The objective of the proposed studies is to investigate quantitative [F- 18]fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) as a measure of non-small cell lung cancer (NSCLC) aggressiveness in vivo (i.e. grading) and to make comparisons with patients' outcomes and with specimen-derived measures of cellular proliferation previously shown to predict poor outcome (S-phase fraction, Ki-67 index). We postulate that, in clinically resectable NSCLC patients, pre-operative FDG PET will show that tumors with higher FDG uptake: (a) will recur sooner after surgical resection than same stage tumors with low uptake; (b) are more likely to have mediastinal or distal metastatic disease than tumors of the same clinical stage but low uptake; (c) have higher S-phase fraction of Ki-67 scores in their resected specimen.
The specific aims of the proposal are: (1) Perform whole-body pre- operative FDG PET imaging and correlate FDG uptake in primary NSCLC with outcome. FDG uptake will be quantified by the following methods that will be compared. Standardized Uptake Value (SUV) and SKM-FDGMR (FDG Metabolic Rate determined by a Simplified Kinetic Method). (2) Perform whole-body pre-operative FDG PET imaging and correlate FDG uptake (quantified as SUV and SKM-FDGMR) in primary NSCLC with disease extent as demonstrated by PET and surgical staging. (3) Correlate pre-operative FDG uptake in primary NSCLC with markers of cellular proliferation measured from the resected specimen and previously shown to predict poor outcome. Outcome will be measured by recurrence-free survival, time-to recurrence and survival. In summary, by studying NSCLC patients pre-operatively, prior to any form of chemotherapy or radiotherapy, we will gain valuable information about the biology of lung cancer, the leading cause of cancer death in the United States. By performing a biologic grading of resectable NSCLC with FDG PET, we will predict which patients will have a worse outcome. This information will allow individualized therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA080907-02
Application #
6342155
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Croft, Barbara
Project Start
2000-01-12
Project End
2004-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
2
Fiscal Year
2001
Total Cost
$346,960
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Toney, Lauren K; Vesselle, Hubert J (2014) Neural networks for nodal staging of non-small cell lung cancer with FDG PET and CT: importance of combining uptake values and sizes of nodes and primary tumor. Radiology 270:91-8
Hawes, Stephen E; Stern, Joshua E; Feng, Qinghua et al. (2010) DNA hypermethylation of tumors from non-small cell lung cancer (NSCLC) patients is associated with gender and histologic type. Lung Cancer 69:172-9
Vesselle, Hubert; Salskov, Alexander; Turcotte, Eric et al. (2008) Relationship between non-small cell lung cancer FDG uptake at PET, tumor histology, and Ki-67 proliferation index. J Thorac Oncol 3:971-8
Feng, Qinghua; Hawes, Stephen E; Stern, Joshua E et al. (2008) DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients. Cancer Epidemiol Biomarkers Prev 17:645-54
Vesselle, Hubert; Freeman, Joseph D; Wiens, Linda et al. (2007) Fluorodeoxyglucose uptake of primary non-small cell lung cancer at positron emission tomography: new contrary data on prognostic role. Clin Cancer Res 13:3255-63
Muzi, Mark; Mankoff, David A; Grierson, John R et al. (2005) Kinetic modeling of 3'-deoxy-3'-fluorothymidine in somatic tumors: mathematical studies. J Nucl Med 46:371-80
Muzi, Mark; Vesselle, Hubert; Grierson, John R et al. (2005) Kinetic analysis of 3'-deoxy-3'-fluorothymidine PET studies: validation studies in patients with lung cancer. J Nucl Med 46:274-82
Vesselle, Hubert; Turcotte, Eric; Wiens, Linda et al. (2004) Relationship between non-small cell lung cancer fluorodeoxyglucose uptake at positron emission tomography and surgical stage with relevance to patient prognosis. Clin Cancer Res 10:4709-16
Vesselle, Hubert; Turcotte, Eric; Wiens, Linda et al. (2003) Application of a neural network to improve nodal staging accuracy with 18F-FDG PET in non-small cell lung cancer. J Nucl Med 44:1918-26
Vesselle, Hubert; Grierson, John; Peterson, Lanell M et al. (2003) 18F-Fluorothymidine radiation dosimetry in human PET imaging studies. J Nucl Med 44:1482-8

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