bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical effectiveness of modified method of laparoscopic partial nephrectomy.
Authors: Dimitriadi Sergey N , Kit Oleg Ivanovich 
Published: March 2020

e15602 Background: Warm ischemia time (WIT) is the most important factor predicting postoperative renal function condition after laparoscopic partial nephrectomy (LPN). Methods: During 1 year (2012) 22 LPN was performed on T1 stage renal cell carcinoma (RCC) patients. Our current laparoscopic technique involves transperitoneal approach, atraumatic hilar clamping (in all patients), tumor excision by cold endoshears. In 12 cases (54.5%) pelvicaliceal system (PCS) of the kidney was opened. These patients underwent LPN modification, which consists of excluding of separate PCS suture repair of the kidney after tumor excision. This technique allowed reducing WIT. Tumor bed excision was sutured using “sliding clip” technique without using any addition hemostatic materials. Control group consist of 10 (45.5%) patients whose PCS were not opened during LPN. Results: Mean age in the main and control groups was 59.3±10.6 years (range 42-77) and 52.5±11.7 years (range 33-68), mean tumor size – 39.3±7.5 mm (range 29-57) and 39.5±7.5 mm (range 25-52), mean RENAL nephrometry sum - 7.6±1.2 (range 6-10) and 6.8±0.9 (range 5-8), mean WIT – 12.6±2.3 min.(range 9-16) and 11.3±3.1 (range 6-15), mean blood loss – 207.5±237.9 ml (range 50-800) and 97±32.7 ml (range 50-150) respectively. In all 12 cases PCS defect was up to 2 cm. Conversion was performed in one case with RENAL nephrometry sum 10 and one kidney lost due to complexity of resection. Mean follow up was 5.4±3.1 month (range 1-10). Intraoperative hemorrhage was in 2 main group patients. Delayed hemorrhage, urine leak, postoperative renal failure did not occur. All patients confirmed RCC, and all of them had negative inked surgical margins for cancer. Conclusions: Thus, use of modified technique of LPN allowed carrying out difficult partial nephrectomies (up to 10 RENAL nephrometry sum) with no significant deference of WIT (p=0.334 Mann Whithitney U-test) from more simple LPN (without opening PCS). This explains absence of kidney injury in the postoperative period. We suppose, that meticulous suture repair of a tumor bed using “sliding clip” technique with defects of PCS up to 2 cm is safe, considered urine leak development. This approach will allow to expand indications to LPN.
Outcomes associated with sunitinib alternative schedule compared to traditional schedule: a single-center experience.
Authors: Atkinson Bradley J. , Kalra Sarathi , Wang Xuemei , Bathala Tharakeswara , Perpich John , Corn Paul Gettys , Tannir Nizar M. , Jonasch Eric 
Published: March 2020

e15611 Background: Sunitinib is a front-line therapy for metastatic renal cell cancer (mRCC). Recommended dose is 50 mg daily; 28 days (d) on/14 d off (traditional schedule; TS). Sunitinib is associated with several adverse events (AEs). An ideal treatment modification algorithm is not known. We sought to identify 1) common AEs, 2) alternative schedules (AS) that maintained dose intensity while decreasing AEs, and 3) the impact of AS on outcomes. Methods: Single-center retrospective review of mRCC pts performed from 1/26/06 to 3/1/11. Pts > 18 years of age with mRCC who received first-line antiangiogenic therapy with sunitinib were eligible. A subset of pts were switched at first intolerable AE from TS to a 14 d/7 d, or further adjusted to 7 d /3 d, or other AS. Control group underwent standard dose reduction. Pt characteristics including demographics, disease status, laboratory data, AEs, AS, and treatment outcomes were analyzed. Results: 186 eligible pts were identified. At baseline, 87% received sunitinib 50 mg and 88% were on TS. 99 pts (53%) continued TS and 87 pts (47%) were switched to AS. Baseline characteristics were similar. Median age was 61 yrs; by MSKCC criteria 5% were good, 50% intermediate, and 45% poor prognosis. Pts had median 2 visceral mets and 42% had primary tumor in place. AEs included fatigue (47%), diarrhea (24%), and hand-foot syndrome (26%). Median time to AS was 126 d with 14 d/7 d the most common (82%). Median time on treatment was 14.9 months (mo) (95% CI:10.2 – 17.0 mo) in AS pts vs 4.2 mo (95% CI: 3.6 – 5.7 mo), respectively (p < 0.0001). Median OS was 32.9 mo (95% CI:28.3-54.1 mo) vs 18.5 mo (95% CI: 10.3-21.5 mo), respectively (p = 0.0001). ECOG PS > 2 (HR 3.9), elevated LDH (HR 2.04), and > 2 mets (HR 1.79) were associated with decreased OS. MSKCC intermediate vs poor (HR 0.57) and AS (HR 0.54) were associated with improved OS by multivariate regression analysis (p < 0.05). Conclusions: In our cohort study, AS sunitinib significantly prolonged time on treatment and was predictive of OS. Prospective investigations of alternate dosing schemas are warranted.
Inactivation of the nuclear receptor TR3 as an important new drug target for treating RCC.
Authors: Abdelrahim Maen , Safe Stephen , Abudayyeh Ala 
Published: March 2020

e15618 Background: The high mortality of patients with RCC is due to poor performance of most chemotherapy. There is a critical need for development of new mechanism-based drugs.The nuclear orphan receptor NR4A1 (TR3, Nur77) are immediate early genes activated by various stressors. NR4A is highly expressed in multiple tumors. TR3 knockdown studies show that TR3 plays an important role in cancer cell growth and angiogenesis. The pro-oncogenic activity of this receptor is an excellent example of “non-oncogene addiction” which is essential for maintaining the cancer cell/tumor phenotype. Methods: Multiple RCC cell lines have been used. Several different classes of C-substituted DIMs summarized in Fig1 has been screened for TR3 deactivation in RCC cell lines using GAL4-TR3/UAS-luc constructs (Fig1). Effects of the C-DIM compounds on cancer cell growth and expression of Sp-regulated genes has been determined by cell counting, the MTT assay, western blot and activation of caspases 3 and 9 and directly compared to knockdown of TR3 by RNAi. Results: Knockdown of TR3 by RNAi has confirmed that TR3 is pro-oncogenic and we have focused on structure-activity relations (SARs) of C-DIM analogs to identify compounds that inactivate TR3. Renal cancer cells were treated with c-DIM TR3 inactivators and this significantly inhibited cell proliferation (Figs 2 and 3). Expression of TR3 in RCC cell lines has not previously been reported. Fig. 4 presents a western blot of cell lysates showing that TR3 is expressed in these cell lines. TR3 inactivators decreased expression of survivin and bcl-2 and this was accompanied by several apoptotic markers. These results show that RCC cells not only express TR3 but TR3 inactivators decrease the pro-survival genes and induce apoptosis which confirm that TR3 is also a target for renal cancer therapy. TR3 pro-oncogenic activity is due, in part, to the role of TR3 in constitutive expression of survivin and other Sp-regulated genes (VEGF, c-MET..). TR3 also involves in formation of a complex with p53 which inactivates the tumor suppressor gene. Thus inactivation of TR3 activates p53 pathway (Fig 5). Conclusions: TR3 is overexpressed in RCC. We have shown for the first time that TR3 is an important new drug target for treating RCC.
Clinical implications of a prostate cancer risk SNP profile in two treatment cohorts.
Authors: Goh Chee Leng , Saunders Ed , Leongamornlert Daniel , Dadaev Tokhir , Tymrakiewicz Malgorzata , Thomas Karen , Selvadurai Elizabeth , Woode-Amissah Ruth , Mahmud Nadiya , Castro Elena , Olmos David , Guy Michelle , Govindasami Koveela , Wilkinson Rosemary , Sawyer Emma , Amin Al Olama Ali , Easton Douglas , Kote-Jarai Zsofia , Parker Chris , Eeles Ros A. 
Published: March 2020

e16000 Background: Prostate cancer (PCa) has a heritable risk and genome-wide association studies (GWAS) have so far identified 76 single nucleotide polymorphisms (SNPs) associated with PCa risk. Currently these SNPs have only been evaluated against overall PCa risk and several disease parameters. Their clinical utility remains undefined. We explore the potential prognostic role of the risk SNP profile in 2 PCa cohorts; Active Surveillance (AS) and androgen deprivation therapy (ADT). Methods: PCa patients at the Royal Marsden Hospital who consented for DNA analyses were eligible. 2 separate cohorts were identified; those undergoing AS and those receiving ADT. The risk SNPs were genotyped using Sequenom or Fluidigm platforms. The cumulative SNP risk scores for each patient were calculated by summing risk alleles for each loci using the weighted effect as estimated in previous studies (log-additive model). For the AS group, the risk scores were analysed against defined adverse outcomes in AS, including adverse histology on repeat biopsy and time to treatment, to determine their prognostic value. For the ADT group, the risk scores were assessed against time to relapse, defined by either biochemical relapse or evidence of progression on imaging. Results: In the AS group, 391 patients’ DNA were studied. 31% of those have since undergone treatment and 30% have histological upgrade on repeat biopsies. On univariate analysis, there was no significant relationship between the risk scores and biopsy upgrade or time to treatment (p>0.05). When analysing differences in outcomes between the higher and lower risk groups (top 25% and lowest 25% of the genetic risk distribution), there was again no relationship (p>0.05). In the ADT group, 567 patients’ DNA were studied. The mean duration of response was 30 months. No significant associations were found when risk scores were analysed as a continuous variable against time to relapse on ADT, or when analysing difference between the top and bottom 25% of the risk distribution (p>0.05). Conclusions: PCa SNP risk scores have not been shown to be prognostic factors in either AS or ADT. This is the first study analysing the potential prognostic role of the latest GWAS risk SNPs in PCa treatment cohorts.
Effect of addition of docetaxel (D) to hormonal therapy (HT) versus HT alone on quality of life: Results from a phase III study in non-metastatic high-risk prostate cancer (PC) patients (pts) with a rising PSA status.
Authors: Oudard Stephane , Gillaizeau Florence , Peyrard Severine , Latorzeff Igor , Beuzeboc Philippe , Sevin Emmanuel , Rolland Frederic , Mourey Loic , Priou Franck , Culine Stephane 
Published: March 2020

e16009 Background: Around 75% of non-metastatic high risk PC pts undergo PSA recurrence within 2 years after local therapy. Effect of D in addition to HT on Quality Of Life (HRQoL) was assessed using QLQ-C30. Methods: HRQoL was assessed every 3months: baseline, 3m, 6m, 9m and 12m for this multicenter, randomized phase III study comparing arm A: HT+D (70 mg/m2 Q3W, 6 cycles) and arm B: HT (triptorelin) every 3m for 1 year in non-metastatic PC pts at high-risk of recurrence after radical prostatectomy (RP) and/or radiotherapy (RT). Stratification factors (SF) were RP vs RT and PSA-doubling time < or >6m. Inclusion criteria were at least 1 of: Gleason >8, PSA-DT <6m, positive surgical margins, PSA velocity >0.75ng/mL/year, pathological pelvic lymph nodes, time from RP/RT to inclusion < 12m. Primary endpoint was PSA PFS (ASCO2011, abs 84423); secondary endpoints: PSA response, time to metastasis, overall survival, QoL and safety. Treatment effect on QoL was analyzed using 1) linear (L) and non-linear (NL) mixed models with continuous and discrete time points from baseline to 12m. Covariates were: SF, an interaction term between time and treatment and 2) time to 20% degradation of QoL upon Cox regression model. Results: Included =254, ITT=251. Arm A (125) vs B (126): median age(y) 64 vs 66, time(m) initial diagnosis to inclusion 35 vs 34, ECOG=0: 96% vs 93%, Gleason score (%) >8: 32 vs 27, RP (%): 69.6 vs 71.4, RT (%): 37.6 vs 38.1, PSA-DT (%) <6m: 53.6 vs 53.2, respectively. At baseline, mean (SD) Global Health status was 76.8 (19.4) and 81.6 (16.9) for arm A and B respectively (p=0.10). Fatigue dimension score was different at 3M (p<0.0001). Upon linear and non-linear longitudinal analysis, addition of D to HT had no effect on QoL (L: p=0.29; NL: p=0.25). Time to 20% QoL degradation was not significantly different between the 2 arms (p=0.44). Conclusions: Addition of docetaxel to hormonotherapy at an early stage after local therapy in non-metastatic high-risk PC pts with a rising PSA status does not significantly impact QoL during the first 12 months.
The free hormone hypothesis: Correlation of decreases in PSA with free testosterone rather than total testosterone in men with advanced prostate cancer treated with GTx-758.
Authors: Matsumoto Alvin M. , Getzenberg Robert H. , Coss Christopher , Hancock Michael L. , Si Xuemei , Dalton James T. , Steiner Mitchell S. 
Published: March 2020

e16015 Background: Androgen deprivation therapy (ADT) improves disease-free survival but disease progression is related, in part, to ineffective castration. The free hormone hypothesis states that the biological activity of steroid hormones is affected by its unbound (free) rather than its protein-bound concentration. Serum total testosterone (T) concentrations predominantly reflect the T bound to plasma proteins and do not accurately predict prostatic levels of T. Methods: In a Phase II study (G200705), men with advanced prostate cancer (n=159) were randomized to receive 1000 mg or 2000 mg GTx-758 daily or leuprolide as their initial ADT. Serum total T (mass spectrometry), free T (equilibrium dialysis), SHBG and PSA concentrations were measured. A second Phase II study (G20007) was performed in men (n=9) with CRPC who then received GTx-758 2000 mg daily. Results: Although both treatments reduced serum total T levels to < 50 ng/dL, leuprolide decreased them to a greater extent. However, GTx-758 caused greater reductions in serum PSA, suggesting that total T concentrations did not accurately reflect the suppression of androgen activity. Both dosages of GTx-758 reduced free T levels to a greater extent (mean of 0.7 and 0.4 pg/ml at day 60, and 0.4 and 0.4 pg/ml on day 90, respectively) than leuprolide (mean of 1.4 pg/ml on day 60 and 1.4 pg/ml on day 90; p values <0.03). Similar clinical results were observed in CRPC patients where GTx-758 daily resulted in a 71% decrease in %free T and clinically relevant PSA reductions in men maintained on ADT with LHRH agonists. As a result of adverse events at higher doses of GTx-758, the trial was stopped early. Conclusions: The ERα agonist, GTx-758, reduced the biologically active form of T, free T, to significantly lower levels than leuprolide. Reductions in PSA appeared to be more highly associated with changes in free T. These data provide compelling evidence to support the free hormone hypothesis and suggest that serum free T concentrations would provide a better measure of therapeutic efficacy in ADT than total T. A Phase II clinical trial utilizing lower doses of GTx-758 (G200712) is currently being performed. Clinical trial information: NCT01326312.
Detecting lower in addition to the highest Gleason score prostate cancer on core biopsy and the odds of upgrading at radical prostatectomy.
Authors: Phillips John G , Aizer Ayal A. , Chen Ming-Hui , Hirsch Michelle S. , Richie Jerome P. , Tempany Clare M. , Hegde John , Loffredo Marian , D'Amico Anthony Victor 
Published: March 2020

e16026 Background: We evaluated the odds of upgrading at radical prostatectomy when a biopsy core with a lower Gleason score (GS) compared to the core with the highest GS was present (ComboGS) versus not at diagnosis and in a concurrent submission, test ComboGS in a validation data set on the endpoint of prostate cancer-specific mortality. Methods: The study cohort consisted of 134 men with clinically localized PC diagnosed between 4/08 and 9/11 using a 12-core prostate needle biopsy. GS at biopsy and RP were assigned by an expert genitourinary pathologist. Logistic regression multivariable analysis (Table) was performed to assess the impact that ComboGShad on the odds of upgrading at RP adjusting for known predictors of upgrading. Results: Of 134 patients, 46 (34%) were upgraded. Both increasing percent positive biopsies (ppb) (p < 0.001) and PSA level (p=0.001) were associated with an increased odds of upgrading, whereas ComboGSwas associated with a decreased odds of upgrading (0.18 [95% CI: 0.04-0.76); p = 0.02). Men whose ppb was ≥ 33% (median) were upgraded in 47% (28 of 60) versus 14% (3 of 21) of cases (p = 0.009) when ComboGSwas absent versus present. These respective estimates in men with a PSA ≥ 5.2 ng/ml (median) were 43% and 12% (p = 0.019). Conclusions: In men with clinical factors associated with upgrading namely, increasing ppb and PSA, ComboGSis a favorable prognostic factor associated with a high rate of downgrading (> 40%) and a low rate (< 15%) of upgrading. Adjusted odds ratios and associated 95% confidence intervals and p values representing the impact of clinical factors at diagnosis on upgrading at radical prostatectomy. [Table: see text]
Prognostic implications of serum crosslinked-n-terminal telopeptide of type I collagen (NTx) for patients with initial prostate carcinoma.
Authors: Jablonka Fernando , Wroclawski Marcelo L. , Fonseca Fernando L. A. , Szwarc Marcelo , Machado Marcos Tobias , Vitoria Webster de Oliveira , Del Giglio Auro 
Published: March 2020

e16030 Background: NTx is a metabolite of type I collagen, the main constituent of bone matrix, which has been previously shown to be increased in patients with bone metastasis. We wanted to evaluate NTx role in sample PCa patients at diagnosis when most of them have no overt bone involvement. Methods: Men with a histologic diagnosis of PCa at diagnosis were included. Serum Ntx was measured serially every 3 months up to two years by ELISA with the osteomark NTx Serum kit. Results: 55 PCa patients with a median age of 67 years (51 – 83), 86% with stage I, 4% with stage II, 2% with stage III and 10% with stage IV were included. At entry median NTx was of 14.65 nM and it did not correlate with age, Gleason score or PSA but we observed a significant direct correlation with stage (p = 0.0094). With a median follow up of 23 months, at diagnosis, Seum Ntx correlated significantly with biochemical recurrence (p = 0.012) as did Gleason score (p = 0.00056), Stage (p = 0.012) and PSA (p < 0.0001). By multivariate analysis the only 2 independent variables significantly correlated with biochemical recurrence were PSA (p = 0.046) and NTx (p = 0.021). Conclusions: We conclude that Serum Ntx has potential prognostic value in PCa patients at diagnosis and may improve current prognostic models. These data stress the potential prognostic importance of bone metabolism biomarkers for PCa patients even in the absence of overt bone involvement. Supported by: FAPESP.
Incremental cost (IC) analysis of skeletal related events (SREs) among elderly men with stage IV metastatic (M1) prostate cancer (PCa).
Authors: Jayasekera Jinani , Onukwugha Ebere , Bikov Kaloyan A. , Mullins C. Daniel , Seal Brian S. , Hussain Arif 
Published: March 2020

e16034 Background: Patients diagnosed with stage IV M1PCa are predisposed to SREs, such as pathologic fracture (PF), spinal cord compression (SCC) and bone surgery (BS). There is limited information in the literature regarding the ICs associated with SREs among stage IV M1 PCa patients. Methods: We analyzed patients aged 66+ yrs diagnosed with incident stage IV M1 PCa between 2000 and 2007 from the linked SEER-Medicare dataset. Five mutually exclusive SRE categories were created: PF only, PF+concurrent surgery (SRG), SCC only, SCC+SRG, and BS only. Patients with multiple SREs were excluded. A propensity score for the incidence of an SRE was estimated using a logistic regression model including baseline demographic and clinical variables, diagnosis year and SEER region. Patients with SREs (cases) were matched to those without SREs (controls), based on the propensity score. The date of SRE of a case was assigned to a matched control, and the 12 month pre- and post-SRE costs were calculated. A difference-in-difference method was used to estimate the ICs (post-pre) for cases vs. controls. The analysis was conducted from a US Medicare perspective. Results: Application of inclusion criteria resulted in 1,131 stage IV M1 PCa patients with SREs. The average age was 78 yrs and 12% were African American. Using the propensity score, 1,031 cases were matched with 1,031 controls and allocated to the following SRE groups: PF+SRG (n=134), PF only (n=143), SCC+SRG (n=40), SCC only (n=538) and BS only (n=176). The average IC per SRE was $30,548 (vs. controls). The most expensive SRE group was SCC+SRG with a total average IC of $62,412, followed by BS only ($37,554), PF+SRG ($35,520), SCC ($28,027), and PF only ($17,839). Inpatient costs were the major driver of ICs followed by physician/non-institutional provider and skilled nursing facility (SNF) costs. Conclusions: The ICs associated with an SRE are significant. The IC of an SRE varies by type of SRE and service category. [Table: see text]
Effect of immunization with Ii-key modified HER2 (776-790) peptide vaccine (AE37) on immunologic responses in prostate cancer patients.
Authors: Perez Sonia A. , Anastasopoulou Eleftheria , Pappou Efi , Tzonis Panagiotis , Bisias Stratos , Thanos Anastasios , von Hofe Eric , Papamichail Michael , Baxevanis Constantin N. 
Published: March 2020

e16037 Background: We have shown that the AE37 vaccine (Ii-Key modified HER2(776-790) peptide) is safe and induces HER2/neu–specific cellular immune responses in patients with prostate cancer (Perez SA et al Clin. Cancer Res. 2010, 16:3495). We now present data from 4-year immunological assessments of prostate cancer patients who received AE37. Methods: Seventeen patients in a phase I study were given 6 doses of AE37 at monthly intervals and one additional dose a year after initiating treatment. Immunological testing to assess active versus suppressive immunity was conducted one month (intermediate-term immunomonitoring [ITI]) and 3 years (long-term immunomonitoring [LTI]) after the final dose of AE37. ELISPOT and proliferation assays were conducted to assess cytokine secretion and mitogenic response to antigen. DTH reactions were measured to assess in vivo immune response to antigen. All assays were conducted using native HER2(776-790) peptide (AE36). The percent Treg cells and ng/ml TGFβ were determined as markers for immune suppression. Results: Neither ELISPOT nor proliferation assays were statistically different at LTI compared to ITI. While clearly above pre-vaccine responses, the drop in DTH was statistically significant (p < 0.05). Similarly, the increase in Treg cells and circulating TGFβ was also statistically significant. An increase of >200 % in PSA-doubling time at any point during the study was observed in 6/17 patients, with 3 retaining this effect to 5 years. Conclusions: AE37 generates immunological memory associated with possible clinical efficacy in spite of Tregs and TGF-β levels returning at 4 years after being decreased for up to 6 months after initial AE37 vaccination. These results support further randomized testing of the AE37 vaccine. Clinical trial information: 2006-003299-37. [Table: see text]