This study indicated that (18) F-FAZA-PET could be used to identify and quantify tumor hypoxia before and during concomitant radio-chemotherapy in patients with locally advanced HNSCC. In addition to the information on prognostic value, the use of (18) F-FAZA-PET allowed the delineation of hypoxic volumes for dose escalation protocols. However, due to fluctuation of hypoxia during treatment, repeated scan will have to be performed (i.e. adaptive radiotherapy).
In locally advanced head and neck squamous cell carcinoma (HNSCC), the role of imaging becomes more and more critical in the management process. In this framework, molecular imaging techniques such as PET allow noninvasive assessment of a range of tumour biomarkers such as metabolism, hypoxia and proliferation, which can serve different purposes. First, in a pretreatment setting they can influence therapy selection strategies and target delineation for radiation therapy. Second, their predictive and/or prognostic value could help enhance the therapeutic ratio in the management of HNSCC. Third, treatment modification can be performed through the generation of a molecular-based heterogeneous dose distribution with dose escalation to the most resistant parts of the tumour, a concept known as dose painting. Fourth, they are increasingly becoming a tool for monitoring response to therapy. In this review, PET imaging biomarkers used in the routine management of HNSCC or under investigation are discussed.
AbstrActbackground. In the context of dose painting by numbers delivered with intensity-modulated radiotherapy, the robustness of dose distributions against geometric uncertainties can be ensured by robust optimization. As robust optimization is seldom available in treatment planning systems (TPS), we propose an alternative method that reaches the same goal by modifying the heterogeneous dose prescription (based on 18 FDG-PET) and guarantees coverage in spite of systematic and random errors with known standard deviations Σ and s, respectively. Material and methods. The objective was that 95% of all voxels in the GTV PET received at least 95% of the prescribed dose despite geometric errors. The prescription was modified by a geometric dilation of aΣ for systematic errors and a deconvolution by a Gaussian function of width s for random errors. For a 90% confidence interval, a 2.5. Planning was performed on a TomoTherapy system, such that 95% of the voxels received at least 95% of the modified prescription and less than 5% of the voxels received more than 105% of the modified prescription. The applicability of the method was illustrated for two head-and-neck tumors. results. Systematic and random displacements larger than aΣ and s degraded coverage. Down to 62.8% of the points received at least 95% of prescribed dose for the largest considered displacements (5 mm systematic translation and 3 mm standard deviation for random errors). When systematic and random displacements were smaller than aΣ and s, no degradation of target coverage was observed. conclusions. The method led to treatment plans with target coverage robust against geometric uncertainties without the need to incorporate these in the optimizer of the TPS. The methodology was illustrated for head-and-neck cancer but can be potentially extended to all treatment sites.
Objective. To develop a methodology for using FDG PET/CT in adaptive dose painting by numbers (DPBN) in head and neck squamous cell carcinoma (HNSCC) patients. Issues related to noise in PET and treatment robustness against geometric errors are addressed. Methods. Five patients with locally advanced HNSCC scheduled for chemo-radiotherapy were imaged with FDG-PET/ CT at baseline and 2-3 times during radiotherapy (RT). The GTV PET was segmented with a gradient-based method. A double median filter reduces the impact of noise in the PET uptake-to-dose conversion. Filtered FDG uptake values were linearly converted into a voxel-by-voxel prescription from 70 (median uptake) to 86 Gy (highest uptake). A PTV PET was obtained by applying a dilation of 2.5 mm to the entire prescription. Seven iso-uptake thresholds led to seven sub-levels compatible with the Tomotherapy HiArt ® Treatment Planning System. Planning aimed to deliver a median dose of 56 Gy and 70 Gy in 35 fractions on the elective and therapeutic PTVs, respectively. Plan quality was assessed with quality volume histogram (QVH). At each time point, plans were generated with a total of 3-4 plans for each patient. Deformable image registration was used for automatic contour propagation and dose summation of the 3 or 4 treatment plans (MIMvista ®). results. GTV PET segmentations were performed successfully until week 2 of RT but failed in two patients at week 3. QVH analysis showed high conformity for all plans (mean V Q 0.95 93%; mean V Q 1.05 3.9%; mean QF 2.2%). Good OAR sparing was achieved while keeping high plan quality. conclusion. Our results show that adaptive FDG-PET-based escalated dose painting in patients with locally advanced HNSCC is feasible while respecting strict dose constraints to organs at risk. Clinical studies must be conducted to evaluate toxicities and tumor response of such a strategy.
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