Longitudinal FDG-PET As a Surrogate for FMISO-Defined Hypoxia In HPV-Positive Oropharyngeal Cancer
Abstract
Purpose
Tumor hypoxia drives radio-resistance in Head & Neck cancer (HNC) and can guide radiation dose de-escalation. Tumor hypoxia can be imaged using 18F-fluoromisonidazole (FMISO-PET; non-standard-of-care). Because hypoxia drives glycolysis, we assessed correlations between 18F-fluorodeoxyglucose (FDG)-PET (standard-of-care) and FMISO-defined hypoxia.
Methods
We retrospectively analyzed thirteen HPV-positive oropharyngeal cancer patients who underwent baseline FDG-PET (pre-RT), repeat FDG (week-2) and FMISO-PET 2 weeks into radiotherapy under a prospective phase-II trial (NCT03323463). Hypoxic tumor sub-volumes (HSV) were defined using FMISO tumor-to-background (floor-of-mouth) ratio ≥1.2. Tumor volumes (TV), FDG_SUV_max/FDG_SUV_mean, metabolic tumor volumes (MTV50%) and MTV50%_SUV_mean were extracted from FDG-PET. Pearson correlations compared pre-RT FDG, week-2 FDG and ΔFDG metrics with FMISO_SUV_mean and FMISO_SUV_max, HSV_SUV_mean and HSV_volume. Associations with clinical dose de-escalation decisions were assessed. Primary and nodal disease (PD and ND respectively) were analyzed separately.
Results
In ND, FMISO_SUV_mean strongly correlated with baseline TV (r=0.751, p<0.01) and MTV50% (r=0.711, p<0.01), and midtreatment TV (r=0.779, p<0.01) and MTV50% (r=0.702, p<0.01). MTV50% strongly correlated with HSV_volume (Pre-RT: r=0.723, p<0.001; Week2: r=0.592, p<0.05). At both timepoints in primary disease, TV, FDG_SUV_mean and FDG_SUV_max strongly correlated with FMISO_SUV_max (range: r=0.694 - 0.811, p<0.001). FDG_SUV_max, FDG_SUV_mean and MTV50%_SUV_mean strongly correlated with HSV_volume (r=0.712 - 0.862, p<0.001). ΔFDG of GTV and MTV showed no significant correlation with hypoxia. Pre-RT FDG_SUV_max and FDG_SUV_mean in PD were the only metrics significantly lower in the N=2 patients eligible for dose de-escalation (p=0.026).
Conclusion
FDG-PET metrics were associated with FMISO-defined hypoxia, with distinct patterns for primary versus nodal disease. Volumetric parameters best reflected nodal hypoxia. In primaries, pre-RT FDG_SUV_max and FDG_SUV_mean correlated strongest with FMISO and HSV. Correlations were weaker for week-2 FDG metrics and ΔFDG was not correlated. Further work with a larger patient cohort is needed to assess the utility of using FDG instead of FMISO response to select patients for de-escalation.