Radiomic Signature Using Quantitative Ultrasound Integrated with Machine Learning for Predicting Clinical Radiosensitivity in Patients with Head-Neck Squamous Cell Carcinoma Treated with Radical Radiotherapy

Abstract

primary tumors in HNC recommend the "5+5mm" rule wherein both highdose and low-dose clinical target volumes (CTV-P1 and CTV-P2 respectively) are created using successive 5mm expansions on the gross tumor volume (GTV). Histopathological surgical series demonstrate the majority of microscopic extension in HNC can be encompassed within 5mm of the GTV, and the physical properties of modern photon-based HNC radiotherapy plans may result in adequate coverage of the low-dose CTV-P2 merely due to dose fall-off. To our knowledge, the necessity of contouring a low-dose CTV-P2 has never been assessed, therefore we evaluated the dosimetric impact of adding a CTV-P2 expansion using the "5+5mm" rule compared to contouring with a high-dose CTV-P1 alone. Materials/Methods: A retrospective study of clinically-delivered (chemo) radiotherapy HNC treatment plans was conducted. All patients were treated with 70 Gy in 35 fractions using volumetric modulated arc therapy (VMAT). Original treatment plans were generally created using a 5mm expansion from GTV to CTV-P1, and a CTV-P2 was retrospectively contoured using international consensus guidelines (5mm expansion on CTV-P1, carving off specified barriers to spread). Our institutional standard was a 5mm planning target volume (PTV) expansion. The primary outcome was whether 95% of the volume of the PTV for the CTV-P2 contour (i.e. PTV-P2) received at least 56 Gy. To assess dose fall-off, the coverage of a PTV-RING structure (created by subtracting PTV-P1 from PTV-P2) by at least 56 Gy was evaluated as a secondary outcome. Results: Twenty-seven patients from four HNC subsites (base of tongue, tonsil, hypopharynx and supraglottic larynx) were included. In all 108 treatment plans, at least 95% of the PTV-P2 structure received at least 56 Gy (inadequate coverage rate: 0%, 95% confidence interval: 0-3.4%). The mean volume of the PTV-P2 structure receiving at least 56 Gy was 97.4%. Eight of 108 treatment plans had borderline coverage of the PTV-RING substructure alone, where 90-95% of PTV-RING received at least 56 Gy, with the minimum coverage by at least 56 Gy being 90.6%. Conclusion: In the setting of 5mm PTV expansions, the addition of a lowdose CTV-P2 structure using the "5+5mm" rule would have had no dosimetric impact and appears redundant. The "5+5mm" rule adds additional contouring time, treatment planning complexity, and potentially could introduce errors. The "5+5mm" rule may have value in other settings, such as when smaller PTV margins are used or in proton radiotherapy, and warrants further evaluation with prospective or randomized studies addressing the optimal target volumes in HNC.