Hypoxia-guided adaptive radiation dose escalation in head and neck carcinoma: A planning study

<p><b>Objective</b>. To evaluate from a planning point of view the dose distribution of adaptive radiation dose escalation in head and neck squamous cell carcinoma (HNSCC) using ¹⁸F-Fluoroazomycin arabinoside (FAZA) positron emission tomography/computed tomography (PET-CT).</p> <p><b>Material/methods</b>. Twelve patients with locally advanced HNSCC underwent three FAZA PET-CT before treatment, after 7 fractions and after 17 fractions of a carboplatin-5FU chemo-radiotherapy regimen (70 Gy in 2 Gy per fraction over 7 weeks). The dose constraints were that every hypoxic voxel delineated before and during treatment (newborn hypoxic voxels) should receive a total dose of 86 Gy. A median dose of 2.47 Gy per fraction was prescribed on the hypoxic PTV defined on the pre-treatment FAZA PET-CT; a median dose of 2.57 Gy per fraction was prescribed on the newborn voxels identified on the first per-treatment FAZA PET-CT; a median dose of 2.89 Gy per fraction was prescribed on the newborn voxels identified on the second per-treatment FAZA PET-CT.</p> <p><b>Results</b>. Ten of 12 patients had hypoxic volumes. Six of 10 patients completed all the FAZA PET-CT during radiotherapy. For the hypoxic PTVs, the average D_50% matched the prescribed dose within 2% and the homogeneity indices reached 0.10 and 0.12 for the nodal PTV 86 Gy and the primary PTV 86 Gy, respectively. Compared to a homogeneous 70 Gy mean dose to the PTVs, the dose escalation up to 86 Gy to the hypoxic volumes did not typically modify the dose metrics on the surrounding normal tissues.</p> <p><b>Conclusion</b>. From a planning point of view, FAZA-PET-guided dose adaptive escalation is feasible without substantial dose increase to normal tissues above tolerance limits. Clinical prospective studies, however, need to be performed to validate hypoxia-guided adaptive radiation dose escalation in head and neck carcinoma.</p

Evolution of [¹⁸F]fluorodeoxyglucose and [¹⁸F]fluoroazomycin arabinoside PET uptake distributions in lung tumours during radiation therapy

<p><b>Background:</b> Dose painting (DP) aims to improve radiation therapy (RT) outcome by targeting radioresistant tumour regions identified through functional imaging, e.g., positron emission tomography (PET). Importantly, the expected benefit of DP relies on the ability of PET imaging to identify tumour areas which could be consistently targeted throughout the treatment. In this study, we analysed the spatial stability of two potential DP targets in lung cancer patients undergoing RT: the tumour burden surrogate [¹⁸F]fluorodeoxyglucose (FDG) and the hypoxia surrogate [¹⁸F]fluoroazomycin arabinoside (FAZA).</p> <p><b>Materials and methods:</b> Thirteen patients with unresectable lung tumours underwent FDG and FAZA 4D-PET/CT before (pre), and during the second (w2) and third (w3) weeks of RT. All PET/CT were reconstructed in their time-averaged midposition (MidP) for further analysis. The metabolic tumour volume (MTV: FDG standardised uptake value (SUV) > 50% SUV_max) and the hypoxic volume (HV: FAZA SUV >1.4) were delineated within the gross tumour volume (GTV_CT). The stability of FDG and FAZA PET uptake distributions during RT was subsequently assessed through volume-overlap analysis and voxel-based correlation analysis.</p> <p><b>Results:</b> The volume-overlap analysis yielded median overlapping fraction (OF) of 0.86 between MTV_pre and MTV_w2 and 0.82 between MTV_pre and MTV_w3. In patients with a detectable HV, median OF was 0.82 between HV_pre and HV_w2 and 0.90 between HV_pre and HV_w3. The voxel-based correlation analysis yielded median Spearman’s correlation coefficient (r_S) of 0.87 between FDG_pre and FDG_w2 and 0.83 between FDG_pre and FDG_w3. Median r_S was 0.78 between FAZA_pre and FAZA_w2 and 0.79 between FAZA_pre and FAZA_w3.</p> <p><b>Conclusions:</b> FDG and FAZA PET uptake distributions were spatially stable during the 3 first weeks of RT in patients with unresectable lung cancer, both based on volume- and voxel-based indicators. This might allow for a consistent targeting of high FDG or FAZA PET uptake regions as part of a DP strategy.</p