Outcomes with definitive local treatment to the primary site in non-nasopharyngeal head and neck squamous cell carcinoma patients with synchronous distant metastasis.
Authors: Borson Steven , Shuai Yongli , Branstetter Barton , Nilsen Marci Lee , Hughes Marion , Kubik Mark , Sridharan Shaum , Clump David Anthony , Skinner Heath Devin , Johnson Jonas T. , Chiosea Simion I. , Ohr James , Duvvuri Umamaheswar , Kim Seungwon , Traylor Katie , Fenton Moon Jung , Ferris Robert L. , Zandberg Dan Paul 
Published: June 2021

e18014

Background: Data on the efficacy of including definitive local therapy to the primary head and neck disease (PHN) for non-nasopharyngeal head and neck squamous cell carcinoma (HNSCC) patients with synchronous distant metastasis are lacking. Methods: In this single institution retrospective study, we evaluated the outcomes of patients treated from 2000-2020 at UPMC for non-nasopharyngeal HNSCC with synchronous distant metastasis whose therapy included definitive therapy to the PHN. We evaluated overall survival (OS), calculated as date of diagnosis to date of death and progression free survival (PFS), calculated as date of diagnosis to date of death or progression. Based on an initial univariate analysis, the potential significant predictors were evaluated further in the multiple covariates Cox model via stepwise procedures. The relative mortality rates were summarized with hazard ratio (HR), with HR > 1.0 corresponding to increased mortality. Results: A total of 40 patients met inclusion criteria. The median age was 61, primary sites included 52.5% oropharynx (48% HPV +), 40% larynx/hypopharynx, 7.5% oral cavity, and 85% had a solitary metastatic lesion, most commonly in the lung. Definitive treatment of the PHN was with surgery (55%) or chemoradiation (45%), and 45% also underwent local treatment for all distant disease. The median PFS was 8.6 months (95% CI, 6.4-11.6), and OS was 14.2 months (95% CI, 10.9-27.5). In the 28% of patients that received induction therapy, there was a two-fold increase in median OS to 27.5 vs. 13.7 months, p = 0.06. In the 33% of patients that received anti-PD-1 mAb immunotherapy (IO), the median OS was significantly increased to 41.7 months (95% CI, 8.7-NR) vs. 12.1 months (95% CI, 8.4-14.4), p = 0.01, with a numeric increase in PFS as well (11.3 vs. 8.2 months respectively, p = 0.07). Notably no difference in PFS or OS was seen with type of local therapy to the PHN, receipt of local treatment to all distant disease, by HPV status, or year of diagnosis. In multivariate analysis including induction and other variables significant in univariate analysis (age, number of metastatic sites), IO was independently associated with improved OS (HR 3.123 (No IO vs. IO) (95% CI, 1.198-8.137), p = 0.02), as was age and number of metastatic sites. In the patients that received IO started as part of induction the median PFS and OS were 19.5 and 45.5 months respectively. Conclusions: We observed impressive survival in select non-nasopharyngeal HNSCC patients with synchronous distant metastasis treated with definitive local therapy to the primary head and neck disease in addition to induction and/or IO, with IO independently associated with improved OS. To our knowledge this is the first evaluation of the efficacy of definitive local therapy and IO in this population. Prospective evaluation is warranted.