Assessment of biological parameters in head and neck cancer based on in vivo distribution of 18F-FDG-FLT-FMISO-PET/CT images

Objective: Several genetic analyses have identified tumor diversity not only among tumors from different patients (intertumor heterogeneity) but also within individual tumors (intratumor heterogeneity). The aim of this study was to analyze the intratumor heterogeneity and other biological parameters based on in vivo distribution in triple-tracer positron emission tomography with computed tomography (PET/CT) study in patients with newly diagnosed head and neck (H&N) cancer. Methods: Thirty-six patients with newly diagnosed H&N cancer were included in the study. Institutional Bioethical Committee approved the study protocol and informed consent was received from every participant. All patients underwent series of 3 PET/CT scans with [18F]Fluorodeoxyglucose (18F-FDG-PET), [18F]Fluorothymidine (18F-FLT-PET), and [18F]Fluoromisonidazole (18F-FMISO-PET) before treatment. Scans were performed on separate days, within a timeframe of 2 weeks. Several PET/CT parameters grading tumor biology including maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), its equivalent (total hypoxic lesion [TLH] and total proliferative lesion [TLP]), and heterogeneity (area under the curve–cumulative SUV histogram) for the primary tumor were compared. Results: All patients showed increased uptake of 18F-FDG in primary tumor, ranging from 2.29 to 14.89 SUVmax. Respectively, SUVmax values for 18F-FLT ranged from 0.93 to 16.11 and for 18F-FMISO 0.36–4.07. Based on 3-year follow-up, we divided patients in terms of survival forecasts (first with good prognosis and second with worse). Higher values of TLG/TLP/TLH and SUVmax were observed in the second group in all 3 tracers (for 18F-FDG: 167.40 vs 100.32, 11.15 vs 8.95; for 18F-FLT: 116.61 vs 60.67, 7.09 vs 5.47; for 18F-FMISO: 37.34 vs 22.30, 1.70 vs 1.61 respectively). Statistically significant differences were shown in SUVmax in 18F-FDG and 18F-FLT (P<0.034, P<0.034, respectively; in TLG, P=0.05; TLP, P=0.04; and TLH, P=0.05). Conclusion: Our preliminary results suggest worse prognosis in patients with higher heterogeneity values of primary tumor in proliferation and hypoxia images and combination of metabolic and volumetric parameters in TLG and its equivalent and heterogeneity of primary tumor seems to be a prognostic factor.