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

Abstract

There is a debate about the optimal mucosal and nodal dose coverage in head and neck squamous cell carcinoma of unknown primary (HN-SCCUP). We evaluated the geometric and dosimetric-based distribution of mucosal and regional failures (MRFs) in patients with HN-SCCUP using validated typology-indicative taxonomy. Out of 249 patients treated definitively with radiotherapy (RT) for HN-SCCUP with intact imaging data, 23 patients had mucosal and/or regional failures. This retrospective study is approved by the institutional IRB. A total of 28 (recurrent gross mucosal/nodal volumes) rGM/NVs were delineated on follow-up images showing the failures. The images were overlaid on the treatment plan using deformable image registration. rGM/NVs were determined relative to original planning target volumes and dose using a 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. Fifteen patients had regional failure (RF), 4 had mucosal failure (MF), and 4 had MRF. Median age was 60 (range: 47 -84) years. Tonsillectomy was performed in 15 (60%) patients. The most common clinical nodal stage was N2b (40%). Neck dissections were performed in 14 patients – 5 pre-RT and 9 post-RT. Seven patients had induction and 8 patients had concurrent chemotherapy with RT. The median dose delivered was 66 (range: 60 – 70) Gy. IMRT was utilized in 21 (91%) patients, with lower neck split field technique used in 9 patients. The majority (10, 43%) had total pharyngeal mucosa irradiation, followed by nasopharyngeal and oropharyngeal coverage in 6 (26%) patients. Four out of the 8 MF were not covered by the elective mucosal dose. Median time to failure was 16.2(range: 1.7-113.23) months. Mean rGM/N volume was 9.959 cm3 (range 0.4–63.5).For spatial and dosimetric analysis of POF, 17 (72%) patients had type A failure. Non-type A failures were distributed as follows: 2 (8%) type C, 1 (4%) type D and 4 (16%) type E. In those who had MF, the primary lesion was detected within the oropharynx in 3, larynx in 4 patients and 1 in oral cavity. 7 mucosal and 14 regional failures received subsequent salvage treatment. Median overall survival was 46.56(range: 6.8-145.46) months. The majority of RF occurred within the high-dose area and MF occurred within the pharyngeal axis, suggesting that the dose coverage to the mucosa and lymph node regions should be carefully designed for CUP patients. In addition, given the low incidence of geographical misses, future studies should be directed towards dose escalation of high-risk volumes.