low PSA with increased cancer-specific death in men with high-grade prostate cancer.
Authors: Mahal Brandon Arvin Virgil , Aizer Ayal Aaron , Efstathiou Jason Alexander , Nguyen Paul Linh 
Published: February 2017

62 Background: It has been hypothesized that very low PSAs in men with high-grade prostate cancer could reflect dedifferentiation and a poorer prognosis, but clinical evidence to support this is limited. We sought to determine whether a very low-presenting PSA was associated with greater prostate cancer-specific mortality (PCSM) among men with Gleason score (GS) 8-10 disease. Methods: The Surveillance, Epidemiology and End Results Program was used to identify a national cohort of 328,904 men diagnosed with cT1-4N0M0 prostate cancer between 2004 and 2010. Multivariable Fine-Gray competing-risks regression analysis was used to determine PCSM as a function of PSA level (<2.5 ng/mL, 2.6-4 ng/mL, 4.1-10 ng/mL, 10.1-20 ng/mL, 20.1-40 ng/mL, or >40ng/mL) and GS (8-10 vs. <=7). Results: Median follow-up was 38 months. Among men with GS 8-10 disease, using PSA 4.1-10 as the reference group, the Adjusted HR (AHR) for PCSM for men with PSA level <2.5 was 1.86 (95% CI 1.51-2.29; P<0.001), PSA 2.6-4 was1.44 (1.17-1.78; P<0.001), PSA 10.1-20 was 1.58 (1.39-1.78; P<0.001), PSA 20.1-40 was 2.04 (1.78-2.33; P<0.001), and PSA>40 was 3.19 (2.83-3.59; P<0.001), suggesting a U-shaped distribution. There was a significant interaction between PSA level and GS (Pinteraction<0.001) such that PSA <2.5 only significantly predicted for poorer PCSM among patients with high grade GS 8-10 disease. Conclusions: Among patients with high grade GS 8-10 disease, patients with PSA <2.5 and 2.6-4 appear to have a higher risk for cancer-specific death compared to patients with a 10.1-20 PSA level, supporting the notion that low PSA in GS 8-10 disease may be a sign of underlying aggressive and extremely poorly differentiated or anaplastic low PSA-producing tumors. Patients with low PSA GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents in very-high risk prostate cancers.
Quality of life (QOL) and acute toxicities of a pilot study of focal salvage high-dose rate (HDR) prostate brachytherapy in patients with local recurrence after definitive external-beam radiotherapy (XRT).
Authors: Chung Hans T. , D'Alimonte Laura , Loblaw D. Andrew , Ravi Ananth , Wronski Matthew , Davidson Melanie , Haider Masoom A. , Morton Gerard 
Published: February 2017

79 Background: Despite dose-escalated radiotherapy, studies of post-treatment biopsies of the prostate for intermediate-risk prostate cancer suggest that approximately 20% will be positive. Salvage options include surgery, brachytherapy, cryotherapy or high-frequency ultrasound. However, the risk of significant complications (e.g. fistula, incontinence, bladder neck contracture), is not insignificant. The objective of this pilot study is to explore the QOL, toxicities and efficacy of focal salvage HDR prostate brachytherapy. Methods: This study was approved by the institution’s research ethics board. Eligible patients included: biopsy-confirmed local recurrence >30 months after XRT, MRI demonstrating solitary recurrence confined to the prostate, negative metastatic workup, IPSS <15, post-XRT PSA <10ng/mL, prostate volume ≤50cc. Salvage ultrasound-based HDR brachytherapy was performed with a prescription dose of 27Gy divided over two implants separated by 1 week to the target volume (TV) as seen on MRI with dose constraints to the urethra and rectum. Results: Eleven patients (mean age 73 years) have been enrolled in the study. At initial presentation, there were 4, 6 and 1 low-, intermediate- and high-risk disease, and initial XRT received was 70-78Gy. The Gleason score of the local recurrence was 7 and 8-10 in 6 and 5 patients, respectively. The pre-HDR mean PSA was 5.0 (range 1.3 – 9.29). The median size of the recurrence on MRI was 10mm and median volume of the TV was 5.9cc (2.2-16.1), TV V100 96.0%, urethral D10 64.5% and rectal D1cc 42.9%. Ten patients have at least 6 months of follow-up (median 10 months), and no acute GU/GI grade 3-5 toxicities were observed, including urinary retention. The most common acute toxicity was frequency and nocturia. Mean IPSS at baseline, 1-, 3- and 6-months was 6, 8, 7 and 5. At 6-months, 9 of 10 patients had a lower PSA (mean 1.78) than baseline. There was no significant change in EPIC urinary, bowel and sexual domains within the first 6-months. Conclusions: Preliminary data suggests that focal salvage HDR brachytherapy was technically feasible with minimal acute toxicities. Clinical trial information: NCT01583920.
Are men with favorable intermediate-risk prostate cancer candidates for active surveillance?
Authors: Raldow Ann Caroline , Zhang Danjie , Chen Ming-Hui , Braccioforte Michelle H. , Moran Brian Joseph , D'Amico Anthony Victor 
Published: February 2017

82 Background: Active surveillance (AS) is considered appropriate for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, with grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may also be an initial option for men with favorable intermediate-risk PC. We estimated and compared the risk of PC-specific mortality (PCSM) following high dose radiation therapy and androgen deprivation therapy as appropriate amongst men with low, favorable intermediate, unfavorable intermediate, and high-risk PC. Methods: The study consisted of 6,595 consecutively treated men (median age: 68 years) with localized or locally advanced PC at the Chicago PC Center between 1997 and 2013. Fine and Gray competing risks regression analyses (table) were used to assess the risk of PCSM in men with favorable intermediate, unfavorable intermediate or high-risk compared to low-risk PC, adjusting for age at and year of treatment. Results: After median follow-up of 7.76 years, 820 men died: 72 of PC. While men with favorable intermediate-risk did not have significantly increased risk of PCSM as compared to low-risk PC (adjusted hazard ratio (HR) 1.28, 0.63-2.62 95% confidence interval (CI), p-value 0.49), men with high (adjusted HR 9.91, 5.48-17.94 95% CI, p-value <0.0001) or unfavorable intermediate-risk PC (adjusted HR 3.17, 1.60-6.30, p-value 0.001) did. Eight-year point estimates of PCSM were low: 0.68% [0.32-1.31% 95% CI] and 0.44% [0.25-0.75% 95% CI] for men with favorable intermediate and low-risk PC, respectively. Conclusions: Men with low and favorable intermediate-risk PC have similar and low estimates of PCSM during the first decade following standard management. These results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC. [Table: see text]