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Abstract Objective To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT). Methods and materials From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ‘‘In-Field (IF)’’, “Marginal recurrence” or ‘‘Out-of-Field (OF)’’ if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose. Results We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6–28.9 cc), while the mean MTVrec was 4.3 cc (1.1–12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61–91%) and 4 recurrences were marginal to MTVpre (1–33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5–69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV). Conclusion Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse.