The association between long-term prognoses and FDG-PET parameters of biliary cancer - Comparison to the expression of KRAS, BRAF, EGFR, Ki-67, VEGFA and HIF-1

Objectives: The biliary cancer is one of the malignant tumors of poor-prognosis. In most malignant tumor, influencing factors to the poor prognosis are maximum standardized uptake value (SUVmax) or total lesion glycolysis (TLG) in FDG-PET. Also, the association between several oncogene expressions and the poor prognosis is known. The current study was done to determine the independent factors predicting the long-term prognoses of biliary cancer among FDG uptake indices, various oncogene expressions, clinical and pathological parameters. Methods: We conducted a retrospective study of 62 patients (44 men and 18 women) with histologically proven biliary cancer that underwent FDG PET/CT before treatment. As FDG uptake parameters, SUVmax, peak of standardized uptake value (SUVpeak), metabolic tumor volume (MTV), and TLG were calculated. The threshold value for calculating MTV was 40% of SUVmax. Using RT-PCR methods, the expression of KRAS, BRAF, EGFR, Ki-67, VEGFA and HIF-1 were measured. Then, we quantified the expression of these oncogenes by calculating the ratio to the housekeeping gene GAPDH expression. By univariate analysis, we analyzed the association between overall survival (OS) and various parameters including FDG uptake parameters, various oncogene expressions, histopathological differentiation and clinical parameters. Among the significant prognostic parameters determined by univariate analysis, we analyzed the independent prognostic factor by multivariate analysis. The mean follow-up period was 1,280 days. Results: Statistically significant shorter OS were noted by the univariate analysis in patients with FDG parameters higher than cut-off value, SUVmax (...5),SUVpeak (...4), and TLG (...30). In addition, the poorly differentiated adenocarcinoma group had a significant shorter OS than moderate and well differentiated type group. However, each oncogene expression was not a significant independent factor for predicting OS of biliary cancer. Although the group of higher expression of HIF-1 showed relatively shorter OS compared to that of the lower expression of HIF-1, it was not statistically significant. Age, gender, tumor locations or pathological stage did not show any significant association with OS, either.The multivariate analysis showed that the value of SUVmax, SUVpeak and the histopathological differentiation were independent prognostic factors of OS. However, TLG was not independent prognostic parameter. Conclusion: In the prediction of lon