bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic impact of a negative confirmatory biopsy in men on active surveillance for prostate cancer.
Authors: Salari Keyan , Zlatev Dimitar V. , Kuppermann David , Preston Mark A. , Dahl Douglas M. , Efstathiou Jason A. , Blute Michael L. , Zietman Anthony L. , Feldman Adam S. 
Published: February 2018

76 Background: Active surveillance (AS) is increasingly used in managing low-risk and favorable intermediate-risk prostate cancer. To mitigate the risk of unsampled higher risk disease, most institutional AS protocols call for a confirmatory prostate biopsy within 12-18 months following initial diagnostic biopsy. Here, we investigate whether the results of confirmatory biopsy impact the outcomes of men on AS. Methods: We retrospectively reviewed our institutional database of men enrolled in AS between 1997-2014 with a minimum follow-up of 6 months (n = 974). Biopsies with any prostate cancer were considered positive. Biopsies containing only benign prostatic tissue, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation (ASAP) were considered negative. Statistical analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: At diagnosis, median age was 67 years (IQR 62-72) and median PSA was 5.1 ng/mL (IQR 3.9-6.8). The vast majority of patients had Gleason ≤6 (97%) and clinical stage T1 (92%) disease. With a median follow-up of 4.8 years, 702 (72%) patients underwent a confirmatory biopsy. 67% of confirmatory biopsies were positive for prostate cancer; 33% were negative (167 benign, 40 PIN, and 22 ASAP). Of the 702 patients, 33% progressed to treatment, with pathologic progression the most common reason (77%). Univariate predictors of progression to treatment included initial clinical stage ( P= 0.04), involvement of > 20% of any core on diagnostic biopsy ( P < 0.01), PSA density ≥0.15 ( P < 0.001), and confirmatory biopsy status ( P < 10-14). In multivariate analysis, a negative confirmatory biopsy remained the strongest predictor of progression to treatment (HR 0.12 [95%CI 0.06-0.24], P < 10-8). Confirmatory biopsy status was not associated with risk of adverse pathology on RP, metastasis-free survival, disease-specific survival, or overall survival. Conclusions: A negative confirmatory biopsy is associated with a significantly lower rate of progression to treatment among men on AS. This may serve as a useful tool for prognostication and help determine the need for further repeat biopsies for men on AS.
Perspectives of prostate cancer patients about active surveillance.
Authors: Saad Fred , Fitch Margaret , Pang Kittie , Ouellet Veronique , Loiselle Carmen , Chevalier Simone , Drachenberg Darrel , Finelli Antonio , Sutcliffe Simon , So Alan I. , Tanguay Simon , Mes-Masson Anne-Marie 
Published: February 2018

82 Background: In prostate cancer (PC), men diagnosed with low risk disease may be monitored through an active surveillance (AS) approach that runs counter to the traditional message of undergoing treatment as soon as possible following a cancer diagnosis. This research explored the perspectives of men with PC regarding their decision-making process for AS to identify the factors that influenced their decision and assisted health care professionals in discussing AS as an option. Methods: Focus group interviews (n = 7) were held in several Canadian cities with men (n = 52) diagnosed with PC and eligible for AS. The men’s viewpoints were captured regarding their understanding of AS, the factors that influenced their decision to engage in AS, and their experience with the approach. A content and theme analysis was performed on the verbatim transcripts from the interviews. Results: All patients described the perception that their disease was not “large enough” to require treatment. They understood that the waiting process avoided the side effects associated with treatments, and they were comfortable about postponing treatment while undergoing close monitoring. Conversations with their doctor and how AS was described were cited as key influences in their decision. Other influences included availability of information on treatment options, distrust in the health system, personality, experiences and opinions of others, and personal perspectives on quality of life. Conclusions: AS is a relatively new approach for the care of men with low risk PC. Men require a thorough explanation on AS as a safe and valid option, as well as guidance towards supportive resources in their decision-making.
Active surveillance in prostate cancer patients: Modeling upgrading and upsizing at 1 year rebiopsy.
Authors: Nicolai Nicola , Alvisi MariaFrancesca , Rancati Tiziana , Avuzzi Barbara , Badenchini Fabio , Catanzaro Mario , Colecchia Maurizio , Di Florio Teresa , Magnani Tiziana , Marenghi Cristina , Morlino Sara , Noris Chiorda Barbara , Paolini Biagio , Stagni Silvia , Tesone Antonio , Torelli Tullio , Villa Sergio , Zaffaroni Nadia , Salvioni Roberto , Valdagni Riccardo 
Published: February 2018

90 Background: Prostate biopsy findings at diagnosis and follow-up are essential criteria in Active Surveillance (AS). In a previous work (Nicolai Eur Urol Suppl 2013) upgrading (UPG) and upsizing (UPS) at 1-yr rebiopsy resulted to be independent outcomes with different predictors. Aim of the present work is to validate these models on an independent population and to evaluate the probability of not-developing UPG, thus the chance of continuing AS Methods: Pts enrolled in 2011-2017 were considered for validation, while 318 AS pts enrolled in 2005-2011 were considered for model development. UPG model included: age (risk), PSA density (risk), prostate volume (>60 cc, protective); UPS model: age (protective), % core length containing cancer (>5%, risk), number of positive cores (>1, risk) Performance on the independent population was evaluated through AUC and calibration. Logistic model for not-developing UPG at 1 yr was fitted using all available AS pts Results: 433 pts were included in the validation set. UPG and UPS were registered in 43 and 29 pts, respectively; 38 pts had UPG+UPS. Predictors for UPG and UPS were mainly confirmed in the validation cohort (Table), with Odds Ratios (OR) very similar to the development model. Discrimination was confirmed (AUCs) and calibration was excellent (slope~1, R2>0.90). Probability of not-developing UPG (evaluated on 751 pts) was associated to age, prostate volume and PSA density (Table). Conclusions: UPG and UPS in AS pts should be considered as independent events and their management implying different strategies. Specifically, age, volume and PSA density play a key role in the chance to continue AS, i.e. in not developing UPG. A nomogram estimating the likelihood of continuing AS has been developed and will be presented. [Table: see text]
The validity of repeat prostate biopsy in prior biopsy negative patients: MRI-TRUS fusion guided biopsy.
Authors: Hwang Jinho , Kim Jung Jun , Oh Jong Jin , Jeong Chang Wook , Lee Sangchul , Hong Sung Kyu 
Published: February 2018

95 Background: To investigate validity of magnetic resonance imaging (MRI)-transrectal ultrasound fusion target biopsy (Fusion-Bx) compared with transrectal ultrasound-guided biopsy (TRUS-Bx) by evaluating detection rate of prostate cancer (PCa). Methods: Medical records of 376 patients with prior negative TRUS-Bx who underwent repeat prostate biopsy between Aug. 2015 and Apr. 2017 were retrospectively reviewed. The cohort was stratified into two groups (TRUS-Bx and Fusion-Bx) and clinical and biopsy characteristics patterns were analyzed. Conventional systemic randomized 12-core biopsy was performed in TRUS-Bx group whereas Fusion-Bx group applied additional 2-croes of target biopsy against suspicious lesions in MRI. Results: There were total 195 and 181 patients in TRUS-Bx and Fusion-Bx group, respectively. The overall cancer detection rate was slightly higher in Fusion-Bx group, but no statistical significance was observed (24.6% vs 28.7%, p = 0.367). Fusion-Bx group showed a significantly greater detection rate in target core analysis (5.0% vs 17.7%, p = 0.044). In confirmed positive biopsy patients, Fusion-Bx group had a higher rate of clinically significant prostate cancer (CsPCa) cases, but failed to achieve statistical significance (85.4% vs 92.3%, p = 0.271). When the patients with highly or very highly suspicious MRI (maximum image grade 4-5) findings in Fusion-Bx group was compared to the whole cohort of TRUS-Bx group, Fusion-Bx group was significantly greater in terms of overall detection rate (24.6% vs 38.0%, p = 0.017) and CsPCa detection rate (85.4% vs 97.0%, p = 0.009). Higher the target image grade, greater biopsy yield was achieved. Conclusions: For the patients who underwent repeat biopsy due to prior negative results, fusion-Bx showed better clinical significance including detection rate. A further study with a larger cohort size and prospective design is still needed to confirm the validity of Fusion-Bx.
The role of proton beam therapy for patients with intermediate- and high-risk prostate cancer.
Authors: Arimura Takeshi , Kondo Naoaki , Matsukawa Kyoko , Wada Kiyotaka , Kitano Ikumi , Chuman Ikuko , Nagata Ichiro , Ogino Takashi 
Published: February 2018

97 Background: Although there are many patterns of treatment in localized prostate caner, proton beam therapy has no definite role in them. We aimed to assess the outcomes of proton beam therapy (PBT) alone for patients with intermediate- and high-risk prostate cancer, and to clarify the role of PBT in the treatments. Methods: Between Jan. 2011 and Sep. 2014, 204 patients with intermediate- and high-risk prostate cancer who declined to receive hormonal treatments until biochemical or clinical recurrence were enrolled in the study. All patients were irradiated a 70-78 GyE in 28-39 fractions, and pre-treatment risk groups were classified in accordance with the D’Amico criteria. The 5-year (biochemical or clinical) recurrence-free survival (RFS), late gastrointestinal (GI) and genitourinary (GU) toxicity (NCI-CTCAE ver.4.0) were evaluated. We conducted a survey on sexual quality of life (QOL) every six months to evaluate any long-term damage to the sexual function using the Expanded Prostate Cancer Index Composite (EPIC). Results: The mean age and the follow-up period were 66 (range: 39-86) and 52 months (range: 24-76 months), respectively. The 5-year RFS rates in intermediate- (n = 112) and high- (n = 92) risk groups were 96.9% and 83.4%, respectively. There was a significant difference between the two groups (p = 0.002). The incidence of grade 2+ GI and GU toxicity were 4% and 3%, respectively. We found a significant difference in the GI toxicity between the two radiation protocols of 78GyE/39fractions (n = 6, 11%) and 70GyE/28fractions (n = 0, 0%) (p < 0.01). A 5.8% decrease in average after adjusting for aging was found in sexual summary score in six years after treatment, which was equivalent to aging of three years. Conclusions: Proton beam therapy alone demonstrated favorable results in patients with intermediate- and high-risk prostate cancer. Although more patients and longer follow-up are necessary to confirm the outcomes, these results suggested a hypothesis that proton beam therapy might not require androgen deprivation therapy in the treatment of localized prostate cancer, which could lead to a possibility of preserving of sexual function. Clinical trial information: MPTRC-N2 and N3.
The association between HSD3B1 genotype and steroid metabolism in normal and prostate cancer (PCa) tissue.
Authors: Emamekhoo Hamid , Barata Pedro C. , Magi-Galluzzi Cristina , Berk Mike , Taylor Jennifer , Tyler Allison Janine , Rini Brian I. , Grivas Petros , Gilligan Timothy D. , Ornstein Moshe Chaim , Stephenson Andrew J. , Klein Eric A. , Kaouk Jihad , Haber Georges-Pascal , Sharifi Nima , Garcia Jorge A. 
Published: February 2018

TPS155 Background: The common germline variant HSD3B1(1245C) encodes for a gain-of-function in 3βHSD1 which is associated with a shorter duration of response to androgen deprivation therapy (ADT) and more rapid disease progression to castration resistant PCa (CRPC) as shown previously in 5 independent cohorts. Therefore, evaluating the effect of such genotype variation on the level of steroid metabolites and the intratumoral dihydrotestosterone (DHT) concentration in benign and tumor tissue of men on ADT is of significant importance. We hypothesize that patients with homozygous HSD3B1 (1245C) genotype (HZ) will have a sustained androgen synthesis from extragonadal precursor steroids and higher concentrations of DHT compared to patients with wild-type HSD3B1 (1245A) (WT) inheritance in the context of testosterone suppression. In addition, it is expected that heterozygous HSD3B1 (1245C) patients (HTZ) will have intermediate levels of DHT. We also hypothesize that treatment with androgen receptor (AR) antagonist (apalutamide) will reverse the effects of elevated DHT on AR signaling in benign and malignant prostate tissue. Methods: In this Phase II trial (NCT02770391), men with newly diagnosed intermediate or high-risk PCa (GS ≥ 4+3, ≥cT2b, or PSA ≥ 10) who are scheduled to undergo radical prostatectomy (RP) will be enrolled into 3 groups based on their HSD3B1 genotype. All pts will receive one dose of 7.5 mg leuprolide injection and apalutamide 240 mg/day orally for 28 ± 3 days prior to RP. DHT and 7 other androgens (including testosterone, Dehydroepiandrosterone, Androstenedione) will be evaluated in the normal and malignant prostate tissue as well as serum samples obtained at the time of RP. AR regulated genes expression (including PSA, FKBP5, TMPRSS2) will be compared across 3 genotypes. A sample size of 57 pts (WT = 30, HTZ = 15, HZ = 12) will allow a statistical power of > 80% (with two-sided α = 0.05) to detect a 4-fold trend in DHT concentrations in the resected prostate tissue (primary endpoint) as well as similar trend in other androgens (secondary endpoint). As of Oct 2017, 16 of planned 57 pts have been enrolled. Clinical trial information: NCT02770391.
ProBio II: An adaptive and randomized multi-arm biomarker driven phase 2 study in men with castrate resistant prostate cancer (CRPC).
Authors: Gronberg Henrik , Eklund Martin , Lindberg Johan , Ullén Anders , Bjartell Anders , Andren Ove , Robinson David , Franck Lissbrant Ingela , Enblad Gunilla , Stahl Olof , Thellenberg Camilla 
Published: February 2018

TPS397 Background: Castrate-resistant prostate cancer (CRPC) affects around 3,000 men in Sweden every year. New drugs are available but they have moderate effect, low response rates, are expensive, and lack predictive treatment markers. This will lead to an unsustainable situation for prostate cancer care. Our hypothesis is that treatment decisions based on molecular profiling will significantly increase the response rate at 3 months compared to current clinical care, translating into improved progression free and overall survival. The vast majority of CRPC metastasize to the bone, with low success rate in obtaining sufficient material. Therefore, we will sequence circulating tumor DNA (ctDNA) being present at high levels in plasma. Methods: ProBio-II is an adaptive, multi-arm, open-label, multiple assignment randomized biomarker driven phase 2 trial in men with CRPC . Men (n=750) will be randomized to receive either standard of care (following Swedish national guidelines) or treatment with Enzalutamide, Abiraterone, PARP inhibitors, RA-223, Cabazitaxel, or immune modulators based on molecular subtypes. The molecular subtypes are defined as tumor properties or mutations in certain genes/pathways including: Microsatellite instability; Androgen receptor alterations; DNA-repair deficiency; TP53 inactivation; PTEN inactivation etc. The molecular subtypes will be identified by ctDNA profiling. A specially designed ctDNA profile for CRPC has been developed by our group to detect: mutations, amplifications and genomic rearrangements in the androgen receptor (AR); mutations, genomic rearrangements and amplifications/deletions in 300 key genes involved in prostate cancer; and microsatellite instable and hypermutated cancers. ProBio-II’s design is novel and inspired by successful studies as I-SPY (breast cancer) and the NCI-MATCH trial (metastatic cancer). Novel aspects of the study design includes using prior probability of treatment response; re-randomization of non-responders; and adaptive design. The ProBio II study will start recruiting patients in Sweden in Q1 2018 and recruit patients during a 18 month period. All major oncology departments in Sweden will participate.
Intergroup study EORTC-1532-gucg: A phase 2 randomized open-label study of oral darolutamide (ODM-201) vs. androgen deprivation therapy (ADT) with LHRH agonists or antagonist in men with hormone naive prostate cancer (PCa).
Authors: Tombal Bertrand F. , Gillessen Silke , Loriot Yohann , Marreaud Sandrine , Collette Laurence , Saad Fred 
Published: February 2018

TPS406 Background: Androgen deprivation therapy (ADT) by LHRH analogues aims to lower serum testosterone. ADT is associated with several side effects that include hot flushes, depression, loss of libido, metabolic disturbances leading to an increase risk of cardiovascular disease, increased bone resorption leading to increased risk of osteoporosis and skeletal fracture. AR antagonists may circumvent these side effects by suppressing AR transcription by competitive inhibition of AR, without lowering systemic testosterone. In Europe, first generation AR antagonists bicalutamide 150 mg is registered for the treatment of non-metastatic hormone-naïve PCa. is a novel AR antagonist that is structurally distinct with higher AR-binding affinity compared to bicalutamide, enzalutamide, and apalutamide. The aim of this trial is to investigate the activity, safety and tolerability of darolutamide as single agent, as an alternative to LHRH analogues in men requiring ADT. Methods: EORTC-1532-GUCG (NCT02972060) will randomize 250 men with hormone-naïve PCa 1:1 to 600 mg (2× 300-mg tablets) bid of darolutamide1 or LHRH agonist or antagonist, stratified for type of ADT (agonist vs. antagonist), disease extent (measurable, non-measurable, vs. no metastasis) and age (≥70 vs < 70 years). Key inclusion criteria include histologically confirmed asymptomatic PCa (all stages) for whom continuous ADT is indicated for a minimum period of 24 weeks. Patients with up to 4 confirmed not visceral metastases, are allowed. Baseline total testosterone should be ≥ 8 nmol/L or 230 ng/dL. Primary endpoint is PSA response assessed at 24 weeks, defined as a ≥ 80% decline in PSA at week 24 in the darolutamide study arm. The ADT arm is used as an internal non comparative control. Key secondary endpoints include: Change in hormone-treatment related symptoms scale of the EORTC QLQ-PR25 at 24 weeks (comparison between arms); objective response rate at 24 weeks in patients with measurable disease at baseline, safety according to NCI-CTC version 4.0. Clinical trial information: NCT02972060.
EV-201 study: A single-arm, open-label, multicenter study of enfortumab vedotin for treatment of patients with locally advanced or metastatic urothelial cancer who previously received immune checkpoint inhibitor therapy.
Authors: Rosenberg Jonathan E. , Heath Elisabeth I. , O'Donnell Peter H. , Hahn Noah M. , Balar Arjun Vasant , Gartner Elaina M. , Melhem-Bertrandt Amal , Petrylak Daniel Peter 
Published: February 2018

TPS542 Background: The majority of patients with locally advanced or metastatic urothelial cancer (la/mUC) will not respond to immune checkpoint inhibitors (CPIs) given in the post-platinum or cisplatin ineligible setting, and there are currently no approved standard therapies after disease progression. Enfortumab vedotin (EV), an antibody-drug conjugate, delivers the microtubule-disrupting agent monomethyl auristatin E to tumors expressing Nectin-4, which is overexpressed in mUC. Preliminary results from an ongoing phase 1 study of EV monotherapy in pts with mUC (Petrylak ASCO 2017) showed that EV was well tolerated in pts with mUC. Nausea (36%), pruritus (31%), and fatigue (30%) were the most commonly reported treatment-related AEs. The most common grade ≥3 AEs (regardless of attribution) were urinary tract infection (11%) and hypophosphatemia (9%). EV showed an objective response rate (ORR) of 41% (29 out of 71 pts) across all dose levels and 53% (16 out of 30 pts) ORR at the recommended phase 2 dose of 1.25 mg/kg. The ORR was not diminished in pts with prior CPI use (44%), prior taxane use (41%) or in pts with liver metastases (47%). These encouraging results along with a favorable safety and tolerability profile warrant further investigation of EV as a monotherapy. Methods: This single-arm, open label, multicenter phase 2 study (NCT03219333) evaluates the antitumor activity and safety of EV monotherapy in ~120 pts with la/mUC. Pts must have previously received a CPI and either have received prior platinum or be ineligible for cisplatin. Pts must have histologically or cytologically documented transitional cell carcinoma of the urothelium that progressed during or following receipt of most recent therapy. The primary objective is to determine antitumor activity of EV as measured by ORR. Secondary objectives include assessment of duration of response, disease control rate, PFS, OS, and safety/tolerability of EV. Pts must have tumor tissue available for exploratory analyses. Response is assessed per RECIST v1.1. Study enrollment began in Sept 2017. Clinical trial information: NCT03219333.
Forced lipophagy reveals that lipid droplets are required for early embryonic development in mouse
Authors: Tatsumi Takayuki , Takayama Kaori , Ishii Shunsuke , Yamamoto Atsushi , Hara Taichi , Minami Naojiro , Miyasaka Naoyuki , Kubota Toshiro , Matsuura Akira , Itakura Eisuke , Tsukamoto Satoshi 
Published: February 2018

ABSTRACT
Although autophagy is classically viewed as a non-selective degradation system, recent studies have revealed that various forms of selective autophagy also play crucial physiological roles. However, the induction of selective autophagy is not well understood. In this study, we established a forced selective autophagy system using a fusion of an autophagy adaptor and a substrate-binding protein. In both mammalian cells and fertilized mouse embryos, efficient forced lipophagy was induced by expression of a fusion of p62 (Sqstm1) and a lipid droplet (LD)-binding domain. In mouse embryos, induction of forced lipophagy caused a reduction in LD size and number, and decreased the triglyceride level throughout embryonic development, resulting in developmental retardation. Furthermore, lipophagy-induced embryos could eliminate excess LDs and were tolerant of lipotoxicity. Thus, by inducing forced lipophagy, expression of the p62 fusion protein generated LD-depleted cells, revealing an unexpected role of LD during preimplantation development.
Case Report: “Incognito” proteus syndrome
Authors: Vestita Michelangelo , Filoni Angela , Arpaia Nicola , Ettorre Grazia , Bonamonte Domenico 
Published: February 2018

Proteus syndrome (PS) is a postnatal mosaic overgrowth disorder, progressive and disfiguring. It is clinically diagnosed according to the criteria reported by Biesecker et al. We describe the case of a 49-year-old woman who presented with a 10-year history of pauci-symptomatic infiltrating plaque lesions on the sole and lateral margin of the left foot, which had been diagnosed as a keloid. The patient had a positive history for advanced melanoma and a series of subtle clinical signs, such as asymmetric face, scoliosis, multiple lipomas on the trunk, linear verrucous epidermal nevi, and hyperpigmented macules with a mosaic distribution. Even if the clinical presentation was elusive, she had enough criteria to be diagnosed with PS. This case describes the first evidence, to the best of our knowledge, of pauci-symptomatic PS in adulthood, reports its rare association with advanced melanoma, and illustrates the importance of even minor cutaneous clinical signs, especially when atypical, in formulating the diagnosis of a complex cutaneous condition such as this.