bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of BAP1 expression in clear cell renal cell carcinoma with inferior vena cava tumor thrombosis.
Authors: Oka Suguru , Inoshita Naoko , Miura Yuji , Oki Ryosuke , Miyama Yu , Nagamoto Shoichi , Ogawa Kohei , Sakaguchi Kazushige , Kondoh Chihiro , Kurosawa Kazuhiro , Urakami Shinji , Takano Toshimi , Okaneya Toshikazu 
Published: September 2018

e16080 Background: Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC), and affected patients have a poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts a poor prognosis. The aim of this study was to elucidate the association between BAP1 expression and clinicopathologic outcomes in patients with ccRCC with an IVC tumor thrombus. Methods: Thirty-nine patients with ccRCC with an IVC tumor thrombus who underwent radical nephrectomy and tumor thrombectomy at our institution from 1999 to 2010 were retrospectively evaluated. Immunohistochemical analyses were performed for the expression of BAP1, and the associations between the expression of BAP1 and clinical outcomes were assessed. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Multivariate analyses of the associations between overall survival (OS) and clinical variables were performed using a Cox proportional hazard model. For all analyses, P < 0.05 was considered statistically significant. Results: The median follow-up time was 58.8 months (range, 2–130 months). The median age was 66 years (range, 37–80 years). Four patients (10.3%) had lung metastasis at the initial diagnosis. The primary tumor was right-sided in 27 (69.2%) patients and left-sided in 12 (30.8%). The IVC tumor thrombus extended above and below the diaphragm in 11 (28.2%) and 28 (71.8%) patients, respectively. The KPS score was > 80 in 23 patients (59.0%). BAP1 expression was positive in 26 (67.0%) cases and negative in 13 (33.0%). BAP1-negative tumors were associated with a significantly shorter OS than BAP1-positive tumors (median OS, 42.0 vs. 81.5 months, respectively; P = 0.019). The median disease-free survival in BAP1-negative and -positive tumors was 10.0 and 19.0 months, respectively (P = 0.019). Multivariate analysis showed that only a BAP1-negative status was significantly associated with shorter OS (P = 0.026). Conclusions: A BAP1-negative tumor status was significantly associated with a poor prognosis in patients with ccRCC with an IVC tumor thrombus who underwent radical nephrectomy and tumor thrombectomy.
Outcomes of metastatic adrenocortical carcinoma (ACC): A 16-year single institutional experience.
Authors: Owen Dwight Hall , Patel Sandipkumar , Phay John E , Shirley Lawrence Andrew , Kirschner Lawrence S , Schmidt Carl Richard , Abdel-Misih Sherif , Brock Pamela , Wei Lai , Shah Manisha H. , Konda Bhavana 
Published: September 2018

e16088 Background: ACC is a rare malignancy with limited data to guide management of metastatic disease. Prior research regarding survival has focused on pts with locoregional disease, but has not offered insight into the management and outcomes of pts with metastatic disease. Methods: We retrospectively reviewed patients (pts) with metastatic ACC who were treated with systemic therapy between January 2000 and October 2016 at The Ohio State University Comprehensive Cancer Center. Kaplan-Meier and Cox proportional hazards regression models were used for survival analysis. Results: A total of 18 pts received systemic therapy for distant metastatic disease. Median age at diagnosis was 51 (range 31 – 72). Median overall survival (OS) from time of diagnosis of ACC was 15.5 months (95% CI 4.8 – 28.2), and from time of systemic treatment (ST) was 7.1 months (95% CI 3.3 – 26). A germline variant of uncertain significance in MSH2 (c.138C > G) was identified in one patient. Baseline FDG-PET scans were obtained in 11/18 pts, and demonstrated avidity in all patients. Maximum SUV ranged from 4.1 to 47.6, with a median of 15. First line therapy was etoposide, doxorubicin, cisplatin, and mitotane (EDPM) in 13/18 pts and clinical trial with IMC-A12 (IGF-1 receptor antibody) in four pts. Median duration of first line therapy was 1.8 months (95% CI 0.9 – 2.8). Survival was not statistically different for patients receiving EDPM as first or second line therapy (median OS 23.3 vs 12.0 months, p = 0.96). Additional lines of therapy included EDPM, IMC-A12, AT-101, mifepristone, OSI-906 (IGF-1R inhibitor), and nivolumab. Median lines of therapy given were 2. The presence of bone metastases (p = 0.69) or lung metastases (p = 0.21) at the time of initiation of ST was not associated with OS from ST. Conclusions: In our experience, the prognosis of pts with metastatic ACC receiving systemic therapy is poor with most pts receiving ≤ 2 lines of therapy. Patients receiving first or second line EDPM seemed to have worse outcomes than noted in previously published trials, possibly due to our patients being sicker at baseline. Metastasis to the lung or bone at initiation of ST did not impact OS.
Adverse effects of androgen deprivation therapy on cognitive impairment for men with prostate cancer: A meta-analysis.
Authors: Sun Maxine , Cole Alexander P , Hanna Nawar , Trinh Quoc-Dien 
Published: September 2018

e16506 Background: Use of androgen deprivation therapy (ADT) may confer a higher risk of cognitive impairment. Published results are variable and lack consensus. Our objective was to perform meta-analysis of the risk of overall cognitive impairment in men receiving ADT for prostate cancer. Methods: Relevant studies were identified through the search of English language articles indexed in PubMed Medline, PsycINFO, Cochrane Library and Web of Knowledge/Science until December 21st2016. Articles were included if they were published in English, reported on original research with adult male subjects undergoing treatment for prostate cancer, incorporated longitudinal comparisons, and included a control group. Controlled intervention studies were required to assess an established cognitive-related endpoint that was measured by a validated instrument, and measure cognitive impairment based on the International Cognition and Cancer Task Force (ICCTF) criteria. The effect of ADT on cognitive impairment was pooled using a random-effects model for controlled intervention and case-control studies separately. Results: Of 221 abstracts, 25 were selected for full-text review, and 8 studies, with 2 controlled studies and 6 case-control studies were identified. Overall cognitive impairment was not significantly different when the results of the 2 prospective studies were pooled (OR: 1.57, 95% CI: 0.50–4.92, P= 0.44), with significant heterogeneity between estimates ( I2: 83%). In retrospective data, the odds of developing any cognitive impairment were significantly higher in men treated with ADT (HR: 1.37, 95% CI: 1.06–1.77, P= 0.02), with considerable heterogeneity ( I2: 84%). Conclusions: The relationship between overall cognitive impairment and use of ADT defined according to the ICCTF criteria in a pooled-analysis of two prospective studies was inconclusive. Although retrospective studies suggest a higher risk of overall cognitive impairment after ADT, we caution readers not to over-interpret this finding given the limitations of retrospective data. Better well-designed prospective studies are needed to assess the effect of ADT on cognitive impairment with long-term follow-up.
Biomarkers for early prognostication of outcome in patients with bone-metastatic castration-resistant prostate cancer treated with enzalutamide.
Authors: Schlack Katrin , Boegemann Martin , Krabbe Laura-Maria , Kannen Karoline , Semjonow Axel , Klaile Yvonne 
Published: September 2018

e16507 Background: Enzalutamide (Enza) prolongs survival in men with mCRPC in pre- and post chemotherapy setting. Commonly used prostate-specific antigen (PSA) may lead to non-straightforward prognosis. This is especially true for bone mCRPC (bmCRPC) in which initial bone-flare may add to difficult decision making. During other therapies, bouncing of alkaline phosphatase (ALP-Bounce) was shown as a promising surrogate for survival outcome. The purpose of this study was to evaluate the prognostic ability of ALP-Bounce compared to standard PSA and lactate dehydrogenase (LDH) after initiation of Enza. Methods: Patients with bmCRPC were included and analyzed. PSA, LDH and ALP were monitored at 2, 4, 8 and 12 weeks under very early Enza treatment. ALP-Bounce vs. no Bounce was analyzed using Kaplan-Meier estimates and uni- and multivariate (UV/MV) cox-regression models. ALP-Bounce was defined as an increase of ALP after initiation of Enza with a subsequent, significant decline below baseline during the first 8 weeks of therapy. Results: Eighty-nine men were evaluable for analysis. The median overall survival (OS) of men with ALP-Bounce was 19 months (95% confidence interval: 7.9-30.1) compared to 12 months (7.7-16.3) for no Bounce. Analysis of progression-free survival (PFS) showed similar results with 8 (0-16.3) vs. 3 months (1.9-4.1). In UV no ALP-Bounce (Hazard Ratio (HR): 1.9 (1.1-3.3); p = 0.02), no PSA-decline ≥50% (HR: 2.3 (1.5-3.7); p < 0.01) and no LDH-Normalization (HR: 2.5 (1.6-4.1); p < 0.01) were significantly associated with worse PFS. In MV only no ALP-Bounce showed a trend towards worse PFS (HR: 2.1 (0.9-4.5); p = 0.09). In UV no LDH-normalization was a significant prognosticator of poor OS (HR: 2.6 (1.6-4.2); p < 0.01) while ALP-Bounce and PSA decline ≥50% were non-prognostic. In MV no LDH-normalization remained an independent prognosticator of poor OS (HR: 2.0 (1.1.-3.5); p = 0.02). Conclusions: ALP-Bounce and LDH-Normalization may add to identification of bmCRPC-patients with favorable prognosis during early therapy with Enza. The early occurence of ALP-Bounce might be beneficial. These results have to be validated in a prospective trial.
Expression of androgen receptor, somatostatin receptor subtypes, aurora kinase A, and interleukin-6 in prostate cancer before androgen ablation.
Authors: Gernone Angela , Trabucco Senia , Cascardi Eliano , Resta Leonardo , Silvestris Franco , Napoli Anna 
Published: September 2018

e16508 Background: Neuroendocrine differentiation (NED) in prostate cancer (PC) can be detected by immunohistochemistry as single cells in conventional adenocarcinoma. NEPC is a poor-recognized late presentation of hormone refractory subtype of PC AR-negative. NEPC correlates with poor prognosis, tumor progression during androgen-deprivation therapy and frequent visceral metastases. Aurora kinase A (AURKA) and Interleukin-6 (IL-6) cooperate to induce NED. The aim of this study was to correlate the expression of somatostatin receptor (SSTR) 1- 2- 3- 4- 5 subtypes, AURKA and IL-6 in primary PC with NED pattern before androgen ablation and OS. Methods: PC tissues were reviewed from 60 pts who had undergone biopsy or radical prostatectomy for previously untreated advanced or metastatic PC from 2010 to 2016. 10 samples expressed histologically chromogranin A (CgA), a marker of NED expression. Median age was 67 years (47-80), Gleason score ≥ 7, median PSA was 60 ng/ml (1.3-1000), ECOG 0/1 and bone-visceral sites measurable in 90% of cases. For comparison purposes, 8 pathology specimens from pts with primary PC negative for CgA expression were used. Results: SSTR1-2-4-5 were detected only in the nucleus of PC cells in 10/10 samples. AR was expressed in all 10 samples CgA positive. SSTR3 and AURKA were not expressed in all 10 samples. IL-6 was detected in 9/10 samples. All 10 pts developed early onset of CRPC, more aggressive clinical course with rapid occurrence of visceral metastases and OS was < 12 mos. Conclusions: In metastatic prostate cancer, pretreatment NED pattern can be a predictor for progression and survival after hormonal and during standard chemotherapy. Most likely NEPC become AR negative during disease progression and in response to androgen deprivation therapy. We supposed, according to other data, that the novel potent AR-targeted drugs should be not used in this subset of patients. SSTRs and somatostatin analogs are not potential targets for prostate cancer.
Prevalence of oligoprogressive, metastatic castration-resistant prostate cancer (mCRPC) amenable to stereotactic ablative radiotherapy (SABR) in men undergoing abiraterone acetate (AA) therapy.
Authors: McDonald Erica , Cheng Sierra , Arciero Vanessa Sarah , Saluja Ronak , Zukotynski Katherine A. , Cheung Patrick , Emmenegger Urban 
Published: September 2018

e16509 Background: SABR is increasingly used for treating men with oligometastatic prostate cancer, a state between loco-regional and widespread metastatic disease that exists de novo, presents as oligorecurrence, is treatment-induced, or occurs as oligoprogression. The latter is a clinical situation where a limited number of metastatic tumor sites progress (usually defined as ≤3-5), while all other metastases are controlled by a given systemic therapy. The frequency of oligoprogression amenable to SABR is unknown. Methods: Thus, in a retrospective chart analysis we studied the progression pattern of 35 men with chemotherapy-naïve mCRPC undergoing AA therapy, and of 20 men undergoing AA therapy after docetaxel chemotherapy. Applying RECIST1.1 and/or PCWG2 criteria, patients (pts) were considered SABR candidates if they radiologically progressed in ≤5 distinct metastatic locations, while all other sites were stable or responding. Results: In chemotherapy-naïve men, pre-AA metastatic lesions were located in bone (94%), lymph nodes (49%), lungs (17%) and liver (3%), whereas progression during AA therapy occurred in bone (89%), lymph nodes (49%), lungs (14%) and liver (9%). 12 pts (34%) met the criteria of oligoprogression with a median of 2 progressive lesions/pt (range 1-5). 8 pts presented with bone progression only, 3 with nodal progression, and 1 pt with combined bone/nodal progression. Post-docetaxel pts had pre-AA metastatic lesions located in bone (75%), lymph nodes (35%), lungs (5%) and liver (5%). Progression during AA therapy occurred in bone (80%), lymph nodes (75%), lungs (20%) and liver (5%). Only 1 pt met oligoprogression criteria with a single progressive bone metastasis. Conclusions: A sizeable number of men with chemotherapy-naïve mCRPC progressing during AA therapy might be considered for SABR. By contrast, progression of post-docetaxel mCRPC treated with AA is typically widespread. Further efforts are needed to identify criteria for oligoprogressive pts most suitable for SABR with sustained benefit versus men that may progress rapidly with widespread metastases following radiotherapy.
A pilot study of the effects of androgen deprivation therapy on physical function and comprehensive geriatric health in older men with prostate cancer.
Authors: Kessler Elizabeth Riley , Flaig Thomas W. , Lam Elaine Tat , Breaker Kathryn M. , Wacker Michael , Jankowski Catherine 
Published: September 2018

e16510 Background: Alteration of the androgen axis through androgen deprivation therapy (ADT) is the mainstay of prostate cancer (PCa) treatment. Unfortunately, the resultant hypogonadal state has detrimental effects on muscle and bone and may impair physical function (PF). Older patients may be more vulnerable to PF changes while on ADT. We conducted a pilot study to evaluate the changes in PF and geriatric health in older men initiating ADT using tests easily employed in routine clinical practice. Methods: Men with PCa initiating ADT were enrolled and were assessed every 3 months (mos) for up to 12 mos. PF was measured using the short physical performance battery (SPPB) and geriatric health was screened using the Vulnerable Elders Survey (VES13) which predicts potential death or decline over 2 years. The primary endpoint was change in SPPB and VES13 at 3 mos. Results: We enrolled 17 patients with a median age of 75 years (range 67-85) beginning ADT therapy. Fourteen patients had metastasis, 2 had locally advanced disease, and 1 had biochemical recurrence. The majority had Gleason score (GS) 7 cancer (9/17), 7/17 GS 8-10, and 1/17 with GS 6. Eight patients had normal SPPB baseline scores and 9 had moderate impairment (moderate frailty risk) (Mean 10, SD 1.71). Seven had a clinically significant decline in the SPPB at 3 mos, with 1 patient testing as severely impaired. The VES13 screening tool identified 6/17 patients as vulnerable at baseline (Mean 3, SD 3.92). At 3 months, 3/17 patients had a decline in VES13 and 6/17 with an improvement. Of the 10 patients who were followed for at least 6 months, 5 had worsening of the VES13 and 2 had a worsening in SPPB. Conclusions: Older patients initiating ADT have baseline vulnerabilities in geriatric health with little immediate detriment after treatment initiation, perhaps due to overall health improvement with treatment initiation. Changes in PF, however, are seen within the first 3 months of ADT in nearly half of our patients, warranting further investigation into early rehabilitation of men even on short-term ADT. The SPPB is easily employed in clinic and important as reliance on VES13 alone is likely to miss patients with PF impairments.
Hospital admissions (HA) among chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients newly treated with enzalutamide (ENZA) or abiraterone (ABI).
Authors: Quek Ruben G.W. , Gilligan Adrienne M. , Kent Shia T. , Gregory Christopher , Schultz Neil M. , Flanders Scott , Brown Bruce A. , Wong Elaine Karol , Barlev Arie 
Published: September 2018

e16524 Background: ENZA and ABI are approved to treat mCRPC in chemotherapy-naïve patients; few real-world analyses exist to compare HA pre- and post-treatment. This study characterized and compared incidence and incidence rate ratios (IRRs) of HA pre/post initiation of ENZA or ABI in chemotherapy-naïve mCRPC patients in the US. Methods: Patients aged ≥ 18 years who initiated ENZA or ABI (2 cohorts) from Jan 2014–Dec 2015 were identified retrospectively from MarketScan® Databases. The index date was the initiation of ENZA or ABI after ≥ 6 months of pre-index continuous health plan enrollment. We identified the top 10 HA incidences using ICD-9/10 CM inpatient claims (separate primary and any position) and assessed pre-/post-index IRRs within each cohort. Generalized estimating equations accounting for within-patient correlation and difference-in-differences regression were fitted to compare IRRs between cohorts. Results: A total of 1603 (ENZA, 656; ABI, 947) patients were included. Mean age was 73 years in both cohorts; mean (standard deviation) Deyo-Charlson Comorbidity Index was 7.9 (2.8) for ENZA and 7.8 (2.9) for ABI; the top 10 HA incidences included cardiac disorder, dyspnea, hypokalemia, liver toxicity, pneumonia, renal impairment, skeletal-related events (any, surgery and fracture) and urinary tract infection. IRRs of HA (any position) due to cardiac disorder, dyspnea, hypokalemia, liver toxicity and pneumonia were significantly higher for post- vs pre-ABI-treated patients (IRR [95% CI]: 1.63 [1.22–2.17], 1.90 [1.21–2.98], 3.13 [1.46–6.71], 2.24 [1.36–3.69] and 2.40 [1.41–4.10]). IRRs of HA (any position) due to cardiac disorder, dyspnea and hypokalemia were significantly lower in the ENZA cohort than ABI cohort (1.02 vs 1.63, 0.84 vs 1.90, 0.65 vs 3.13; all P < 0.05). No statistical significance was observed for any other HA comparisons (primary or any position) between or within ENZA and ABI cohorts. Conclusions: Among chemotherapy-naïve mCRPC patients, significant increases in multiple HA IRRs were observed post- vs pre-ABI treatment, and IRRs were significantly lower for ENZA- vs ABI-treated patients for multiple HA.
Racial differences in patterns of treatment among men first diagnosed with advanced prostate cancer.
Authors: Beebe-Dimmer Jennifer Lynn , Ruterbusch Julie J. , Schwartz Ann G. , Schwartz Kendra L. , Holowatyj Andreana , Heath Elisabeth I. 
Published: September 2018

e16527 Background: A small proportion of men (~4%) are newly-diagnosed with advanced stage prostate cancer (PCa) and experience poorer survival compared to men diagnosed with local or regionally-advanced disease. Prostate cancer mortality is higher in African Americans (AA) than in non-Hispanic whites (NHW), with a marginally higher proportion of AA men first diagnosed with advanced disease. We sought to describe recent patterns of treatment among men diagnosed with de novo AJCC stage IV PCa. Methods: We used the Surveillance, Epidemiology and End Results database linked to Medicare Claims files to identify men diagnosed with advanced PCa between 2007 and 2011, with follow-up through 12/31/2013. We examined patterns of treatment (surgery, radiation, chemotherapy, and hormonal therapies) as well as rarer modalities and drugs included in Medicare Part D, both overall and by race. Results: Of the 6,906 men eligible for this study, 74.6% were NHW and 13.1% were AA with a median survival of 32 months among all patients. Survival was poorer among AA compared to NHW (p < 0.0001). Among the significant predictors of mortality were TNM stage, age at diagnosis, race, Gleason grade, and the presence of comorbid conditions. Androgen Deprivation Therapy (ADT) was the most widely-used treatment (78.7%), followed by radiation therapy (31.2%) and chemotherapy (30.2%). AA patients were significantly more likely to go without treatment (p < 0.0001) compared to NHW patients. This finding did not change after excluding men who died within 3 months of diagnosis or men without distant metastatic disease (T4 or N1 and M0/MX). The frequency of nearly all forms of treatment was lower among AA patients with two notable exceptions; orchiectomy was significantly higher (11.8% vs. 6.9%), and among Medicare Part D enrollees, use of the progesterone Megace (27.7% vs. 17.2%). Conclusions: ElderlyAA patients newly diagnosed with stage IV PCa have shorter overall and disease-specific survival compared with NHW. Results from this study suggest less aggressive treatment may contribute to poorer survival. Understanding drivers of treatment-related decisions are critical in reducing racial disparities in survival among men with advanced PCa.