Abstract
INTRODUCTION: The impact of neoadjuvant immune checkpoint inhibitor (ICI)-based therapies on mediastinal nodal recurrence patterns after resection for patients with locally advanced non-small cell lung cancer (NSCLC) is unknown. We reported cases of mediastinal nodal failure after receipt of neoadjuvant ICI and provided a descriptive analysis of patients who experienced mediastinal recurrences. METHODS: We identified patients with stage I-IIIA NSCLC treated on a prospective trial with nivolumab-based therapies prior to resection between August 2015 and August 2021. We reviewed patient, tumor, treatment, pathological, recurrences, and post-operative therapy data. Variables including central tumor location at or within 2 cm of the central airways or primary lobar bronchi and initial mediastinal involvement by tumor or lymph nodes were obtained via chart review. Patients with mediastinal recurrences were qualitatively analyzed. RESULTS: Of the 23 NSCLC patients who underwent neoadjuvant ICI-based therapy followed by definitive resection, two patients developed mediastinal nodal recurrence. Both of these patients had pre-induction clinical stage IIIA, centrally located disease, and mediastinal involvement by the primary tumor or lymph nodes. Together, the patients with mediastinal nodal recurrence represent 29% of patients who presented with initial stage IIIA disease (n=2 out of 7), 20% of patients with mediastinal involvement (n=2 out of 10), and 13% of patients with centrally located disease (n=2 out of 16) prior to neoadjuvant ICI. Neither patient with mediastinal nodal recurrence achieved a pathological complete response (pCR) but one had major pathological response (MPR). CONCLUSIONS: In this analysis, we provide the first report of mediastinal nodal failure in patients with resectable stage I-IIIA NSCLC who have received neoadjuvant ICI-based therapies. Patients who developed mediastinal failure had: pre-induction clinical stage IIIA disease, central location, mediastinal involvement by the tumor or lymph nodes, and did not achieve pCR. Multi-institutional efforts are needed to better characterize the risk factors associated with mediastinal recurrence after neoadjuvant ICI.