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Original Articles: General Thoracic

Invited Commentary

NYU School of Medicine, NYU Langone Medical Center, 530 1st Ave, Ste 9V, New York, NY 10016

(Email: jessica.donington{at}med.nyu.edu).

The article from Shimizu and colleagues [1] is a retrospective comparison of the degree of fluorodeoxyglucose (FDG) uptake on preoperative positron emission tomography to tumor expression of cyclooxygenase-2 (COX-2), Ki-67, vascular endothelial growth factor, epidermal growth factor receptor, insulin-like growth factor receptor, and platelet-derived growth factor receptor by immunohistochemical analysis in a cohort of 60 resected lung adenocarcinomas smaller than 3 cm. A significant correlation was found between maximum SUV uptake (SUV_max) and the expression of both COX-2 and Ki-67, with the strongest association between SUV_max and COX-2. The research premise is intriguing for two reasons: (1) the importance of better delineating prognostic factors in resected non-small cell lung cancer (NSCLC) and (2) because COX-2 is a biologically important and potentially targetable marker that is overexpressed in up to 70% of NSCLCs. It makes biologic sense that there should be a correlation between COX-2 expression and SUV_max. FDG tissue accumulation is associated with levels of membrane glucose transporters, tumor grade differentiation, stage, and doubling time, all of which suggest that SUV_max is an indicator of increased cell proliferation and aggressive behavior. Similarly, elevated COX-2 levels from tumor are implicated in increases in angiogenesis and tumor invasion, resistance to apoptosis, and alterations in antitumor immunity. COX-2 and SUV_max have each been independently associated with poor survival, so a correlation between the two is not surprising. The clinical relevance and potential treatment implications are more intriguing. The authors suggest two possible treatment modifications based on these findings. The first is that high SUV_max could serve as an indication for adjuvant COX-2 inhibitory therapy. Unfortunately, the recent publication from the NVALT-4 trial [2] diminishes interest in this approach. This large randomized trial noted no benefit with the addition of celecoxib to doublet chemotherapy in advanced NSCLC, regardless of COX-2 tumor expression levels. This trial also failed to find prognostic value for COX-2 tumor expression, which differs from the finding here and those from several other sources. Shimizu and colleagues [1] also suggest that since SUV_max can be correlated with biologically relevant markers for tumor proliferation and malignant potential, and can therefore be used to guide decisions with regard to extent of resection. Unfortunately, SUV remains a semiquantitative measurement, which can be affected by numerous factors aside from tumor biology. Until these factors can be better quantified and controlled for cutoff values to guide treatment, decisions remain unrealistic. This correlation between SUV_max and COX-2 and Ki-67, along with worse clinical outcome in a uniform population of patients with NSCLC who have undergone resection, provides further evidence for an association between SUV_max and a malignant biological profile that one day may be helpful in guiding treatment decisions.

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1. Shimizu K, Hirami Y, Saisho S, et al. Maximal standardized uptake value on FDG-PET is correlated with cyclooxygenase-2 expression in patients with lung adenocarcinoma Ann Thorac Surg 2012;93:398-404.[Abstract/Free Full Text]
2. Groen HJ, Sietsma H, Vincent A, et al. randomized, placebo-controlled phase iii study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: The NVALT-4 Study J Clin Oncol 2011;29:4320-4326.[Abstract/Free Full Text]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Jessica S. Donington Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Donington, J. S. Search for Related Content PubMed PubMed Citation Articles by Donington, J. S. Related Collections Lung - cancer Related Article