Origin of Locoregional Recurrences After Definitive Intensity-modulated Radiation Therapy (IMRT) for Laryngeal Cancer Determined Based on Follow-up PET/CT Imaging

Purpose: The aim of our study was to report on patterns of failure using detailed information from follow-up positron emission tomography-computed tomography (PET/CT) scans for patients with laryngeal squamous cell carcinoma (SCCA) treated with definitive radiation therapy using intensity-modulated radiation therapy (IMRT). Methods: One hundred and sixty-eight patients with laryngeal SCCA treated with definitive IMRT using a simultaneous integrated boost were included. The point of recurrence origin on follow-up PET/CT was determined using two separate data-driven methods. The first method, the mathematical epicenter point of origin (PO(Epi)), calculated the mathematical focal epicenter point for which the maximum distance to the surface of the surrounding volume was smaller than for any other point. The second method, maximum standardized uptake value point of origin (PO(Max)), calculated the voxel with maximum standardized uptake value (SUV) uptake within the recurrence volume. The failure pattern was then determined by whether the point of recurrence origin fell within the low, intermediate, or high-risk target volumes in the original treatment planning CT. Results: Thirty-five primary/nodal recurrences in 33 patients were included in the analysis. In the PO(Epi) method, 94% (33/35) of all recurrences originated either within the high-risk gross tumor volume (GTV(High-risk)) or within an average of 0.9 ± 1.3 mm from it. In the PO(Max) method, 91% (32/35) of all recurrences originated either within the GTV(High-risk) or within an average of 1.8 ± 1.7 mm from it. There were no recurrences outside the low-risk planning target volume (PTV(Low-risk)) for the PO(Epi) method but there was one for the PO(Max) method, which was 19.8 mm away from the edge of the gross tumor volume receiving 70 Gy (GTV(70)). Increasing distance between the two different origin points was strongly correlated with the size of the recurrence volume. Conclusion: The majority of recurrences for laryngeal cancer patients treated with definitive IMRT originated from within the high-dose treatment region. This can have implications for reducing clinical target volumes while using a risk-adaptive treatment approach to both constrain dose to critical areas and further escalate the dose to the gross tumor to improve locoregional control rates.