Article

Prognostic PET F-18-FDG Uptake Imaging Features Are Associated with Major Oncogenomic Alterations in Patients with Resected Non-Small Cell Lung Cancer

Division of Pulmonary & Critical Care Medicine, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
Cancer Research (Impact Factor: 9.28). 06/2012; 72(15):3725-34. DOI: 10.1158/0008-5472.CAN-11-3943
Source: PubMed

ABSTRACT Although 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here, we analyzed 25 tumors from patients with NSCLCs to identify tumor PET-FDG uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and coexpressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived, and a prognostic model was identified in an external cohort and then tested in a validation cohort of patients with NSCLC. Four of eight single genes associated with FDG uptake (LY6E, RNF149, MCM6, and FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature [maximum standard uptake value (SUV(max)), SUV(variance), and SUV(PCA2)], each highly associated with survival in the external [HR, 5.87; confidence interval (CI), 2.49-13.8] and validation (HR, 6.12; CI, 1.08-34.8) cohorts, respectively. Cell-cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis.

0 Bookmarks
 · 
147 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-small-cell lung cancer is the most common type of lung cancer and one of the leading causes of cancer-related death worldwide. For this reason, advances in diagnosis and treatment are urgently needed. With the introduction of new, highly innovative hybrid imaging technologies such as PET/CT, staging and therapy response monitoring in lung cancer patients have substantially evolved. In this review, we discuss the role of FDG PET/CT in the management of lung cancer patients and the importance of new emerging imaging technologies and radiotracer developments on the path to personalized medicine.
    European journal of nuclear medicine and molecular imaging 01/2015; 42(4). DOI:10.1007/s00259-014-2974-5 · 5.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Owing to their integral involvement in cell cycle regulation, the Polo-like kinase (Plk) family, particularly Plk1, has emerged as an attractive therapeutic target in oncology. In recent years, several Plk1 inhibitors have been developed, with some agents showing encouraging results in early-phase clinical trials. This review focuses on volasertib (BI 6727; an investigational agent), a potent and selective Plk inhibitor. Volasertib has shown promising activity in various cancer cell lines and xenograft models of human cancer. Trials performed to date suggest that volasertib has clinical efficacy in a range of malignancies, with the most promising results seen in patients with acute myeloid leukemia (AML). Encouragingly, recent phase II data have demonstrated that volasertib combined with low-dose cytarabine (LDAC) was associated with higher response rates and improved event-free survival than LDAC alone in patients with previously untreated AML. Based on these observations, and its presumably manageable safety profile, volasertib is currently in phase III development as a potential treatment for patients with AML who are ineligible for intensive remission induction therapy. Given that many patients with AML are of an older age and frail, this constitutes an area of major unmet need. In this review, we discuss the biological rationale for Plk1 inhibitors in cancer, the clinical development of volasertib to date in solid tumors and AML, and the future identification of biomarkers that might predict response to volasertib and help determine the role of this agent in the clinic.Leukemia accepted article preview online, 16 July 2014; doi:10.1038/leu.2014.222.
    Leukemia 07/2014; 29(1). DOI:10.1038/leu.2014.222 · 9.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Radiographic-imaging modalities like computerized tomography, positron emission tomography, and magnetic resonance imaging are playing a major role in the diagnosis and prognosis of cancer. Gene and protein expression patterns, from the tumor genome, are seen to facilitate individualized selection of therapies. Along with breakthroughs in biotechnology, applicable within cancer radiation biology, a new research field called Radiogenomics has been born in radiation oncology. Associating genotypes with imaging phenotypes holds promise for personalized optimal treatment. Segmentation and feature selection from the region of interest in an image are followed by correlation with the gene expression profile of the tumor in order to determine its noninvasive surrogates. This paper highlights the roles of quantitative imaging, genomics, and radiogenomics for a patient-specific tumor management.
    10/2014; 44(5):664-677. DOI:10.1109/THMS.2014.2325744

Full-text

Download
147 Downloads
Available from
Jun 1, 2014