Patterns of Failure after IMRT in Head and Neck Squamous Cell Carcinoma of Unknown Primary: Implication of Elective Nodal and Mucosal Dose Coverage

Abstract Background and Purpose: We evaluated the geometric and dosimetric-based distribution of mucosal and nodal recurrences in patients with metastatic head and neck squamous cell carcinoma to cervical lymph nodes of unknown primary (HN-SCCUP) after IMRT using validated typology-indicative taxonomy. Materials and methods We reviewed the data of 260 of patients who were irradiated between 2000-2015, and had a median follow-up for surviving patients of 61 months. The mucosal and nodal recurrences were manually delineated on CT images demonstrating the recurrences. The images were overlaid on the treatment plan using deformable image registration. The locations of the recurrences were determined relative to the original planning target volumes and dose using centroid-based approaches. The pattern of failures (POF) were then classified into five types based on combined spatial and dosimetric criteria; A (central high dose), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose). For patients with type A failure with simultaneous non-type A lesions, the overall POF was defined as type A. Results Thirty-two patients had mucosal and/or nodal recurrences. The most common clinical nodal stage was N2b (66%). Pre-RT neck dissections were performed in 6 patients. The median dose delivered to CTV1 was 66 Gy. The majority (84%) had total/ partial pharyngeal mucosa elective irradiation. Twenty-three patients had nodal recurrences, 8 had mucosal recurrences and one had both nodal and mucosal recurrences. Twenty-one patients (91%) had type A nodal failure. Seven (89%) of the mucosal failures were type C. Conclusions The majority of nodal recurrences occurred within the high-dose area, demanding the need for identification of radioresistant areas within malignant nodes. Future studies should be directed towards either dose escalation of high-risk volumes or novel radiosensitizers.