(18)F-FDG PET/CT imaging in rectal cancer: relationship with the RAS mutational status

Treating metastatic colorectal cancer with anti-EGFR monoclonal antibodies is recommended only for patients whose tumour does not harbour mutations of KRAS or NRAS. The aim of this study was to investigate the biology of rectal cancers and specifically to evaluate the relationship between fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) intensity and heterogeneity parameters and their mutational status.

151 patients with newly diagnosed rectal cancer were included in this retrospective study. All patients underwent a baseline (18)F-FDG PET/CT within a median time interval of 27 days of tumour tissue sampling, which was performed before any treatment. Standardized uptake values (SUVs), volume-based parameters and texture analysis were studied. We retrospectively performed KRAS genotyping on codons 12, 13, 61, 117 and 146, NRAS genotyping on codons 12, 13 and 61 and BRAF on codon 600. Associations between PET/CT parameters and the mutational status were assessed using univariate and multivariate analysis.

83 (55%) patients had an RAS mutation: 74 KRAS and 9 NRAS, while 68 patients had no mutation (wild-type tumours). No patient had BRAF mutation. First-order features based on intensity histogram analysis were significantly associated with RAS mutations: maximum SUV (SUVmax) (p-value = 0.002), mean SUV (p-value = 0.006), skewness (p-value = 0.049), SUV standard deviation (p-value = 0.001) and SUV coefficient of variation (SUVcov) (p-value = 0.001). Both SUVcov and SUVmax showed an area under the curve of 0.65 with sensitivity of 56% and 69%, respectively, and specificity of 64% and 52%, respectively. None of the volume-based (metabolic tumour volume and total lesion glycolysis), nor local or regional textural features were associated with the presence of RAS mutations.

Although rectal cancers with KRAS or NRAS mutations display a significantly higher glucose metabolism than wild-type cancers, the accuracy of the currently proposed quantitative metrics extracted from (18)F-FDG PET/CT is not sufficiently high for playing a meaningful clinical role.

RAS-mutated rectal cancers have a significantly higher glucose metabolism. However, the accuracy of (18)F-FDG PET/CT quantitative metrics is not as such as the technique could play a clinical role.