Quantification of Tumor Oxygenation Based on FMISO PET: Influence of Location and Oxygen Level of the Well-Oxygenated Reference Region.

Tumor hypoxia may play a fundamental role in determining the radiotherapy outcome for several cancer types. Functional imaging with hypoxia specific radiotracers offers a way to visualize and quantify regions of increased radioresistance, which may benefit from dose escalation strategies. Conversion of the uptake in positron emission tomography (PET) images into oxygenation maps offers a way to quantitatively characterize the microenvironment. However, normalization of the uptake with respect to a well-oxygenated reference volume (WOV), which should be properly selected, is necessary when using conversion functions. This study aims at assessing the sensitivity of quantifying tumor oxygenation based on 18F-fluoromisonidazole (FMISO) PET with respect to the choice of the location and the oxygenation level of the WOV in head and neck cancer patients. WOVs varying not only in shape and location but also with respect to the assigned pO2 level were considered. pO2 values other than the standard 60 mmHg were selected according to the specific tissue type included in the volume. For comparison, the volume which would be considered as hypoxic based on a tissue-to-muscle ratio equal to 1.4 was also delineated, as conventionally done in clinical practice. Hypoxia mapping strategies are found highly sensitive to selection of the location of well-oxygenated region, but also on its assigned oxygenation level, which is crucial for hypoxia-guided adaptive dose escalation strategies.

Textural features of hypoxia PET predict survival in head and neck cancer during chemoradiotherapy.

PURPOSE: The aim of this study was to investigate whether textural features of tumour hypoxia, assessed with serial [18F]fluoromisonidazole (FMISO)-PET, were able to predict clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC, T1-4, N+, M0) during chemoradiotherapy (CRT). METHODS: In a preliminary evaluation of a prospective trial, tumour hypoxia was evaluated in 29 patients via serial FMISO-PET before and during CRT. All patients received an initial [18F]fluorodeoxyglucose (FDG)-PET before CRT, and tumour regions were defined on this FDG-PET. The first-order metrics tumour-to-background ratio (TBRmean, TBRmax, TBRpeak), coefficient of variation, total lesion uptake and integral non-uniformity were calculated for all scans. Further, 3 second-order (textural) features from two grey-level matrices were calculated, as well as differential non-uniformity (udiff). Prognostic value was examined by median split for group separation (GS) in Kaplan-Meier estimates and correlated with overall survival (OS), quantified via log-rank tests (p ≤ 0.05) and group-relative hazard ratios (HR). RESULTS: Within a median follow-up of 29.6 months (95% CI: 16.8-48.0 months), no first-order metrics predicted OS with a significant GS (all p > 0.05) on any FMISO-PET scan. Only udiff before and in week 2 during CRT (p = 0.03, HR = 10.8 and p = 0.05, HR = 5.2) and non-uniformity from grey-level run length matrix in week 2 separated prognostic groups (p = 0.05, HR = 5.3); lower values were correlated with better OS. Further, the decrease in udiff from before CRT to week 2 was correlated with better OS (p = 0.04, HR = 9.4). FDG-PET before CRT did not predict outcome in any measure. CONCLUSIONS: Textural features on FMISO-PET scans before CRT, in week 2 and, to a limited degree, the change of features during CRT, were able to identify head and neck squamous cell carcinoma patients with better OS, suggesting that a higher homogeneity of the degree of hypoxia in tumours could correlate with a better outcome after CRT.