Hypoxia imaging using¹⁸F-FMISO PET/CT in predicting treatment response in patients with head and neck cancer

Objectives: Pretherapy hypoxia imaging using ¹⁸F-FMISO PET/CT in head and neck cancer is a valuable non-invasive tool to differentiate between treatment responders and non-responders. This study was performed to assess the extent of hypoxic tumor tissue in patients with head and neck cancers using ¹⁸F-FMISO PET/CT and to compare the metabolic response in hypoxic and non-hypoxic tumors by ¹⁸F-FDG PET/CT imaging post radiotherapy. Materials and Methods: 30 patients (28 men, 2 women; mean age 54.47±8.03 years) with biopsy-proven squamous cell carcinoma of oropharynx (n=21), hypopharynx (n=4), larynx (n=4) and retromolar trigone (n=1) were prospectively enrolled in the study. An initial pre-treatment ¹⁸F-FDG PET/CT whole body scan (WBS) was done followed by ¹⁸F-FMISO PET/CT regional scan of the head and neck at 2.5 hours and 4 hours. A post-treatment ¹⁸F-FDG PET/CT WBS was also performed minimum 3 months after completion of radiotherapy. Standardized uptake value maximum (SUVmax) was used to assess uptake in both ¹⁸F-FDG and ¹⁸F-FMISO PET/CT images. The uptake of ¹⁸F-FMISO by posterior cervical muscle was also assessed to calculate tumor to muscle ratio at both 2.5 and 4 hours (TMR_2.5; TMR₄). Pre and post-treatment ¹⁸F-FDG PET was used for response assessment using PERCIST criteria and was categorized into complete metabolic response (CMR), partial metabolic response (PMR), progressive metabolic disease (PMD) and stable metabolic disease (SMD).

Results: ¹⁸F-FDG PET/CT detected primary tumor in all 30 patients with mean SUVmax 14.81± 6.08. 27/30 patients showed regional lymph node involvement with variable FDG avidity. ¹⁸F-FMISO PET/CT images showed abnormal tracer activity in primary tumor in 28/30 patients with mean SUVmax 2.14±0.53 and 2.25±0.69 at 2.5 and 4 hours respectively. TMR of primary tumor was 1.59±0.33 at 2.5 hours and 1.7±0.41 at 4 hours. Two patients were lost to follow-up and five others died during the course of study, likely due to disease progression. Follow-up ¹⁸F-FDG PET/CT was performed in 23 out of 30 patients. In these patients (n=23) residual primary or resolved primary tumor site had mean SUVmax 4.70±3.75. CMR, PMR, PMD and SMD was seen in 15, 5, 1 and 2 patients respectively. Cases with CMR and PMR were considered responders (n=20) while patients with SMD, PMD and those who died during the study were considered non-responders (n=8). Independent t-test was used to compare different parameters between responders and non-responders. Both TMR_2.5 and TMR₄ showed significant difference between responders and non-responders with higher tracer avidity in non-responders (p-value 0.005 and 0.021 respectively) while SUVmax in both ¹⁸F-FDG and ¹⁸F-FMISO PET/CT showed no significant difference (p-value >0.05). TMR_2.5 with a cut-off value 1.76 (AUC: 0.834; 95 % CI: 0.676-0.993), sensitivity of 80 % (95 % CI: 56.3-94.3 %), specificity of 75 % (95 % CI: 34.9-96.8 %) and p-value 0.007 was used for segregation of patients into ¹⁸F-FMISO positive and negative groups because the p-value (0.098) was not significant for TMR₄. 6/8 (75%) non-responders and 4/20 (20%) responders had TMR_2.5more than 1.76 resulting in 76.8% diagnostic accuracy of TMR_2.5 to correctly identify hypoxic or non-hypoxic tumors.

Conclusions: In the present study, ¹⁸F-FMISO PET/CT imaging at 2.5 hours showed more reliable results for evaluation of tumor hypoxia compared to imaging at 4 hours and proved useful in terms of predicting the final treatment outcome.