Ann Thorac Surg 2012;93:403-404. doi:10.1016/j.athoracsur.2011.11.037
© 2012 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Jessica S. Donington, MD, MSCR
NYU School of Medicine, NYU Langone Medical Center, 530 1st Ave, Ste 9V, New York, NY 10016
The article from Shimizu and colleagues  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 (SUVmax) and the expression of both COX-2 and Ki-67, with the strongest association between SUVmax 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 SUVmax. FDG tissue accumulation is associated with levels of membrane glucose transporters, tumor grade differentiation, stage, and doubling time, all of which suggest that SUVmax 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 SUVmax 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 SUVmax could serve as an indication for adjuvant COX-2 inhibitory therapy. Unfortunately, the recent publication from the NVALT-4 trial  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  also suggest that since SUVmax 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 SUVmax 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 SUVmax and a malignant biological profile that one day may be helpful in guiding treatment decisions.
- 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]
- 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]
Maximal Standardized Uptake Value on FDG-PET Is Correlated With Cyclooxygenase-2 Expression in Patients With Lung Adenocarcinoma
- Katsuhiko Shimizu, Yuji Hirami, Shinsuke Saisho, Takuro Yukawa, Ai Maeda, Koichiro Yasuda, and Masao Nakata
Ann. Thorac. Surg. 2012 93: 398-403.