bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective evaluation of low-dose ketoconazole plus hydrocortisone (HC) in chemotherapy-pretreated castration-resistant prostate cancer (CRPC) patients.
Authors: Lo Ernest N. , Beckett Laurel A. , Pan Chong-xian , Robles Daniel , Suga Jennifer Marie , Sands Jacob , Lara Primo 
Published: February 2017

227 Background: Ketoconazole (keto), a known CYP17 inhibitor, is a traditional systemic treatment for CRPC. However, most of the published data has been in the pre-chemo setting; its efficacy in the post-chemo setting has not been as widely reported. Chemo-naive patients treated with attenuated doses of keto (200-300 mg TID) had prostate specific antigen (PSA) response rate (> 50% decline) ranges from 21%-62% and treatment was well tolerated. We hypothesized that low dose keto would likewise possess efficacy and tolerability in the CRPC post-chemo state. Methods: CRPC patients with ECOG PS 0-3, adequate end organ function, who had received at least one chemo were treated with low-dose keto (200 mg PO TID) and HC (20 mg PO q AM and 10 mg PO q PM) until progression, as defined by either RECIST or PSA rise > 50% from nadir or baseline. Primary endpoint was PSA response rate (> 50% reduction from baseline). A Simon minimax design was used. PSA response of > 25% was to be considered promising for further study (versus null rate of < 5%); 25 patients were required. Secondary endpoints included PSA response > 30%, progression-free survival (PFS), duration of stable disease, and evaluation of adverse events (AE). Results: 29 patients were accrued: median age was 71 (range 55-86) and median pretreatment PSA was 76 ng/mL (range 7-11,420 ng/ml); all had prior docetaxel-based chemotherapy. 28 patients were evaluable for response; all were evaluable for toxicity. PSA response of >50% was seen in 48% of patients and 59% of patients had a PSA response of > 30%. Median PFS was 138 days; median duration of stable disease was 123 days. 12 patients had grade 3 or 4 toxicity on treatment. Of the 17 grade 3 AEs, only 3 were considered ‘probably’ or ‘possibly’ related to treatment, while none of the 2 grade 4 AEs were considered related to treatment. Conclusions: In docetaxel pre-treated CRPC patients, low-dose keto + HC is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response with low-dose keto appears comparable to that of abiraterone in this patient context. A prospective randomized study of available post-chemo options is needed to assess comparative efficacy. Clinical trial information: NCT00895310.
Transurethral (TURP) biopsy of suspected anterior prostate cancers identified by MRI: Pilot study of a novel technique.
Authors: Dason Shawn , Allard Christopher Brian , Barrett Keith , Wright Ian , Shayegan Bobby 
Published: February 2017

230 Background: Prostatic MRI allows for identification of cancerous lesions in patients with a prior negative TRUS biopsy. Although in-gantry and MR-ultrasound fusion technologies have been reported, access to these technologies is limited. Here we present a novel technique to sample anterior lesions suspicious for prostate cancer (PCa) identified by MRI with transurethral (TURP) biopsy. Methods: MRI studies ordered by a single uro-oncologist at a tertiary center from 2007 to 2013 were reviewed. Patients were included if their studies met the following criteria: prostate MRI (n=148), indication for MRI was prior negative TRUS biopsy (n=48), PCa considered likely by reading radiologist (n=25) and anterior tumor location (n=7). Anterior tumors were those 17mm or more from the posterior prostate margin. Medical records were thoroughly reviewed. Additionally, regional medical databases were searched for 30 day readmission, emergency room (ER) visit, or positive bacterial culture result. Biopsy patients were treated with the standard monopolar TURP clinical pathway at our center. TURP sampling was directed by pre-procedural review of MRI images and report by the surgeon. MRI imaging was read by a single radiologist and obtained with a 3-T MRI with no endorectal coil employing T1, T2, DWI, and DCE sequences. Results: All seven patients identified with anterior tumors received TURP biopsy. Patients had a mean age of 63.6, Prostate-specific antigen of 13.3 ng/mL and a mean of 2.3 prior negative TRUS biopsies. There were no immediate complications reported. In 30 day follow-up data, no patients had a postoperative infection, although one patient was assessed in the ER for self-resolving hematuria and one patient was admitted for hematuria. Mean specimen weight was 4g and all but one patient had Gleason 7 or higher PCa on biopsy. This study demonstrated that MRI followed by TURP biopsy for anterior PCa had an 85.7% cancer detection rate for clinically significant anterior cancers. Conclusions: This pilot study demonstrates that cognitively directed TURP biopsy for MRI-identified anterior prostate lesions is feasible, has an excellent pickup rate for clinically significant cancer, and does not require access to limited technology.
What is the optimal management of Gleason score 7 (GS7) prostate cancer (PC) at biopsy? A comparison of disease control for prostatectomy (RP) versus radiation therapy (RT).
Authors: Watkins John Morgan , Watkins Patricia L. , Dufan Tarek A. , Koleilat Nadim 
Published: February 2017

250 Background: Optimal therapy for Gleason score 7 (GS7) prostate cancer (PC) remains to be defined, with consensus guidelines identifying both prostatectomy (RP) and radiation therapy (RT) as acceptable. The present investigation seeks to compare outcomes between these treatment approaches. Methods: Patients were retrospectively identified for inclusion by clinically localized disease, GS7, and a prostate-specific antigen (PSA) less than 30 at diagnosis. Comparison of demographic, tumor, staging, and outcome variables was performed. Disease recurrence was defined as per contemporary society guidelines. Kaplan-Meier method employed for disease control estimates. Results: Between 2003 and 2010, 267 patients were diagnosed with GS7 prostate cancer, of whom 207 were eligible for the current analysis (120 RP/87 RT). Excepting older age for RT patients (median age 73 vs. 62), the groups were well-balanced. For RP patients, 82 patients (60%) had at least one high-risk feature, of whom only four (5%) received adjuvant RT. For RT patients, 71 of patients (82%) received hormone therapy (median duration 6 months), and 48% (42) underwent external beam RT alone, 41% (36) brachytherapy (BT) alone, and 10% (9) external beam RT plus BT boost. At a median follow-up of 62.2 months (range, 13.1-136.6; with no difference between treatment groups), 64 patients had PSA relapse (51 RP/13 RT) and 15 had died (five of or with disease). Five-year disease-free and disease-specific survivals for RP versus RT were 55.4% versus 82.6% (p<0.0001) and 97.6% versus 98.8% (p=NS), respectively. Conclusions: For GS7 prostate cancer patients, RT is associated with superior disease-free survival at 5 years when compared with RP alone. Whether this difference remains in the setting of appropriately employed adjuvant RT remains to be determined. No difference in survival endpoints was detected, though there were few events at 5 years.
A sector-based postimplant dosimetric comparison of sagittal and axial ultrasound-guided source placement during I-125 permanent prostate brachytherapy.
Authors: Mohamed Yoosuf Ahamed Badusha , Mitchell Darren M. , Byrne Monica M. , Flynn Margaret A. , Napier Eoin , Jain Suneil , Workman Geraldine 
Published: February 2017

262 Background: To use sector based pre- and postimplant dosimetric analysis to evaluate the effect of changes in implant technique in a developing I-125 permanent prostate brachytherapy program (PPB). Methods: 109 men treated with PPB were divided into two groups by implant technique. The first 50 patients (group 1) had needle-by-needle seed deposition under axial ultrasound (USS) guidance and subsequent 59 patients (group 2) having needle placement row-by-row then seed deposition under sagittal USS guidance. Twelve sector dose volume analysis of pre-implant ultrasound (USpre) and postimplant CT (CTpost) study was performed in all cases. Individual sectors were created by dividing the cranio-caudal prostate into three equal lengths creating prostate base, midgland and apex. Each of these volumes was then divided into four axial sectors (right and left anterior, right and left posterior). The difference in the minimum dose delivered to 90% of prostate volume (D90) and the prostate volume receiving 100%, 150%, and 200% of the prescribed dose (V100, V150, and V200) was compared between both groups. Results: In both groups, the volume of prostate in sectors one through six (entire base and anterior midgland) were significantly larger on CTpost when compared to equivalent sectors in USpre (p < 0.001), conversely the volumes in sectors 11 and 12 (posterior apex) were significantly smaller (p =0.001). When comparing dosimetric parameters of all equivalent sectors in CTpost of both groups, it was found that D90 of sector seven and eight (posterior midgland) in Group 1 received increased dose leading to elevated dose to the rectum but was significantly reduced in Group 2 (p < 0.01), which resulted in achieving the dose as planned in USpre. Prostate implant dosimetry was significantly improved in group 2 with a trend to increased equivalent dose between CTpost and USpre to each sectors and significant decrease in V150 and V200 in majority of the sectors. Conclusions: The row-by-row technique under sagittal USS guidance significantly improved our post implant dosimetric parameters when compared to single needle source placement under axial USS guidance as assessed by 12 sector analysis.
The REQUITE project: Validating predictive models and biomarkers of radiotherapy toxicity to reduce side effects.
Authors: Rancati Tiziana , Talbot Christopher , Azria David , Brookes Antony , Burr Tom , Chang-Claude Jenny , Davidson Susan , Ruysscher Dirk De , Dunning Alison , Elliot Rebecca M. , Gutierrez-Enríquez Sara , Lambin Philippe , Rosenstein Barry , Symonds R. Paul , Thierens Hubert , Valdagni Riccardo , Vega Ana , Wenz Frederik , Yuille Martin , West Catharine 
Published: February 2017

276 Background: Recently the first replicated genetic associations for adverse reactions to radiotherapy (RT) have been reported. These will help to build predictive statistical models for optimising RT delivery or interventions to alleviate the side effects. It is now timely to start a project that aims to validate known predictors of adverse reactions and develop the statistical models to become clinically useful. REQUITE is a European Union funded FP7 project that aims to do this. Methods: REQUITE’s objectives: (1.) Perform a multi-centre, cohort study collecting: blood samples, epidemiology and treatment data, longitudinal side-effect and QOL data (before and after treatment, yrs 1 and 2). (2.) Produce a centralised biobank of DNA from 5,300 patients and a centralised data management system. (3.) Validate published biomarkers of radiosensitivity. (4.) Validate clinical predictors of RT toxicity in breast, prostate, and lung cancer and incorporate biomarker data. (5.) Design interventional trials to reduce long-term side effects. (6.) Provide a resource for dissemination and exploitation to the RT community. Results: REQUITE is funded for 60 mos and organised into 7 work packages. Overall management and scientific oversight is run by Manchester. The central activity of the project is a multi-centre, observational study. Enrolment will proceed for 2 yrs in 9 clinical centres, with 2 yrs follow-up. The primary endpoints are change in breast appearance; rectal bleeding (prostate); pneumonitis (lung). Blood samples will be collected before radiotherapy. Tracking, biobanking, DNA preparation and validation of biomarkers (genetic markers and apoptosis assays) as predictive factors will be carried out in WP3-4. Some clinical factors have suggested predictive value for RT side-effects, but there is no consensus. Validation of published models in existing cohorts will be performed, leading to replicated models that can be validated using the REQUITE cohorts. Conclusions: The predictive models will be used to design clinical interventional trials and produce protocols that seek to lower RT side-effects in those individuals at high risk of developing them without affecting tumour control. Dissemination will follow.
Relationship of bone scan index and progression-free survival after docetaxel treatment for CRPC patients with bone metastases.
Authors: Mizokami Atsushi , Izumi Kouji , Ueno Satoru , Kadono Yoshifumi , Wakabayashi Hiroshi , Nakajima Kenichi , Namiki Mikio 
Published: February 2017

280 Background: A computer-aided diagnosis system for bone scintigraphy using semiquantitative index [Bone Scan Index (BSI)] has been used to measure the tumor burden of bone metastases. We examined relationships of BSI, bone turnover marker, and prostate-specific antigen (PSA)-progression free survival (PFS) after docetaxel-treatment for castration resistant prostate cancer (CRPC) with bone metastasis. Methods: Sixteen CRPC patients with bone metastases (median age 72, range 52 to 82) were treated with docetaxel. We evaluated bone metastasis by bone scintigraphy before or around six months after docetaxel-treatment retrospectively. BSI was automatically calculated by BONENAVI software version 1 (FUJIFILM RI Pharma, Co. Ltd., Tokyo, Japan; Exini Bone, Exini Diagnostics, Sweden). Serum PSA, bone alkaline phosphatase (BAP), carboxyterminal telopeptide of type I collagen (I-CTP) were examined every months. PSA-PFS was evaluated after docetaxel-treatment and compared with baseline of BSI, BAP, I-CTP, and change of these value after treatment. Overall survival (OS) was also evaluated by these markers. The rate of patients with PFS and OS was estimated by the Kaplan-Meier method. Results: Baseline of BSI, the serum BAP, and I-CTP before docetaxel-treatment did not affect PFS. The change of BAP and I-CTP by the docetaxel-treatment also did not affect PFS. Only the change of BSI affected PFS and the median PFS of CRPC patients with increased BSI and decreased BSI was 5.5 months and 10 months, respectively (p=0.026). Although OS showed a longer tendency in CRPC patients with decreased BSI than with increased BSI, there was not the significant difference (p=0.12). Conclusions: The change of BSI affected PFS in CRPC patients with bone metastases. Bone scan and its evaluation with BONENAVI was effective to monitor the clinical course during chemotherapy.
Long-term outcomes among patients who achieve complete or near-complete responses after the induction phase of bladder-preserving combined modality therapy for muscle-invasive bladder cancer: A pooled analysis of RTOG 9906 and 0233.
Authors: Mitin Timur , George Asha , Zietman Anthony L. , Kaufman Donald S. , Uzzo Robert G. , Dreicer Robert , Heney Niall M. , Wallace H. James , Souhami Luis , Dobelbower M. Chris , Sandler Howard Mark , Shipley William U. 
Published: February 2017

284 Background: Bladder preserving combined-modality therapy for muscle-invasive bladder cancer (MIBC) includes transurethral resection and concurrent chemo-RT given in two phases. After the induction phase with chemo-RT to 40 Gy the tumor response is assessed by cystoscopic biopsies and urine cytology. Early salvage cystectomy is promptly offered in case of persistent disease, otherwise patients proceed to consolidation chemo-RT to 64 Gy. The two most recent RTOG protocols 9906 and 0233 allowed patients with near-complete response (Ta or Tis) after the induction phase to proceed to consolidation. Methods: We performed a pooled analysis of 119 eligible patients with MIBC enrolled on RTOG trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose of at least 60 Gy. We estimated bladder recurrence, salvage cystectomy rates and disease-specific survival by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. Results: Among 119 eligible patients, 101 (85%) achieved T0 and 18 (15%) achieved Ta or Tis after induction chemo-RT and proceeded to consolidation. After a median follow-up of 5.9 years, 36/101 (36%) T0 patients vs. 5/18 (28%) Ta or Tis patients experienced bladder recurrence (p=0.52). Fourteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, in comparison to one patient among near-complete responders (p=0.47). Disease-specific, bladder-intact, and overall survivals were not significantly different. Conclusions: There is no apparent difference in the bladder recurrence and salvage cystectomy rates between complete and near-complete responders as judged at the time of cystoscopic evaluation after induction phase of bladder preserving CMT. It is appropriate to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy. This project was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the NCI.
Population-based analysis of a novel prognostic model for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with abiraterone acetate (AA).
Authors: Azad Arun , Lester Renee , Leibowitz-Amit Raya , Joshua Anthony Michael , Heng Daniel Yick Chin , Eigl Bernhard J. , Chi Kim N. 
Published: February 2017

29 Background: Using data from the COU-AA-301 trial, a novel prognostic model was recently developed for predicting overall survival (OS) in post-chemotherapy mCRPC pts treated with AA (J Clin Oncol 31, 2013 (suppl; abstr 5013)). The model is comprised of six pre-treatment risk-factors (RF) associated with poor outcome: ECOG performance status (PS) ≥ 2, presence of visceral metastases, time from start of LHRH agonists to start of AA ≤ 36 months, low albumin, high ALP and high LDH. The aim of this study was to evaluate this model in an unselected population-based cohort. Methods: Cancer registries at three Canadian centers were used to identify mCRPC pts treated with AA. OS was estimated using the Kaplan-Meier method. Multivariate Cox proportional hazard regression was used to determine independent prognostic factors for OS. Results: A total of 415 pts received AA – 286 were post-docetaxel and 129 were chemotherapy-naïve. In post-docetaxel pts, 21%, 50% and 28% were classified into good (0-1 RF), intermediate (2-3 RF) and poor (4-6 RF) prognosis (prog) groups respectively based on the COU-AA-301 model. Median OS in the post-docetaxel cohort was significantly longer for pts with good prog disease (23.9 months) compared to intermediate (17.6 months) and poor prog pts (8.4 months) (Table). ECOG PS (p<0.001), LDH (p=0.025), albumin (p=0.007) and visceral metastases (p<0.001) were confirmed as independent prognostic factors. Although the number of events in chemotherapy-naïve pts was low, median OS was significantly longer in good prog pts (not reached) compared to both intermediate (22.9 months; p=0.011, log-rank) and poor prog pts (10.3 months; p<0.001, log-rank). Conclusions: In a population-based setting, our data validate the COU-AA-301 model as a tool for prognostic stratification of mCRPC pts treated with AA after docetaxel. Prospective evaluation of this prognostic model in post-docetaxel and docetaxel-naive pts commencing AA is warranted. [Table: see text]
BASE47 gene set predictor as an identifier of “basal-like” subtype of urothelial carcinoma of the bladder in African Americans.
Authors: Chism David D. , Damrauer Jeffrey S. , Miller Andrew S. , Milowsky Matthew I. , Kim William Y. 
Published: February 2017

300 Background: African-Americans [AAs] have a higher cancer-specific mortality when compared to whites with urothelial carcinoma (UC) of the bladder. Recent gene expression studies identified two intrinsic, molecular subsets of high-grade bladder cancer: “luminal” and “basal-like”, which can be accurately classified using the BASE47 gene set predictor. We applied the BASE47 gene set predictor to AA tumors and assessed enrichment for basal-like bladder tumors. Methods: Gene expression data from 179 high-grade, muscle invasive bladder tumors—9 AAs and 170 non-AAs (whites, Asians, and race not defined) from the TCGA was analyzed. Prediction analysis of microarrays (PAM) was used to derive the Bladder cancer Analysis of Subtypes by Expression (BASE47) gene set predictor and validated with 2 independent datasets. Comparisons of gene expressions patterns between bladder and breast intrinsic subtypes were peformed. Results: The BASE47 subtype classifier was highly concordant with Consensus Cluster subtype calls on 2 independent datasets. Based on the BASE47 gene classifier, a significant fraction of the tumors from AA (7/9) were classified as “basal-like” (P=0.07 Two tail). Basal-like bladder tumors trended strongly towards a worse prognosis (P=0.09 TCGA, 0.0194 MSKCC). Gene expressions patterns for“basal-like” and luminal bladder cancer correlated highly with basal-like breast and luminal A/B subtypes respectively. In addition, a subset of “basal-like” bladder cancer was found to be a claudin-low subtype. Conclusions: We have identified two molecular subtypes of high-grade bladder cancer that highly reflect the intrinsic subtypes of breast cancer. The BASE47 is a robust subtype classifier that can reliably distinguish basal and luminal bladder cancers. African-Americans have enrichment in the “basal-like” subtype of bladder cancer. These results will be validated in an independent set of samples as well as on FFPE tumors.
PECULIAR study: Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer.
Authors: Lee Jae-Lyun , Lee Se-Hoon , Choi Yoon Ji , Ahn Jin-Hee , Song Cheryn , Hong Bum-Sik , Hong Jun Hyuk , Kim Choung-Soo , Ahn Hanjong 
Published: February 2017

301 Background: Pemetrexed has demonstrated a favorable response with minimal toxicity when used as single agent as first-line and second-line treatment for advanced urothelial carcinoma. The safety and tolerability of pemetrexed plus cisplatin combination has been widely recognized in malignant mesothelioma. This trial was performed to evaluate the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma. Methods: Eligible criteria included chemotherapy-naïve advanced urothelial carcinoma, ECOG PS 0-2 and measurable disease. Pemetrexed 500mg/m2 on day 1 with cisplatin 70 mg/m2on day 1 were administered every 3 weeks til disease progression or a maximal of 8 cycles. Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicities. Response was evaluated every 6 weeks according to the RECIST criteria v.1.0 and toxicities were assessed with NCI CTCAE v.3.0. Results: A total of 42 patients were enrolled and 2 patients were excluded because of different histology and concomitant malignancy. At the time of this analysis, 36 patients (median age 66 years, ECOG 0-1 100%, visceral metastasis 50.0%, recurrent disease 61.1%) were evaluable; 6 patients were too early to assess. Twenty four partial responses for an overall response rate of 66.7% [95% confidence interval (CI) 50.3-79.9%] were documented. Six patients had stable disease. The median PFS was estimated to be 6.9 months [95% CI 6.2-7.7 months]. The median OS was 16.3 months [95% CI 12.9-19.7 months]. The most common grade 3 or 4 toxicities were neutropenia in 33.3% of patients. No one experienced febrile neutropenia. Other grade 3 or 4 hematological and non-hematological toxicities were rarely observed (thrombocytopenia 6%, anemia 6%, transaminitis 6%, nausea 3%, anorexia 3%, edema 3%, dyspnea 3%). Conclusions: The combination of pemetrexed and cisplatin is very active, with an overall response rate of 66.7% and well tolerated in patients with advanced urothelial cancer. The final mature results will be presented in the meeting. Clinical trial information: NCT01490437.