Abstract
OBJECTIVE: We report the patterns of failure and survival with carcinoma of unknown primary of the head and neck (CUP-HN). MATERIALS AND METHODS: This is a retrospective audit of CUP-HN patients treated with curative radiotherapy (RT) between January 2006 and December 2020. All patients received RT to the neck-definitive RT (DRT) or surgery (Sx) + adjuvant RT (ART), ± chemotherapy. RESULTS: Of the 108 eligible patients, 81 (75%) used tobacco. Positron emission tomography with computed tomography was performed in 102 patients (94.4%). Seventy-five patients (69.4%) were treated with DRT ± chemotherapy, while 33 (30.6%) underwent Sx + ART ± chemotherapy. Median lymph node size was significantly different between DRT and ART groups (5 vs. 3.5cm, p = 0.001). At a median follow-up of 60 months, 35.1% patients had a neck failure (within treatment portal 37, outside portal 1). Nine patients (8.3%) developed 10 sites of subsequent mucosal primary (SMP)-all occurred in the oral cavity, six of whom had received comprehensive mucosal irradiation (CMI). Three-year survival outcomes were significantly better with Sx + ART compared to DRT (local control in neck: 96.8 ± 3.2 vs. 50.6 ± 6.2, p < 0.001, locoregional control: 89.7 ± 5.7 vs. 48.6 ± 6.3, p < 0.001), progression-free survival: 80.7 ± 7.1 vs. 38.7 ± 6, p < 0.001, and overall survival [OS]: 67.2 ± 8.5 vs. 41.9 ± 6.2, p = 0.01), respectively. After propensity score matching, all survival outcomes (except OS) were better with Sx + ART compared to DRT. CONCLUSION: All SMPs developed in the oral cavity in this tobacco-driven population. Inclusion of oral cavity for CMI may be considered in tobacco-driven populations; however, this has to be weighed against the toxicity involved.