Radiotherapeutic management of cervical lymph node metastases from an unknown primary site – experiences from a large cohort treated with modern radiation techniques

PURPOSE: To analyze management and outcomes following (chemo)radiation therapy in patients with cervical lymph node metastases from an unknown primary site (CCUP) in a large single-center cohort. METHODS: Between 2008 and 2019, 58 patients with CCUP were treated with (chemo)radiation therapy at the University of Freiburg Medical Center and were included in this analysis. Overall survival (OS), locoregional progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method. The use of diagnostic procedures and their impact on oncological outcomes was analyzed by Cox regression, and treatment-related toxicities were quantified. RESULTS: Median follow-up was 29.9 months (range 4.6–121.9). Twenty-one patients (36.2%) received definitive RT, 35 (60.3%) underwent adjuvant RT, and 2 (3.4%) were treated for oligometastatic disease. Concurrent chemotherapy was prescribed in 40 patients (69.0%). 89.6% of patients completed the prescribed RT, and 65.0% completed the prescribed simultaneous chemotherapy. Locoregional recurrence was observed in 7 patients (12.1%) and distant metastases in 13 cases (22.4%). OS was 81,1, 64.9% and 56,6% after 1, 3 and 5 years, respectively. Univariate analysis of age, gender, extracapsular spread, tumor grading, neck dissection, diagnostic utilization of (18)F-fluorodeoxyglucose positron-emission tomography and concomitant chemotherapy showed no effect on OS (p > 0.05 for all), while smoking was significantly associated with decreased survival (p < 0.05). There was a trend towards impaired OS for patients with advanced nodal status (pN3) (p = 0.07). Three patients (5.2%) experienced grade 3 radiation dermatitis, and 12 (22.4%) developed grade 3 and 1 (1.7%) grade 4 mucositis. CONCLUSIONS: RT of the panpharynx and cervical lymph nodes with concurrent chemotherapy in case of risk factors demonstrated good locoregional control, but the metachronous occurrence of distant metastases limited survival and must be further addressed.