bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contrast enhanced CT (CE-CT) changes and nephrometry down-scoring of unresectable primary renal cell carcinoma (RCC) tumors in patients (Pts) treated with neoadjuvant sunitinib.
Authors: Salem M. , Shah S. N. , Wood L. S. , Elson P. , Medsinge A. , Campbell S. , Rini B. I. 
Published: February 2017

299 Background: The impact of neoadjuvant sunitinib on CE-CT parameters and nephrometry score of primary RCC tumors remains unknown. Methods: Retrospective review of baseline and prenephrectomy CE-CT from a prospective phase II trial of neoadjuvant sunitinib (50 mg sunitinib continuous dosing) in unresectable primary RCC tumors with or without metastatic disease. CE-CT parameters and R.E.N.A.L. nephrometry score for each lesion were determined in pts who underwent subsequent surgery. RECIST and MASS criteria were used to assess primary tumor radiographic response. CT changes were analyzed using the sign test and Wilcoxon signed rank test. Results: Twenty nine pts were enrolled, of which 13 pts (85%M; median age 63y) underwent post-sunitinib resection of 16 primary tumors (3 pts had multifocal RCC). Post-therapy, 88% of tumors had decreased long diameter (median 32% decrease, p<0.001 vs. baseline), 88% decreased attenuation (median 30 HU reduction, p=0.006) and 69% increased necrosis (p=0.001). 56% of tumors had a decrease in nephrometry score (median 1 point decrease; 10 to 9, p=004). At baseline, 81% of tumors were highly complex by nephrometry score; following therapy 46% of the highly complex tumors became moderately complex. At baseline 13 tumors abutted renal hilar vital structures, whereas following treatment 4 tumors demonstrated abutment. Adenopathy decreased (range, 23%-83%) in 4/4 patients with enlarged baseline lymph nodes, with complete resolution in 1 patient. RECIST objective response was seen in 38% and SD in 56% of primary tumors; 1 tumor had PD based on size despite > 95% necrosis. MASS criteria response was favorable 38%, intermediate 62%. Two of four pts had reduction in extent of venous thrombus (1 pt from level 0 to resolved and 1 pt from level IV to II). Conclusions: Neoadjuvant sunitinib resulted in decreased size/attenuation, increased necrosis of the primary tumor and reduction in lymphadenopathy and venous thrombus in pts who underwent subsequent surgery. Sunitinib reduced the RENAL nephrometry score and facilitated nephrectomy, notably due to impact on tumor proximity to vital structures in the renal hilum. [Table: see text]
The relationship of HIF2 and the progression of PTEN-deficient mouse prostate tumors.
Authors: Kim W. Y. , Zhou B. , Thomas G. 
Published: February 2017

30 Background: The hypoxia-inducible factor (HIF) transcription factor has already cemented its oncogenic role in the development of renal cell carcinoma (RCC). However, its role in the tumorigenesis of other solid tumors remains unspecificed. Our studies focus on a novel link between HIF and prostate carcinogenesis. Methods: Using both in vitro cell culture studies as well as in vivo studies (orthotopic xenograft and genetically engineered mouse models) we investigate the role of HIF in prostate cancer cell proliferation, invasion, and progression. Results: Both HIF1 and HIF2 appear to be necessary for the proliferation and invasion of prostate cancer cell lines in vitro. Preliminary analysis of a PTEN deficient mouse model of prostate cancer suggests that expression of a stabilized form of HIF2 promotes the development of a larger prostate tumor burden and a more aggressive histology (high grade prostate intraepithelial neoplasia [PIN] at earlier stages). Moreover, PTEN-deficient prostate tumors producing HIF2 are more proliferative and vascular and express increased levels of genes associated with epithelial to mesenchymal transition (EMT). Conclusions: There has been much interest in the role of angiogenesis and hypoxia in prostate cancer progression. Our preliminary data suggest that HIF2 is able to promote PTEN-deficient prostate cancer progression in mice by increasing proliferation, angiogenesis, and EMT. No significant financial relationships to disclose.
Postoperative complications from cytoreductive nephrectomy after neoadjuvant targeted therapy for metastatic renal cell carcinoma.
Authors: Chapin B. F. , Delacroix S. E. , Culp S. H. , Gonzalez G. , Wood C. G. 
Published: February 2017

300 Background: Neoadjuvant treatment of metastatic renal cell carcinoma (RCC) with targeted systemic therapies is under investigation. Postoperative complications that occurred after cytoreductive nephrectomy (CRN) preceded by neoadjuvant systemic therapy were assessed. Methods: A retrospective review of all patients with clinical evidence of metastasis that underwent CRN was performed. Of 683 surgical patients with metastatic disease, 67 had received preoperative targeted therapy. Preoperative, operative, and postoperative characteristics were evaluated for each patient. Surgical complications were assessed using the modified Clavien system. A multivariate was sued to determine preoperative variables in an attempt to predict surgical complications within 1 year of CRN. Results: Complications occurred in 64% (43/67) of patients within 365 days of CRN. Clavien grade ≥ 3 complications occurred in 30% (20/67) patients. The most common occurrences were superficial wound dehiscence (25%), and wound infection (15%). On univariate analysis there were no statistically significant differences between groups in regards to age, race, gender, smoking history, follow-up, Charlson comorbidity index, MSKCC risk groups, or time from cessation of targeted therapy to surgery. Significant predictors of complications included BMI ≥ 30 (p=0.007), EBL (p=0.019), matted nodes (p=0.043), and surgical approach (p=0.001). Clinical T-stage and N-stage (p=0.068, p=0.073) approached significance. On multivariate analysis Charlson comorbidity index ≥ 8(OR 5.2, 95% CI 1.23, 21.99) and clinical N-stage (OR 5.11, 95%CI 1.21, 21.66) were significant predictors of postoperative complications. Conclusions: In this series of patients treated with neoadjuvant targeted therapy, a majority of patients experienced a postoperative complication after CRN. A Charlson comorbidity index ≥ 8 or clinical node positivity predicted for an increased risk of postoperative complications. The use of neoadjuvant systemic targeted therapy prior to CRN is investigational and adequate assessment of operative morbidity is needed prior to wide spread adoption. No significant financial relationships to disclose.
Comparison of low-temperature-sensitive liposome encapsulated docetaxel and doxorubicin in a murine model of prostate cancer.
Authors: Chokshi S. , Ranjan A. , Benjamin C. J. , Chung P. H. , Rastinehad A. , Dreher M. R. , Wood B. J. , Pinto P. A. 
Published: February 2017

31 Background: Low-temperature-sensitive liposomes (LTSLs) release their encapsulated drug into targeted tissue when activated by a source of hyperthermia. The efficacy of an LTSL formulation of docetaxel (DOC) or doxorubicin (DOX) was compared against prostate cancer in a xenograft mouse model. Methods: Under an approved IACUC protocol, Luciferase transfected human prostate PC-3M-luciferase cells were inoculated (3x106 cells) subcutaneously in the right hind leg of 8 wk old female athymic nude mice. When tumors reached a volume of 200–300 mm3, mice were randomized to receive one intravenous injection of saline, Stealth liposomal DOX (5 mg/kg), LTSL DOX (5 mg/kg), or LTSL DOC (15 mg/kg), with or without hyperthermia treatment (LTSL DOX and LTSL DOC were supplied by Celsion Corp., Columbia MD). Mice undergoing hyperthermia treatment were anesthetized and stabilized in a holder that allowed for only the leg with tumor to be heated to 41–42°C that triggered LTSL drug release. Mice were monitored daily for tumor volume and body weight. Study end-points included growth of tumor to 5x the initial treatment volume or monitoring of survival for 60 days. Results: The LTSL DOC delayed tumor growth longer (> 14 days) than DOX (0 day) and LTSL DOX (1 day) with hyperthermia (P<0.05). Mice treated with LTSL DOC and hyperthermia survived longest (60 days) compared to all other mice (range 6–8 days, P<0.05). LTSL in the setting of hyperthermia demonstrated complete regression of tumor in 57% of mice. Conclusions: LTSL DOC with hyperthermia delayed tumor growth more than all other treatments. Survival studies suggest LTSL DOC is a more effective temperature sensitive delivery system against PC-3M prostate tumors. No significant financial relationships to disclose.
Everolimus in patients with metastatic renal cell carcinoma (mRCC) who are intolerant of or have progressed after prior vascular endothelial growth factor receptor–tyrosine kinase inhibitor (VEGFr-TKI) therapy: An international expanded access program (EAP).
Authors: Grunwald V. , Bodrogi I. , Miller K. , Machiels J. H. , Lee S. , Chowdhury S. , Yuan R. , Rosamilia M. , Booth J. L. , Karakiewicz P. I. 
Published: February 2017

314 Background: The mammalian target of rapamycin (mTOR) inhibitor everolimus is the first agent to show efficacy in a randomized, controlled phase III trial in patients with mRCC after progression on VEGFr-TKIs (RECORD-1). Progression-free survival (PFS) was significantly improved (4.9 vs 1.9 months) and the risk of disease progression was reduced by 67% with everolimus compared with placebo. To fulfill an unmet medical need, everolimus was offered globally in this EAP. Presented here are preliminary results on 605 patients. Methods: The program began in July 2008 (ClinicalTrials.gov: NCT00655252 ; EudraCT: 2007-005460-28), and since then over 1,000 patients in 34 countries have been enrolled. Patients with clear cell and non–clear cell mRCC who failed or became intolerant of VEGFr-TKIs received daily oral doses of everolimus with investigator assessment every 3 months. Results: Data were collected for 605 patients who had discontinued treatment as of January 15, 2010. Evaluable patients had a mean age of 63 years, and most (94%) had progressed after prior VEGFr-TKI therapy. The adverse event (AE) profile did not differ significantly from that reported in the RECORD-1 trial. Most frequently reported grade 3–4 AEs were anemia (6.1%), stomatitis (4.6%), fatigue (4.6%), hyperglycemia (4.0%), and infection (3.6%). Grade 3–4 noninfectious pneumonitis was reported in 2.8%. Best overall response was stable disease, which was evident in 42% of patients. Conclusions: The EAP has allowed patients with mRCC access to everolimus before marketing approval. The rapid enrollment rate of this EAP confirms the unmet medical need after failure of VEGFr-TKIs. Everolimus has shown good tolerability, and no new safety issues have been identified. The investigator-assessed response rate is consistent with that reported in the RECORD-1 trial. The EAP provides an efficient framework for the development of other programs for innovative anticancer agents in patients without satisfactory therapeutic options. [Table: see text]
Incidence and risk of congestive heart failure risk in renal cell cancer (RCC) and non-RCC patients treated with sunitinib.
Authors: Richards C. J. , Je Y. , Schutz F. A. , Dallabrida S. M. , Moslehi J. J. , Choueiri T. K. 
Published: February 2017

316 Background: Sunitinib is a multitargeted receptor tyrosine kinase inhibitor that is widely used in the treatment of renal cell cancer (RCC) and several other malignancies. Congestive heart failure (CHF) has been reported with sunitinib, but the overall incidence and relative risk (RR) remain undefined. We preformed an up-to-date comprehensive meta-analysis to determine the risk of developing serious CHF in patients with both RCC and non-RCC tumors treated with sunitinib. Methods: Medline databases were searched for articles from January 1966 to September 2010. Eligible studies were limited to phase II and III trials of sunitinib in cancer patients with any primary tumor type and adequate safety profile reporting. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI), using random-effects models. Results: A total of 5,497 patients were included. Overall incidence for all-grade and high-grade CHF in sunitinib-treated patients was 4.9% (95% CI, 1.6–14.1%) and 1.8% (95% CI, 0.8–3.9%), respectively. The RR of all-grade and high-grade CHF in sunitinib-treated patients compared to placebo-treated ones was 1.81 (95% CI, 1.30–2.50; p<0.0001) and 3.17 (95% CI, 1.12–8.97; p=0.030), respectively. On subgroup analysis there was no difference observed in the CHF incidence for RCC vs. non-RCC patients. No evidence of publication bias was observed. Conclusions: This is the first comprehensive report to demonstrate that sunitinib use is associated with an increased risk of significant heart failure in cancer patients. [Table: see text]
Effect of angiotenstin system inhibitors (ASIs) on the outcome of sunitinib treatment (tx) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Keizman D. , Huang P. , Eisenberger M. A. , Pili R. , Kim J. J. , Hammers H. J. , Carducci M. A. 
Published: February 2017

317 Background: The VEGFR inhibitor sunitinib is a standard tx for mRCC. ASIs include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). ASIs are used in the tx of hypertension (HTN), kidney disease, and heart failure. Preclinical and clinical studies in several cancer types have shown that they may inhibit tumor growth. Their effect on the outcome of sunitinib in mRCC is poorly defined. Aims: to study the effect of ASIs on the outcome sunitinib tx for mRCC. Methods: We performed a retrospective study of an unselected cohort of pts with mRCC, who were treated with 50 mg of oral sunitinib in cycles of 4 weeks followed by 2 weeks of rest. Pts were divided into 2 groups: (1) ASIs users and (2) ASIs naive. The effect of ASIs use on objective response, time to progression (TTP), and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chisquare test and partial likelihood test from cox model. Results: Between 2004–2010, 124 pts with mRCC were treated with sunitinib. There were 44 ASIs users (group 1) and 80 nonusers (group 2). With regard to sunitinib tx initiation time, 39 users started ASIs before, 3 within 1 month, and 2 after 5 months. The groups were balanced regarding the following known clinical prognostic factors: past nephrectomy, RCC histology, time from diagnosis to tx, ≥ 2 metastatic sites, lung/liver/bone metastasis, ECOG performance status, Hb level, corrected ca > 10 mg/dL, platelets count, prior cytokines/ targeted tx, sunitinib induced HTN, % pts that had dose reduction/tx interruption, and mean dose/cycle. Objective response in group 1 vs. 2 was partial response (PR) 48% vs 38% (p=0.24), stable disease (SD) 38% both, and progressive disease (PD) 14% vs. 24% (p=0.19). Median TTP was 12 vs. 6 ms (HR 0.635 in ASIs users, p=0.034). Median OS was 25 vs. 22 ms (p=0.3). Conclusions: ASIs may improve the outcome of pts with mRCC that are treated with sunitinib. This should be investigated prospectively, and if validated, applied in clinical practice and clinical trials. No significant financial relationships to disclose.
Stimulation of prostate cancer cell proliferation by bone-derived factors.
Authors: Sluka P. , Whitty G. , Davis I. D. 
Published: February 2017

32 Background: Interactions between cancer cells and their microenvironment affect the establishment and metastasis of cancer. The most common site of prostate cancer (PC) metastasis is bone. This study examined the effects of selected factors known to be produced by bone stroma (EGF, aFGF, HGF, β-NGF, TGF-β, and TNFα) on the proliferation of PC cells. The effect of cell culture medium (CM) conditioned by osteoblasts (OBCM) was also examined. Methods: The PC-derived cell lines PC3, LNCaP, and DU145 were used. Expression of receptors for the above-mentioned cytokines was assessed using real-time RT-PCR. After 5 days of continuous cytokine treatment, proliferation was assessed by MTS conversion, and cell survival and apoptosis was assessed by 7-AAD staining and flow cytometry. OBCM was generated using the HOS, MG63, and SaOs2 cell lines. CM from the HT1080 fibrosarcoma cell line was used as a non-bone control. Results: The PC cell lines expressed receptors for all of the cytokines examined at the mRNA level. LNCaP cell proliferation was increased by aFGF and decreased by TGF-β. Treatment with TNFα decreased proliferation of all PC cell lines. These effects were not due to apoptosis. EGF, HGF, and β-NGF did not affect proliferation of any line despite receptor expression. OBCM increased proliferation of PC3 and DU145 cells but not LNCaP cells, while HT1080 CM did not affect proliferation of any line. Conclusions: PC cells are able to respond to defined bone-derived factors and that the nature of this response varies between individual cancers. Acidic FGF increased proliferation of LNCaP cells while TGF-β and TNFα decreased proliferation of LNCaP and all cell lines, respectively; an effect not mediated by apoptosis. Current studies are examining the effect of these cytokines on other functional parameters (cell survival, adhesion and migration) and on primary PC epithelial cells. No significant financial relationships to disclose.
Comparison of partial nephrectomy for tumors greater than 7 cm to radical nephrectomy and effect on overall survival.
Authors: Vourganti S. , Linehan W. , Bratslavsky G. 
Published: February 2017

323 Background: As growing evidence indicates the importance of renal functional preservation, there is an increased utilization of partial nephrectomy (PN) performed for small renal masses (SRM). The optimal cutoff size for PN has been based on historical observation of low metastatic rates for SRM and increasing metastatic potential with increase in size of the primary tumor. We aim to evaluate the outcomes of patients treated by PN or radical nephrectomy (RN) for tumors greater than 7 cm. Methods: SEER 17 database was queried to identify patients treated for kidney tumors between 1983 and 2007. We excluded cases treated for non-RCC histology, not treated surgically, and those without specified size. Patients were included if treated by PN or RN with tumor size between 7 and 20 cm. Demographic information included age, gender, and race. The comparison of RCC-specific and overall survival was performed for the entire cohort and stratified by SEER stage (localized, regional, or distant). The survival was compared using Kaplan-Meier method with log rank test to identify significant differences. Results: We identified a total of 18,927 patients treated for RCC that included 18,575 cases of RN and 352 treated with PN. There were no differences in age, gender, or race (Caucasian vs. non-Caucasian) between patients treated by RN or PN (p>0.05). The mean size for tumors treated by PN was 9.7 cm vs. 10.2 cm for RN (p<0.01) and there was more localized disease in the PN group (p<0.01). The overall median survival for patients treated with PN was 108 months vs. 80 months for patients treated with RN (p<0.01). The cancer-specific survival for the entire cohort treated with PN was 195 months vs. 145 months for RN (p<0.01). When stratified by stage, there were no differences in the cancer specific survival between PN and RN groups (p>0.05). Conclusions: PN for tumors 7 to 20 cm is not associated with inferior oncologic outcomes but may provide survival advantage. While patient selection may have influenced overall survival outcomes, PN may provide survival advantage by maximizing renal reserve. These findings may be best answered in a randomized trial to establish if there should be a size cutoff for nephron sparing surgery. No significant financial relationships to disclose.
Effect of routine ipsilateral adrenalectomy on cancer-specific survival and risk of adrenal insufficiency for patients with pT3/4 renal cell carcinoma.
Authors: Weight C. J. , Kim S. P. , Thompson R. H. , Boorjian S. A. , Leibovich B. C. 
Published: February 2017

324 Background: The indications for the removal of the ipsilateral adrenal gland in patients with renal cell cancer (RCC) have not been well defined. Most continue to advocate ipsilateral adrenalectomy in patients with risky features such as a tumor thrombus, large, locally advanced tumors, and/or upper pole tumors. We evaluated the oncologic outcomes of concurrent adrenalectomy with either partial (PN) or radical nephrectomy (RN) in a large single institution cohort. Methods: From 1970–2006, 4,019 consecutive patients with RCC treated by RN (n=3,107) or PN (n=912) from Mayo Clinic were studied for adrenal involvement. Risk of asynchronous adrenal metastasis and cancer specific survival (CS) were also compared between those who underwent concomitant adrenalectomy (n=1,464) and those who did not (n=2,555) using multivariate cox models. Results: Median postoperative follow-up was 6 years. Synchronous ipsilateral adrenal involvement was rare even for those with large (>7cm) tumors (2.5%), upper pole (1.3%), and locally advanced (pT3/4) tumors (3.5%). The development of asynchronous adrenal metastasis occurred in 109 patients (2.7%) at a median of 3.7 years after initial surgery. The risk of developing an ipsilateral (1.4% 95% CI 0.8, 2.0) vs. contralateral (1.8% 95% CI 1.0, 2.6) asynchronous adrenal metastasis was equivalent at 10 years, in those who did not undergo adrenalectomy at initial surgery. At 10 years, 7.3% (99% CI: 4.4, 10.2) of patients with higher stage tumors (pT3/4) are predicted to develop a contralateral adrenal metastasis. On multivariate analysis, routine adrenalectomy was associated with a decreased risk of subsequent adrenal metastasis (HR 0.88: 99% CI 0.81, 0.95), but did not significantly impact CS (HR 1.15: 99% CI 0.99, 1.34). Conclusions: Asynchronous metastasis can usually be salvaged without apparent effect on CS. Ipsilateral adrenal involvement from RCC was uncommon even in large, locally advanced, and/or upper pole tumors. Routine adrenalectomy in these high risk patients may lead to an unacceptably high rate of adrenal insufficiency when a significant subset develops a contralateral adrenal metastasis. No significant financial relationships to disclose.