bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regression tree analysis to identify the best candidates for neoadjuvant chemotherapy (NAC) in patients with clinically lymph node-positive penile squamous cell carcinoma (PSCC).
Authors: Bandini Marco , Zhu Yao , Ye Dingwei , Ornellas Antonio Augusto , Watkin Nick , Ager Michael , Hakenberg Oliver W. , Heidenreich Axel , Raggi Daniele , Catanzaro Mario , Haidl Friederike , Pederzoli Filippo , Briganti Alberto , Montorsi Francesco , Chipollini Juan , Azizi Mounsif , Albersen Maarten , Brouwer Oscar , Spiess Philippe E. , Necchi Andrea 
Published: February 2020

2 Background: PSCC patients (pts) with palpable inguinal lymph node (ILN) disease have a poor overall survival (OS). For them, use of neoadjuvant chemotherapy (NAC) is recommended in guidelines, but limited data are available to inform pt selection. We aim to identify predictors of poor OS in clinically ILN-positive (ILN+) pts to define the optimal candidates for NAC. Methods: Within an international, multicenter database of 924 PSCC pts, we identified 334 ILN+ pts with available data. ILN involvement was defined either with the presence of palpable ILN disease or based on preoperative CT-scan. FDG-PET/CT-scan was performed based on clinical judgment of the treating physician. Univariable and multivariable analyses (MVA) assessed predictors of overall mortality (OM). A regression-tree method for censored data was used to generate a risk stratification tool for prediction of 24m OM after diagnosis of ILN+ PSCC. Kaplan-Meier method was used to define the OS benefit related to the use of NAC according to the regression-tree stratified sub-groups. Results: Median age at diagnosis was 58yrs, and 105 (31.4%) had ECOG≥1. Of all, 120 (35.9%), 152 (45.5%), and 62 (18.6%) harbored cN1, cN2, and cN3 disease. Additionally, 152 (45.5%) and 117 (35%) had monolateral vs bilateral clinical ILN involvement. FDG-PET/CT was adopted in 42 (12.2%) pts, and 16 (4.8%) had pelvic LN uptake. Median OS was 107m, with 24m OS = 66%. At MVA, cN2 (HR: 2.28, p=0.006), cN3 (HR: 2.15, p=0.02), PET/CT scan-detected pelvic and ILN involvement (HR: 2.57, p=0.007) were independently associated with higher OM, whether bilateral clinical ILN+ was only univariably significant (HR: 1.56, p=0.02). At regression-tree analysis (AUC 70%), pts with cN3 and cN2 with PET/CT-detected pelvic and ILN involvement had the higher risk of 24m OM (>54%). NAC was associated with improved 24m OS rates (54 vs. 33%) only in this pt subgroup (p=0.002). Conclusions: NAC improves OS in pts with cN3 or cN2 and pelvic FDG-PET/CT scan-detected disease. Our regression-tree may serve to screen ILN+ pts, to identify the optimal NAC candidates before radical treatments.
Circulating tumor DNA (ctDNA) landscape in metastatic castrate-resistant prostate cancer patients with germline alterations.
Authors: Moses Marcus W. , Steinwald Peter , Jaeger Ellen , Hatton Whitley , Cotogno Patrick , Manogue Charlotte , Layton Jodi Lyn , Lewis Brian E. , Barata Pedro C. , Sartor A. Oliver , Ledet Elisa Marie 
Published: February 2020

200 Background: Circulating tumor-DNA (ctDNA) in mCRPC patients (pts) provides a viable approach for examining the genetic landscape of prostate cancer. In this follow-up, we report ctDNA variants in germline tested mCRPC pts. Methods: ctDNA alterations in 73 genes were detected using Guardant360 (G360) assays. Alteration types assessed were missense, frameshift, insertions, splice variants, truncations, amplifications (amp), deletions, and other. Pts included in the analysis received germline genetic testing (Invitae Corporation, San Francisco, CA) and ctDNA assays at various treatment timepoints. Statistical analyses were performed using chi-square and fisher exact test with p-value <0.05 for significance. Results: Germline and ctDNA testing was completed in 270 mCRPC pts. 13% (35/270) of pts had pathogenic germline alterations. Germline alterations detected were BRCA2 (43%, n=15), ATM (8.5%, n=3), CHEK2 (8.5%, n=3), and BRCA1 (6%, n=2). Of the 673 alterations detected in G360 assays, TP53 (25%, n=167) and AR (17%, n=117) were most commonly observed. ctDNA alteration breakdown for germline negative/positive pts is summarized in Tables A/B. Germline negative pts had more AR alterations compared to germline positive (p = 0.023). Also, germline negative pts presented with more amps (p < 0.001) and germline positive pts with more frameshift alterations (p = 0.005). The association of ctDNA alteration to clinical outcomes in germline positive/negative pts was also assessed and is ongoing. Conclusions: Pts with germline positive alterations had few somatic AR alterations and higher frequency of deleterious mutation in comparison to their germline negative counterparts.[Table: see text][Table: see text]
Family history and germline alterations in metastatic prostate cancer patients.
Authors: Hatton Whitley , Jaeger Ellen , Moses Marcus W. , Zaheri Alexa , Cotogno Patrick , Manogue Charlotte , Lewis Brian E. , Barata Pedro C. , Layton Jodi Lyn , Ledet Elisa Marie , Sartor A. Oliver 
Published: February 2020

231 Background: Recent literature has highlighted the importance of germline genetic testing in metastatic prostate cancer (PCa)patients (pts). This retrospective study evaluated family history (FH), evaluate treatment outcomes in metastatic patients with pathogenic germline mutations, and compared family history in Caucasian (CA) and Africans Americans (AA). Methods: At Tulane Cancer Center, 428 metastatic PCa pts had germline testing in at least 79 genes. Comprehensive family histories were obtained in all. Analysis of prevalent FH, including breast, ovarian, prostate, and pancreatic cancers was assessed for all metastatic pts. Statistical analyses including chi square were performed. Results: 64 (64/428; 14.9%) pts had at least one or more pathogenic mutations, while 166 (166/428; 38.7%) had were normal. The remaining 199 (199/428; 46.4%) of pts had a variant of uncertain significance (VUS). Pts with a DNA repair pathogenic mutation were more likely to have >2 family members affected by cancer, regardless of cancer type or degree of relationship (p=0.0047); 6 pts without any family history of cancer had a pathogenic mutation. In CA, the presence of either a breast or PCa family history was associated with pathogenic germline findings (p=.022/.0367) However, in AAs neither breast nor prostate cancer predicted pathogenic germline alterations. Conclusions: The correlation between family history of breast and PCa cancer in CA pts with pathogenic mutations is notable as is the finding of >2 family members with cancer predicting germline pathogenic alterations. With AA pathogenic pts, there was no correlation of family history of breast and PCa, which highlights the need to learn more about the genetic factors which influence AA prostate cancer risk.[Table: see text]
Survey of ADT-induced estrogen deficiency-related side effects in a contemporary cohort of men with advanced prostate cancer.
Authors: Getzenberg Robert H. , Scholz Mark C. , Scholz Alexandra , Steiner Mitchell S. 
Published: February 2020

235 Background: Androgen Deprivation Therapy (ADT) is a mainstay in the treatment of advanced prostate cancer. ADT-induced estrogen deficiency related side effects may cause men to delay, pause, or discontinue ADT, increases morbidity and mortality, and can significantly impact quality of life. ADT-induced effects include hot flashes, bone loss and fractures, fatigue, decreased libido, and metabolic and lipid changes. Currently there are no FDA approved treatments for ADT-induced hot flashes in men with advanced prostate cancer. In this study, a survey was conducted on the impact of hot flashes, one of the hallmark ADT-induced estrogen deficiency effects, in a contemporary cohort. Methods: During the period of August/September 2019, 212 men with advanced prostate cancer on ADT participated in a digital survey conducted by the Prostate Cancer Research Institute (PCRI) focused on the frequency, severity and impact of their hot flashes. The men were at least 50 years of age with 61% being 70 or older. ADT types included LUPRONÒ(64%), ELIGARDÒ(12%), ZOLADEXÒ(7%) and other forms of hormonal therapy (17%). Results: Of the 212 men surveyed, 99% reported hot flashes with 80% indicating that they experience clinically significant, moderate to severe hot flashes. 77% of men reported that the number of hot flashes stayed the same or increased during their hormonal therapy. 37% of the men experienced more than 5 hot flashes per day and 23% indicated that they felt embarrassed about their hot flashes. Only 51% had either researched how to address their hot flashes or discussed them with their physician. Importantly, 16% considered halting ADT as a result of their hot flashes. Conclusions: This contemporary survey underscores the significant unmet medical need to treat moderate to severe hot flashes which occurred in 80% of the men studied. As about half of the men have not discussed their symptoms with a physician either because of embarrassment or lack of treatment options, the number of men with moderate to severe hot flashes appears to be greatly under-reported. As men on ADT are living longer with prostate cancer, finding an effective and safe treatment for debilitating hot flashes must be a priority.
Lymph node metastasis to predict overall survival in oligometastatic prostate cancer in Asian patients.
Authors: Rii Junryo , Sakamoto Shinichi , Yamada Yasutaka , Imamura Yusuke , Nakamura Kazuyoshi , Komiya Akira , Nakatsu Hiroomi , Ichikawa Tomohiko 
Published: February 2020

237 Background: The oligometastatic cancer has been suggested as an intermediate state between localized disease and wide range metastases. Clinical significance of local treatment in oligometastatic prostate cancer (PCa) has been a recent topic. However, due to racial differences, there are no standard definitions of oligometastasis, especially in Asians. Here we studied the risk factor among Japanese oligometastatic PCa patients. Methods: We retrospectively analyzed the medical record of 207 patients, including locally advanced (T3 or T4N0M0), lymph-node-positive (N1), and ≤10 bone metastases cancer. All patients received androgen deprivation therapy only. The number of bone metastasis and clinical factors were evaluated in association with OS. Results: Median age, PSA at baseline and OS were 73 years, 48.8ng/ml and 121 months respectively. The cutoff value for the number of bone metastases that have the greatest impact on OS was ≥2 (HR 3.05, p = 0.0001), followed by ≥7 (HR 3.03, p = 0.0005). In multivariate analysis, lymph node metastasis (HR 2.54, p = 0.003) and ≥2 bone metastases (HR 2.67, p = 0.009) were independent predictors of OS. In risk classification based on independent predictors, OS was significantly classified in High (3-4 factors), Intermediate (1-2 factors), and Low (no factor) risk groups (p <0.0001). Furthermore, even among same risk factors group, inclusion of lymph node metastasis significantly increased the HR by 2.34 (p = 0.039). Conclusions: Not only the number of bone metastasis but also lymph node metastasis predict OS of oligometastatic PCa patients.[Table: see text]
Blood platelet volume to predict treatment-specific outcomes of metastatic castration-resistant prostate cancer.
Authors: Fukuokaya Wataru , Kimura Takahiro , Urabe Fumihiko , Kimura Shoji , Tashiro Kojiro , Tsuzuki Shunsuke , Koike Yusuke , Sasaki Hiroshi , Miki Kenta , Egawa Shin 
Published: February 2020

242 Background: In the present guidelines for the management of metastatic castration-resistant prostate cancer (CRPC), it is unclear who benefits from androgen receptor axis-targeted agents (ARATs) or docetaxel as a first-line treatment. Methods: We conducted a single-institutional retrospective study to explore treatment-specific biomarkers for treatment response of metastatic CRPC. A cohort of 211 patients with metastatic CRPC treated with either ARAT (abiraterone acetate or enzalutamide) or docetaxel as a first-line treatment was evaluated. In addition to well-established biomarkers such as hemoglobin, neutrophil-to-lymphocyte ratio, alkaline phosphatase, and lactate dehydrogenase, we also assessed red cell distribution width, platelet count, and mean platelet volume (MPV). Laboratory measures were assessed within 1 month before starting treatment. Prostate-specific antigen progression-free survival (PSA-PFS) and radiographic progression-free survival (RPFS) were evaluated. Multivariable Cox regression models were used to assess the association between biomarkers and the risk of events. We also studied the statistical interaction between biomarkers and clinical outcomes. Results: Of all blood-based biomarkers, multivariable Cox regression models identified pre-treatment MPV (≤9.0 fL) as an independent prognostic factor of both PSA progression (hazard ratio [HR]: 2.62, 95% confidence interval [CI]: 1.25-5.48, P = 0.011) and radiographic progression (HR: 4.46, 95% CI: 1.79-11.1, P = 0.001). In addition, these models showed a lower risk of PSA progression (HR: 0.38, 95% CI: 0.15-0.96, P = 0.041) and radiographic progression (HR: 0.16, 95% CI: 0.05-0.50, P = 0.002) with docetaxel compared with ARAT when pre-treatment MPV was small. Conclusions: The present study identified MPV as a significant treatment-specific prognostic factor of PSA progression and radiographic progression in patients with metastatic CRPC treated with a first-line treatment. Furthermore, our results suggested that small MPV was associated with superior survival benefit on docetaxel over ARAT.
Exosomal TUBB3 mRNA expression level to predict prognosis for abiraterone treatment in metastatic prostate patients.
Authors: Zhu Sha , Sun Guangxi , Dai Jindong , Zhang Xingming , Chen Junru , Zhu Xudong , Zhao Jinge , Zhang Haoran , Ni Yuchao , Wang Zhipeng , Shen Pengfei , Zeng Hao 
Published: February 2020

244 Background: TUBB3 (Class III β-tubulin), a dynamic component of microtubules, is considered a prognostic biomarker of tumor aggressiveness and poor survival. Previous studies have researched into its indication of resistance to chemotherapeutic drugs. However, its association with abiraterone, a next-generation androgen-axis targeting drug in prostate cancer has not been studied yet. In this study, we aimed to find out if exosomal TUBB3 expression could predict the efficacy of abiraterone in metastatic prostate cancer patients. Methods: Blood samples of metastatic prostate cancer patients during different disease stages were collected. We isolated the exosomes and extracted the RNA for analysis of TUBB3 by ddPCR. Absolute target mRNA concentration was measured by ddPCR as copies per milliliter (copies/20ul). Clinical data were collected for all patients. Primary study endpoint was progression-free survival (PFS). Statistical analyses were performed with SPSS 25.0. Results: A total of 54 metastatic prostate cancer patients who have received abiraterone treatment were enrolled. Baseline characteristics are comparable between high (≥10 copies/20ul) and low (<10 copies/20ul) TUBB3 expression groups. Univariate analyses revealed that baseline hemoglobin≤120g/L, baseline sodium concentration >140 mmol/L, baseline potassium concentration >4.39 mmol/L and high exosomal TUBB3 expression were associated with shorter PFS, while only baseline sodium concentration and exosomal TUBB3 expression were independent prognosticators in multivariate analyses. In subsequently subgroup analyses, high exosomal TUBB3 expression demonstrates particularly high hazard ratio in multiple subgroups (patients younger than 70 years old, without neuroendocrine differentiation and immunohistochemical androgen-receptor splice variant 7 expression, with baseline PSA >100 ng/mL, and patients receiving abiraterone as first-line therapy). Conclusions: Exosomal TUBB3 expression has potential in making treatment plan and predict prognosis in metastatic prostate cancer patients. High exosomal TUBB3 expression indicates poor response to abiraterone, especially as first line therapy.
Preliminary results of a prospective assessment of androgen receptor splice variants in mCRPC patients undergoing androgen receptor targeted agents.
Authors: Francolini Giulio , Loi Mauro , Detti Beatrice , Mangoni Monica , Desideri Isacco , Muntoni Cristina , Ciccone Lucia Pia , Aquilano Michele , Pinzani Pamela , Salvianti Francesca , Lucidi Sara , Mariotti Matteo , Garlatti Pietro , Salvatore Giulia , Sottili Mariangela , Livi Lorenzo 
Published: February 2020

246 Background: Different treatment options for metastatic castrate resistant prostate cancer (mCRPC) are currently available, including Androgen Receptor Targeted Agents (ARTA) and Taxane based chemotherapy. However, selection criteria aiming to drive the therapeutic choice in this setting are lacking, and no standardized therapeutic sequence is validated. In our institution, a prospective study testing predictive value of circulating tumor cells (CTC) in patients (pts) receiving a first line ARTA for mCRPC is currently ongoing (PRIMERA). Here, we present preliminary results from the first enrolled cohort. Methods: Pts affected by mCRPC eligible for Androgen Deprivation Therapy (ADT) plus ARTA were prospectively enrolled and underwent baseline determination of androgen-receptor splice variant 7 (AR-V7) and androgen-receptor-full length (ARFL) variants on CTC at baseline (ARTA start). Fisher Exact Test was conducted to explore the correlation between baseline features and CTC detection rate. Results: Overall, 26 pts were enrolled and baseline results are available for 13 pts. CTC were found in 5 (38.5%) pts. No significant difference was reported in terms of CTC detection probability for pts with high vs low burden of disease according to CHARTEED definition (p=0.42), neither for pts with PSA at CRPC diagnosis < or > 10 ng/ml, (p=0.2). However, a PSA > 10 ng/ml at ADT start in metastatic hormone sensitive setting (mHSPC) was significantly related to CTC detection probability (p=0.01). AR-V7 variants were found in 1 out 5 (20%) CTC-positive pts. Conclusions: PSA at ADT start may significantly be related to CTC detection rate. CTC detection could be particularly useful in pts with a high burden of disease at the beginning of systemic therapy. Metastatic disease could remain dormant until development of CRPC status, with consequent release of increased amount of CTC, more likely to be detected in this setting. AR-V7 expression was found in 20% of CTC positive pts, in line with literature data.[Table: see text]
Analysis of small non-coding RNAs in urinary exosomes to classify prostate cancer into low-grade (GG1) and higher-grade (GG2-5).
Authors: Klotz Laurence , Tilki Derya , Fleshner Neil Eric , DiRienzo Albert Gregory , Wang Wei-Lin Winnie , Tenniswood Martin 
Published: February 2020

277 Background: To develop a new predictive test for prostate cancer, based on the interrogation of small non-coding RNAs (sncRNA) isolated from urinary exosomes. We report the development and performance of the miR Sentinel PCa Test, that distinguishes patients with prostate cancer from those with no evidence of prostate cancer (NEPC) and the miR Sentinel CS Test, that distinguishes low grade from higher grade disease. Methods: Affymetrix miR 4.0 arrays were used to identify informative sncRNAs isolated from urinary exosomes. sncRNA from 233 subjects undergoing a prostate biopsy [89 men with benign biopsies, 88 with grade group 1 (GG1) cancer and 56 patients with grade group 2-5 (GG2-5)] were interrogated on these arrays. A custom OpenArray platform was designed to interrogate the 280 most informative sncRNAs, identified using a data-driven selection algorithm. The platform was designed to categorize patients as either no cancer or cancer using the miR Sentinel PCa Test, and subclassify the patients with cancer into GG1 or GG2-5 cancer using the miR Sentinel CS Test. The performance of the miR Sentinel PCa and CS Tests was validated in an independent cohort. Results: In 233 men, theSentinel PCa Test correctly classified 89/89 subjects with no cancer and 144/144 with cancer. The Sentinel CS Test correctly identified 55/56 patients with GG2-5 and 87/88 patients with GG1. Sensitivity was 98%, Specificity 98%, NPV 98% and PPV 93%. For validation, a prospective observational study of 329 subjects (NEPC = 139; GG1= 88; GG2-5 = 102) with elevated PSA correctly classified 134/139 as no cancer [Sensitivity 98% (195/199); Specificity 96% (134/139), PPV 98% and NPV 97%]. The Sentinel CS Test classified 87/88 as GG1 and 102/102 as GG2-5 [Sensitivity 100% (102/102), Specificity 99% (87/88), PPV 99%, and NPV=100%]. Conclusions: Initial evaluation of the miR Sentinel PCa and CS Tests demonstrated the high precision of these tests to detect prostate cancer and distinguish high grade (GG2-5) disease. Further validation is ongoing.[Table: see text]
Risk factors which predict biopsy upgrading over time in active surveillance for prostate cancer.
Authors: Lonergan Peter Eoin , Washington Samuel L. , Zhao Shoujun , Cowan Janet E. , Nguyen Hao , Shinohara Katsuto , Cooperberg Matthew R. , Carroll Peter 
Published: February 2020

290 Background: Active surveillance (AS) is recognized as the preferred treatment for low risk prostate cancer (PCa). No validated clinical tools currently exist to standardize the frequency of biopsies. We aimed to determine predictors of biopsy upgrading in a contemporary cohort of patients on AS. Methods: Men enrolled on AS at UCSF between 2000-2016 were included. The genomic tests used were Oncotype DX, Decipher and Prolaris. Biopsy upgrade was defined as ISUP grade group ≥ 2 on subsequent biopsy. PSA kinetics was calculated using a linear mixed-effects model for log of PSA, adjusted for clinical characteristics. Multivariable Cox proportional hazards regression models were utilized to identify factors associated with risk of upgrade on follow-up at first surveillance biopsy and at 3, 5 and 10 years. Results: 1,303 men were included. Upgrade-free survival at 3, 5 and 10 years was 73%, 53% and 27% respectively. Median time between diagnostic biopsy and first surveillance biopsy was 13 months (IQR 9-16) with the risk of upgrade at first surveillance biopsy associated with PSA density (hazard ratio [HR] 2.761, 95% confidence interval [CI] 1.895-4.023), and “high” risk genomic score (HR 1.867, 95% CI 1.025-3.401) on multivariable analysis after adjustments. Independent variables significantly associated with risk of upgrade at first surveillance biopsy and at 3, 5 and 10 years on multivariable analysis after adjustments are shown. Conclusions: Our findings suggest that genomic scores and PSA density are risk factors for biopsy upgrading within 3 years of starting AS, however PSA kinetics is associated with risk of upgrade at 5 and 10 years. When used in tandem, genomic scores may identify a subset eligible for AS who could potentially adopt a less intensive surveillance regimen.[Table: see text]