Showing papers by "Paul Nathan published in 2011"
TL;DR: CT texture analysis reflecting tumor heterogeneity is an independent factor associated with time to progression and has potential as a predictive imaging biomarker of response of metastatic renal cancer to targeted therapy.
Abstract: Purpose: To assess the changes in tumor CT texture following 2 cycles of TKIs; and to determine if tumor texture correlates with measured time to progression in metastatic renal cell cancer treated with TKIs
Materials and Methods: Institutional review board waiver was obtained for this retrospective analysis Contrast enhanced CT texture parameters were assessed in 39 patients with metastatic renal cell cancer treated with a TKI 87 metastases were analysed at baseline and following 2 cycles of treatment: changes in tumor entropy and uniformity, derived using a software algorithm that selectively filters and extracts texture at different scales (fine to coarse detail: 10 to 25), were recorded Response assessment was also obtained using RECIST, Choi and modified Choi criteria The correlation of texture parameters and standard criteria to measured time to progression was assessed by Kaplan-Meier analysis and a Cox regression model Statistical significance was set at 5%
Results: Tumor entropy decreased by 3-45% and uniformity increased by 5-21% for the different scale values following TKI treatment Using a threshold change of ≤-2% for uniformity at a coarse scale value of 25, Kaplan Meier curves of the proportion of patients without disease progression were significantly different, and better than for standard response assessment (p=0008 versus p=0267, p=0053, p=0042 for RECIST, Choi, and Modified Choi criteria respectively) Cox regression analysis showed that texture uniformity was an independent predictor of time to progression (odds ratio, OR =402; 95% CI 152,1065; p=0005)
Conclusion: CT texture analysis, reflecting tumor heterogeneity, is an independent factor associated with time to progression, and has potential as a predictive imaging biomarker of response of metastatic renal cancer to targeted therapy
325 citations
TL;DR: Testing the hypothesis that sequential 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a correlative marker in metastatic clear cell renal cancer (mRCC) yields prognostic significant data found responses occur in the majority of patients after 4 weeks of therapy but it is not until 16 weeks when the results become prognostically significant.
Abstract: Purpose: To test the hypothesis that sequential 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a correlative marker in metastatic clear cell renal cancer (mRCC), patients were treated with sunitinib. Three sequential scans were conducted to determine whether the timing of the investigation was relevant. Experimental Design: Forty-four untreated mRCC patients were enrolled into this prospective phase II study. 18 F-FDG-PET/CT scans were conducted before ( n = 44) and after 4 weeks ( n = 43) and 16 weeks ( n = 40) of sunitinib given at standard doses. The primary endpoint was to correlate FDG-PET/CT response (20% reduction in SUV max ) at 4 and 16 weeks with overall survival (OS). Results: Forty-three (98%) patients had FDG-PET/CT avid lesions at diagnosis (median SUV max = 6.8, range: max and an increased number of PET-positive lesions correlated with shorter OS [HR: 3.30 (95% CI: 1.36–8.45) and 3.67 (95% CI: 1.43–9.39), respectively]. After 4 weeks of sunitinib, a metabolic response occurred in 24 (57%) patients, but this did not correlate with progression-free survival (HR for responders = 0.87; 95% CI: 0.40–1.99) or OS (HR for responders = 0.80; 95% CI: 0.34–1.85). After 16 weeks of treatment, disease progression on FDG-PET/CT occurred in 28% ( n = 12) patients which correlated with a decreased OS and PFS [HR = 5.96 (95% CI: 2.43–19.02) and HR = 12.13 (95% CI: 3.72–46.45), respectively]. Conclusions: Baseline FDG-PET/CT yields prognostic significant data. FDG-PET/CT responses occur in the majority of patients after 4 weeks of therapy; however, it is not until 16 weeks when the results become prognostically significant. Clin Cancer Res; 17(18); 6021–8. ©2011 AACR .
118 citations
TL;DR: Upfront sunitinib prior to planned nephrectomy in intermediate-risk disease is associated with a median survival of >2 yr despite frequent progression during treatment break, and progression in metastatic sites prior toplanned surgery and MSKCC poor- risk disease was associated withA poor outcome.
104 citations
TL;DR: The current understanding of targeted therapy in renal cancer is addressed, including the identification of correlative biomarkers and mechanisms of drug resistance and the major areas of clinical research that will report over the next few years.
Abstract: Targeted therapy has radically altered the way metastatic renal cancer is treated. Six drugs are now licensed in this setting, with several other agents under evaluation. Sunitinib is currently the most widely used in the first line setting with impressive efficacy and an established toxicity profile. However, as further randomised studies report and as newer drugs become available this may change. In this review, we address our current understanding of targeted therapy in renal cancer. We also discuss areas in which our knowledge is incomplete, including the identification of correlative biomarkers and mechanisms of drug resistance. Finally, we will describe the major areas of clinical research that will report over the next few years.
53 citations
TL;DR: Oral sorafenib combined with dacarbazine had acceptable toxicity and some antineoplastic activity against metastatic melanoma in patients with metastatic, histologically confirmed melanoma.
Abstract: Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies
40 citations
9 citations
TL;DR: Evaluating the efficacy of nilotinib in KIT mutated advanced mucosal and acral melanoma with a primary endpoint of progression free survival at 6 months and possible mechanisms of resistance by analysis of biopsies obtained at disease progression is evaluated.
Abstract: TPS229 Background: Recent studies have indicated that KIT mutations occur in approximately 20% of acral and mucosal melanomas (Curtin, al. 2006; Beadling, et al. 2008). Several case reports have sh...
3 citations
TL;DR: HPCs are over expressed in the peripheral blood in the majority of patients with mRCC and higher levels are associated with poor prognosis, which was not the case for IGF-1 levels.
2 citations
01 Jan 2011
TL;DR: Poster: "ECR 2011 / C-1405 / Whole-Body Diffusion Weighted MRI (WB-DWI) in the Assessment of Bony Metastatic Disease and Treatment Response" by: "A. Gogbashian, A. R. Padhani, J. Juttla, S. d'sa, P. Nathan, A Makris; Northwood, Middlesex/UK"
Abstract: Poster: "ECR 2011 / C-1405 / Whole-Body Diffusion Weighted MRI (WB-DWI) in the Assessment of Bony Metastatic Disease and Treatment Response" by: "A. Gogbashian, A. R. Padhani, J. K. Juttla, S. d'sa, P. Nathan, A. Makris; Northwood, Middlesex/UK"
1 citations
TL;DR: Baseline FDG PET prior to sunitinib yields prognostically significant data, which is not the case at 4 weeks, but subsets of patients with a poor prognosis at 16 weeks could be investigated within the context of a randomized clinical trial.
Abstract: 301 Background: The purpose of this study was to investigate sequential FDG PET-CT as a correlative marker in metastatic clear cell renal cancer (mRCC) patients treated with first line sunitinib. Three sequential scans were performed to determine the importance of the timing of scans. Methods: Forty-four untreated mRCC patients with MSKCC intermediate risk and poor risk disease were enrolled into a prospective study. FDG PET-CT scans were performed before (n=44), after 4 weeks (n=43) and 16 weeks (n=40) of sunitinib given at standard doses as the translational aspect of this trial (NCT01024205). The primary endpoint was to determine whether 18F-FDG PET-CT response (defined as a 20% reduction in SUVmax) correlated with survival. Results: Forty-three (98%) patients had FDG PET-CT avid lesions at diagnosis (median SUVmax 6.8 range: <2.5–18.4). In multivariate analysis a high SUVmax and increased number of PET positive lesions correlated with worse overall survival (OS) (HR: 3.30 (95%CI: 1.36–8.45) and 3.67 (...
1 citations
TL;DR: Dose reduction was the most commonly used form of trx modification for AEs in comparison to trx interruption or trx discontinuation, and the results suggest that SU tolerability is a challenge for clinicians in the treatment of advanced RCC pts.
Abstract: e15150 Background: This study evaluated the rates of and reasons for trx modifications and occurrence of adverse events (AEs) amongst pts treated with the angiogenesis inhibitor (AI) SU in UK clinical practice. Methods: Data from medical records were retrospectively abstracted at three large UK oncology centers for advanced RCC pts who were ≥18 years and received SU (N=132) as 1st-line AI trx from 1/1/2005 to 11/15/2010; prior cytokine therapy was permitted. The proportion of pts and reasons for trx modification, i.e. discontinuation, interruption, or dose change were determined. Timing of trx modifications and the proportion of pts with all grade and grade 3/4 AEs were also determined. Data on clinician assessed response rates were collected. Results: 91% of pts had not received cytokine therapy. Mean daily dose over initial cycle was 31.23 mg; 73.5% of pts started trx with dosing of 50 mg QD 4/2. Tumor response assessments were available for 96 pts among which 38.5% had an objective response (complete o...
21 Mar 2011