Metastasis Directed Therapy with Definitive Intent is Associated with Improved Survival in Metastatic Head and Neck Cancer

Abstract

Metastasis directed therapies (MDT) for patients with a limited burden of metastatic disease are increasingly being administered with definitive intent in the context of clinical trials. However, outcomes in metastatic head and neck cancer (HNC) patients who have been treated with MDT have not been well characterized. We identified 256 patients with HNC who developed metastatic disease following definitive therapy with radiation (either definitive or adjuvant) for localized non-metastatic disease including patients with the following cancers: oropharynx (n=88), oral cavity (n=20), larynx (n=25), hypopharynx (n=13), nasopharynx (n=29), salivary gland (n=51), sinonasal (n=21) and unknown primary (n=9), diagnosed from the years of 1989-2013. In each case, the number of clinically and/or radiographically apparent lesions at the time of diagnosis of metastatic disease was enumerated. Forty-three patients (16.8%) underwent definitive intent MDT with either surgery (n=38), stereotactic body radiotherapy (n=4) or radiofrequency ablation (n=1) to all sites of metastatic disease. Kaplan Meier methods were used to estimate median and annual survival with 95% confidence intervals (CI). Univariable and multivariable (MVA) Cox regression were used to assess the relationship between number of metastases, MDT and other potential confounding factors with outcome. At 5 years, the overall survival for the entire cohort was 12% (95%CI 8-17%). Five year survival rates for patients with 1, 2-4 and 5+ metastases were 41% (95%CI 24-57%), 9% (95%CI 4-17%) and 5% (95%CI 2-11%), respectively. Factors associated with increased risk of death on MVA included multiple metastases (HR 3.30, 95%CI 1.94-5.62, p<0.001), multiple organs involved with metastases (HR 1.45, 95%CI 1.05-2.00, p=0.02), oral cavity or sinonasal primary (OC HR 2.52 95%CI 1.43-4.44, SNC HR 4.07 95%CI 1.12-14.88, p=0.008), squamous histology (HR 6.67 95%CI 1.56-28.39, p=0.005), as well as lower performance status and shorter time from initial diagnosis to metastasis. In subgroup analysis of patients with oropharynx cancer, human papillomavirus (HPV)/p16 status was not associated with significantly improved survival (HPV/p16+ median survival 20.0 mo vs HPV/p16- 8.64 mo, p=0.68). Five year survival in patients who received MDT was 48% (95% CI 32-62%) compared to 4% (95%CI 2-8%) in patients who did not. On MVA controlling for number of metastases, number of organs with metastasis, performance status and age, MDT was associated with improved survival (HR 0.36, 95%CI 0.20-0.65, p<.001). To our knowledge, this is the largest study to date assessing MDT in head and neck cancer. MDT is associated with significantly improved survival in patients with metastatic HNC particularly for patients with a limited disease burden. Prospective clinical trials are needed to evaluate the benefit of MDT in the multidisciplinary approach to metastatic HNC.