Patterns of Failure After Intensity Modulated Radiation Therapy in Head and Neck Squamous Cell Carcinoma of Unknown Primary: Implication of Elective Nodal and Mucosal Dose Coverage

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 after intensity modulated radiation therapy using validated typology-indicative taxonomy. Methods and Materials: We reviewed the data of 260 patients who were irradiated between 2000 and 2015 and had a median follow-up time for surviving patients of 61 months. The mucosal and nodal recurrences were manually delineated on computed tomography 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 doses using centroid-based approaches. Subsequently, the pattern of failures were classified into 5 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 nontype A lesions, the overall pattern of failures was defined as type A. Results: Thirty-two patients had mucosal or nodal recurrences. The most common clinical nodal stage was N2b (66%). Preradiation therapy neck dissections were performed in 6 patients. The median dose delivered to clinical tumor volume 1 was 66 Gy. The majority (84%) had total/partial pharyngeal mucosa elective irradiation. Twenty-three patients had nodal recurrences, 8 had mucosal recurrences, and 1 had both nodal and mucosal recurrences. Twenty-one patients (91%) had type A nodal failure, and 7 of the mucosal failures (89%) 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 focus on either dose escalation of high-risk volumes or novel radiosensitizers.