PD-L1 Tumor Proportion Score is Associated with Distant Failure after Stereotactic Ablative Radiotherapy in Early Stage Non-Small Cell Lung Cancer

Abstract

Stereotactic ablative radiotherapy (SABR) is standard treatment for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). Ten to 30% of patients experienced disease progression or distant metastases afterwards. Molecular profiles such as status of oncogenic driver mutations and tumor PD-L1 have been associated with prognosis for surgically resected early stage disease. We aimed to analyze the outcomes and prognostic potentials of major driver gene mutations and tumor PD-L1 expression for early stage NSCLC treated by SABR. We retrospectively collected and reviewed early stage NSCLC patients received SABR at a single medical center between 2008 and 2018. Epidermal growth factor receptor (EGFR) mutation status was determined by either polymerase chain reaction-based genotyping or mass spectrometry-based assay. Status of tumor expressions of PD-L1, and ALK were assessed by immunohistochemistry stain. Survival was estimated by the Kaplan-Meier method and Log-rank test was performed for evaluation of prognostic factors. In total, 75 patients were enrolled for analysis with a median age of 82-year-old (range, 30-94) at SABR delivery. The median biological equivalent dose delivered was 105.6 Gy10 (range 91.7-180). Men (n=50) and ever smokers (n=46) comprised the majority of the study cohort. Adenocarcinoma and squamous cell carcinoma accounted for 61% and 31% of histology subtypes, respectively. EGFR mutation status were identified in 36 patients, and 41.7% harbored mutant EGFR. All patients with available ALK expression data were negative. PD-L1 expression data, recorded as tumor proportion score (TPS), was available in 34 patients. With a median follow-up time of 18.5 months for all patients, the 3-year overall survival (OS) rate, local control (LC) rate, and distant metastases (DM) rate were 71.7%, 85.8%, and 43.7%, respectively. Patients with adenocarcinoma histology showed a significant favorable OS compared to those with squamous cell carcinoma (3-year OS rate 81.6% versus 54.7%, p=0.002). All tested driver mutations and PD-L1 TPS classification had no significant impact on LC or OS. Noteworthy, PD-L1 TPS ≥ 50% was associated with a significant worse distant control (median DM-free survival of TPS ≥ 50% 7.1 months versus TPS < 50% not reached, p=0.02). SABR achieved excellent local control, with the majority of failures being distant in medically inoperable early stage NSCLC. While EGFR mutation status had no impact on clinical outcomes in our study cohort, PD-L1 TPS ≥ 50% seemed to significantly increase the risk of distant failure. Further study with a larger cohort is warranted to validate our findings and adjuvant immunotherapy might be evaluated for patients with high-risk feature for distant metastases.