bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment decision making in metastatic prostate cancer (mPC).
Authors: Morgans Alicia K. , Fought Angela , Lee Benjamin , VanderWeele David James , Hussain Maha H. A. , Moses Kelvin A. , Penson David F. 
Published: February 2020

224 Background: Multiple treatments exist for mPC, and optimal treatment choice is not defined. Shared decision making (SDM) in which physicians communicate treatment purpose, risks, and benefits, and patients (pts) communicate values/preferences can be used to determine treatment. SDM is associated with superior health outcomes in non-cancer populations, but whether it is used in mPC is unknown. We assessed mPC pt and caregiver perceptions of decision locus of control (DLOC) (SDM vs physician (PD) or pt (PtD) directed decisions), and characteristics associated with DLOC. Methods: Between 12/16 and 11/17, mPC patients and caregivers completed surveys of decision making practices after a clinical encounter in which a decision occurred. To evaluate the relationship between pt perception of DLOC type and categorical variables we used Fisher’s exact test, and Kruskal-Wallis was used to evaluate the relationship between DLOC and age. Results: 50 pt/caregivers participated, with median pt age of 72 yo. Most pts were Caucasian (96%), married (90%), and reported good health or better (18% excellent, 58% good, 24% fair). 66% of pts reported SDM, 10% reported PD only, 12% reported PD considering patient’s preferences, and 12% reported PtD considering physician’s recommendation. Caregivers reported numerically lower rates of SDM (56%), PD only (6%), and PD considering patient’s preferences (8%), but greater PtD considering physician’s recommendation (30%), (p=0.28). Neither reported PtD without considering physician recommendations. There was no association between pt DLCO and age (p=0.70) or clinician type, (p=0.13). All pts reporting PtD considering physician’s recommendation saw medical oncologists rather than urologists. Conclusions: Both pts and caregivers perceived a majority of decisions as SDM, indicating a high level of patient engagement in mPC decision making, and clinician type and patient age were not associated with pt reported DLOC. Pts seen by medical oncology in this cohort reported directing treatment choice when considering physician’s recommendation. Efforts to assess and support decision making in more diverse patient populations and explore the association between SDM, pt satisfaction and quality of life are underway.
Quality of life of prostate cancer (PCa) patients with testosterone deficiency symptoms (TDS) before initiation of gonadotropin-releasing hormone (GnRH) agonist therapy: Subgroup analysis of EQUINOXE study.
Authors: Droupy Stephane , Colson Marie-Helene , Pello Leprince Ringuet Nathalie , Perrot Valérie , Descazeaud Aurelien 
Published: February 2020

232 Background: Both PCa and TDS risk increase with age. Patients may therefore suffer from both conditions, and their quality of life (QoL) be reduced. Unexpectedly, multivariate analysis of the EQUINOXE study (NCT02630641) identified baseline TDS as a significant factor improving QoL after 6 months of GnRH agonist therapy. We therefore aim to analyze baseline parameters of this subgroup. Methods: EQUINOXE was a French prospective, multicenter, non-interventional study. Urologists recruited partner-patient couples with PCa for whom androgen deprivation therapy (ADT) was indicated. Data were collected at inclusion and after 6 months of treatment, on QoL (WHOQOL-BREF), perception of disease (B-IPQ), symptoms of the disease (QLQ-PR25) and perception of cohesion within the patient-partner relationship (dyadic adjustment, DAS-16). TDSat baseline, determined by QLQ-PR25 “treatment related symptoms” score ≥25/100, was the main parameter identified by multivariate analysis in improvement of QoL (OR [95% CI]: 3.0 [1.46, 6.17]. Post hoc subgroup analysis was made to compare baseline parameters of patients with and without TDS. Results: 487 patients were included in this analysis, 26% of whom had TDS at baseline. Symptoms were (quite a bit or very much): feeling of less masculinity (55.2%), hot flushes (41%), weight gain (40.1%) and enlarged nipples (23.1%). Patients with TDS were slightly older than those without TDS (75.3±8.3vs 73.8±8y.o), had significantly worse performance Status (0-1-2+ in 37.0-45.7-17.3% vs 52.8-36.4-10.8%, p=0.0153) and suffered more frequently from recurrent PCa (35.7% vs 24.7%, p=0.0175). Symptoms other than urinary and sexual (but including asthenia) were more frequent (p=0.0126). All dimensions of WHOQOL-BREF were rated significantly worse. Total score of illness (B-IPQ) was worse: 42.2±8.2 vs39.1±9.4, p=0.0040. Cohesion in the couple (DAS score) was worse: 98.6±22.3 vs107.3±20.9, p=0.0006. Conclusions: Patients with TDS experienced at baseline a worse cohesion of the couple and a lower QoL than patients without TDS but benefited relatively more from ADT in term of QoL. Clinical trial information: NCT02630641.
A phase IIa randomized placebo-controlled trial of pomegranate fruit extract/POMx in subjects with clinically localized prostate cancer undergoing active surveillance.
Authors: Jarrard David Frazier , Filon Miko , Huang Wei , Kim KyungMann , Havighurst Tom , Konety Badrinath R. , Saltzstein Daniel , Mukhtar Hasan , House Margaret , Suen Chen S. , Parnes Howard L. , Bailey Howard Harry 
Published: February 2020

285 Background: Due to its high prevalence and often indolent natural history, prostate cancer(PC) active surveillance(AS) is an ideal setting for chemoprevention. Studies assessing pomegranate and its extracts have shown promising anti-proliferative and pro-apoptotic effects in cell lines and animal models and a single-arm clinical trial of pomegranate fruit extract(PFE) reported an increase in PSA doubling time(PSADT) during AS. The primary objective of this trial was to assess the effect of PFE supplementation on plasma levels of Insulin-like Growth Factor-1(IGF-1). Secondary objectives addressed PSA doubling time(PSADT), tumor volume on end-of-study(EOS) biopsy and plasma and prostate tissue biomarkers. Methods: Men with organ-confined favorable-risk PC on AS were randomly assigned to receive PFE 1,000 mg(n=15) or placebo(n=15) once daily for twelve months. Prostate biopsies were performed at study entry and upon completion of the one-year intervention. Tissue biomarkers were assessed by immunohistochemistry(IHC) with automated quantitation. Results: PFE was well-tolerated with no significant toxicities. One patient withdrew before study initiation and 29 completed the one-year intervention. No differences in plasma IGF-1 levels(p=0.5), PSADT, or tissue biomarkers of apoptosis or proliferation were observed. A significant increase in urolithin A(a urinary metabolite of pomegranate) was observed in the PFE arm. IHC analyses of both tumor (Table) and normal-appearing tissue adjacent to tumor showed reductions from baseline in IGF-1, 8-OHdG(DNA damage marker), and androgen receptor expression associated with PFE treatment. A trend towards a reduction in the maximum percent of biopsy core tumor involvement was observed(p=0.06) in PFE. Conclusions: PFE administration for 12-months was not associated with a decrease in plasma IGF-1 levels nor an increase in PSADT. However, exploratory analyses suggest that PFE may contain bioactive compounds capable of altering biomarkers in PC and normal-appearing adjacent tissue providing a rationale for further investigation of PFE in the active surveillance population.
A comparison of sipuleucel-T (sip-T) product parameters from two phase III studies: PROVENT in active surveillance prostate cancer and IMPACT in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Ross Ashley , Armstrong Andrew J. , Pieczonka Christopher M , Bailen James L. , Tutrone Ronald F. , Cooperberg Matthew R. , Pavlovich Christian P. , Renzulli Joseph F. , Haynes Heather , Sheikh Nadeem Anwar , Shore Neal D. 
Published: February 2020

321 Background: Sip-T is an FDA approved, autologous cellular immunotherapy for mCRPC, manufactured by activating peripheral blood mononuclear cells collected by apheresis and culturing them with PA2024 (PAP fused to human GM-CSF). Overall survival (OS) in mCRPC is positively correlated with key product parameters of sip-T: CD54 upregulation; CD54+ cell count; and total nucleated cell (TNC) count. Product parameters were amplified in men with earlier stage prostate cancer vs mCRPC, including increased T cell trafficking to the prostate (Fong L, JNCI 2014) and greater CD54 upregulation and larger immune responses (Antonarakis ES, Clin Can Res 2017). Methods: ProVENT (NCT03686683) will evaluate sip-T in men with Gleason grade 1/2 prostate adenocarcinoma receiving active surveillance (target, 450 men; randomized 2:1 to receiving sip-T or not). We evaluated apheresis and final key product parameters (CD54 upregulation; CD54+ cell count; and TNC count) for each infused product as well as cumulative values while also comparing with IMPACT (NCT00065442) study results. Results: This preliminary analysis describes data from the first 184 sip-T men in ProVENT. CD54 upregulation profiles were consistent between IMPACT and ProVent, peaking in week 2 products; however, values at each treatment week, and subsequently cumulative CD54 upregulation, were statistically significantly higher for ProVENT (P<0.001 per comparison; Table). The number of CD54+ cells was significantly greater at each treatment for both incoming apheresis as well as the final product, including cumulative values, in ProVENT compared to IMPACT (P<0.001 per comparison) as was TNC count (P<0.001 per comparison). Conclusions: This preliminary analysis of product parameters in ProVENT suggest sip-T potency is higher in pts undergoing active surveillance. Clinical trial information: NCT03686683. [Table: see text]
Stereotactic pelvic radiotherapy with HDR boost for dose escalation in intermediate and high-risk prostate cancer (SPARE): Efficacy, survival, and late toxicity outcomes.
Authors: Loblaw Andrew , Musunuru Bindu , Cheung Patrick , Vesprini Danny , Liu Stanley K. , Chu William , Chung Hans T. , Morton Gerard , Deabreu Andrea , Davidson Melanie , Ravi Ananth , Helou Joelle , Ho Ling , Zhang Liying 
Published: February 2020

328 Background: The ASCO/CCO guidelines recommend brachytherapy boost for all eligible intermediate- or high-risk localized prostate cancer patients. We present efficacy, survival and late toxicity outcomes in patients treated on a prospective, single institutional protocol of MRI dose painted HDR brachytherapy boost (HDR-BT) followed by pelvic stereotactic body radiotherapy (SBRT) and androgen deprivation therapy (ADT). Methods: A phase I/II study was performed where intermediate (IR) or high-risk (HR) prostate cancer patients received HDR-BT 15Gy x 1 to the prostate and up to 22.5Gy to the MRI nodule and followed by gantry-based SBRT 25Gy in 5 weekly fractions delivered to pelvis, seminal vesicles and prostate. ADT was used for 6-18 months. CTCAEv3 was used to assess toxicities and was captured q6months x 5 years. Biochemical failure (BF; nadir + 2 definition), nadir PSA, proportion of patients with PSA < 0.4 ng/ml at 4 years (4yPSARR), incidence of salvage therapy, cause specific survival and overall survival were calculated. Day 0 was HDR-BT date for all time-to-event analyses. Results: Thirty-two patients (NCCN 3% favorable IR, 47% unfavorable IR and 50% HR) completed the planned treatment with a median follow-up of 50 months; 31 of these had an MRI nodule. Four patients had BF with actuarial 4-year BF rate of 11.5%; 3 of these received salvage ADT. Median nPSA was 0.02 ng/ml; 4yPSARR was 68.8%. One patient died (of prostate cancer) at 45 months. For late toxicities, grade 1, 2 and 3+ GU and GI toxicities were: 40.6%, 37.5%, 3% and 28.1%, 0%, 0%, respectively. Conclusions: This novel treatment protocol incorporating MRI-dose painted HDR brachytherapy boost and SBRT pelvic radiation for intermediate- and high-risk prostate cancer in combination with ADT is feasible, effective and well tolerated. Clinical trial information: 12345678. [Table: see text]
Phase II trial of neoadjuvant chemohormonal therapy (NAC) in prostate cancer (PC) with response assessment using PSMA PET/MRI.
Authors: Kyriakopoulos Christos , Johnson Brian , Heninger Erika , Khemees Tariq A. , Roldán-Alzate Alejandro , Huang Wei , Beebe David J. , Emamekhoo Hamid , Wells Shane A. , Jarrard David Frazier , Cho Steve Y. , Lang Joshua Michael 
Published: February 2020

334 Background: Previous studies have shown that addition of docetaxel to androgen deprivation therapy (ADT) significantly improves progression-free survival (PFS) and overall survival (OS) in men with metastatic hormone-sensitive PC. Removal of the primary may also improve outcomes by reducing tumor self-seeding. We are conducting a phase II trial in men with PC to examine the feasibility of NAC, response using PSMA PET/MRI imaging and molecular mechanisms of resistance. Methods: This is an open-label, single-arm trial. Thirty patients with newly diagnosed very high risk localized, locally advanced or oligometastatic PC will receive ADT/docetaxel for three cycles before prostatectomy. The primary endpoint is rate of complete pathologic response. Key secondary objectives include PSA recurrence at month 12 after surgery. Exploratory objectives include tumor response and response heterogeneity in primary and metastatic tumors before and after treatment assessed by PSMA PET/MRI and evaluation of gene expression signatures in cancer cells, prostate stroma, bone marrow microenvironment and circulating tumor cells. Results: To date, 26 of 30 patients have enrolled and completed treatment. Mean age was 61 and mean PSA at time of diagnosis was 32.1 ng/dl. All patients had multi-focal prostate cancer with 23/26 patients with Gleason Grade Group 5. Metastatic disease by conventional imaging was identified in 6/26 patients (5 in lymph nodes [LN] and bone, 1 in LN only). Treatment was overall well tolerated. All patients had multi-focal primary prostate cancer detected on PSMA PET/MRI. All patients had a decline in PSMA PET SUVmax in at least one intraprostatic lesion. Two patients had an increase in SUVmax in at least one intraprostatic lesion that correlated with a resistant tumor focus on histopathology. Conclusions: NAC prior to surgery generates high rates of local tumor control with a heterogeneous response between foci. Primary resistance, identified by increasing PSMA PET SUVmax, is uncommon, however incomplete responses were observed in nearly all patients, suggesting that more cycles of treatment would improve response. PSMA PET/MRI can be used to monitor response and resistance in PC. Clinical trial information: NCT03358563.
Head-to-head comparison between decipher and prolaris tests: Two commercially available post-prostatectomy genomic tests.
Authors: Shahait Mohammed , Alshalalfa Mohammed , Schaeffer Edward M. , Huang Huei-Chung , Cronican Andrea , Nguyen Paul L. , el-Fahmawi Ayah , Lal Priti , Davicioni Elai , Lee David I. 
Published: February 2020

348 Background: Several post-prostatectomy genomic tests are available; which are used to improve prognostication and to guide additional treatment after radical prostatectomy (RP). There has been no head to head comparison between these tests. The objective of this study is to compare the performance of two genomic tests in predicting oncological outcomes. Methods: 16 patients who underwent RP at the University of Pennsylvania (UPenn) (2013-2018), had adverse pathology (margin, and/or pT3a/b) and had each been tested with both Decipher (D) and Prolaris (P). Pearson correlation was used to compare scores from D and P as well as CCP scores and microarray derived CCP (mCCP). The associations of D and P with biochemical recurrence (BCR) and metastasis (M) was evaluated in survival analysis in a large cohort of RP patients treated at Johns Hopkins University (1992-2010) (JHU). Results: The median follow-up of the UPenn cohort was 24 months. 6 patients developed BCR and two distant M. There was a significant correlation between the D and P score (r=0.67,p=0.004), and between the 10-year BCR risk reported by P and the 5-year M risk reported by D (r=0.69, p=0.003). Each test called 7 patients to be high risk; 5 were in common. Both tests correctly called the 2 M cases as high risk and 4/6 BCR patients to be high risk. A microarray-derived CCP (mCCP) was highly correlated to the CCP scores reported from P (r=0.88, p=6.7e-6) in the UPenn cohort. To compare the prognostic performance of mCCP to D for predicting BCR and M, we used Post-RP cohort from JHU (N=355). Both scores were correlated (r=0.36, p2e-12). D and mCCP were stratified into 5 groups of incremental 20%. When including mCCP groups, D groups, Gleason score, SVI, EPE, LNI, and PSA; D remained independent prognostic variable of BCR (HR 1.16, 95%CI [1.05-1.3], p=0.005) and M (HR 1.3, 95%CI [1.12-1.52], p=0.0005). However, mCCP was not prognostic of BCR (p=0.59) nor M (p=0.62). Conclusions: The findings from this study show that P and D scores post-RP were highly correlated and help in identifying patients who at high risk of progression in this small cohort with short follow up. However, D outperformed mCCP for predicting BCR and M in larger cohorts with longer follow up.
Stereotactic body radiotherapy boost toxicity for high and intermediate-risk prostate cancer: Report of a multi-institutional study.
Authors: Kaplan Irving D. , Appelbaum Limor , Aghdam Nima , Martin Jarad , Sidhom Mark , Pryor David , Aronovitz Joseph A. , Mahadevan Anand , Kennedy Kevin F. , Collins Sean P. 
Published: February 2020

365 Background: External beam radiation therapy (EBRT) with androgen suppression (AS) and low dose rate (LDR)brachytherapy boost has been shown to improve biochemical progression free survival in unfavorable intermediate risk and high-risk prostate cancer (PC) compared to EBRT and AS. Excellent rates of local control in locally advanced prostate cancer with EBRT with high dose rate brachytherapy (HDR) boost. Prostate Stereotactic Radiosurgery (SBRT) may be an alternative to brachytherapy in patients with unfavorable intermediate and high-risk PC. Here we report the toxicity of pelvic lymph node/prostate EBRT and SBRT as the radiation boost in a large retrospective cohort. Methods: 473 patients with intermediate or high-risk PC, from the Radiosurgery Society Registry, Beth Israel Deaconess Medical Center, Georgetown University, and 5 Australian centers, were included. Patients received treatment from 3/2004- 9/2018 were the basis of this IRB approved retrospective study. The prostate and pelvis nodes were treated with between 36-50.4 Gy in 1.8/2.0 Gy fractions of radiation therapy EBRT. Patients received a SBRT boost to the prostate. Boost dose was 19-19.5 Gy (range 19-36.25 Gy). 274 and 199 patients presented with unfavorable or high-risk disease. The median follow-up was 33 months (IQR:18-63). Results: 33 deaths of 473 patients occurred in this cohort, 8 of which were caused by PC. There were 13.9% (n=66) acute Grade 1 or 2 GI toxicities (11.8% grade 1, 2.1% grade 2). There were 27.7% (n=131) acute Grade 1 or 2 GU toxicities (19.2% grade 1, 8.5% grade 2). No severe acute GU or GI toxicities were reported. There were 32 (6.8%) Grade 1 and 3 (0.6%) Grade 2 late GI toxicities. There were 9 (1.9%) Grade 3 and 1 (0.2%) Grade 4 late GI toxicities. There were 60 (12.7%) Grade 1 and 23 (4.9%) Grade 2 late GU toxicities. 15 (3.2%) Grade 3, but no Grade 4 late GU toxicity were reported. Conclusions: In this large multi-institutional retrospective cohort SBRT boost to pelvic/prostate EBRT had acceptable acute and late toxicities. The high dose per fraction of SBRT is similar to the dose delivered with HDR. This data raises the hypothesis that SBRT boost should be evaluated in additional clinical trials.
Detailed evaluation of hearing loss (HL) associated with high-dose (HD) carboplatin for salvage treatment of germ cell tumors (GCT).
Authors: Feldman Darren R. , Knezevic Andrea , Wilson Kaamilah , Bromberg Maria , Budnick Amy , McHugh Deaglan Joseph , Larsen Erik , Bajorin Dean F. , Motzer Robert J. , Tonorezos Emily S. , Patil Sujata , Funt Samuel Aaron 
Published: February 2020

401 Background: HD carboplatin is an essential part of curative salvage high-dose chemotherapy (HDCT) for GCT. Although ototoxicity is a known side effect of HD carboplatin, data on severity and characteristics of HL in this population are limited. Methods: Eligible patients (pts) received salvage HD carboplatin for GCT at our center from 1993-2017 and had audiograms pre- and post-HDCT. All pts were planned for 3 sequential cycles of HD carboplatin; some had audiograms after each cycle. HL severity was classified by ASHA criteria (slight: 15-24dB; mild: 25-40dB; moderate: 41-55dB; moderately severe: 56-70dB; severe: 71-90dB; profound: >90dB). Change in hearing threshold at each frequency (0.25 – 8 kHz) was analyzed by clinical and treatment variables using the Wilcoxon rank-sum test. The proportion of pts recommended for hearing aids was also recorded. Results: Of 115 pts (median age 31, 77% nonseminoma), 96 received TI-CE and 19 received TI-TIC on a clinical trial (Feldman CGUC 2015). Pts varied by prior cisplatin exposure (77% with ≤4 vs 23% with 5-9 cycles) and number of HD carboplatin cycles (89% had 3, 10% had 2, and 2% had 1). Carboplatin AUC was 21 in 23%, 24 in 75%, and 28 in 3%. Moderate to profound HL was present in 23% pre-HD carboplatin vs 82% post, preferentially at high frequencies (Table). Of 89 pts with normal to mild HL at baseline, 78% developed moderate or worse HL post-HD carboplatin, including 61% with moderately severe or severe HL. Higher AUC (24 vs 21) and number of HD carboplatin cycles were associated with greater HL with HD carboplatin whereas prior cisplatin exposure was not. Due to moderate or severe HL in the vital speech frequency range (2 – 4kHz), 20 (17%) pts were recommended for hearing aids post-HD carboplatin. Conclusions: In the largest series to detail ototoxicity in pts receiving salvage HD carboplatin for GCT, we show HL, particularly at high frequencies, is a major dose-dependent toxicity. Most pts will have at least moderate high frequency HL after HD carboplatin with approximately 1 in 6 recommended for hearing aids. [Table: see text]