Preoperative Metabolic Tumor Volume2.5 Associated with Early Systemic Metastasis in Resected Pancreatic Cancer: A Transcriptome-Wide Analysis

BACKGROUND/AIMS: (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) reflects biological aggressiveness and predicts prognoses in various tumors. Evaluating the oncologic significance of the preoperative metabolic phenotype might be necessary for planning the surgical strategy in resectable pancreatic cancers. METHODS: From January 2010 to December 2015, a total of 93 patients with pathologic T3 (pT3) pancreatic cancer were included in this study. Clinicopathological parameters and PET parameters were evaluated, and transcriptome-wide analysis was performed to identify the oncologic impact and molecular landscape of the metabolic phenotype of resectable pancreatic cancers. RESULTS: Preoperative metabolic tumor volume (MTV)(2.5) was significantly higher in the pN1 group compared to the pN0 group (11.1±11.2 vs 6.5±7.8, p=0.031). Higher MTV(2.5) values (MTV(2.5) ≥4.5) were associated with multiple lymph node metastasis (p=0.003), and the lymph node ratio was also significantly higher in resected pT3 pancreatic cancer with MTV(2.5) ≥4.5 compared to those with MTV(2.5) <4.5 (0.12±0.13 vs 0.05±0.08, p=0.001). Disease-specific survival of patients with MTV(2.5) <4.5 was better than that of patients with MTV(2.5) ≥4.5 (mean, 28.8 months; 95% confidence interval [CI], 40.1 to 57.0 vs mean, 32.6 months; 95% CI, 25.5 to 39.7; p=0.026). Patients with MTV(2.5) ≥4.5 who received postoperative adjuvant chemotherapy showed better survival outcomes than patients with MTV(2.5) ≥4.5 who did not receive adjuvant treatment in resected pT3 pancreatic cancers (p<0.001). Transcriptome-wide analysis revealed that tumors with MTV(2.5) ≥4.5 demonstrated significantly different expression of cancer-related genes reflecting aggressive tumor biology. CONCLUSIONS: Resectable pancreatic cancer with high MTV(2.5) is not only associated with lymph node metastasis but also early systemic metastasis. The molecular background of resectable pancreatic cancer with high MTV(2.5) may be associated with aggressive biologic behavior, which might need to be considered when managing resectable pancreatic cancers. Further study is mandatory.