bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic value of glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80) positive myeloid derived suppressor cells (MDSCs) in peripheral blood of metastatic renal cell carcinoma (mRCC) patients.
Authors: Kato Tomoyuki , Takeda Yuji , Kurota Yuta , Naito Sei , Ito Hiromi , Araki Akemi , Asao Hironobu , Tsuchiya Norihiko 
Published: March 2019

601 Background: Myeloid derived suppressor cells (MDSCs) are found to play essential roles in various tumors and to associate with the prognosis of patients. However, the prognostic values of MDSCs in metastatic renal cell cancer (mRCC) are still undefined. Glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80) is known as a regulator of Mac-1 (CD11b/CD18) and closely related with differentiation of myeloid cells. The object of our study was to interrogate the association of MDSCs in peripheral blood with clinical outcomes of mRCC patients by using GPI-80. Methods: Peripheral blood samples, collected from 23 mRCC patients before treatment and 16 healthy volunteers, were stained with several myeloid cell antigens such as CD16, CD15, CD33, and GPI-80 to mark neutrophils and monocytes. We measured the expression levels (mean of florescence intensity, MFI) and deviation (coefficient variation, CV) of myeloid antigens by flow cytometry. To investigate the immunosuppressive function of GPI-80 positive cells, reactive oxygen species (ROS) and LAP-1 (precursor of TGF-β1) were measured. The impact of the cell surface antigens on overall survival (OS) was evaluated using the univariate and multivariate Cox regression analysis. Results: The MFI or CV of GPI-80 on neutrophilic or monocytic cells were significantly difference in between patients and healthy volunteers. LAP-1 expression and ROS production in monocytic cells were increased in patients than in healthy volunteers, and correlated with expression of GPI-80 MFI (p = 0.0107 and p = 0.0381, respectively). Regarding the prognostic values, both GPI-80 CV of neutrophilic cells and GPI-80 MFI of monocytic cells were associated with poor OS of mRCC patients (p < 0.01). Multivariate analysis showed that GPI-80 MFI of monocytic cells were independent unfavorable prognosis marker (HR 2.427, p = 0.044). Conclusions: These results showed that change of GPI-80 expression on myeloid cells in peripheral blood representing appearance of MDSCs was likely to be negative predictors in patients with mRCC.
PAzopanib as first line in MEtastatic RCC patients: A “real-world” ITalian experience (PAMERIT study)—Preliminary results.
Authors: Mosca Alessandra , De Giorgi Ugo , Procopio Giuseppe , Basso Umberto , Carteni Giacomo , Buti Sebastiano , Naglieri Emanuele , Galli Luca , Caffo Orazio , Fornarini Giuseppe , Boccardo Francesco , Facchini Gaetano , Morelli Franco , Zucali Paolo Andrea , Caserta Claudia , Di Lucca Giuseppe , Sirotova Zuzana , Gennari Alessandra , Bruzzi Paolo , Porta Camillo 
Published: March 2019

611 Background: Pazopanib (Pazo) became a standard of care in metastatic renal cell cancer (mRCC) patients (pts) based on 2 prospective trials, but “real life” data are slight. Methods: We retrospectively analyzed clinical outcomes in a large series of mRCC pts routinely treated with 1st line Pazo, among 39 Italian Centers. Descriptive statistics has been performed using Chi-Square and Pearson rank correlation test. Progression-free survival (PFS), overall survival (OS) and safety data are still under investigation. Results: 474 mRCC pts have been collected and divided in 4 age categories: 1) ≤50 yrs old (9.4%); 2) 51-64 yrs old (32.6%); 3) 65-74 yrs old (33.0%); 4) ≥75 yrs old (25.0%). According to Heng score, 25.6%, 48.4% and 10.4% pts had good, intermediate and poor prognosis, respectively, without correlations with age (p = 0.128). Clear cell was the most represented histology (87.3%), independently from age (p = 0.556). 84.6% pts underwent nephrectomy, mainly younger pts (p = 0.000). Pazo initial daily dose was 800 mg in 76.5% pts, 600 mg in 10.8% pts and 400 mg in 12.7% pts, with a significant dose reduction in elderly pts: Pazo 800 was administered in 86.7% of ≤50 yrs old pts and in 54.2% of ≥75 yrs old pts (p = 0.000). Complete (CR)/partial response (PR), stable and progressive disease have been recorded in 37%, 39.5% and 23.5% pts, respectively. Radiological response directly correlated either with age (CR/PR in 55.6% of ≤50 yrs old pts vs 28.8% of ≥75 yrs old pts; p = 0.009) and with Heng score (CR/PR in 47.1% of good prognosis pts vs 24.5% of poor prognosis pts; p = 0.002). Conclusions: “Real world” data showed that younger (≤50 yrs old) mRCC pts more frequently underwent nephrectomy, received Pazo 800 mg daily and obtained CR/PR, with respect to elderly pts (≥75 yrs old). CR/PR to Pazo is associated with good prognosis. PFS and OS will be provided.
Association of inflammation and clinical outcomes (CO) in metastatic renal cell carcinoma (mRCC) patients (pts) treated with cabozantinib (cabo).
Authors: Martini Dylan J , Shabto Julie M. , Liu Yuan , Carthon Bradley Curtis , Speak Alexandra , Hitron Elise , Russler Greta , Caulfield Sarah , Ogan Kenneth , Harris Wayne , Kucuk Omer , Master Viraj A. , Bilen Mehmet Asim 
Published: March 2019

612 Background: Ratios of neutrophils, monocytes, and platelets to lymphocytes (NLR, MLR, and PLR) are associated with poor CO in cancer pts. We investigated the association of NLR, MLR, and PLR and CO in mRCC pts treated with cabo. Methods: We performed a retrospective study of 65 mRCC pts treated with cabo at Winship Cancer Institute from 2016-2018. Overall survival (OS) and progression free survival (PFS) were calculated from first dose to date of death and radiographic or clinical progression, respectively. NLR, MLR, and PLR were obtained at baseline (BL) and 6 (±2) weeks (6W) after cabo initiation. Optimal cut (OC) was determined searching all cuts and testing them by bias adjusted log rank test to associate with PFS. Multivariate analysis (MVA) was performed using Cox proportional hazard model. Results: The medians were: 2.8 (NLR), 0.4 (MLR), and 176.7 (PLR). Increased NLR, MLR, and PLR were significantly associated with worse CO (Table). Conclusions: High NLR, MLR, and PLR may be poor prognostic factors in mRCC pts treated with cabo. Larger studies are needed to validate the results of this study. [Table: see text]
Activity of NEO2734, a novel dual inhibitor of both BET and CBP-P300, in SPOP-mutated prostate cancer.
Authors: Yan Yuqian , Wang Dejie , Ma Jian , Pang Xiaodong , Lin Dong , Giles Francis , Wang Yuzhuo , Huang Haojie 
Published: March 2019

62 Background: We have previously reported that mutations in SPOP promote bromodomain and extra-terminal motif (BET) protein upregulation and BET inhibitor resistance in prostate cancer (Zhang et al., Nature Medicine 23(9):1055-1062, 2017). Other studies indicate that histone acetyltransferases (HATs) such as P300 are also upregulated in SPOP-mutated prostate cancer (Blattner et al., Cancer Cell 31: 436-451, 2017). Methods: We examined the anti-cancer effect of NEO2734 (Epigene Therapeutics Inc), a novel dual inhibitor of both BET and CBP-P300, in prostate cancer using cell line, organoid and patient-derived xenografts (PDX) as working models. We examined the anti-cancer effect of NEO2734 (Epigene Therapeutics Inc), a novel dual inhibitor of both BET and CBP-P300, in prostate cancer using cell line, organoid and patient-derived xenografts (PDX) as working models. Results: We demonstrated that while prostate cancer cell lines expressing F133V, the most frequent SPOP mutant, are very resistant to both BET inhibitor JQ1 and CBP/P300 inhibitor CPI-637, they are very sensitive to simultaneous cotreatment with JQ1 and CPI-637. Similarly, we demonstrated that F133V mutant cells are also very sensitive to NEO2734. We established PDX and organoid models from a patient with prostate cancer expressing a novel SPOP mutation Q165P. Computer simulation analysis reveals that the Q165P mutation causes larger conformational fluctuation, indicating that the structure of Q165P is less stable than that of wild type SPOP. Accordingly, co-immunoprecipitation assay showed that Q165P mutation impaired the dimerization ability of SPOP. We further showed that the Q165P mutant organoid was very sensitive to NEO2734 in vitro and the Q165P mutant PDX was very sensitive to NEO2734 in mice. Conclusions: These PDX-based pre-clinical studies indicate that the inhibition of both BET and CBP-P300, either by co-administration of two agents, or by treatment with the dual inhibitor, NEO2734, is effective in SPOP-mutated prostate cancer. These data provide a strong rationale for the inclusion of patients with SPOP-mutated prostate cancer in clinical studies of NEO2734.
Fumarate hydratase expression in localized, radically-resected clear cell renal cell carcinoma and its association with clinical outcomes.
Authors: FucÃ Giovanni , Vernieri Claudio , Massa Simona , Bertolotti Alessia , Garzone Giovanna , Hosseini Amir , Verzoni Elena , Ratta Raffaele , Pruneri Giancarlo , Minucci Saverio , De Braud Filippo G. , Colecchia Maurizio , Procopio Giuseppe 
Published: March 2019

620 Background: Prognostic stratification of localized clear cell renal cell carcinoma (lccRCC) mainly relies on clinical characteristics and TNM staging system, while biological biomarkers are currently lacking. We previously showed that reduced expression of the tricarboxylic acid cycle enzyme fumarate hydratase (FH) was associated with better clinical outcomes in patients (pts) with metastatic ccRCC. In the present study we aimed at assessing the association between intratumor FH expression and clinical outcomes in pts with radically-resected lccRCC. Methods: Pts with radically-resected lccRCC and available formalin-fixed, paraffin-embedded (FFPE) primary (renal) tumor tissue were included. FH protein expression was assessed by means of immunohistochemistry (IHC) and defined as normal (comparably to non-neoplastic tubular cells) or low (lower than in non-neoplastic tubular cells). Results: Out of 50 pts included, we found a normal FH expression in 20 cases (40%) and a low FH expression in 30 cases (60%). Median age was 57 years (interquartile range 49-68) and 48 pts (96%) had pN0 disease, while 2 pts (4%) had pN1 disease. Low FH expression was associated with pT ( P= .003) but not with sex, age, Fuhrman grade or pN. After a median follow-up of 76.9 months, low FH expression was associated with a lower relapse rate (13% vs 50%; odds ratio for relapse 0.16; 95% confidence interval [CI] 0.04-0.62; P= .005), longer relapse-free survival (RFS) (5-years RFS rate 90% vs 50%; HR 0.20; 95% CI 0.06-0.63; P= .006) and a trend toward a better overall survival (OS) (5-years OS rate 100% vs 77.3%; HR 0.14; 95% CI 0.02-1.23; P= .07) when compared with normal FH expression. In the multivariable model including other characteristics associated with RFS, low FH expression confirmed an independent association with RFS (adjusted HR 0.25; 95% CI 0.06-0.91; P= .03). Conclusions: In our study, low intratumor FH, as detected by IHC, was associated with lower relapse rate, better RFS and a trend toward a better OS in patients with lccRCC when compared with normal FH levels. The role of FH expression as a prognostic biomarker in this setting warrants further investigation.
Nivolumab in second or third line setting for the treatment of metastatic renal cell carcinoma (mRCC): The real-world experience from Guy’s Hospital.
Authors: Le Ha Mo Linh , Josephs Debra Hannah , Chowdhury Simon , Rudman Sarah Maria , Enting Deborah 
Published: March 2019

624 Background: Nivolumab (Nivo) has been approved by the FDA for patients (pts) with mRCC who have received prior VEGF tyrosine kinase inhibition based on the Checkmate 025 study. However following various new anti-angiogenic therapies licensed over the past decade, optimal sequence of treatments in mRCC remains unknown. Methods: This is a retrospective review of mRCC pts who received nivo at Guy’s Hospital. Pts were divided based on treatment line setting. Clinical characteristics, response rate (RR), progression free survival (PFS), duration on treatment and safety are reported. Results: Between March 2016 and April 2018, 50 pts with mRCC received nivo, 25 as second line (2L) and 25 as third line treatment or beyond (3L+). In 2L setting, median age was 62 years and 68% were male. 76% had a nephrectomy, with a majority of clear cell (cc) histology (92%). 96% of pts had visceral metastases. 88% received pazopanib in the first line setting (1L). Median age for pts in 3L+ was 60 years and 88% were male. 60% had a nephrectomy and 80% had cc histology. 96% had visceral metastases. Pazopanib was given in 72% in 1L. RR was 28% and 16% in 2L and 3L+ respectively. Median duration of treatment was 4.3 months in 2L and 2.2 months in 3L+, with 11 patients (22%) still on treatment. Median follow-up time was 12.4 months in 2L and 9 months in 3L+. Median PFS was 4.8 months and 3.7 months respectively in 2L and 3L+ groups. Median OS was not reached in either group. Adverse events leading to treatment discontinuation occurred in 7 pts (14%). 5 pts experienced grade 3/4 toxicities (colitis, pneumonitis, hepatitis, arthritis and nephritis), with 4 pts in 3L+. Overall 22 pts received subsequent treatments: 8/25 (32%) had cabozantinib (cabo) and 4/25 (16%) were treated with axitinib following nivo given in 2L. For pts who received nivo in the 3L+ setting 7/25 (28%) received cabo and 2/25 (8%) had axitinib as subsequent therapy. Conclusions: Our real world data supports the efficacy and safety of nivo following VEGF inhibition for pts with mRCC. Nivo was associated with a trend towards superior clinical responses in the 2L setting. For the entire cohort no new safety signals were reported.
Prognostic value of loss of chromosome 10q in patients with localized renal cell carcinoma.
Authors: Lebacle Cedric Michel , Pooli Aydin , Rao Nagesh , Wood Erika Louise , Kroeger Nils , Liu Sandy , Faiena Izak , Chamie Karim , Belldegrun Arie S. , Shuch Brian , Drakaki Alexandra , Pantuck Allan J. 
Published: March 2019

626 Background: Several tumor-suppressor genes have been mapped to chromosome 10q, including PTEN. While loss of 10q is a frequently seen cytogenetic abnormality noted to occur in patients with renal cell carcinoma (RCC), little is known about its prognostic significance. We investigated the association of loss of 10q with pathological features and disease-free survival (DFS) in patients with localized RCC. Methods: All patients from UCLA with primary localized RCC who had tumor cytogenetic analysis were included. Alterations in chromosome 10q was specifically reviewed for this study. Logistic regression analyses were used to assess association of loss of 10q with ISUP grading, and T-stage. Cox proportional hazard modeling and Kaplan-Meier analyses were used to assess the impact of loss of 10q on DFS and OS. Recurrence was defined as any local recurrence or development of new metastasis after surgery. Results: A total of 886 patients were included in this study. Loss of 10q occurred in 68 (7.7%) patients and was more commonly seen in chromophobe subtype (24% vs. 6% in non-chromophobe RCC, p < .0001). Loss of 10q was associated with greater tumor size (mean 6.3 vs 5.1 cm, OR = 1.085 [1.024-1.150], p = .008), T3-stage (37% vs 23%, OR = 1.99 [1.17-3.39], p = .011), and ISUP 3-4 (61% vs 37%, OR = 2.64 [1.58-4.40], p < .0001). On survival analysis, after a mean follow-up of 55 months, these patients had a shorter time to recurrence (Log-rank p = .026) and a worse DFS (HR = 2.15 [1.32-3.50], p = .002) than those without loss of 10q. These findings were confirmed on clear-cell RCC subgroup with also a worse OS (HR = 2.00 [1.09-3.67], p = .026) with an estimated 34% risk of death at 5 years for patients with loss of 10q. Conclusions: Loss of chromosome 10q is a prognostic factor associated with larger tumor size, higher grade and T-stage, and worse survival in patients with localized RCC. Identifying patients with loss of 10q can provide additional prognostic information to clinicopathologic variables.
The UCLA Histo-Genetic Risk Classification (U-HGRC) to predict outcomes of localized clear cell renal cell carcinoma.
Authors: Lebacle Cedric Michel , Pooli Aydin , Rao Nagesh , Wood Erika Louise , Kroeger Nils , Kim Hyun J. , Faiena Izak , Liu Sandy , Chamie Karim , Belldegrun Arie S. , Shuch Brian , Drakaki Alexandra , Pantuck Allan J. 
Published: March 2019

627 Background: Thirty percent of patients with localized clear cell renal cell carcinoma (ccRCC) will ultimately develop recurrence (local or metastatic) after nephrectomy. Current risk stratification systems still misclassify patients. We have developed a novel classification integrating cytogenetic findings to better stratify the risk of recurrence and overall survival (OS) after surgery for localized ccRCC. Methods: A total of 646 patients from UCLA with ccRCC and tumor cytogenetic analysis, were included in this study. After a selection of histologic parameters using logistic regression and cytogenetic parameters using principal component analysis a CHAID decision tree and Kaplan Meier analysis were used to build the UCLA Histo-Genetic Risk Classification (U-HGRC). Survival analyses of the model were validated on two random samples of 323 patients. Recurrence was defined as any local recurrence or development of new metastasis after surgery. Results: The T-stage, tumor size, presence of sarcomatoid features, gain of chromosome 5q, loss 10q, or loss X/Y were used to stratify the risk of recurrence of ccRCC into three U-HGRC groups of low (1), intermediate (2) or high-risk (3). After a mean follow-up of 55 months, risk of recurrence (HR = 2.44, p = .001 for U-HGRC 2; HR = 9.90, p < .0001 for U-HGRC 3), disease-free survival (DFS) (Log-rank p < .0001), risk of death (HR = 1.72, p = .033 for U-HGRC 2; HR = 4.74, p < .0001 for U-HGRC 3) and OS (Log-rank p < .0001) were significantly different between groups. These findings were validated on two random samples. For high-risk group, median DFS and OS were 2.7 and 6.3 years, respectively. The 5-year risks of recurrence for U-HGRC group 1, 2 and 3 were 9%, 25% and 62%, respectively. The AUC of the model was significantly improved comparing to the current UISS system (0.72 for U-HGRC vs 0.65 for UISS, p = .008) with an accuracy of 82.8% for the U-HGRC high-risk group. Conclusions: The U-HGRC, which integrates genomic alterations with clinical and pathologic features, allowed a better stratification of recurrence risk and overall survival that could help to select appropriate patients for surveillance and adjuvant therapy protocols.
Are patients ready to participate in diet intervention trials in oncology? Experience from renal cell carcinoma (RCC) patients.
Authors: Colomba Emeline , Raynard Bruno , Guida Annalisa , Derosa Lisa , Escudier Bernard , Albiges Laurence 
Published: March 2019

628 Background: Diet intervention in oncology is currently under investigation. Nevertheless, some cancer patients are increasingly using various diet interventions with the hope to optimize the anti-tumor response or to control the side effects of oncological treatment. Thus, well conducted prospective trials are required. In order to design such trials, we conducted a prospective study in order to estimate(a) the number of patients already using diet interventions on their own and (b) the percentage of patients who would agree to follow a restrictive diet in combination to antitumoral treatment within a prospective trial, if offered by their oncologist. Methods: Metastatic RCC patients seen at a single institution as outpatient clinic between April and May 2018, were offered to take part in an anonymous feasibility questionnaire. Questions included current treatment status for RCC, gender, height, and weight and explored (a) self diet restriction practices and (b) willingness to take part in trial(s) that would evaluate various diet interventions: fasting, ketogenic, vegetarian or vegan diets (each of them being explained). The proposed diet intervention was supposed to be for a minimum of 3 months. Results: Overall, 119 patients filled out the questionnaire. Median age was 61,5 years, 79(66.3%) were under systemic treatment. At time of data collection, 7.5% patients reported ketogenic diet practices, 0.9% fasting, none vegan or vegetarian diet. Regarding willingness to take part in “diet therapeutic trials”, 42.0% of patients claimed to agree to participate in a ketogenic diet trial, 29.4% of patients would agree to take part in a trial exploring fasting, 28.5% a vegetarian diet trial, and 14.2% of patients a vegan diet trial. No link between being under treatment and willingness to participate in trial was observed (p = 0.365). Conclusions: For the first time, we report feasibility of diet intervention within an homogenous population of patients with RCC. Almost half of patients are really keen in participating, with more interest for ketogenic diet and fasting. Such study raises the question of the feasibility of such trials, and obviously would make randomized trials very challenging.
A study of intense neoadjuvant testosterone lowering therapy with goserelin and enzalutamide (Enza) in high-risk prostate cancer (PC) with multiparametric MRI (mpMRI).
Authors: Karzai Fatima , Madan Ravi Amrit , VanderWeele David James , Chun Guinevere , Bilusic Marijo , Cordes Lisa M. , Carrabba Nicole , Wilkinson Scott , Ye Huihui , Harmon Stephanie , Sowalsky Adam G. , Turkbey Baris , Pinto Peter A. , Choyke Peter L. , Gulley James L. , Dahut William L. 
Published: March 2019

63 Background: Neoadjuvant therapy with novel androgen receptor inhibitors, like enza, offer an opportunity to improve cure rates in men with high risk PC but also emphasizes the need for improved imaging techniques and genomic studies to evaluate treatment (trt) responses. We conducted a feasibility study using mpMRI to evaluate tumor responses and resistance in newly diagnosed, high-risk PC. Methods: Patients (pts) were treated with androgen deprivation therapy (ADT) + enza 160 mg po qdaily for 6 months (mos). Pts underwent 2 mpMRI: baseline and post 6 mos of therapy. Post-trt mpMRI was followed by radical prostatectomy (RP). Primary endpoint was feasibility of mpMRI for localization and detection of PC before and after therapy with ADT + enza. Results: 31 out of 33 pts completed 6 mos of therapy and underwent RP. Median on-study PSA was 9.58 (1.18-984.72 ng/dL). Median PSA post 6 mos of ADT + enza was <0.02 (0.02-0.35 ng/mL). No pt was taken off-trt for adverse events. Median residual cancer burden (RCB) defined as volume of tumor corrected by tumor cellularity was 0.1584 (0.0001-12.32 cc). Using RCB of <0.05 cc, 12 patients had minimal residual disease of which 4 pts were pathologic complete responses. Post-trt mpMRI volume correlated with final pathology in all cases. Conclusions: Neoadjuvant enza + ADT is tolerable and shows activity in a newly-diagnosed, high-risk population. mpMRI can be utilized to assess responses to trt. Analysis of genomic characteristics and resistance mechanisms is on-going. Clinical trial information: NCT02430480.