bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active surveillance of pulmonary metastases in renal cancer patients.
Authors: Abdul Rahman Rozana , Teo MinYuen , Osman Noorsyakira , Jayaram Anuradha , o'Donnell Dearbhaile M. , McDermott Raymond 
Published: February 2017

445 Background: Biology of pulmonary metastases (PM) in renal cancer (RCC) patients (pts) is variable and not all pts require immediate treatment. We examined the role of active surveillance in PM predominant metastatic RCC pts. Methods: Pts with a diagnosis of RCC and presence of PM were identified. PM had to be ≥ 5mms (solitary) or 2mms (multiple), classified as metastatic by the treating physician, and definitive local therapy was deemed not possible. Metastatic disease could also be present elsewhere if small volume. Pts, disease and treatment details were extracted from chart review. Kaplan-Meier method was used to perform time-to-event analyses. Primary endpoint was time on surveillance. Also studied were time from PM appearance to treatment initiation and duration of treatment. Results: Between Nov 2005 and Sept 2013, 48 pts were identified. Median age at PM diagnosis was 66 years (39 – 88 yrs), 81% were male, 94% had prior nephrectomy and were of clear cell histology. 31/45 pts (69%) had pT3 tumours with median Fuhrman grade of 3. Median MSKCC score was 1. PMs were present at diagnosis in 20 pts and developed subsequently in 27 pts at a median of 19.4 months (interquartile range (IQR) 9.5 - 64.3). Twelve (25%) of PMs were biopsy proven. 14 pts had solitary PM while 31 were multiple. Median size of metastases was 9mm (2 – 32mm). Metastases elsewhere were present in 10 pts. Median follow-up duration for all pts was 24.5 mos (IQR 12.9 – 44.1). 28/48 pts (58%) remain on surveillance at median 18.6 mos (IQR 10.6 - 28.5). In 11 pts there had been no progression while 17 pts have experienced RECIST progression of PM but remain on surveillance due to lack of symptoms/slow growth. 20/48 pts commenced on treatment. Median time from PM diagnosis to treatment was 12.5 mos (IQR 7.9 – 19.3). 18/20 pts started on VEGF TKI (Sunitinib 12 pts, Pazopanib 5, Sorafenib 1), while 2 pts had mTOR inhibitors. Median duration of follow-up on treatment was 13.4 mos (IQR 5.4 – 35.8), with 2 patients having died at 40.1 mos and 37.5 mos. Number of pts who received 2nd/3rd/4th/5th line of treatment were 7/2/2/1 respectively. Conclusions: Active surveillance of PM in RCC pts is safe and may avoid unnecessary treatment related toxicity. Once treatment is commenced, outcomes do not appear to be adversely affected.
Prognostic value of flare-up phenomenon after discontinuation of sunitinib (SU) or pazopanib (PA) in metastatic renal cell carcinoma (mRCC).
Authors: Iacovelli Roberto , Massari Francesco , Albiges Laurence , Escudier Bernard 
Published: February 2017

448 Background: SU and PA are VEGFR inhibitors, approved for the treatment of mRCC. Cessation of treatment has been reported to induce flare-up, with increased tumor growth rate (TGR). We aimed to investigate this phenomenon and its prognostic role in mRCC. Methods: Patients who discontinued first line SU or PA with available data about CT scans performed before (t-1), at the time of discontinuation (t0) and after (t+1), were included in this analysis. TGR was evaluated as the difference between the sum of longest diameters (SLD) of the target lesions during the interval time between the CTs (TGR1=SLD0–SLD-1/t0-t-1 and TGR2=SLD+1-SLD0/t+1-t0) and expressed in cm/month. Flare-up was evaluated as the difference between the TGRs. Median overall survival was evaluated from t0 (OS0) to death by the Kaplan-Meier method and correlation with variables was evaluated with Cox model. Results: Sixty-three patients treated from Oct 2006 to Nov 2012 at the Institut Gustave Roussy were eligible. Median age was 57.1 y, 81% were males, 89% had SU and 11% PA. Heng prognostic groups were good in 33% and intermediate in 67% of the pts. Median OS0 was 24.1 months (95%CI, 8.3 – 40.0). Major reasons for discontinuation were durable partial/complete response (16%), severe toxicity (22%) and progression of disease (62%). The median TGR1 and TGR2 were 0.2 and 0.7 cm/month, respectively (p=0.001), no correlation was found (p=0.33) and no differences were found between SU and PA in TGR1 (p=0.95) and TGR2 (p=0.53). Median flare-up was 0.5 cm/month (IQR: 0.1 – 1.2); in pts who discontinued for response, toxicity, or PD it was 0.1 (IQR: -0.2 – 0.6), 0.5 (IQR; 0.2 – 2.0) and 0.8 (0.1 – 1.7), respectively. At the univariate analysis flare-up was a prognostic factor for OS0 (HR: 1.13, 95%CI: 1.02 – 1.24; p=0.018). When compared to Heng criteria in the multivariate analysis, it was confirmed to be an independent prognostic factor: each increase of 1 cm in flare-up increases the risk of death by 11% (HR: 1.11, 95%CI: 1.00 – 1.23; p=0.048). Conclusions: Flare-up is an independent prognostic factor present in patients affected by mRCC who discontinued SU or PA. This is independent by the reason for discontinuation and the type of therapy.
Using biologic knowledge to discover molecular correlations between human renal cell carcinoma pathways.
Authors: Medina Villaamil Vanessa , Aparicio Gallego Guadalupe , Veiga Francisco Gomez , Valladares Ayerbes Manuel , Quindós Varela Maria , Fernandez Nunez Natalia , Molina Diaz Aurea , Santamarina Cainzos Isabel , Anton Aparicio Luis Miguel 
Published: February 2017

451 Background: Renal cell carcinoma (RCC) is known to be resistant to chemotherapy. There is need for the identification of biomarkers capable to determine RCC prognosis factors and metastatic potential obtainable from non-invasive or minimally invasive techniques. Our aim was to derive predictive models which could predict more accurately than any one factor alone. Methods: To studythe cascade of events leading to the formation and progression of RCC, we assessed 29 markers by immunohistochemistry and qRT-PCR using tissue micro-array (TMA). Results: Multivariate logistic regression showed the best proteins combination for node status (NOTCH1 and GLUT5) and pelvis invasion (EGFR and DLL3). ROC curve analyses were made to analyse the accuracy of the best candidate proteins; it should be noted NOTCH1 and GLUT5 for node status prediction (AUC=0.833, 95% CI, 0.744-0.922; p<0.001) and EGFR and DLL3 for pelvis invasion (AUC=0.777, 95% CI, 0.631-0.922; p=0.007). Furthermore, we carried out the correlation between these candidate proteins and all mRNA measured in order to deepen in the cellular transcripts traffic associated with them. To highlight the correlation between high DLL3 protein levels and low Hif1-β expression, and the negative correlation between GLUT5 protein and low levels of Baxβ. Conclusions: In the age of individual therapy, the approach to percutaneous image-guided RCC biopsy procedures plays an expanded role. Applying a 2 mm punch needle for constructing a TMA we could describe for the first time how are combined and correlated 29 markers in regression equations to predict in the most optimal way a number of pathological variables associated with RCC. [Table: see text]
Treatment (tx) patterns and drug (Rx) costs for patients (pts) with metastatic renal cell carcinoma (mRCC) in the United States.
Authors: Geynisman Daniel M. , Shih Ya-Chen T. 
Published: February 2017

457 Background: The tx paradigm for mRCC has rapidly morphed from cytokine-based and cytotoxic tx to targeted therapy (TT). Five oral (O) and two intravenous (IV) TTs are approved for mRCC. No consensus exists on the sequence of TT use. This study aimed to examine the evolution of 1st through 3rd line tx patterns since 2004 and their associated costs. Methods: LifeLink Health Plan Claims Database (October 1, 2003-March 31, 2011), a commercial claims database, was used to create a cohort of age ≥ 18 yo, mRCC pts with at least 12 months of continuous enrollment. We examined tx patterns and sequences by year. When evaluating cost, we limited analysis to pts <65 yo because the database does not have information on claims paid by Medicare. We described pt characteristics and tx patterns over time and applied a nonparametric bootstrapping method to compare costs. Results: 1,561 mRCC pts met the inclusion criteria with 71% men and a mean age of 62 yo (SD=11); 39% were from the South; 57% had a modified Charlson comorbidity score of zero. In 2010: 9 unique Rx regimens were used for 1st line tx, 8 for 2nd, 8 for 3rd; most common 1st/2nd/3rd line tx was sunitinib (44%)/temsirolimus (24%)/everolimus=sunitinib (26%); most common sequence was VEGF->mTOR for the 1st switch and VEGF->VEGF->VEGF for 2nd switch. From 2004 to 2011, 1st line cytotoxic tx decreased from 47% to 6%, IFN-α from 47% to 3%, bevacizumab from 33% to 9%. Over time, more pts were able to go from 1st to 2nd line tx (p=0.01) and 2nd to 3rd line tx (p=0.025). Median time to switch (TTS) from 1st to 2nd line was 175 days (SD 103) with a longer TTS if started on O vs. IV tx (188 vs. 143 days) (p<0.001). For 959 pts <65 yo, stratifying by whether the 1st line tx was O or IV, mean total 1st-yr tx cost/pt was $130,962 (IV) vs. $121,676 (O) (P=0.18) and total 1st-yr Rx cost was $36,636 (IV) vs. $54,596 (O) (p<0.001). Also, costs increased by the number of switches, from $108,428 for no switch to $190,976 for > 1 switch. Conclusions: The results support a drastic shift in the tx of mRCC with wide heterogeneity in tx patterns, reflecting a lack of clear guidelines. Over the years, more pts are able to receive more lines of tx, TTS was longer with initial O tx, but 1st-yr Rx costs were lower with initial IV tx.
Significance of preoperative butyrylcholinesterase as an independent predictor of overall survival in patients with renal clear cell carcinoma treated with nephrectomy.
Authors: Koie Takuya , Yamamoto Hayato , Imai Atsushi , Hatakeyama Shingo , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara 
Published: February 2017

458 Background: Prognostic factors for overall survival (OS) of the patients with clear cell renal cell carcinoma (cRCC) treated with nephrectomy are still not defined well. Butyrylcholinesterase (BChE) is an α-glycoprotein found in the nervous system and liver. Advanced cancer is a condition with mild to moderate inflammation and interacts with various degree of protein-energy malnutrition. In this study, we analyzed the potential preoperative prognostic significance of BChE in patients with cRCC undergoing nephrectomy. Methods: etween 1992 and 2013, we treated 551 patients with renal cell carcinoma. Of these 400 patients with cRCC who underwent radical or partial nephrectomy were enrolled. Serum BChE was routinely measured before operation in all patients. Covariates included age, gender, performance status (PS), preoperative laboratory data, clinical T stage, and distant metastasis status. Univariate analyses were performed using the Kaplan-Meier and log-rank methods. Multivariate analysis was performed using a Cox proportional hazard model. Univariate and multivariate analyses were performed to determine clinical factors that associated with OS. Results: Of these, 302 patients had an organ-confined disease (T1-2N0M0) and 56 patients had a distant metastasis (any T, any N, and M1). The median BChE level was 250U/L (normal range from 168 to 470U/L). The median follow-up period was 34 months. At the time of analysis, 26 patients (6.5%) had alive with recurrent cRCC and 38 patients (9.5%) had died from cRCC. The 3-year OS rate for our entire cohort of 400 patients was 88%. The 3-year OS rates were 89.3% and 77.7% in the BChE ≥100 and <100U/L groups (p= 0.004). In the univariate analysis, PS, anemia, hypoalbuminemia, BChE, corrected calcium, C-reactive protein, and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that BChE and distant metastasis status were significantly associated with OS. Conclusions: These data suggest a possible role of pre-operative BChE as an independent predictor of OS after nephrectomy for cRCC.
DNA hypermethylation biomarkers to predict therapy response of antiangiogenic therapy in metastatic renal cell carcinoma patients.
Authors: Peters Inga , Dubrowinskaja Natalia , Abbas Mahmoud , Seidel Christoph , Kogosov Michael , Scherer Ralph , Gebauer Kai , Merseburger Axel S. , Kuczyk Markus A. , Gruenwald Viktor , Serth Juergen 
Published: February 2017

459 Background: Antiangiogenic therapy has demonstrated to increase progression-free (PFS) as well as overall survival (OS) in RCC patients. Clinical scoring systems like the Memorial Sloan Kettering Cancer Center (MSKCC) help to stratify patients for treatment options. However, identification of molecular phenotypes of RCC patients would improve stratification of specific targeted therapies. We investigated whether DNA hypermethylation based markers can predict the PFS following first-line therapy. Methods: We examined primary tumors from formalin-fixed paraffin embedded tissue specimens obtained from 18 patients receiving anti-VEGF based targeted therapy. Quantitative methylation-specific PCRs were carried out following bisulphite conversion of DNA for CpG island methylation analysis of the five candidate genes, CST6, GATA5, LAD1, hsa-miR124-3 and hsa-miR9.1 identified in advance as potential prognosticators for RCC. For Kaplan Meier survival analysis relative methylation values were uniformly dichotomized and logrank statistics calculated. The analyses of sensitivity and specificity were carried out using a cutoff of 6 months for PFS to categorize for therapy failure and response, as described in the literature. Results: Hypermethylation of CST6 and LAD1 shows a highly significant association with a shortened PFS following first-line therapy (p=0.009, p=0.004, logrank test). The median survival observed for the high and low methylation group was 2.0 and 11.4 months for CST6 and LAD1. Moreover, LAD1 methylation showed a specificity of 1.0 (0.65-1.0, 95%CI) and a sensitivity of 0.73 (0.43-0.90, 95%CI) for detection of therapy failure. For CST6 methylation analysis a specificity of 0.86 (0.49-0.97, 95%CI) and a sensitivity of 0.82 (0.52-0.95, 95%CI) was detected. Conclusions: The analysis of our discovery cohort revealed that CGI methylation of CST6 and LAD1 predicts a shortened PFS of patients after anti-VEGF therapy. Provided, these results can be confirmed in an independent larger evaluation cohort, detection of hypermethylated loci in primary RCC would allow, to our knowledge for the first time, a molecular-based clinical management of patients.
Comparison of radical treatment and mortality in patients with nonmetastatic prostate cancer in England and the United States.
Authors: Sachdeva Ashwin , van der Meulen Jan , Cathcart Paul 
Published: February 2017

46 Background: Prostate-cancer mortality in the U.S. is amongst the lowest globally. Given historical differences in management between England and the U.S., this paper aims to determine if risk-adjusted prostate-cancer mortality is inferior amongst men in England compared to the U.S. Methods: Patients diagnosed with non-metastatic prostate-cancer between 2004 and 2008 were identified using English hospital admission records linked to national cancer registry data, and the American Surveillance, Epidemiology and End Results program. Complete data were available for 222,163 patients. Patients were stratified into low-, intermediate-, and high-risk groups according to disease characteristics. Patient demographics from the two countries were compared using the Chi-square test. Competing-risks survival analyses were used to estimate relative six-year prostate-cancer mortality. Results: In comparison to patients in the U.S., English patients were more likely to present at an older age (70 to 79: England 44.2%, USA 29.3%, p<0.001), with higher clinical tumour stage (cT3-4: England 25.1%, USA 8.6%, p<0.001) and higher Gleason score (GS 8-10: England 20.7%, USA 11.2%, p<0.001). They were also less likely to receive radical therapy, with greatest disparity amongst patients with high-risk disease (England 30%, U.S. 83%, p<0.001). After adjusting for age, ethnicity, year of diagnosis, Gleason score, and tumour stage, English patients were more likely to die of prostate cancer (all risk groups: HR 1.9, 95% CI 1.7-2.0, p<0.001). However, this difference was no longer statistically significant on adjustment for radical therapy (all risk groups: HR 1.0, 95% CI 1.0-1.1, p=0.336). Conclusions: After risk adjustment, prostate-cancer mortality is significantly higher in England compared to the U.S. for men with intermediate- and high-risk disease. This difference appears to be explained by decreased use of radical therapy in England.
Pharmacist-led monitoring program for patients on sunitinib for metastatic renal-cell carcinoma: A Canadian experience.
Authors: Edwards Scott , Wood Lori , McCarthy Joy S. , Collins Andrew , Hartery Lynn , Abbott Rick , Whelan Maria 
Published: February 2017

479 Background: Sunitinib is a standard of care for first-line treatment of metastatic clear cell renal-cell carcinoma (mRCC). Despite having a relatively good safety profile, Sunitinib does have several clinically important toxicities. With the rapid rise in the use of Sunitinib and other oral cancer agents, we instituted a pharmacist-led monitoring program in the ambulatory care setting to prospectively document, monitor, and manage toxicities in our Canadian province. Methods: The pharmacist-led monitoring program consisted of patient assessments in clinic with the oncology team combined with a call back program. The program consisted of a patient assessment in the oncology clinic on day 1 of a Sunitinib cycle followed with a call back on day 14. A chart review of consecutive patients who were prospectively monitored by this progam after receiving Sunitinib for mRCC was conducted. Treatment specific data for the first six cycles of therapy included dose reductions, therapy delays/interruptions, therapy discontinuation, and reason for each was recorded. Toxicity data including the occurrence and severity grade was collected. The time to treatment failure (TTF) defined as the time from therapy initiation to treatment discontinuation for any reason was measured. Results: Fifty six patients are included in the study cohort. Of these, 52 (92.86%) started at the standard 50 mg once daily and the remainder at a reduced dose. Additionally, 15 patients experienced hypertension requiring drug therapy adjustment or additional antihypertensive therapy. Two patients required drug therapy for hypothyroidism. There were a total of 39 dose reductions in this patient population over a six cycle period. The majority of dose reductions (46.2%) and therapy interruptions (34.5%) occurred during cycle one. The time to treatment failure for the 45 patients that discontinued therapy was 9.72 months. Conclusions: Pharmacist-Led monitoring of oral cancer therapies is a practical and feasible method of monitoring patients on Sunitinib for mRCC. The success has led to its implementation with other agents and disease sites.
Brain metastasis from renal cell carcinoma: Are we missing our chance to treat?
Authors: Hanzly Michael 
Published: February 2017

485 Background: Brain metastasis from renal cell carcinoma (RCC) occurs approximately 8% of patients with metastatic RCC. The guidelines from the NCCN, EAU, and AUA recommendcerebral imaging only in patients who have symptomatology. The purpose of our study was to review the presenting symptomatology that led to their diagnosis of brain metastases followed by their overall treatment and survival. Methods: Our IRB-approved prospectively-maintained kidney cancer data base was reviewed between from 1995 to 2012. Brain metastases from a primary RCC was identified in 52 patients. Patient demographics including family and social history, primary treatment for RCC, elapsed time between primary diagnosis and brain metastasis, associated symptomatology, treatment of metastatic site and overall survival following diagnosis of brain metastasis were examined. Results: Primary RCC was diagnosed in 986 patients between 1995 and 2012. Brain metastases were identified in 52 patients, 79% were male and 100% Caucasian, 87% had no family history of renal malignancy. Primary treatment for RCC included 75% radical nephrectomy, 10% observation, 7.6% cytoreductive nephrectomy, 5.4% sunitinib, 2% interleukin-2 treatment. Central nervous system (CNS) symptoms were absent in 37% of patients diagnosed with brain metastases, while 73% presented with symptoms. The average number of metastases was 1.78 per patient in the asymptomatic group, and 2.7 metastases in patients with CNS symptoms (p=.18). Elapsed time from primary RCC treatment to diagnosis of brain metastases was an average of 730 days in the asymptomatic group and 1170 days for the symptomatic group (p=0.02). The symptomatic group has overall survival (OS) at one year of 81% and 69% at three years, while the asymptomatic group had an OS of 81% at one year and 31% at 3 years. Pulmonary involvement existed in 75% of both cohorts of patients (p=0.003). Conclusions: Our findings suggest that patients without CNS symptoms with brain metastases had a worse overall survival. The urologic guidelines recommending CNS imaging only in patients with symptoms may be missing a subset of the metastatic RCC population who could potentially benefit from early intervention, thus prolonging overall survival.
Patients with metastatic papillary renal cell carcinoma (RCC) who may benefit from sunitinib therapy (tx): Results from an international metastatic RCC database.
Authors: Kejzman Daniel , Gottfried Maya , Maimon Natalie , Hammers Hans J. , Eisenberger Mario A. , Carducci Michael Anthony , Sinibaldi Victoria J. , Neiman Victoria , Rosenbaum Eli , Sarid David , Gez Eliahu , Peer Avivit , Sella Avishay , Mermershtain Wilmosh , Rouvinov Keren , Berger Raanan , Lee Jae-Lyun 
Published: February 2017

486 Background: The VEGFR inhibitor sunitinib is a standard tx for metastatic clear cell RCC. Data on the activity of sunitinib in metastatic non clear cell RCC, is limited by small or heterogeneous (mixed histology or targeted therapies) studies, that revealed a lower antitumor activity than in patients with clear cell histology. We aimed to analyze the activity of sunitinib in a large international cohort of patients with metastatic papillary RCC, and to characterize patients who may benefit for this therapy. Methods: Records from metastatic papillary RCC patients treated with sunitinib in 10 centers across 3 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and clinical outcome were performed using Cox regression. Results: Between 2004-2013, 74 patients (median age 60, 68% male) with metastatic papillary RCC were treated with sunitinib. 78% had a prior nephrectomy. HENG risk was good 11%, intermediate 56%, and poor 33%. 21% were active smokers, and 31% users of angiotensin system inhibitors. 24% and 41% had liver and bone metastases, respectively. 55% had a pre-treatment neutrophil to lymphocyte ratio (NLR) >3. 40% had dose reduction/treatment interruption. Sunitinib induced hypothyroidism and hypertension (HTN) occurred in 30% and 43%, respectively. 70% achieved a clinical benefit (partial response + stable disease), while 30% had disease progression within the first 3 months of therapy. Median progression free survival (PFS) and overall survival (OS) were 5 and 12 months, respectively. 27% had a PFS ≥ 1 year, and 26% survived ≥ 2 years. Factors associated with PFS were sunitinib induced HTN (HR 0.31, p=0.002), pre-treatment NLR >3 (HR 5.3, p=0.001), and active smoking (HR 2.5, p=0.01). Factors associated with OS were sunitinib induced hypothyroidism (HR 0.4, p=0.024), past nephrectomy (HR 0.41, p=0.02), pre-treatment NLR >3 (HR 2.25, p=0.036), and active smoking (HR 2.3, p=0.027). Conclusions: Clinicopathologic factors may be used to identify patients with metastatic papillary RCC who may benefit from sunitinib tx. A prolonged PFS and OS were noted in 26-27% of patients.