bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant ascites as a manifestation of advanced papillary renal cell cancer (pRCC).
Authors: Friend Julia C. , Su Daniel , Thimmapuram Rashmi , Peterson James , Hawks Geri , Ninos Martha , Linehan W. Marston , Srinivasan Ramaprasad 
Published: February 2017

465 Background: Peritoneal carcinomatosis and ascites are frequent and clinically challenging complications associated with several malignancies such as ovarian cancer. Although ascites is rarely reported in patients with advanced renal cell carcinoma (RCC), its true incidence, particularly in non-clear cell variants, remains poorly defined. Here, we describe the incidence of and clinical characteristics associated with ascites in patients with pRCC. Methods: Patients with metastatic renal cell carcinoma (RCC) seen at the NCI Urologic Oncology Branch were identified in a review of our clinical database. The incidence of radiologically and/or cytologically evident ascites, relevant associated clinical characteristics, and survival were evaluated as was the incidence of ascites in a contemporaneous clear cell RCC (ccRCC) cohort. Results: 241 patients with metastatic RCC were seen between 2002 and 2014, including 109 with pRCC and 125 with ccRCC. Seventeen patients with metastatic pRCC (17/109,15.5%) had evidence of malignant ascites, while only 1/125 pts (0.8%) with ccRCC developed this complication. Median age of PRCC patients with ascites was 45.8 years (range: 26.1 to 76.6 years). Ascites was seen in both patients with type 1 (15.6%, 10/64) and those with type 2 pRCC (15.5%, 7/45). Median time to development of ascites from initial diagnosis of metastatic disease was 16 months (95% CI 7-23 months). Median survival from diagnosis of metastatic disease was 25 months (95% CI 13-41months) in patients with ascites, compared to 20 (95% CI 14-31 months) in those without this complication. (p = 0.59). Conclusions: To our knowledge, this is the largest series evaluating the incidence of and outcome associated with ascites in RCC. Although rare in ccRCC, malignant ascites is a fairly common manifestation of metastatic pRCC. In our cohort, patients with ascites appeared to have outcomes comparable to patients with metastatic pRCC without ascites.
The impact of renal cell carcinoma histopathological subtype on disease prognosis: A Canadian multi-institutional analysis.
Authors: Bjazevic Jennifer , Nayak Jasmir G. , Patel Premal , Kapoor Anil , Tanguay Simon , Finelli Antonio , Rendon Ricardo A. , Black Peter C. , Moore Ronald Brian , Breau Rodney H. , Kawakami Jun , Lacombe Louis , Klotz Laurence , Pautler Stephen E. , Drachenberg Darrel E 
Published: February 2017

480 Background: Renal cell carcinoma (RCC) is divided into several histopathological subtypes, each with significantly different clinical features. However, current data regarding the prognostic value of histological subtype is limited and conflicted. We examined the impact of RCC histology on disease prognosis in a large, multi-institutional Canadian analysis. Methods: The Canadian Kidney Cancer Information System (CKCis), a prospective database from 14 Canadian institutions, was utilized for the study. 1284 patients with non-metastatic RCC, who underwent surgical intervention with curative intent, were included in the study. Patients were stratified according to their primary histology and the Chi-squared test was used to determine associations between histopathology and clinical features. The impact of histology of disease-free survival (DFS) was determined with a multivariate analysis adjusted for age, gender, tumor size, tumor grade, and pathological stage. Results: Clear cell RCC was the most prevalent histological subtype found in 80.5% of patients. Histopathology was significantly associated with patient age, tumor grade, and pathological stage. Advanced stage disease (>T3) was associated with clear cell and papillary type II RCC (p<0.05). 90.7%, 86.7%, 78.5%, and 78.8% of patients with chromophobe, papillary type I, papillary type II, and clear cell RCC respectively, were free of disease after a median follow-up of 1.2 years. On multivariate analysis, histological subtype was a significant predictor of disease-free survival (DFS). When compared to clear cell histology, chromophobe RCC had a significantly higher DFS (HR=0.38, 95% CI 0.15-0.95, p<0.05), and papillary type I RCC had a trend towards a lower rate of disease progression (HR=0.31, 95% CI 0.08-1.28, p=0.05). Conclusions: This study demonstrates that histological subtype impacts disease progression. Histological subtype was independently associated with DFS in surgically treated RCC, specifically chromophobe RCC was shown to have the highest DFS. This may be used to help individualize patient treatment and follow-up based on primary tumor histology.
Prognostic biomarker exploration for patients with metastatic renal cell carcinoma receiving VEGFR TKI.
Authors: Park Inkeun , Cho Yong Mee , Lee Jae-Lyun , Ahn Jin-Hee , Lee Dae Ho , You Dalsan , Jeong In Gab , Song Cheryn , Hong Bum-Sik , Hong Jun Hyuck , Ahn Hanjong 
Published: February 2017

491 Background: To verify the prognostic importance of selected tumor tissue biomarkers in metastatic renal cell carcinoma (mRCC) patients (pts), we performed immunohistochemical (IHC) staining in tumor sample and statistical analyses. Methods: The clinicopathological features, treatment, and outcome of mRCC pts treated with vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI) between July 2006 and March 2011 at our center were reviewed. IHC staining for FGF base, FGFR1, 2, 3, and 4, HGF, PTEN, CAIX, pS6, HIF-1a, HIF-2a, IL-8, mTOR was done, and each specimen was scored based on the staining intensity and the percentage of positive cells. We performed univariate and multivariable analyses to verify prognostic factors for overall survival (OS). Results: We found 123 pts who met inclusion criteria. Most pts had clear cell carcinoma (107 pts, 87.0%). Fuhrman’s nuclear grade (NG) was 2 in 21 (17.1%), 3 in 49 (39.8%), and 4 in 52 (42.3%), respectively. Sarcomatoid change and coagulative necrosis were found in 51 pts and 58 pts. Using Heng’s criteria, 20 pts (16.3%), 87 (70.7%), and 16 (13.0%) belonged to favorable, intermediate, and poor risk group, respectively. First-line VEGFR TKIs prescribed were sunitinib (97 pts, 78.9%), sorafenib (23 pts, 18.7%), and pazopanib (3 pts, 2.4%). In univariate analysis, CAIX (less than 47.5% vs 47.5% or more, p=0.001), mTOR (20% or less vs more than 20%, p=0.0032), Heng risk group (good vs intermediate vs poor, p<0.001), sarcomatoid change (40% or less vs more than 40%, p<0.001), coagulative necrosis (20% or less vs more than 20%, p<0.001), Furhman NG (2 vs 3 vs 4, p=0.037) were statistically significant. In multivariable analysis, CAIX, Heng risk group, sarcomatoid change, and hyaline necrosis were identified as independent prognostic factors (Table). Conclusions: All investigated biomarkers but CAIX did not show prognostic importance for mRCC pts receiving VEGFR TKI. [Table: see text]
The predictive value of ARv7 expression in localized prostate caner treated with abiraterone, degarelix, and bicalutamide.
Authors: Corcoran Niall , Hovens Christopher , Howard Nicholas , Bugeja Patricia , Kerger Michael , Peters Justin , Clarke David , Grummet Jeremy , Dundee Phillip , Pedersen John , Ryan Andrew , Costello Anthony , Ruljancich Paul , Parente Phillip 
Published: February 2017

71 Background: Androgen receptor splice variants (ARvs) are upregulated in response to castration, and can activate transcription in the absence of ligand. Recent evidence indicates that CTC ARv7 expression is an accurate predictor of absence of response to abiraterone and enzalutamide, providing strong clinical support for ARv7 upregulation as potential overarching mechanism of castration resistance. There is however limited data regarding the expression of ARv7 in clinically localized prostate cancer (CaP), and it is unknown if expression in the primary tumor is similarly predictive. We were therefore interested to determine the expression of ARv7 in high-risk disease, and correlate this with response to an abiraterone-containing castrating regimen. Methods: We performed an open label non-randomized Phase II neoadjuvant study of ‘supercastration’ in men with high-risk clinically localized CaP using an optimal 2-stage design (ACTRN12612000772842). Treatment consisted of degarelix 240/80mg q 1/12, abiraterone 1000mg OD, bicalutamide 50mg OD and prednisolone 5mg OD for 24 weeks. The primary endpoints were safety/tolerability and pT0 response rate. ARv7 expression was determined by immunohistochemistry and qRT-PCR in both pre- and post treatment tumor specimens, and correlated with pathological response. Fresh specimens from resistant tumors are currently being profiled by RNA-seq. Results: 17 patients were recruited to the study. The combination treatment was well tolerated, with hot flushes and fatigue being the most commonly reported side effects, and all patients completed six months of treatment. Six patients with asymptomatic elevation of liver transaminases required Abiraterone dose reductions, and there were no unexpected toxicities. 16 patients proceeded to prostatectomy, and a pT0 response observed in one patient, with minimal residual disease present in a further three patients. ARv7 expression was uniformly present in all pre-treatment specimens, and neither level nor localization of expression predicted tumor response. Conclusions: ARv7 expression in primary CaP does not predict response to abiraterone-based castration. Clinical trial information: ACTRN12612000772842.
Clinical performance of PCA3 and TMPRSS2:ERG urinary biomarkers for African American men undergoing prostate biopsy.
Authors: Feibus Allison H. , Sartor Oliver , Thomas Raju , Maddox Michael M. , Lee Benjamin , Levy Justin , Stewart Carrie A. , Wang Julie , Moparty Krishnarao , Silberstein Jonathan L. 
Published: February 2017

91 Background: Urinary assaysfor PCA3 and TMPRSS2:ERG (T2:ERG) fusion are established biomarkers for the detection of prostate cancer (PCa). However few African Americans (AA) have been included in previous studies. We sought to determine the performance characteristics of these assays in a racially diverse group of men who elected to undergo prostate biopsy. Methods: Following IRB approval, from 12/2013-10/2014, post digital rectal exam urine was collected in 152 patients without a diagnosis of PCa, prior to biopsy. PCA3 and T2:ERG RNA copies were quantified using transcription-mediated amplification assays and normalized to PSA mRNA copies. Results: Of the 152 patients who met study inclusion, 93 (61%) were AA, 59 were non-AA (39%); 72(47%) were diagnosed with PCa (55% AA, 36% non-AA). Both PCA3 and T2:ERG scores were greater in men with biopsy-proven PCa, those with ≥3 PCa cores, ≥33.3% PCa cores, >50% PCa involvement of greatest biopsy core and Epstein significant PCa (all p-values ≤ 0.02). PCA3 but not T2:ERG scores were greater in men with Gleason grade ≥7 (p = 0.0003). ROC analyses for prediction of biopsy outcome resulted in AUCs of 0.7, 0.61 and 0.59 for PCA3, T2:ERG and serum PSA. For the subgroup of AA, PCA3 and T2:ERG scores were greater in men with biopsy-proven PCa, those with ≥3 PCa cores, ≥33.3% PCa cores, >50% PCa involvement of greatest biopsy core and Epstein significant PCa (all p-values ≤0.01). Both PCA3 and T2:ERG scores were greater in men with Gleason grade ≥7 (p ≤ 0.03). ROC analyses for prediction of biopsy outcome for AA only resulted in AUCs of 0.66, 0.66 and 0.58 for PCA3, T2:ERG and serum PSA. For the non-AA cohort, PCA3 scores were greater in men with biopsy-proven PCa, those with ≥3 PCa cores, ≥33.3% PCa cores, >50% PCa involvement of greatest biopsy core, Epstein significant PCa and Gleason grade ≥7 (all p-values ≤ 0.03). T2:ERG did not reach significance for any of these variables. In this subgroup, ROC analyses for prediction of biopsy outcome resulted in AUCs of 0.73, 0.54 and 0.56 for PCA3, T2:ERG and serum PSA. Conclusions: In AA men undergoing prostate biopsy, both PCA3 and T2:ERG urinary assays demonstrate clinical utility in predicting biopsy outcome and PCa disease characteristics.
Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Onartuzumab Plus Bevacizumab Versus Placebo Plus Bevacizumab in Patients With Recurrent Glioblastoma: Efficacy, Safety, and Hepatocyte Growth Factor and O
6
-Methylguanine–DNA Methyltransferase Biomarker Analyses
Authors: Cloughesy Timothy , Finocchiaro Gaetano , Belda-Iniesta Cristóbal , Recht Lawrence , Brandes Alba A. , Pineda Estela , Mikkelsen Tom , Chinot Olivier L. , Balana Carmen , Macdonald David R. , Westphal Manfred , Hopkins Kirsten , Weller Michael , Bais Carlos , Sandmann Thomas , Bruey Jean-Marie , Koeppen Hartmut , Liu Bo , Verret Wendy , Phan See-Chun , Shames David S. 
Published: February 2017

Purpose
Bevacizumab regimens are approved for the treatment of recurrent glioblastoma in many countries. Aberrant MET expression has been reported in glioblastoma and may contribute to bevacizumab resistance. The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma.

Methods

At first recurrence after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once every 3 weeks) or Pla + Bev until disease progression. The primary end point was progression-free survival by response assessment in neuro-oncology criteria. Secondary end points were overall survival, objective response rate, duration of response, and safety. Exploratory biomarker analyses correlated efficacy with expression levels of MET ligand hepatocyte growth factor, O
6
-methylguanine–DNA methyltransferase promoter methylation, and glioblastoma subtype.

Results

Among 129 patients enrolled (Ona + Bev, n = 64; Pla + Bev, n = 65), baseline characteristics were balanced. The median progression-free survival was 3.9 months for Ona + Bev versus 2.9 months for Pla + Bev (hazard ratio, 1.06; 95% CI, 0.72 to 1.56;
P
= .7444). The median overall survival was 8.8 months for Ona + Bev and 12.6 months for Pla + Bev (hazard ratio, 1.45; 95% CI, 0.88 to 2.37;
P
= .1389). Grade ≥ 3 adverse events were reported in 38.5% of patients who received Ona + Bev and 35.9% of patients who received Pla + Bev. Exploratory biomarker analyses suggested that patients with high expression of hepatocyte growth factor or unmethylated O
6
-methylguanine–DNA methyltransferase may benefit from Ona + Bev.

Conclusion
There was no evidence of further clinical benefit with the addition of onartuzumab to bevacizumab compared with bevacizumab plus placebo in unselected patients with recurrent glioblastoma in this phase II study; however, further investigation into biomarker subgroups is warranted.
Randomized trial of early integrated palliative and oncology care.
Authors: Greer Joseph A. , El-Jawahri Areej , Pirl William F. , Jackson Vicki A. , Park Elyse R. , Back Anthony , Muzikansky Alona , Kamdar Mihir , Rinaldi Simone , Jacobsen Juliet , Gallagher Emily R. , Fishbein Joel , Eusebio Justin , VanDusen Harry , Temel Jennifer S. 
Published: February 2017

104 Background: Early palliative care (PC) improves outcomes in patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) and in patients identified by clinicians as having poor prognosis, advanced cancer. We evaluated the impact of early, integrated palliative and oncology care in patients with newly diagnosed lung and gastrointestinal (GI) cancer. Methods: Between 5/2/11 and 7/20/15, we randomly assigned patients with newly diagnosed incurable lung (NSCLC, small cell, mesothelioma) or GI (pancreas, hepatobiliary, gastric, esophageal) cancer to PC integrated with oncology care (monthly visits with PC) or usual oncology care. We used the Functional Assessment of Cancer Therapy-General (FACT-G) to assess quality of life (QOL) and the Patient Health Questionniare-9 (PHQ-9) for mood at baseline, weeks 12 and 24. We also assessed patients’ coping styles (Brief COPE), perceptions of likelihood of cure and communication about end-of-life (EOL) preferences. To evaluate intervention effects on patient-reported outcomes, we performed chi square tests and linear regression, controlling for baseline values and clinical factors. Results: We randomized 350 patients (175 per group), including 191 lung and 159 GI cancer patients. Patients assigned to early PC had higher QOL (B = 5.36, 95% CI: 2.04 to 8.69, p = 0.002) and less depression on the PHQ-9 (B = -1.17, 95% CI: -2.33 to -0.01, p = 0.048) at 24 weeks, but not at 12 weeks. Also at 24 weeks, the intervention group was significantly more likely to report using active and engaged coping styles compared to the usual care group (B = 1.09, 95% CI: 0.23 to 1.96, p = 0.013). Similar proportions of patients at 24 weeks reported that their cancer was unlikely to be cured (36/105 [33.6%] in PC and 43/115 [37.4%] in usual care) but more patients assigned to early PC reported they discussed their EOL preferences (35/116 [30.2%] versus 17/117 [14.5%], p = 0.004). Change in QOL over time differed between the lung and GI cancer cohorts. Conclusions: Early PC improved QOL, mood, coping, and the frequency of EOL discussions in patients with newly diagnosed lung and GI cancer. The benefits of the integrated care model extend to other populations with advanced disease and include improved communication about EOL care. Clinical trial information: NCT01401907.
Advance care planning and palliative care consultation for stem cell transplant patients.
Authors: Wang Winnie S , Ma Joseph D. , Nelson Sandahl H , Revta Carolyn , Buckholz Gary T , Mulroney Carolyn M. , Roeland Eric 
Published: February 2017

113 Background: Advance care planning (ACP) in stem cell transplantation (SCT) is particularly challenging given the potential for cure for patients with blood cancers despite an increased risk of suffering and even death. Data regarding ACP and palliative care (PC) integration in SCT is limited. Methods: A retrospective chart review was conducted of patients with hematologic malignancies who underwent SCT at UCSD from January 2011 to December 2015. The primary objective was to determine the medical discipline of the initial and last code status documentation. Secondary objectives included evaluation of AD and/or POLST completion, PC consultation, hospice enrollment, and location of death. Data were compiled from a single electronic medical record and descriptive statistical analyses performed. Results: A total of 633 SCT were performed from 2011 to 2015 including 39% (n = 245) allogeneic and 61% (n = 388) autologous transplants (n = 29 patients had 2 transplants). Mean age of SCT patients was 55 years (±13). All but one (n = 632) had code status documentation, and 0.8% (n = 5) were initially DNR. The initial code status was documented outpatient for 3% (n = 17), and by the primary SCT physician for 1 patient. The final code status was documented outpatient for 22% (n = 14), and by the primary SCT physician for 0.9% (n = 6). Nearly half (44%, n = 279) had an AD and/or POLST completed. PC consultation occurred for 19% (n = 121) with the majority (83%, n = 101) completed inpatient. PC consultation requests were made by the primary SCT physician (18%, n = 22), inpatient SCT team (68%, n = 82), critical care (8%, n = 10), or other (5%, n = 6).The most common reason for consultation was symptom management (80%, n = 94). As of January 2016, 20% (n = 127) of SCT patients died with a mean time from transplant of 312 days (± 317). Of those that died, the majority (83%, n = 106) died in the hospital, 15% (n = 19) were full code, 48% (n = 62) had an AD and/or POLST, and 14% (n = 18) were enrolled in hospice. Conclusions: These single center data suggest ACP and PC integration in SCT is limited. Opportunities exist to expand integration to the outpatient setting and earlier in the course of illness.
Equity in patient-provider communication regarding treatment-related symptoms and health-related quality of life (HRQOL) among breast cancer survivors.
Authors: Samuel Cleo A. , Schaal Jennifer , Robertson Linda , Eng Eugenia , Kollie Jemeia G , Yongue Christina , Foley Karen , Smith Beth , Yee Mellissa K , Black Kristin , Ellis Katrina , Hoffman Lucretia , Lightfoot Alexandra , Morse Claire , Padilla Neda , Cykert Sam 
Published: February 2017

127 Background: Compared with white breast cancer patients, black patients more often report inadequate symptom control and decrements in health-related quality of life (HRQOL). Racial differences in patient-provider communication (PPC) are well-documented and linked to worse health outcomes for minorities; however, less is known about inequities in symptom and HRQOL discussions among cancer patients and providers. As part of an NCI-funded systems change intervention to improve racial equity in treatment completion among Black and White cancer patients, we assessed racial differences in PPC regarding treatment-related symptoms, HRQOL issues (e.g., physical, psychosocial, financial, and spiritual well-being), and symptom management among breast cancer survivors (BCS). Methods: We conducted 6 focus groups (FGs) and semi-structured interviews with 22 stage 1-3 BCS (3 black FGs; 3 white FGs) from 2 cancer centers. Guided by a community-based participatory research approach, our diverse community-academic-medical team facilitated FGs and conducted qualitative analyses. Results: Although both black and white BCS reported multiple treatment-related symptoms and changes in HRQOL, perspectives on PPC differed. Some black and white BCS described positive aspects of PPC, including providers’ thorough explanations of treatment side effects and responsiveness to symptom concerns. However, white BCS expressed greater satisfaction with PPC, while black BCS more often described concerns regarding providers’ verbal (e.g., nondisclosure, dismissiveness) and non-verbal communication (e.g., unapproachability, poor eye contact) skills in the context of symptom management. Most BCS, regardless of race, indicated that providers typically discussed physical symptoms/HRQOL issues, but often failed to mention non-physical side effects of treatment (e.g., social isolation, financial toxicity). Conclusions: Racial differences in PPC exist among BCS and may contribute to inequities in symptom management and HRQOL. Inadequate communication regarding non-physical symptoms likely represents a critical missed opportunity for improving the quality and equity of palliative care.