Session Item

Aim of this study was to combine the tumour clonogenic cell information derived from FDG PET images with tumour oxygen distribution derived from FMISO PET images synergistically to attain a patient-tailored dose escalation strategy in advanced Head and Neck (H&N) cancer and to test its feasibility to be delivered. 

Ten H&N cancer patients imaged with FDG and FMISO PET/CT before radiochemotherapy were included in the study. The required radiation dose to counteract the increased tumour cell radioresistance at voxel level was calculated based on maps of oxygen partial pressure (pO₂ maps) derived from FMISO PET images by the use of non-linear conversion functions of radiotracer uptake, following a previously developed method. This method requires information on the initial number of clonogens in the tumour, which is typically heterogeneous. In our approach, we retrieved this information from FDG PET images of the tumour metabolism by applying a linear conversion of the corresponding radiotracer uptake. The dose distribution at voxel level was used as input for a dose escalation strategy by contours in the hypoxic target volume (HTV) included in the GTV, in the GTV-HTV, and in the rest of the CTV. The HTV was contoured at a10 mmHg threshold in pO₂ maps.

RayStation (v10, RaySearchLaboratories) was used to perform photon treatment plans with ±3mm setup errors (7 scenarios) for the robust optimization. The clinical feasibility of applying the proposed dose prescription method and delivering the total dose in 35 fractions involving an integrated boost, was assessed based on a dosimetric evaluation of the treatment plans accounting for target coverage and constraints for the organs at risk (OAR). 

The workflow of the proposed dose escalation strategy is shown for an exemplifying patient case (Figure 1). The results indicate that doses expressed as equivalent doses in 2 Gy per fraction (EQD2) for D_50% in the range of 80.7-87.8 Gy in the HTV, 74.6-80.1 Gy in the GTV-HTV and 69.7-72.3 Gy in the CTV-GTV are needed in order to counteract the hypoxia induced radioresistance and account for the heterogeneous number of tumour clonogens derived from FMISO and FDG PET scans, respectively.

The dosimetric assessment of the calculated treatment plans for the whole patient dataset shows that for 8 patients out of 10 (80%) the plan is clinically feasible (Table 1). Patients having OARs very close to the boost volume reported doses above the OAR constraints (Table 1 in red) and may be candidates for alternative beam qualities, e.g. protons.

The proposed novel dose escalation strategy targeting hypoxia and considering a heterogeneous density of clonogens in the tumour based on functional imaging is clinically feasible and may be used for individualised radiation therapy.