Long-Term Outcomes of Stereotactic Body Radiation Therapy with or without PD-1 Inhibitors in Metastatic Nasopharyngeal Carcinoma

Abstract

Data on the benefit of stereotactic body radiation therapy (SBRT) in patients with metastatic nasopharyngeal carcinoma (mNPC) remain limited. The purpose of this study is to assess the outcomes of mNPC treated with SBRT and programmed death-ligand 1 (PD-1) inhibitors. We reviewed all SBRT performed in patients with mNPC during the period of 2013-2022 in our institution. Treatments carried out with ablative intent in stereotactic conditions with dose/fraction ≥ 5 Gy were considered. The local control (LC), overall survival (OS), and progression-free survival (PFS) rates were calculated using Kaplan-Meier analyses. Risk factors were assessed through univariate and multivariate analysis by Cox regression. A total of 55 patients with 77 metastatic lesions treated with SBRT were analyzed. All of these patients received systemic treatment, either chemotherapy alone (n = 34) or chemotherapy with PD-1 inhibitors (n = 21). 28 patients (50.9%) had ≤ five metastatic lesions in the metastatic sites. The number of irradiated tumors ranged from 1 to 6, and 36 patients (65.5%) with 47 lesions received a physical dose ≥48 Gy (BED≥75Gy, α/β = 10). After a median follow-up of 43.6 months (range 1.9-115.3 months), 20 patients (36.4%) experienced local recurrence after completion of SBRT for metastatic lesions. The 1- and 3-year LC rates were 76.9% and 61.9%, respectively. The 1- and 3-year OS rates were 84.4% and 58.2%, and the 1- and 3-year PFS rates were 50.0% and 29.9%, respectively. Patients with ≤ 2 metastatic lesions (n = 24, 43.6%) had significant better LC (HR 0.11, 95% CI 0.036-0.313, p<0.001), OS (HR 0.24, 95% CI 0.08-0.74, p = 0.013) and PFS (HR 0.16, 95% CI 0.063-0.42, p<0.001) than patients with>2 metastatic lesions. Total dose≥48 Gy was also found to be a significant prognostic factor for better OS (HR 0.44, 95% CI 0.18-1.09, p = 0.044) and PFS (HR 0.42, 95% CI 0.17-0.88, p = 0.005), but not LC (HR 0.84, 95% CI 0.36-1.97, p = 0.678). In addition, adding PD-1 inhibitors to SBRT showed a significant benefit, improving the 2-year LC to 87.7% vs. 50.6% for SBRT (HR 0.27, 95% CI 0.18 - 0.41, p = 0.002). No patients experienced grade 4 or 5 toxicity. SBRT is an effective and safe treatment option for mNPC patients. Adding PD-1 inhibitors to SBRT offers a benefit in LC. Additional studies exploring the clinical benefit and predictive biomarkers of combined SBRT and PD-1 directed immunotherapy are warranted.