Sequential FDG-PET/CT as a Biomarker of Response to Sunitinib in Metastatic Clear Cell Renal Cancer

Kayani, Irfan; Avril, Norbert; Bomanji, Jamshed; Chowdhury, Simon; Rockall, Andrea; Sahdev, Anju; Nathan, Paul; Wilson, Peter; Shamash, Jonathan; Sharpe, Kevin; Lim, Louise; Dickson, John; Ell, Peter J.; Reynolds, Andrew R.; Powles, Thomas

doi:10.1158/1078-0432.ccr-10-3309

Cited by 119 publications

(86 citation statements)

References 20 publications

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“…A correlation between the primary renal lesion and the metastatic sites was examined. The correlation between changes in SUV and outcome in this population had been previously published (22).…”

Section: Radiologic and Fdg-pet-ct Assessmentmentioning

confidence: 89%

The Effect of VEGF-Targeted Therapy on Biomarker Expression in Sequential Tissue from Patients with Metastatic Clear Cell Renal Cancer

Sharpe

Stewart

Mackay

et al. 2013

Clinical Cancer Research

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Purpose: To investigate how biologically relevant markers change in response to antiangiogenic therapy in metastatic clear cell renal cancer (mRCC) and correlate these changes with outcome.Experimental Design: The study used sequential tumor tissue and functional imaging (taken at baseline and 12-16 weeks) obtained from three similar phase II studies. All three studies investigated the role of VEGF tyrosine kinase inhibitors (TKI) before planned nephrectomy in untreated mRCC (n ¼ 85). The effect of targeted therapy on ten biomarkers was measured from sequential tissue. Comparative genomic hybridization (CGH) array and DNA methylation profiling (MethylCap-seq) was performed in matched frozen pairs. Biomarker expression was correlated with early progression (progression as best response) and delayed progression (between 12-16 weeks).Results: VEGF TKI treatment caused a significant reduction in vessel density (CD31), phospho-S6K expression, PDL-1 expression, and FOXP3 expression (P < 0.05 for each). It also caused a significant increase in cytoplasmic FGF-2, MET receptor expression in vessels, Fuhrman tumor grade, and Ki-67 (P < 0.05 for each). Higher levels of Ki-67 and CD31 were associated with delayed progression (P < 0.05). Multiple samples (n ¼ 5) from the same tumor showed marked heterogeneity of tumor grade, which increased significantly with treatment. Array CGH showed extensive intrapatient variability, which did not occur in DNA methylation analysis.Conclusion: TKI treatment is associated with dynamic changes in relevant biomarkers, despite significant heterogeneity in chromosomal and protein, but not epigenetic expression. Changes to Ki-67 expression and tumor grade indicate that treatment is associated with an increase in the aggressive phenotype of the tumor.

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Section: Radiologic and Fdg-pet-ct Assessmentmentioning

confidence: 89%

The Effect of VEGF-Targeted Therapy on Biomarker Expression in Sequential Tissue from Patients with Metastatic Clear Cell Renal Cancer

Sharpe

Stewart

Mackay

et al. 2013

Clinical Cancer Research

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“…PET CT has increasingly been implemented in the diagnosis and monitoring of RCC 4. Furthermore, PET CT has been shown to be invaluable in monitoring progression of local and metastatic RCC and been shown to be more accurate than conventional CT imaging 5 6Patient's perspective

I have been diagnosed with a very rare testicular tumour which has not been reported before.

…”

Section: Discussionmentioning

confidence: 99%

Primary clear cell carcinoma of the rete testis: 1st report

et al. 2015

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SUMMARYPrimary tumours of the rete testis, either benign or malignant, are very rare. Such lesions require careful scrutiny including immunohistochemical analysis to exclude malignant lesions such as mesothelioma or papillary serous carcinoma. To the best of our knowledge this is the first report of a primary clear cell carcinoma of the rete testis. The possibility of a primary renal cell carcinoma or other primary site with metastatic spread to rete testis was excluded by thorough clinical and radiological work-up. BACKGROUND

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“…A recent investigation using this technique before and after a one-month treatment successfully predicted progression-free survival (PFS) in patients with mRCC [6], but a similar study could only predict overall survival (OS) [7] after 4 months treatment. In both cases the maximal standardized uptake (SUVmax) was the sole FDG-PET parameter utilized as an indicator of metabolism.…”

Section: Introductionmentioning

confidence: 99%

Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma

et al. 2014

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BackgroundTo determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression- free patient survival.MethodsThirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression- free survival.ResultsThirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression- free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively).ConclusionsAssessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression- free and overall survival in patients with mRCC.

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Sequential FDG-PET/CT as a Biomarker of Response to Sunitinib in Metastatic Clear Cell Renal Cancer

Cited by 119 publications

References 20 publications

The Effect of VEGF-Targeted Therapy on Biomarker Expression in Sequential Tissue from Patients with Metastatic Clear Cell Renal Cancer

The Effect of VEGF-Targeted Therapy on Biomarker Expression in Sequential Tissue from Patients with Metastatic Clear Cell Renal Cancer

Primary clear cell carcinoma of the rete testis: 1st report

Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma

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