bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opinions on the role of brachytherapy boost in management of high-risk prostate cancer: A survey of North American genitourinary expert radiation oncologists.
Authors: McClelland Shearwood , Sandler Kiri A , Degnin Catherine , Chen Yiyi , Mitin Timur 
Published: February 2018

373 Background: Three randomized clinical trials have established brachytherapy (BT) boost in combination with external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) as superior to definitive EBRT and ADT alone in terms of biochemical control (but not overall survival) at the expense of increased toxicity in men with high-risk (HR) prostate cancer (PCa). The current view regarding these two treatment algorithms among North American genitourinary (GU) experts is not known. Methods: A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to opinions regarding BT as monotherapy for low-risk (LR) PCa and BT boost for HR PCa. Responders were asked to self-identify as BT experts vs non-experts. Treatment recommendations were correlated with practice patterns using Fisher’s exact test. Results: Forty-two radiation oncologists completed the survey, of whom 23 (55%) recommend EBRT and ADT alone and 19 (45%) recommend addition of BT boost. Twenty-five participants (60%) identified themselves as BT experts. Nearly 90% of those recommending BT boost were BT experts versus approximately 10% of non-BT experts (p < 0.001). Responders who recommended BT monotherapy as first-choice treatment for LR PCa were more likely to recommend BT boost for HR PCa (p < 0.0001). Conclusions: There is a dramatic polarization in opinions regarding incorporation of BT boost into EBRT+ADT therapy for patients with HR PCa among North American GU radiation oncology experts, who serve on decision-making committees and influence the national treatment guidelines and future clinical trials. Those who identify themselves as BT experts are significantly more likely to recommend BT boost, which may serve as a self-fulfilling prophecy regarding the role of BT in North American clinical practice. These findings are likely to influence the national guidelines and implementation of BT boost in current and future North American PCa clinical studies.
Metastases-directed therapy (MDT) for oligometastatic prostate cancer.
Authors: El-Modir Ahmed 
Published: February 2018

375 Background: Stereotactic ablative radiotherapy (SABR) is emerging as a treatment option for patients with oligometastatic prostate cancer. The primary aim of this approach is to prolong disease free survival and delay the initiation of systemic therapies. This retrospective study is aimed to analyse local control, biochemical progression-free survival (b-PFS), toxicity and systemic therapy-free survival in a cohort of patients treated by a single clinician. Methods: Eighteen patients (26 lesions) in patients with relapsed oligometastatic prostate cancer ( 1-3 sites) were treated with SABR, delivered using both cyberknife and VMAT. Doses used were 24 Gy in 2 or 3 fractions for spine and 30 - 40 Gy in 3 fractions for lymph nodes and other bony metastases. All patients had either a Choline or PSMA- PET scan prior to treatment. Response was assessed with PSA testing and repeat scanning when feasible. CTCAE acute and late toxicity was prospectively recorded. Results: Mean age was 68. Previous treatments for the primary prostate cancer included surgery (7 patients), surgery and salvage prostate bed radiotherapy (6 patients), radical radiotherapy (4 patients) and cryotherapy (1 patient). Twelve patients had a single metastatic site, four patients had 2 sites and two patients had 3 sites. Six patients patients were treated with a short course of androgen deprivation therapy (ADT) in addition to SABR. All patients had a fall in PSA with a mean reduction of 75%. Median pre-SABR PSA was 1.83μg/L and median post-SABR PSA was 0.28μg/L. At a median follow-up of 14 months (range 2 - 28.5), 14 patients (78%) remained systemic therapy free. Three patients with a single pelvic lymph node metastases achieved a sustained undetectable PSA level. All 8 patients who had a post-treatment PET scan showed no residual activity at the treated site. One patient experienced G2 acute bowel toxicity, otherwise there was no toxicity above G1. Conclusions: MDT using SABR for relapsed prostate cancer is a safe treatment with promising results in terms of local control, b-PFS and delaying the initiation of systemic therapies. This minimally invasive approach has the potential to improve patients' quality of life, but requires further evaluation in randomised clinical trials.
Cause of radium 223 treatment discontinuation in elderly mCRPC patients.
Authors: Costa Renato Patrizio , Raiti Fabio , Bordonaro Sebastiano , Tripoli Vincenzo , Murabito Alessandra , Licari Maria , Tralongo Paolo 
Published: February 2018

376 Background: Prostate cancer is the most common cancer among adult men. Bones are the main metastatic site of prostate cancer. Radium-223 is indicated to treat metastatic castrate-resistant prostate cancer ( mCRPC) with symptomatic skeletal metastases. We evaluate the tolerability of Ra223 treatment in real life setting. Methods: We reported the cases of 38 consecutive non-selected patients with mCRPC symptomatic bone metastases treated in two Italian hospital cancer center from August 2016 to October 2017. The cause of Ra 223 treatment discontinuation in elderly prostate cancer patients were evaluated. Results: due bones metastases, 38 patients were treated with Radium-223; 20 were ≥75 years old (range 75-85 yrs). Patients characteristics and main toxicity are reported (Table). Regarding the elderly patients, hematologic toxicity were the most common adverse events reported. Anemia G2-G3 was observed in 10 pts (50%), thrombocytopoenia G3 in 2 patients (10%) and neutropenia G3 in 4 patients (20%); 12/20 patients interrupted the treatment, of which 10 were ECOG PS2. The number of patients who discontinued the drug because of hematologic adverse events was higher than ALSYMPCA clinical trial. Fatigue G1-G2 incidence was 32%. Unexpectedly we did not record any cases of gastrointestinal toxicity (diarrhea, nausea or constipation). Conclusions: In patients ≥75 years old, anemia G2-G3 was more frequent than data reported in literature, while diarrhea is not found. The data of this experience suggest that elderly vulnerable patients are more exposed to hematologic toxicity that may compromise the outcome of the treatment. For these patients surveillance for early supportive care is relevant. Characteristics of patients with ≥75y. [Table: see text]
Immune checkpoint molecule expression measured using circulating cell-free RNA isolated from the blood of metastatic prostate cancer patients.
Authors: Kollengode Kanthi Athreya , Grussie Erwin , Danenberg Genevieve , Usher Joshua L. , DANENBERG KATHLEEN , Danenberg Peter , Pinski Jacek K. 
Published: February 2018

380 Background: Recent studies have identified panels of immune-related genes linked to progression and survival. Expressions usually are measured using RNA from tissue samples. The aim of the present study was to utilize circulating RNA (cfRNA) isolated from hormone-naïve (HN) and castrate-resistant prostate cancer (CRPC) patients to measure gene expressions of PD-L1, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), T-cell immunoglobulin and mucin domain 3 (TIM-3) and lymphocyte activated gene 3 (LAG-3). Androgen receptor (AR) and AR-variant 7 (AR-v7) expressions were also measured in these samples to test for any possible relationships with the immune checkpoint genes. Methods: Blood samples were collected from 53 metastatic prostate cancer patients. cfRNA was extracted from patients’ plasma and reverse transcribed into complementary DNA. The gene expressions (mRNA levels) of the above genes were determined by quantitative reverse transcription-PCR. Beta-actin was used to normalize gene expressions to total RNA content. Results: Each of the immune signatures tested (PD-L1, TIM-3, LAG-3, CTLA-4) was expressed in over 50% (29/53) of the patients’ blood samples. AR was expressed in 25/53 (47%) samples. Four of these patients (8%) expressed AR-v7, indicating resistance to anti-AR drugs. Patient disease status included: 25% (13/53) CRPC, 74% (39/53) HN, and 1 unknown. Within the CRPC group, a significant negative correlation was found between TIM-3 and CTLA-4 expression (-0.833), and CTLA-4 also correlated with disease progression (0.719). Within the HN group, a significant negative correlation was measured between TIM-3 and PD-L1 (0.589). AR expression did not correlate with other targets measured among all patients or within the CRPC or HN groups. Conclusions: This study demonstrates successful quantitation of immune checkpoint gene expressions as well the AR and AR-v7 genes in plasma of prostate cancer patients. This result opens the possibility of the use of a noninvasive method to measure, monitor and track the dynamic interplay of these genes with changing disease status. Clinical trial information: NCT02853097.
Prospective analysis of 4,474 prostate biopsies to evaluate potential treatment management impact of combined clinical-genomic risk classification.
Authors: Nguyen Paul L. , Zhang Jingbin , Yousefi Kasra , Davicioni Elai , Den Robert Benjamin , Feng Felix Y , Spratt Daniel Eidelberg 
Published: February 2018

39 Background: Prior studies suggested integrated clinical-genomic risk grouping can more accurately prognosticate prostate cancer (PCa) outcome than NCCN clinical risk. We evaluated the potential for genomic testing to reclassify patients in a manner that could change management compared to NCCN risk groups. Methods: We evaluated 4,474 consecutive patients with PCa who received the Decipher Biopsy test between 01/2016-08/2017 and had information to determine NCCN risk. Genomic categorizations with the potential to change management were defined as NCCN very low/low to genomic intermediate or high (active surveillance to active treatment), NCCN favorable intermediate to genomic high (radiation therapy [RT] alone to RT plus androgen deprivation therapy [ADT]), NCCN unfavorable intermediate to genomic low (RT + ADT to RT alone), NCCN high risk to genomic low (RT + long term ADT to RT + short term ADT). Results: There were 927 NCCN low-risk, 2,427 intermediate, and 1,120 high-risk patients. Among NCCN low-risk, the incidence of genomic low, intermediate, and high risk was 58.7%, 25.0%, and 16.3% respectively, for NCCN intermediate it was 36.5%, 27.6%, and 35.8%, and for NCCN high risk it was 15.9%, 17.1%, and 67.1%. Management could have been changed in the 41.3% of NCCN low risk patients with intermediate or high genomic risk, 26.7% of favorable intermediate risk patients who had high genomic risk, 32.4% of unfavorable intermediate risk patients with low genomic risk, and 15.9% of high risk patients with low genomic risk. Conclusions: A slight majority (54%) of Decipher Biopsy users have NCCN intermediate-risk disease, likely reflecting a need for further prognostic information to refine recommendations in intermediate risk. Reclassification of NCCN groups by genomic risk was common and an integrated clinical-genomic risk system could have altered treatment recommendations in 41.3% of NCCN low, 26.7% of favorable intermediate, 32.4% of unfavorable intermediate risk, and 15.9% of high risk patients.
Life after prostate cancer diagnosis: One step beyond.
Authors: Glaser Adam , Downing Amy , Wright Penny , Hounsome Luke , Kind Paul , Selby Peter John , Wilding Sarah , Donnelly David , Butcher Hugh , Watson Eila , Richard Wagland , Catto James , Cross William , Mason Malcolm David , Sharp Linda , Velikova Galina , Mottram Rebecca , Allen Majorie , Kearney Therese , Anna Gavin 
Published: February 2018

40 Background: Prostate cancer (PCa) outcome studies are frequently restricted to specific disease stage or treatments. Interpretation may be restricted through lack of population control data & selection bias. We report a whole population evaluation of health-related quality of life (HRQL) following diagnosis of PCa compared to a general population (GenPop) cohort. Methods: Cross-sectional postal survey of all men diagnosed with PCa in the UK 18-42 months earlier. Measures of generic HRQL (EQ-5D) and PCa specific outcomes (EPIC-26 & interventions for erectile dysfunction), as defined in ICHOM minimum dataset, were utilized. Comparable GenPop data was collected from men never diagnosed with PCa in Northern Ireland. Results: 35,823 PCa survivors responded (60.8% response rate), median age 71, and 2,995 from the GenPop (30%). Overall HRQL was slightly lower in the PCa men than the GenPop, this difference was significant only in stage 4 disease. Men with PCa were less likely to report problems in individual EQ5D domains than men in the GenPop (62.0% vs. 68.8%). Both populations were most likely to report pain/discomfort, this was lower in PCa men than the GenPop (42.1% vs. 60.8%). Problems increased with age in all domains, with the exception of anxiety/depression. Men generally reported good function on EPIC-26; however PCa survivors reported poorer sexual function (78.9% vs 48%) except in the oldest. Medications/devices/services to aid or improve erections were offered to 45.4%, 26.0% & 16.9% respectively (and considered helpful by 14.7%, 7.5% & 3.2%). Men with PCa reported more problems with urinary leakage (13.1% vs. 7.1%), particularly after surgery. Hormonal symptoms were linked with receiving Androgen Deprivation Therapy and, to a lesser extent, external beam radiation. Conclusions: 18-42 months following diagnosis of PCa significant sexual and urinary morbidity is experienced relative to the GenPop. Specialist support for sexual dysfunction is not always offered. With the exception of men with stage 4 disease, overall HRQL is only mildly reduced. Funding The Life After Prostate Cancer Diagnosis study was funded by the Movember Foundation, in partnership with Prostate Cancer UK, as part of the Prostate Cancer Outcomes programme, grant number BO26/MO.
RNA-sequencing to identify three different molecular grades and immune checkpoint cascades with distinct clinical behaviour in NMIBC.
Authors: Chandrasekar Thenappan , Zlotta Alexandre , Shen Jess , Noon Aidan , Jiang Haiyan , Erlich Annette , Kuk Cynthia , Ni Ruoyu , Sukhu Balram , Chan Kin , Roupret Morgan , Seisen Thomas , Comperat Eva , Sweet Joan , Kulkarni Girish S. , Fleshner Neil Eric , Azad Azar , van der Kwast Theodorus , Wrana Jeff L 
Published: February 2018

412 Background: NMIBC has a highly variable clinical behavior not adequately predicted by histological grade or clinical parameters. Some are indolent; others quickly progress to MIBC. Discrepancies between phenotype and genotype is compounded further by interobserver variability in pathological grading. There is an unmet need to improve the prediction of NMIBC. Methods: Whole transcriptomic analysis of 178 bladder tumors (158 NMIBC, 20 MIBC/metastatic) was performed from FFPE tissue incorporating messenger RNA expression, splice variants, gene fusion, mutation detection and immune checkpoint inhibitor cascades. CTLA, PD-1, LAG3, TIM3, TIGIT and B7 were compiled as an index including all major cascade genes. Data were integrated and tested for correlations with pathological grading and clinical outcomes. Conventional pathological grading for WHO 1973 (Grade 1, 2, 3) and 2004 (LG vs HG) classifications was reviewed by 3 expert uro-pathologists. Kappa statistic for interobserver variability was calculated. For validation we used an independent RNA-seq dataset (n = 209, Hedegaard et al. 2016 Cancer Cell). Results: Unsupervised clustering of RNA-Seq data distinguished 3 molecular subtypes of NMIBC; Molecular Grade Related Index (MGRI) 1, MGRI2, MGRI3. MGRI1 comprised of almost exclusively LG tumors. MGRI3 clustered with HG MIBC. Kappa for interobserver variability of expert pathologists was 0.40 and 0.78 in 1973 and 2004 WHO classification, respectively. FGFR3 mutations, FGFR3::TACC3 fusion events and MGRI1 genes were associated with components of xenobiotic metabolism (p = 2.51x10-09) signalling systems, in particular, GTPase regulation (p = 0.002), respiratory cycle genes (p = 0.004), HOX cluster (p = 0.005). MGRI independently predicted progression to MIBC (n = 138, HR = 2.96, 95%CI = 1.70-5.13, p = 1.20x10-04). 5-year PFS in a combined data set (n = 347) differed significantly for MGRI1 (100%) vs MGRI2 (92.2%) vs MGRI3 (73.5%, p = 1.99x10-05, Gray’s test). PD-1 ICC independently predicted progression (OR = 2.85, p < 0.05). Conclusions: RNA-seq delineates 3 molecular classes of NMIBC with different risks of progression to MIBC compared to conventional histologic grading.
Real-world systemic therapy utilization in Medicare patients with locally advanced or metastatic urothelial carcinoma.
Authors: Dinan Michaela Ann , Georgieva Mihaela , Shenolikar Rahul , Scales Charles D. 
Published: February 2018

415 Background: Several immunotherapies recently have been approved for the treatment of locally advanced or metastatic bladder cancer that is prevalent in older adults. Utilization patterns in Medicare patients have not been examined and can provide an important context for emerging therapies. Methods: We conducted a retrospective analysis of SEER-Medicare beneficiaries diagnosed with locally advanced (T3-T4, N1-N3, M0) or metastatic urothelial carcinoma (any T, any N, M1) of the bladder or upper urinary tract from 2008 to 2012 and further characterized patients undergoing initial chemotherapy (within 30 days of diagnosis). Individuals receiving neoadjuvant chemotherapy were excluded. Results: A total of 3569 patients met study criteria. Among these, 48% received chemotherapy within 2 years of diagnosis. Receipt of chemotherapy was associated with younger age (median 75 vs 80 years, P< .001) and fewer comorbid conditions, including diabetes (12% vs 16%), renal disease (6% vs 11%), and congestive heart failure (4% vs 8%). A total of 977 patients received chemotherapy, of which 38% had distant metastatic disease and 65% had locally advanced tumors. Most patients had no (70%) or only a single (14%) comorbid medical condition. These patients most commonly received doublet chemotherapy (67%) followed by single-agent (17%) or triple-agent (10%) treatment. Gemcitabine was the most common individual agent received as part of initial chemotherapy (81%), followed by carboplatin (50%), cisplatin (38%), and docetaxel or paclitaxel (each 13%). The most common combination received was gemcitabine/carboplatin (42%) followed by gemcitabine/cisplatin (36%). Conclusions: Only half of Medicare patients with advanced urothelial carcinoma received systemic therapy. Most received a platinum doublet regimen. Gemcitabine in combination with platinum-containing chemotherapy was the preferred treatment. Ongoing assessment of the risks and benefits of emerging treatments for Medicare patients may be warranted with the introduction of targeted and/or immune therapies.
Post-chemotherapy PD-L1 expression correlates with clinical outcomes in Japanese bladder cancer patients treated with total cystectomy.
Authors: Hashimoto Yasuhiro , Noro Daisuke , Hatakeyama Shingo , Yoneyama Takahiro , Koie Takuya , Kawaguchi Toshiaki , Ohyama Chikara 
Published: February 2018

416 Background: Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy that is frequently overexpressed in bladder cancer. In the present study, we examined whether PD-L1 expression is associated with clinical outcomes in bladder cancer patients. Methods: We enrolled 102 bladder cancer patients treated with cystectomy at the Aomori Prefectural Hospital between April 2004 and May 2014. We conducted an immunohistochemical examination of PD-L1 expression using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0/1/2). Results: Of the 102 patients, 82 were men (81.0%) and 20 were women (19.0%) (mean age 60 years, range 43-84 years). Sixty-six patients (64.8%) had previously undergone neoadjuvant chemotherapy [neoadjuvant (+) group]. During the mean observation period of 54.5 months, 42 patients had recurring disease (41.1%) and 34 died (33.3%). The 5-year cause-specific survival (CSS) rate was 66.6%; the 5-year disease-free survival (DFS) rate was 59.7%. In the neoadjuvant (+) group, the 5-year DFS rate was 65.0% for PD-L1 (-) patients and 31.7% for PD-L1 (+) patients (log-rank p = 0.006). In the neoadjuvant (+) groups, the 5-year CSS rate was 69.6% for PD-L1 (-) patients and 48.1% for PD-L1 (+) patients. Differences in CSS and DFS rates between PD-L1 (-) and PD-L1 (+) patients in both treatment groups were statistically significant (log-rank p = 0.006 and 0.039, respectively.) Conclusions: Despite the small study size, our data suggest that post-chemotherapy PD-L1 expression is associated with poor prognosis in patients receiving neoadjuvant chemotherapy who had previously undergone cystectomy.
Comparative effectiveness of bladder-preserving tri-modality therapy versus radical cystectomy for muscle-invasive bladder cancer.
Authors: Royce Trevor Joseph , Feldman Adam S. , Mossanen Matthew , Yang Joanna C. , Shipley William U. , Pandharipande Pari , Efstathiou Jason A. 
Published: February 2018

418 Background: Radical cystectomy (RC) has historically been considered the standard of care for muscle invasive bladder cancer (MIBC). An alternative is tri-modality therapy (TMT), a bladder-sparing approach that often achieves preservation of the native bladder. There are limited randomized data comparing these guideline-recommended approaches but, in appropriately selected patients, both are thought to have similar survival outcomes with different morbidity profiles. Therefore this study compared the effectiveness of TMT and RC using decision-analytic modeling with the primary endpoint of quality-adjusted life years (QALYs). Methods: We developed a Markov model simulating the lifetime outcomes for 67-year-old patients after definitive treatment for American Joint Committee on Cancer clinical Stage T2-T4aN0M0 MIBC using two strategies: TMT or RC +/- neoadjuvant chemotherapy (NAC). Probabilities and utilities were extracted from the literature to determine the incremental effectiveness in QALYs. Sensitivity analyses were performed. Results: TMT was the most effective strategy with an incremental gain of 1.13 QALYs over RC (8.37 versus 7.24 QALYs, respectively; Table). One-way sensitivity analyses demonstrated the model was most sensitive to the quality of life (QoL) parameters (i.e. the utilities) for RC and TMT; TMT was more effective than RC irrespective of the RC utility (the 95% confidence interval of the RC parameter demonstrated an incremental gain with TMT of 0.01 to 4.77 QALYs). The model was relatively less sensitive to the probability of death for either strategy. Probabilistic sensitivity analysis demonstrated that TMT was more effective than RC for 75% of model iterations. Conclusions: Treatment of MIBC with organ-sparing TMT in appropriately-selected patients may result in a gain of over 1 QALY relative to RC. Further prospective investigation into the QoL implications of these treatment modalities is warranted. [Table: see text]