Metabolic and metastatic features of ALK-rearranged lung adenocarcinoma: An FDG PET/CT study

Objectives ALK rearrangement in lung cancer has been identified as a novel molecular target in subsets of the patients with non-small cell lung cancer, especially in adenocarcinoma. In this study, we evaluated metabolic and metastatic features of lung adenocarcinoma by using FDG PET/CT, with regard to specific genotypes of ALK rearrangement and EGFR mutation.

Methods Patients with lung adenocarcinoma initially diagnosed and examined with FDG PET/CT and molecular genotyping with biopsy specimen, from Jan. 2009 to Sep. 2011, were selected retrospectively. ALK rearrangement was confirmed by fluorescence in situ hybridization and EGFR mutation was also tested. Maximum standardized uptake value (SUVmax) and metastatic characteristics on FDG PET/CT were analyzed with regard to ALK and EGFR status.

Results Of the 331 lung adenocarcinoma patients, 27 (8.2%) were ALK-positive, 89 (26.9%) were EGFR mutant, and 215 (64.9%) were wild type (WT) for both ALK and EGFR. ALK-positive tumors were significantly associated with nonsmokers (P<0.04, vs. WT), advanced staging (P<0.01, vs. EGFR, WT), lymph node metastasis (P=0.01 vs. EGFR, P<0.01 vs. WT). The SUVmax of the ALK-positive tumor was significantly higher than those of other genotypes (P<0.01). In a subgroup analysis of small-sized primary tumors (<3cm), ALK-positive lung cancer showed significantly higher SUVmax (P<0.01) as well as more frequent lymph node metastasis (P<0.001) and distant metastasis (P<0.02). In another subgroup analysis of large-sized tumors (≥3cm), ALK-positive tumors still showed significant difference in distant metastasis (P<0.001), without significant difference in SUVmax.

Conclusions ALK-rearranged lung adenocarcinoma represents higher glucose metabolism and earlier metastasis to lymph nodes or distant sites compared with those with WT and EGFR mutation. This would be helpful for understanding and therapeutic utilization of ALK rearrangement in lung cancer