bluuebunny/crossref_metadata_2025_split huggingface dataset:
A feasible and time-efficient adaption of the neurosafe intraoperative frozen section technique to robotic-assisted radical prostatectomy.
Authors: Beyer Burkhard , Tennstedt Pierre , Boehm Katharina , Schiffmann Jonas , Schlomm Thorsten , Steuber Thomas , Graefen Markus , Haese Alexander 
Published: February 2017

147 Background: In robotic-assisted radical prostatectomy (RARP) intraoperative frozen sections are often avoided due to suspected difficulties in harvesting the prostate during this procedure, loss in pneumoperitoneum, increased blood loss and lacking impact on functional outcome. We demonstrate the technique, feasibility and beneficial impact of our NeuroSAFE technique on the rate of nerve-sparing (NS) in RARP and analyse the oncological outcome. Methods: We analyzed 1,570 consecutive patients undergoing RARP from 2004 to 2012. NeuroSAFE was done in 1,178 pts. We compared OR-time, blood loss, frequency of nerve-sparing (NS) and PSM in non-NeuroSAFE versus NeuroSAFE-RARP. The prostate was intraoperatively harvested via an extension of the camera trocar incision without undocking the system. Instrument arms were not undocked. Blood spillage from the dorsal vein complex due to loss of pneumoperitoneum was avoided by upward traction on the transurethral catheter. After prostate removal, pneumoperitoneum was reestablished by closing the extended incision and repositioning of the optical trocar. NeuroSAFE-procedure consisted of intraoperative bilateral frozen sections covering the entire contact area of the prostate and the neurovascular bundles. Results: There was no significant difference in blood loss (253.5±204.4 ml vs. 265.8±246.7 ml, p=0.49) and OR-time. (220 min ± 51 vs. 224 min ± 64, p=0.22). No complications associated with specimen harvesting occurred. NS-rate increased significantly with vs. without NeuroSAFE (overall 97% vs. 81%, pT2 99% vs. 90%, pT3a 94% vs. 74%, pT3b 91% vs. 30). PSM rate dropped significantly with NeuroSAFE (overall 16% vs. 24%, pT2 8% vs. 15%, pT3a 22% vs. 39%, pT3b 49% vs. 67%, all p<0.05). Conclusions: We demonstrate a time-efficient adaption of the NeuroSAFE without patient side cart undocking, easy harvesting process, no increased blood loss or OR-time increased rate of nerve-sparing frequency and reduction of PSMs.
In vitro reproduction and explanation of an abiraterone acetate withdrawal phenomenon.
Authors: Thelen Paul , Jarry Hubertus , Trojan Lutz , Brookman-May Sabine , Bremmer Felix 
Published: February 2017

154 Background: Androgen deprivation and direct androgen receptor (AR) antagonism are standard treatments for castration resistant prostate cancer (CRPC). The advent of new drugs such as abiraterone acetate (AA) and enzalutamide rendered highly efficient implementations of both anti-androgen strategies. However, reports of therapy resistance or cross resistance soon accompanied reports of successful clinical trials of these new drugs. Moreover, case reports of an AA-withdrawal phenomenon surfaced, an outcome normally associated with AR antagonism e.g. by bicalutamide with high AR-affinity and the potential to switch from antagonism to AR-activation. Methods: CRPC cell model VCaP and VCaP resistant to permanent treatment of 5 µmol/L AA (Janssen-Cilag, Germany) were analyzed under AA and for AA withdrawal. Expression of AR, AR-V7, androgen regulated genes, CYP17A1 and AKR1C3 was quantitated by real time RT-PCR. Further analyses were performed by western blots, prostate-specific antigen (PSA) ELISA kits and cell proliferation BrdU tests. Results: VCaP cells resistant to 5 µmol/L AA after 7 months revealed excessive AR and CYP17A1 expression and a marked decline of tumor cell proliferation in response to AA withdrawal or to a similar extent to added 1 nmol/L testosterone. Proliferation dropped to less than 50% when both procedures were combined. Elimination of tumor cells was accompanied by a massive release of PSA which was most pronounced in the combined treatment. Conclusions: Overexpression of AR turning into a liability as a therapeutic target for a testosterone surge has been reported by several research groups. AA withdrawal from AA resistant cells complies with these necessities by overexpression of AR and CYP17A1 formerly arrested by AA. In patients a PSA decline upon AA withdrawal may be explained by an excessive loss of PSA secreting tumor cells. Therefore, AA qualifies uniquely for effective intermittent androgen deprivation of CRPC.
Clinical activity of enzalutamide against metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed on abiraterone acetate: The Princess Margaret experience.
Authors: Vera-Badillo Francisco Emilio , Leibowitz-Amit Raya , Templeton Arnoud , Seah Jo-An , Sridhar Srikala S. , Knox Jennifer J. , Tannock Ian , Joshua Anthony Michael 
Published: February 2017

159 Background: In men with mCRPC enzalutamide and abiraterone acetate have been shown individually to prolong survival after progression on chemotherapy with docetaxel. Little is known about the sequential use of enzalutamide and abiraterone. A PSA response rate of 8% and progression free survival (PFS) of 2.7 months has been reported for 38 men who received abiraterone following enzalutamide [Loriot, Ann Onc, 2013]. Here we report our experience with enzalutamide following abiraterone. Methods: We reviewed all patients with mCRPC treated with enzalutamide following abiraterone and docetaxel at our institution. Primary outcomes were PSA response rate (confirmed decline ≥ 50%) and time to treatment failure (TTF, defined as the time from treatment initiation to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.). Data were analyzed using the Kaplan-Meier method. Results: Twenty-six patients were treated between August 2012 and July 2013. Median age was 72 years (range 56-88); 85% had ECOG performance status 0 or 1; metastatic sites included bone (N=25, 96%), lymph nodes (N=19, 73%) and visceral (N=1, 3.4%). Median number of prior cycles of docetaxel was 8 (range 1 – 12), 6 patients (29%) had previous exposure to ketoconazole, and median duration of previous abiraterone was 8.7 (range 1.4-22.7) months. Seven pts (27%) had a PSA response ≥ 50% and an additional 7 patients (27%) had a ≥ 30% PSA response. Median TTF on enzalutamide was 4.9 (95% CI 3.8-6.2) months. Reasons for discontinuation of enzalutamide were clinical and/or biochemical progression in 24 patients (92%), and toxicity (fatigue grade 3-4) in 3 patients (11.5%). An update of patient numbers and analysis will be presented at the meeting. Conclusions: Treatment of patients with mCRPC with enzalutamide after progression on docetaxel and abiraterone has modest clinical activity.
Patient-reported sexual outcomes and potency following proton therapy for the management of prostate cancer.
Authors: Hoppe Bradford S. , Nichols Romaine Charles , Henderson Randal H. , Mendenhall William M. , Morris Christopher G. , Bryant Curtis , Su Zhong , Williams Christopher R , Li Zuofeng , Mendenhall Nancy Price 
Published: February 2017

160 Background: The present study investigates sexual outcomes and potency rates in men treated with proton therapy for prostate cancer. Methods: Between 2006 and 2010, 1063 men were treated with proton therapy alone (no androgen deprivation therapy) for prostate cancer at University of Florida on an IRB approved outcomes tracking protocol. 99% of men were treated with 78-82 Gy (RBE). The expanded prostate index composite (EPIC) was collected prior to treatment and every 6-12 months after treatment. Potency was defined by question 59 of the EPIC, “How would you describe the usual Quality of your erections during the last 4 weeks”, where an answer of “firm enough for intercourse” was considered potent, while any other answer was considered “impotent”. Results: The EPIC was answered by 97%, 89%, 88%, and 84% at baseline, 6 months, 1 year, and 2 years after treatment. The median sexual summary (SS), sexual function (SF), sexual bother (SB) scores and potency over time are listed in the Table. A restricted analysis of SS, SF, SB and potency rates adjusted to baseline sexual score of 100 (best score) or potency is also included in the Table. Multiple logistic regression of 2 year impotency rate showed that age (<65 vs >=65, p=0.004) and baseline SS score (<68 vs68-99 vs100, p<0.0001) were significant prognostic factors. Among men with baseline potency (n=687), two years following treatment potency rates were 48% if the patient had baseline SS score of <=67 , 68% if the patient had a baseline SS score of 68 to 99 and 84% if their SS score at baseline was 100. Among just men with baseline SS of 100 (n=119), 87% of those age <65 were potent at 2 years, while 78% men age>=65 were potent at 2 years. Conclusions: Although sexual scores and potency decline following proton therapy, men with excellent baseline sexual function have very high rates of potency 2 years following treatment. Longer follow-up is needed. [Table: see text]
Incidence, distribution, and outcomes of node positive patients at radical prostatectomy: Manitoba Prostate Center experience.
Authors: Kaler Kamaljot Singh , Kroczak Tadeusz Jozef , Patel Premal , Rittberg Rebekah , Saranchuk Jeffery Walter , Drachenberg Darrel E 
Published: February 2017

162 Background: Pelvic lymph node dissection at the time of radical retropubic prostatectomy (RRP) varies among surgeons and institutions. Differences focus on candidacy for node dissection and the limit of dissection. Standard lymph node dissection is typically above the obturator nerve to external iliac vessels. We analyzed our local experience of lymph node metastases at time of surgery. Methods: Data from the Manitoba Prostate Center were collected on consective patients undergoing RRP from January 2003 to June 2013 by two urologists with subspecialty training in oncology. Information extracted includes age, prostate-specific antigen (PSA), biochemical recurrence characteristics, and biopsy and pathological results. Results: Four hundred twenty consecutive patients comprised the data set and of whom 411 underwent a RRP and nine aborted prostatectomies. Average age of patients was 60 with an average preoperative PSA of 11. Overall lymph node metastases rate is 16.1%. Of the N1 patients, average number of positive nodes was 2.3. Average nodes removed for all patients were 13.4. Positive nodes on the right were found 53% of the time and 47% on the left. Locations of nodes are as follows: right external iliac, obturator, and hypogastric, 12%, 6%, and 19%, respectively; and for left external iliac, obturator, and hypogastric 9%, 3%, and 16%, respectively of all total nodes. One node was identified as other, and one surgeon sent packets as right pelvic and left pelvic with positive nodes 16% and 19% of all total positive nodes respectively. When looking at zones of a pelvic lymph node dissection separately, 54% are hypogastric, 13% obturator, and 33 external iliac. With an average of 37 months follow-up two patients with N1 disease died and only one from prostate cancer. Seventy nine percent had biochemical recurrence. Median time to treatment for biochemical recurrence was 4.5 months (0 to 33 months) with a median PSA of 0.28. Conclusions: This contemporary series of pelvic lymph node dissection with RRP represents high lymph node metastases (16%) relative to literature. Performing a limited pelvic lymph node dissection would under stage 54% of our patients. Despite high biochemical recurrence only one patient died of prostate cancer.
Effect of prior abiraterone (ABI) or enzalutamide (ENZ) on sipuleucel-T (sip-T) manufacture in PROCEED patients (pts).
Authors: Vogelzang Nicholas J. , Vacirca Jeffrey L. , Kantoff Philip W. , Scholz Mark C. , Dakhil Shaker R. , Nordquist Luke T. , Higano Celestia S. , Sartor A. Oliver , Cooperberg Matthew R. , Sandler Andrew , McCoy Candice , Whitmore James Boyd , Tyler Robert Claude , Armstrong Andrew J. 
Published: February 2017

185 Background: Sip-T is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). PROCEED is an ongoing phase 4 registry, enrolling pts receiving commercial sip-T. There are no exclusions based on prior prostate cancer treatments, so sip-T product parameters can be evaluated in pts receiving prior hormonal agents such as ABI or ENZ. Methods: Pts treated with sip-T within ≤6 mo were eligible to provide informed consent. Prior anticancer interventions were recorded at baseline. Sip-T product parameters were assessed. Results: Of 1,376 pts (as of May 2013), 108 (7.8%) received prior ABI and 58 (4.2%) received ENZ. Patients with ABI or ENZ generally had more advanced disease vs. pts without prior ABI or ENZ (WPT) and a greater proportion of the ABI and ENZ pts received prior docetaxel. There were slight differences in some sip-T product parameters in the ABI and ENZ groups, but neither manufacture nor receipt of sip-T were inhibited, as indicated by the percentage of pts with 3 successful infusions. All groups showed evidence of immune prime boost (Table). Conclusions: A subset of patients in PROCEED have received ABI or ENZ prior to sip-T. We observed no impact of prior ABI/ENZ on sip-t manufacturing or delivery, despite these men having more advanced disease. These results are consistent with prior analyses demonstrating a positive sip-T treatment immune effect in patients who have received prior therapies, including chemotherapy. Further immune monitoring and outcome studies are currently ongoing in the pre-docetaxel mCRPC setting where these agents will likely be used clinically. Clinical trial information: NCT01306890. [Table: see text]
Response of blood flow to hyperthermia in human prostate tumors: Opportunities for enhanced radiation effect and drug delivery.
Authors: Hurwitz Mark , Martin Gregory T , Sidney Daniel A , Welch Charles J , Hansen Jorgen L , Bornstein Bruce A , Kaplan Irving D. , Bowman H F 
Published: February 2017

189 Background: Tissue perfusion may be a significant factor affecting outcome of prostate cancer treatment. Hyperthermia has been shown to have beneficial anti-cancer effects when combined with other anti-neoplastic modalities including radiation, chemotherapy, and immunotherapy. For instance, hyperthermia may increase prostate perfusion resulting in radiosensitization through increased oxygenation and chemotherapy through enhanced drug delivery. We previously reported significant benefit to the addition of hyperthermia to radiation on a phase II trial for men with locally advanced prostate cancer. To better understand tissue perfusion in patients with prostate cancer and response to hyperthermia, we measured perfusion levels in patients on this trial before and after hyperthermia. Methods: Prostate perfusion was measured before and immediately after heating in a total of 21 hyperthermia treatments in 14 patients with prostate cancer. A trans-rectal ultrasound device with a water cooled jacket was used to heat the prostate. Prostate tissue temperatures were measured using three multisensory thermocouple probes. Perfusion was measured with the TDP-200 Thermal Diffusion Probe, a thermistor-based device which quantifies perfusion with a modified wash-out technique. Results: In 19 treatments in which perfusion was measured before heating, average and standard deviation was 18.3 ± 10.6 ml/100g-min and in 17 treatments in which perfusion was measured after heating, it was 30.7 ± 20.8 ml/100g-min. This represents a statistically significant increase of 68% (p = 0.018). Perfusion increased 12 of 15 treatments in which measurements were obtained before and after hyperthermia. Notably, prostate tissue that was most ischemic prior to heating experienced the largest heat-induced perfusion increase. Conclusions: Prostate perfusion increased significantly with a majority of hyperthermia treatments. Enhanced prostate oxygenation may have been a contributing factor to the benefit noted with hyperthermia in this phase II trial. The use of hyperthermia to augment prostate perfusion to enhance radiation, chemotherapy, and immunotherapy warrants further investigation.
Phase II study of weekly cabazitaxel for "unfit" metastatic castration resistant prostate cancer patients progressing after docetaxel treatment: Preliminary toxicity analysis (SOGUG-CABASEM trial).
Authors: Climent Duran Miguel Angel , Perez-Valderrama Begoña , Fernandez Parra Eva , Mellado Begoña , Domenech Montserrat , Fernandez Calvo Ovidio , Anido Urbano , Polo Susana Hernando , Arranz Jose Angel , Caballero Cristina , Ochoa de Olza Maria , Castellano Daniel E. 
Published: February 2017

190 Background: Docetaxel (D) is standard first-line chemotherapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Cabazitaxel (C), a novel taxane developed to overcome D resistance, showed an overall survival improvement in second line CRPC in a three-weekly dose schedule. Its main toxicity is hematological, especially in unfit patients. We aimed to evaluate efficacy and safety of weekly C/pred. in "unfit" mCRPC previously treated with D. Methods: Unfit pts (ECOG 2, dose reduction due to febrile neutropenia during treatment with D or radiation therapy affecting more than 25% of bone marrow reserve) with advanced CRPC progressing after D treatment with ECOG <=2 and adequate bone marrow, liver and kidney functions were included. C 10 mg/m2 was administered on days 1, 8, 15, and 22 of 5-week cycles with daily pred. 5 mg b.i.d. Radiological and prostate-specific antigen response was evaluated according to the PCCTWG II criteria and toxicity according NCI-CTC AE. Results: To date 47 pts have been enrolled and data are available for 38. Median age was 72 (range 56 to 83), 20 (53%) pts had ECOG 2, 29 (83%) had bone metastases. Cycles administered: 124 (median: 3; range: 1 to 9) and 446 weekly administrations (median 11; range 1 to 35). Mean dose intensity was 94%. Most frequent toxicities of all grades as % of cycles were: asthenia (20%), anemia (50%), leukopenia (13%), thrombocytopenia (14%), diarrhea (9%), rash (6%), nauseas (5%), dysgeusia (7%), xerostomia (6%), anorexia (5%), hand-foot syndrome (5%), and neuropathy (2%). Grade 3: thrombocytopenia (10%), anemia (6%), neutropenia (1%), asthenia (3%), anorexia (1%), mucositis (1%), nausea (1%), and vomiting (1%). No grade 4 toxicities were reported. Three patients discontinued the study due to asthenia G3 (2) and mucositis G3 (1). No grade III/IV diarrhea or febrile neutropenia were observed. Conclusions: Administration of weekly C (10 mg/m2) to unfit pts seems to be safe with no grade 3 or greater neutropenia, diarrhea, or febrile neutropenia reported. If activity is confirmed, weekly C may represent an attractive option for unfit pts with mCRPC progressing after D treatment. Clinical trial information: NCT01518283.
Evaluating the safety of abiraterone acetate (AA) and docetaxel (D) administered in combination in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Tagawa Scott T. , Nanus David M. , Posadas Edwin M. , Petrylak Daniel Peter , Bruce Justine Yang , Lim Emerson A. , Peng Weimin , Maul Raymond Scott , Gonzalez Martha , Tran Namphuong 
Published: February 2017

205 Background: D and AA may have complementary mechanisms of action; coadministration may be beneficial. A phase Ib study assesses the safety of escalating doses of D + AA. Methods: Up to4 cohorts (C) of chemo-naïve mCRPC pts would receive D + AA. Data for C1 and C2 are presented. Primary end point: proportion of pts with dose-limiting toxicity (DLT) between Wks 2 and 7, defined as grade (Gr) ≥ 3 non-heme toxicity, Gr 4 neutropenia (absolute neutrophil count < 500/mm3) > 7 days (or febrile neutropenia), Gr 4 thrombocytopenia, or other intolerable toxicity. D + AA was deemed safe if ≤ 33% of pts experienced DLT. Pharmacokinetic (PK) parameters were evaluated for D and AA alone and in combination. Results: 15 pts were treated and 6 pts/C were evaluable for DLT assessment. 2 DLTs were observed in C1, and 1 in C2. 73% and 87% of pts had confirmed ≥ 90% and ≥ 50% prostate-specific antigen (PSA) decline, respectively. Median time to PSA progression has not yet been reached. Systemic exposure, based on maximum plasma concentration (Cmax) and area under the concentration–time curve [(AUC)∞ for D, AUC24 for abiraterone (ABI)], was comparable for both D and AA alone and for D + AA. 3 pts in C3 (D 75 mg/m2+ AA 1000 mg) have been treated past Wk 7 without DLT. Conclusions: D + AA was well tolerated in the cohorts tested. Preliminary results justify further evaluation of safety and efficacy in additional Cs. Clinical trial information: NCT01400555. [Table: see text]
Clinical activity of enzalutamide pre- and post-docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Nadal Rosa , Zhang Zhe , Raheja Hitesh , Eisenberger Mario A. , Antonarakis Emmanuel S. 
Published: February 2017

216 Background: Enzalutamide is an androgen receptor signaling inhibitor that is FDA-approved for post-docetaxel mCRPC patients. Overlapping mechanisms of action and clinical evidence for an interaction between taxanes and androgen-targeted therapies complicates optimal sequencing of taxanes and enzalutamide. We retrospectively evaluated the efficacy of enzalutamide pre- (preD) and post-docetaxel (postD) therapy. Methods: Men with mCRPC who received enzalutamide preD or postD were identified from a single institution database. We investigated factors influencing enzalutamide activity by using univariate and multivariable Cox regression models, with particular attention to whether or not prior docetaxel had been used. Outcome measures of interest were time-to-PSA-progression (TTPP) and progression-free-survival (PFS). Results: A total of 72 patients received enzalutamide at our institution: 22 were preD and 50 were postD. Median duration of enzalutamide therapy was 5.5 mo (range, 0.7–33.6 mo). In univariate Cox regression analysis, the following factors were predictive of TTPP: ECOG status (≥1 vs 0), number of metastases (>5 vs 0-5), hemoglobin and albumin. Prior docetaxel treatment was associated with a trend towards shorter TTPP on enzalutamide (HR 0.54, 95%CI 0.27–1.10, P=0.09). The following factors were predictive of PFS in univariate analysis: ECOG status, number of metastases, hemoglobin and albumin. Prior docetaxel therapy was associated with a trend towards shorter PFS on enzalutamide (HR 0.57, 95%CI 0.29–1.13, P=0.10). Conclusions: These data suggest numerically inferior TTPP and PFS outcomes to enzalutamide in men previously treated with docetaxel compared to men who were docetaxel-naïve, although the small sample size precludes statistically significant results. This potentially supports the hypothesis of cross-resistance between enzalutamide and docetaxel.