18F-FDG PET/CT Scans Can Identify Sub-Groups of NSCLC Patients with High Glucose Uptake in the Majority of Their Tumor Lesions

Abstract

Background: Reprogrammed glucose metabolism is a hallmark of cancer making it an attractive therapeutic target, especially in cancers with high glucose uptake such as non-small cell lung cancer (NSCLC). Tools to select patients with high glucose uptake in the majority of tumor lesions are essential in the development of anti-cancer drugs targeting glucose metabolism. Type 2 diabetes mellitus (T2DM) patients may have tumors highly dependent on glucose uptake. Surprisingly, this has not been systematically studied. Therefore, we aimed to determine which patient and tumor characteristics, including concurrent T2DM, are related to high glucose uptake in the majority of tumor lesions in NSCLC patients as measured by 2-deoxy-2-[fluorine-18]fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) scans. Methods: Routine primary diagnostic ¹⁸F-FDG PET/CT scans of consecutive NSCLC patients were included. Mean standardized uptake value (SUVmean) of ¹⁸F-FDG was determined for all evaluable tumor lesions and corrected for serum glucose levels according to the European Association of Nuclear Medicine Research Ltd guidelines. Patient characteristics potentially determining degree of tumor lesion glucose uptake in the majority of tumor lesions per patient were investigated. Results: The cohort consisted of 102 patients, 28 with T2DM and 74 without T2DM. The median SUVmean per patient ranged from 0.8 to 35.2 (median 4.2). T2DM patients had higher median glucose uptake in individual tumor lesions and per patient compared to non-diabetic NSCLC patients (SUVmean 4.3 vs 2.8, P < 0.001 and SUVmean 5.4 vs 3.7, P = 0.009, respectively). However, in multivariable analysis, high tumor lesion glucose uptake was only independently determined by number of tumor lesions ≥1 mL per patient (odds ratio 0.8, 95% confidence interval 0.7-0.9). Conclusions: ¹⁸F-FDG PET/CT scans can identify sub-groups of NSCLC patients with high glucose uptake in the majority of their tumor lesions. T2DM patients had higher tumor lesion glucose uptake than non-diabetic patients. However, this was not independent of other factors such as the histological subtype and number of tumor lesions per patient.

Keywords: 18F-FDG PET/CT; glycolysis; non-small cell lung cancer; type 2 diabetes mellitus.

Figure 1

CONSORT diagram of 2-deoxy-2-[fluorine-18]fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) scans in non-small cell lung cancer (NSCLC) patients. UMCG: University Medical Center Groningen.

Figure 2

Inter-patient and intra-patient heterogeneity in tumor lesion glucose uptake. Each grey bar represents an individual patient. The length of the grey bars represents the range of the mean standardized uptake values (SUVmean) measured in all tumor lesions (dots) with a volume ≥1 mL visible on the primary diagnostic ¹⁸F-FDG PET/CT scans of the patients. Blue dots represent tumor lesions of non-diabetic patients with non-small cell lung cancer (N=74, N_lesions=1205). Red dots represent tumor lesions of non-small cell lung cancer patients with concurrent type 2 diabetes mellitus (N=28, N_lesions=189).

Figure 3

Median tumor lesion glucose uptake is higher in type 2 diabetes mellitus (T2DM) than in non-diabetic patients. A) Violin plot of all mean standardized uptake values (SUVmean) measured in all tumor lesions with a volume ≥1 mL visible on the primary diagnostic ¹⁸F-FDG PET/CT scans of non-diabetic (N_lesions=1205) and type 2 diabetes mellitus (T2DM) (N_lesions=189) non-small cell lung cancer (NSCLC) patients. B) Violin plot of the median SUVmean value per patient plotted for non-diabetic (N=74) and T2DM (N=28) NSCLC patients. Box plots showing the median (horizontal bar), the first and third quartile.