FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer

James L. Chen*, Daniel E. Appelbaum, Masha Kocherginsky, Charles L. Cowey, Wendy Kimryn Rathmell, David F. Mcdermott, Walter M. Stadler

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The mTOR (mammalian target of rapamycin) inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and delays renal cell carcinoma (RCC) progression. Preclinical evidence suggests that baseline elevated tumor glucose metabolism as quantified by FDG-PET ([18F] fluorodeoxy-glucose positron emission tomography) may predict antitumor activity. Metastatic RCC (mRCC) patients refractory to vascular endothelial growth factor (VEGF) pathway inhibition were treated with standard dose everolimus. FDG-PET scans were obtained at baseline and 2 weeks; serial computed tomography (CT) scans were obtained at baseline and every 8 weeks. Maximum standardized uptake value (SUVmax) of the most FDG avid lesion, average SUVmax of all measured lesions and their corresponding 2-week relative changes were examined for association with 8-week change in tumor size. A total of 63 patients were enrolled; 50 were evaluable for the primary endpoint of which 48 had both PET scans. Patient characteristics included the following: 36 (72%) clear cell histology and median age 59 (range: 37-80). Median pre- and 2-week treatment average SUVmax were 6.6 (1-17.9) and 4.2 (1-13.9), respectively. Response evaluation criteria in solid tumors (RECIST)-based measurements demonstrated an average change in tumor burden of 0.2% (-32.7% to 35.9%) at 8 weeks. Relative change in average SUVmax was the best predictor of change in tumor burden (all evaluable P = 0.01; clear cell subtype P = 0.02), with modest correlation. Baseline average SUVmax was correlated with overall survival and progression-free survival (PFS) (P = 0.023; 0.020), but not with change in tumor burden. Everolimus therapy decreased SUVs on follow-up PET scans in mRCC patients, but changes were only modestly correlated with changes in tumor size. Thus, clinical use of FDG-PET-based biomarkers is challenged by high variability.

Original languageEnglish (US)
Pages (from-to)545-552
Number of pages8
JournalCancer medicine
Volume2
Issue number4
DOIs
StatePublished - Jan 1 2013

Fingerprint

Renal Cell Carcinoma
Positron-Emission Tomography
Biomarkers
Glucose
Tumor Burden
Neoplasms
Therapeutics
Sirolimus
Metabolic Networks and Pathways
Vascular Endothelial Growth Factor A
Disease-Free Survival
Histology
Tomography
Cell Proliferation
Everolimus
Survival
Growth

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Chen, J. L., Appelbaum, D. E., Kocherginsky, M., Cowey, C. L., Kimryn Rathmell, W., Mcdermott, D. F., & Stadler, W. M. (2013). FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer. Cancer medicine, 2(4), 545-552. https://doi.org/10.1002/cam4.102
Chen, James L. ; Appelbaum, Daniel E. ; Kocherginsky, Masha ; Cowey, Charles L. ; Kimryn Rathmell, Wendy ; Mcdermott, David F. ; Stadler, Walter M. / FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer. In: Cancer medicine. 2013 ; Vol. 2, No. 4. pp. 545-552.
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abstract = "The mTOR (mammalian target of rapamycin) inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and delays renal cell carcinoma (RCC) progression. Preclinical evidence suggests that baseline elevated tumor glucose metabolism as quantified by FDG-PET ([18F] fluorodeoxy-glucose positron emission tomography) may predict antitumor activity. Metastatic RCC (mRCC) patients refractory to vascular endothelial growth factor (VEGF) pathway inhibition were treated with standard dose everolimus. FDG-PET scans were obtained at baseline and 2 weeks; serial computed tomography (CT) scans were obtained at baseline and every 8 weeks. Maximum standardized uptake value (SUVmax) of the most FDG avid lesion, average SUVmax of all measured lesions and their corresponding 2-week relative changes were examined for association with 8-week change in tumor size. A total of 63 patients were enrolled; 50 were evaluable for the primary endpoint of which 48 had both PET scans. Patient characteristics included the following: 36 (72{\%}) clear cell histology and median age 59 (range: 37-80). Median pre- and 2-week treatment average SUVmax were 6.6 (1-17.9) and 4.2 (1-13.9), respectively. Response evaluation criteria in solid tumors (RECIST)-based measurements demonstrated an average change in tumor burden of 0.2{\%} (-32.7{\%} to 35.9{\%}) at 8 weeks. Relative change in average SUVmax was the best predictor of change in tumor burden (all evaluable P = 0.01; clear cell subtype P = 0.02), with modest correlation. Baseline average SUVmax was correlated with overall survival and progression-free survival (PFS) (P = 0.023; 0.020), but not with change in tumor burden. Everolimus therapy decreased SUVs on follow-up PET scans in mRCC patients, but changes were only modestly correlated with changes in tumor size. Thus, clinical use of FDG-PET-based biomarkers is challenged by high variability.",
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Chen, JL, Appelbaum, DE, Kocherginsky, M, Cowey, CL, Kimryn Rathmell, W, Mcdermott, DF & Stadler, WM 2013, 'FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer', Cancer medicine, vol. 2, no. 4, pp. 545-552. https://doi.org/10.1002/cam4.102

FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer. / Chen, James L.; Appelbaum, Daniel E.; Kocherginsky, Masha; Cowey, Charles L.; Kimryn Rathmell, Wendy; Mcdermott, David F.; Stadler, Walter M.

In: Cancer medicine, Vol. 2, No. 4, 01.01.2013, p. 545-552.

Research output: Contribution to journalArticle

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AU - Chen, James L.

AU - Appelbaum, Daniel E.

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