bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes for a multi-institutional cohort of patients treated with intra-operative radiation therapy for advanced or recurrent renal cell carcinoma.
Authors: Paly Jonathan J. , Hallemeier Christopher Leigh , Biggs Peter J. , Niemierko Andrzej , Roeder Falk , Martinez-Monge Rafael , Whitson Jared Myers , Calvo Felipe A. , Fastner Gerd , Wong William , Ellis Rodney J. , Efstathiou Jason Alexander 
Published: February 2017

442 Background: For patients with advanced or locally recurrent (LR) renal cell carcinoma (RCC), the role of intra-operative radiation therapy (IORT) remains controversial. We analyzed outcomes in a multi-institutional cohort of patients with RCC who received IORT. Methods: Between 1985 and 2010, 98 patients were treated with IORT for advanced or LR RCC at 9 institutions. We collected demographic, clinical, treatment, and outcomes data for all patients. Overall (OS), disease specific (DSS), and disease-free survival (DFS) was estimated using the Kaplan-Meier method. A multivariate Cox hazards regression was used to test significance. Results: IORT was delivered at nephrectomy for advanced disease (28%) or during resection of LR RCC in the renal fossa (72%). 69% of patients were male and mean age at RCC diagnosis was 57. At initial nephrectomy, primary T-stage was 17% T1, 12% T2, 55% T3, and 16% T4. Prior to IORT, 87% had visibly complete surgical resection of tumor. Mean IORT dose delivered was 14.7Gy (range 9-20Gy). Average post-op hospitalization was 10.7 days. Median follow-up after IORT was 1.6 years. OS at 1 and 5 years after IORT was 69% and 37% for advanced patients and 94% and 55% for LR patients, respectively. DFS at 1 and 5 years was 72% and 39% for advanced patients and 96% and 52% for LR patients, respectively. DSS at 1 and 5 years was 72% and 41% for advanced patients and 96% and 60% for LR patients, respectively. For the entire cohort, higher IORT dose (HR 1.3, p < 0.001), positive initial node status (HR 2.9-3.6, p < 0.01), and presence of sarcomatoid features (HR 3.7-6.9, p < 0.05) had a significant association with decreased OS, DFS and DSS. Patients who received adjuvant systemic therapy after IORT showed decreased DSS (HR 2.4, p = 0.03). When analyzing LR tumors alone, positive margin (HR 2.6, p = 0.01) was associated with decreased OS. Conclusions: We report on the largest known cohort of patients with RCC managed with IORT and we have identified factors associated with survival. Outcomes in our cohort with LR RCC treated with local resection and IORT compare favorably to similar groups treated with resection alone suggesting improved DSS may be possible with IORT.
Association of topoisomerase II expression and cancer-specific death in patients with surgically resected clear cell renal cell carcinoma.
Authors: Gardner Faithlore Patrice , Joseph Richard Wayne , Serie Daniel , Hilton Tracy W. , Parasramka Mansi , Eckel-Passow Jeanette , Cheville John , Leibovich Bradley C. , Parker Alexander S. 
Published: February 2017

446 Background: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death. Methods: We identified 947 patients who underwent nephrectomy to treat clinically localized ccRCC between January 16, 1990, and September 27, 2006. TOP2a expression was assessed using IHC and scored as number of positive cells per mm2. We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features, we employed Kruskal-Wallis tests and for associations with cancer-specific survival, we generated Cox proportional hazard regression models. Results: HigherTOP2a expression is associated with later stage, higher grade and higher Mayo SSIGN score (all p < 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend < 0.0001). Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.31 95% CI 1.64-3.25; p < 0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ~95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.09 95% CI 1.29-7.40; p = 0.01). Conclusions: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients.
mTOR inhibitor therapy for metastatic sarcomatoid clear cell renal cell carcinoma (ccRCC).
Authors: Bastos Diogo Assed , Voss Martin Henner , Karlo Christoph , Ajeti Albulena , Patil Sujata , Feldman Darren Richard , Molina Ana M. , Motzer Robert John 
Published: February 2017

450 Background: Sarcomatoid variant describes a histomorphologic pattern with presence of spindle-cell features that can be seen across all subtypes of RCC. It is associated with an aggressive phenotype and poor prognosis. Outcome to mTOR inhibitor therapy was accessed in patients (pts) with ccRCC with sarcomatoid features. Methods: Patients with metastatic sarcomatoid ccRCC treated with mTOR inhibitors at our center were retrospectively identified. Demographic characteristics and treatment outcome were assessed. Overall response rate (ORR) was determined by formal response criteria (RECIST 1.1). Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: 29 pts were treated with temsirolimus (18) or everolimus (11). Median age was 57 years (53 to 61) and there were 21 male pts (72%). Median number of metastatic sites was 3 (1 to 7) and 18 pts (62%) had ≥ 3 metastatic sites. Distribution between Memorial Sloan-Kettering Cancer Center risk groups was 14% favorable, 72% intermediate, and 14% poor-risk disease. Median number of prior therapies was 1 (0 to 5) and 79% of pts received mTOR inhibitor as ≥ 2nd-line of therapy. Three patients (10.3%) achieved a partial response (PR), 11 (38%) stable disease (SD), and 15 (51.7%) had progressive disease (PD). Tumor shrinkage was observed in 9 pts (31%) and the mean change in tumor burden was +24% (-45% to +100%). Median PFS and OS were 3.4 months (CI: 1.4-5.3) and 8.3 months (CI: 4.8- 17), respectively. Conclusions: OS was poor in this heterogeneous group of pts. Future studies to characterize this variant at a molecular level are warranted and might identify predictive markers for clinical outcome in patients treated with mTOR inhibitors. [Table: see text]
Predicting survival in renal cell carcinoma: The role of quality-of-life assessment.
Authors: Gupta Digant , Braun Donald Peter , Lis Christopher G. , Staren Edgar Donald 
Published: February 2017

460 Background: Assessment of quality of life (QoL) with validated instruments has been increasing in the clinical oncology community, but to date few studies have examined its prognostic significance in renal cell carcinoma (RCC). We investigated the association between QoL at presentation and survival in RCC. Methods: A consecutive series of 138 RCC patients treated between January 2001 and December 2009. QoL was evaluated at baseline using EORTC-QLQ-C30 which incorporates 1 global, 5 functional and 8 symptom scales. Scores range from 0-100 with higher scores in the global/functional scales and lower scores in the symptom scales indicating better QoL. Patient survival was the primary endpoint. Cox regression was performed to evaluate the prognostic significance of QoL. Results: Mean age at diagnosis was 53.8 years. 51 patients were newly diagnosed at our hospital, while 87 were previously treated elsewhere. Stage at diagnosis was I, 32; II, 19; III, 32; and IV, 55. Median overall survival was 17.2 months (95% CI: 10.1-24.2 months). QoL scales predictive of survival upon univariate analysis were physical (p=0.003), role (p=0.02), social (p=0.03), fatigue (p=0.02), pain (p=0.03), and constipation (p=0.04). Upon multivariate analyses, after adjusting for age, gender, stage, and treatment history, physical (HR=0.89; 95% CI=0.78, 0.99; p=0.04), social (HR=0.91; 95% CI=0.83, 0.99; p=0.04), fatigue (HR=1.10; 95% CI=1.01, 1.19; p=0.03) and constipation (HR=1.11; 95% CI=1.02, 1.20; p=0.01) scales were significantly associated with survival, such that patients with higher (better) physical and social scores and lower (better) fatigue and constipation scores had better survival. For newly diagnosed patients, physical scale was significant, while for previously treated patients, physical, fatigue, and constipation scales were significant. Conclusions: Baseline QoL elements that reflect specific functional and symptomatic attributes provide useful prognostic information in RCC. Significantly, this held true for physical function for both newly diagnosed and previously treated patients. Such determinations should be considered when designing clinical trials with survival endpoints and may aid decision-making in clinical practice.
Treatment of adenocortical carcinoma: 11-year Birmingham experience.
Authors: Zvirinska Lenka , Tew Alice , Porfiri Emilio 
Published: February 2017

462 Background: Due to the lack of prospective randomized phase III trial data, we have analysed patients with ACC treated between 2000 and 2011. Methods: All the patients given Mitotane (standard treatment of ACC in UHB, Birmingham) where extracted from pharmacy database. Results: 23 patients were identified, age 26-74 (median 53). Follow-up for whole group was 14–167m, median 60. Overall survival (OS) was 3-48m, medium 11.1 patient with slowly growing disease is still alive (167m) with 2nd dg of breast cancer. 19 patients were treated for metastatic disease, 4 in adjuvant setting. 7 patients were managed by endocrinologist only (3 adjuvant, 2 poor PS, 1 reluctant to treatment and 1 details unknown). 16 patients were under shared care. 4 these patients were never exposed to chemotherapy (2 poor PS, 1 returned to Africa, died within 5 months, 1 declined chemotherapy, still alive at 16 months post). 6/19 metastatic patients had chemotherapy as 1st treatment (4 patients etoposide/doxorubicin/cisplatin chemotherapy, 1 etoposide/carboplatin, 1 etoposide/cisplatin), 7 were treated with chemotherapy on PD(6 streptozocin, 1 etoposide/doxorubicin/cisplatin, 1 etoposide/cisplatin). There was no significant difference in OS when those approaches were compared (1st group 7-16 m, median 10, 2nd group 3-14, median 11) But TTP has been slightly worse for treatment on PD as expected (1st group 3-13m, median 6.5; 2nd group 3-14, median 3), although might be due to tendency to use Streptozocin, consistant with preliminary published results of FIRMACT trial.3 patients were treated with 2 lines of chemotherapy (age 30,31, 38), TTP 2- 5 m. Adjuvant patients within our sample has been followed up for limited perion only (11 – 71m, median 22.5), however no recurrence was diagnosed so far.In metastatic patient population 4 patients were treated for recurrence with time to relapse 3-43m, medium 23.5. Conclusions: ACC is heterogenic disease as confirmed by our survival data. In unselected population median OS is comparable to FIRMACT. Consistant with literature review, chemotherapy threatment can be delivered as 1st-line or delayed till PD. 2nd-line chemotherapy is of limited efficacy.
Involvement of miRNAs in the formation and maintenance of self-renewing kidney cancer spheres with stem cell properties.
Authors: Lichner Zsuzsanna , Saleh Carol , Subramaniam Venkateshwaran , Prud'homme Gerard , Yousef George M. 
Published: February 2017

463 Background: Cancer cells may acquire stem cell (CSC) properties by activated TGFβ-epithelial-mesenchymal transition (EMT) axis resulting in formation of cancer stem cells. miRNAs are involved in CSC formation in solid tumors, but their role has not been investigated in renal cell carcinoma (RCC). Methods: RCC spheres were generated and propagated in serum-free defined medium (SFDM). mRNA expression was assessed by qRT-PCR. miRNA expression was screened on a qRT-PCR based panel. Tumorigenicity was assessed by subcutaneous injection of RCC sphere or parental cells into immunodeficient mice in different dilutions. TargetScan and miRPath was used for target prediction and clustering. Results: We isolated self-renewing cancer spheres from ACHN and CAKI-1 RCC cell lines in the stem cell supporting media, SFDM. Spheres were highly clonogenic and tumorigenic in xenograft tumor model and expressed high levels of stem cell-related markers and mesenchymal markers. These spheres were enriched in the mesenchymal marker CD44 and the kidney progenitor maker CD24 indicating that EMT contributed to their formation or maintenance. We compared miRNA expression between the spheres and the parental cells and identified differentially expressed miRNAs. Functional clustering of their predicted targets indicates that TGFβ signaling is a potential regulator of CSC self-renewal and is regulated by the candidate miRNAs. Further, we show that transfection of ACHN and CAKI-1 cells with the miR-17 inhibitor resulted in rapid and highly efficient formation of cancer spheres that were indistinguishable from the spheres formed in SFDM. These spheres were stable and could be propagated indefinitely. Histologic examination and immunohistochemistry of the sphere-derived xenografts confirmed the presence of clear cell RCC with large areas of sarcomatoid dedifferentiation. Finally, we prove that the TGFβ receptor II, and the co-Smad Smad4 are possible direct targets of miR-17. Conclusions: The TGFβ-EMT axis likely contributes to the self-renewing potential of RCC spheres. miRNAs are differentially expressed in RCC spheres and miR-17 inhibition transformed ccRCC cells to highly tumorigenic RCC spheres.
Fluorescence in situ hybridization (FISH) and array-comparative genomic hybridization (a-CGH) from percutaneous needle biopsy compared to renal mass histology.
Authors: Spaliviero Massimiliano , Stratton Kelly Lynn , Donahue Timothy F. , Gowrishankar Banumathy , Ma Charles , Durack Jeremy C. , Solomon Stephen Barnett , Houldsworth Jane , Coleman Jonathan A. 
Published: February 2017

471 Background: Image-guided percutaneous needle biopsies are increasingly utilized for the diagnosis of renal tumors. Histologic diagnosis of renal mass subtypes, including malignant clear cell (ccRCC), papillary (pRCC), chromophobe (chrRCC) renal cell carcinoma, and benign oncocytomas (OC) can be challenging due to the low cellularity and damaged architecture of needle biopsy specimens. However, each subtype exhibits unique genetic aberrations that can assist in histologic classification and potentially assist in guiding management decisions. We report our initial experience correlating renal mass histology to subtype-associated genomic alterations detected by FISH and a-CGH of percutaneous needle biopsy specimens. Methods: In an ongoing IRB-approved blinded study, 17 samples obtained from 15 patients with known renal masses were submitted to FISH (FReCaD) and targeted a-CGH (UroGenRA-Kidney). Specimens were classified using a subtype classification decision tree algorithm based on the presence/absence of genomic abnormalities. The results were compared to biopsy histology or surgical specimen when available. Results: Histology revealed ccRCC in 6 patients, pRCC in 4, OC in 2, Angiomyolipoma in 1, and unclassified type RCC in 2. In 6 of 9 cases FISH achieved a diagnosis, which correlated with histology in 4. FISH incorrectly classified as ccRCC two cases with pRCC on histology. A-CGH was diagnostic in 14 of 15 cases and correlated with histology in 13. In one case, a-CGH showed a genomic profile not consistent with ccRCC, pRCC, chrRCC, or OC according to the algorithm. Conclusions: The addition of genetic tumor tissue studies to complement histology from biopsy tissues may supplement or improve the accuracy of classification and biological characterization of renal tumor biopsies and influence treatment planning. In our initial experience, a-CGH showed better correlation with histology in subtype classification of malignant and benign renal masses than FISH. Prospective testing will be required to validate these results.
Use of preoperative C-reactive protein to improve predictive accuracy in clear cell renal cell carcinoma.
Authors: Kruck Stephan , Chun Felix K. , Merseburger Axel S. , Tezval Hossein , Scharpf Marcus , Kasprzyk Kathrin , Schilling David , Sievert Karl-Dietrich , Stenzl Arnulf , Bedke Jens 
Published: February 2017

474 Background: White blood cell count (WBC) and C-reactive protein (CRP) are reliable biomarkers in clear cell renal cell carcinoma (ccRCC). Nevertheless, accepted cut-offs values for risk stratifications are missing. This study re-evaluated the prognostic and predictive significance of preoperatively WBC and CRP that independently predicts patient prognosis and to determine optimal cut-off values for CRP. Methods: 327 patients with surgery for ccRCC were retrospectively evaluated from 1996 to 2005. Cox-proportional hazard models were used, adjusted for the effects of tumor stage, tumor size, Fuhrman grade, and Karnofsky-Index; and to evaluate the prognostic significance of WBC and CRP; and to identify cut-off values. Identified cut-offs were correlated with clinico-pathological parameters and used to estimate cancer-speciﬁc survival (CSS). To prove any additional predictive accuracy of the identified cut-off it was compared to a clinico-pathological base model using Harrell c-index. Results: In univariable analyses WBC was a significant prognostic marker at a concentration of 9.5/µl (HR: 1.83) and 11.0/µl (HR: 2.09) and supported a CRP value of 0.25 mg/dL (HR: 6.47, p < 0.001) and 0.5mg/dL (HR: 7.15, p < 0.001) as potential cut-off values. If adjusted by the multivariable models WBC showed no clear breakpoint, but a CRP-value of 0.25mg/dL (HR: 2.80, p = 0.027) proved to be optimal. Reduced CSS was proven for CRP 0.25 mg/dL (median: 69.9 vs. 92.3 months). Median follow-up was 57.5 months with 72 (22%) tumor related deaths. The final model built by the addition of CRP 0.25mg/dL did not improve predictive accuracy (c-index = 0.877) than compared to the clinico-pathological base model (c-index =0.881) which included TNM-stage, grading and Karnofsky-Index. Conclusions: Multivariable analyses revealed an optimal breakpoint of CRP at a value of 0.25mg/dL best to stratify patients at risk of cancer-specific mortality, but CRP 0.25mg/dL added no additional information in the prediction model. Therefore we cannot recommend to measure CRP as the traditional parameters of TNM-stage, grading and Karnofsky-Index were already of high predictive accuracy.
Outcomes of patients with metastatic renal cell cancer treated with sunitinib in clinical practice at a reference cancer centre in Manchester, United Kingdom.
Authors: Galvis Victoria , Lawrence Dionne , Howell Matthew , Thistlethwaite Fiona , Hawkins Robert E. 
Published: February 2017

477 Background: The development of anti-angiogenic therapy produced a change in the treatment of metastatic renal cancer (mRCC). There are now a range of drugs available with sunitinib being the most widely used first-line anti-angiogenic therapy. In the United Kingdom, until the advent of pazopanib it was the only such drug routinely funded by the NHS. The aim of this study was to audit the clinical outcomes of patients on routine treatment with sunitinib, to compare them with those obtained on trials and to analyze different subsets of patients. Methods: A database of mRCC patients treated at The Christie was set up to record clinical outcomes. Long-term follow-up data is available. Here we present a detailed analysis of 395 patients treated with sunitinib as a first-line anti-angiogenic therapy from 2005 to 2012. 397 patients treated out of a clinical trial. The outcomes were analysed according to various prognostic features. Results: The median OS of all patients audited was 18 months (m) with a PFS of 10.5m. This included clear cell RCC (n=305) and non-clear cell RCC (n=52). OS of clear cell RCC patients who received treatment second-line after cytokine therapy failure was 20.5m, longer than those treated first line 18.6m. This may be because we offer High-Dose IL2 to selected patients and these patients have a longer OS (24m) measured from the start of sunitinib. Baseline performance status was a predictor of outcome with OS being 23.5m for WHO PS 0/1 and 5.9m for WHO PS 2/3. Elderly age was not a predictor of poor outcome as the OS of patients <60, 60-70, and >70 was 15, 23, and 22m respectively. Time from nephrectomy to treatment with sunitinib had an influence on outcome with OS being 15, 24, and 48m for those <1, 1-5, and >5 years since nephrectomy. Further detailed analysis will be presented. Conclusions: Overall, the outcomes of patients treated in routine clinical practice were very similar to comparable groups treated on trials. Interestingly, the outcome post cytokine patients were particularly good but this may reflect particularly, careful choice of patients who receive cytokines since 2008.
Validation of a genomic classifier that predicts metastatic disease progression in men with biochemical recurrence post radical prostatectomy.
Authors: Ross Ashley E. , Ghadessi Mercedeh , Davicioni Elai , Crisan Anamaria , Buerki Christine , Erho Nicholas , Mitra Anirban Pradip , Thompson Darby J. S. , Triche Timothy J. , Schaeffer Edward M , Feng Felix Yi-Chung 
Published: February 2017

52 Background: The majority of the 29,000 men who die annually from prostate cancer present initially with localized disease and develop biochemical recurrence (BCR) following radical prostatectomy (RP). While the post-RP recurrence group of patients is highly enriched for those who will develop lethal disease, many of these patients will experience BCR without subsequent metastases. Thus, there is a clear need to improve patient risk stratification in this context. Here, we evaluate Decipher, a genomic classifier (GC) in men with BCR for its ability to predict metastasis. Methods: The 22-feature GC model was validated in a prospectively designed case-cohort study of a clinically high-risk population of 1,010 RP patients treated at Mayo Clinic between 2000-06. A random sample of 20% of this population was subjected to microarray analysis and GC scores were generated for 219 patients, including 110 who developed BCR post RP. The c-index for predicting metastatic disease progression (i.e., positive bone or CT scans), Cox modeling, decision curves and multivariable analyses were used to compare the performance of GC to Gleason score (GS), PSA doubling time (PSAdT) and time to BCR (ttBCR). Results: The c-index for predicting metastatic disease progression 3 years after BCR was 0.82 (95% CI, 0.80-0.90) for GC, which compared favorably to GS 0.65 (0.54-0.69), PSAdT 0.60 (0.62-0.78) and ttBCR 0.54 (0.64-0.81). Decision curve analysis showed that GC had a higher overall ‘net benefit’ compared to GS, PSAdT and ttBCR for risk of metastasis. Cumulative incidence of metastasis 3 years after BCR was 9% versus 43% (p<0.001) for patients with low and high GC scores, respectively. In multivariable modeling with clinicopathologic variables, GC (p<0.001) and GS (p=0.02) scores remained the only significant predictors of metastasis. Conclusions: When compared to clinicopathologic variables, GC better predicted metastatic progression among our cohort of men with BCR following RP. While confirmatory studies in additional patient populations are required, these results suggest that use of GC can allow for better selection of men requiring additional treatment at the time of BCR.