Abstract

Simple SummaryWe analyzed data from patients with advanced Non-Small Lung Cancer (NSCLC) and brain metastases (BM) who were treated with PD-1/PD-L1 inhibitors as monotherapy at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece in order to identify parameters that can potentially affect the intracranial (IC) outcome of these individuals. We assessed IC immunotherapy (I-O) efficacy in the patients who had BM prior to I-O administration, radiological evaluation for IC response assessment and they had not received any local CNS treatment modality for ≥3 months before I-O initiation. Age < 70 years old, prior radiation treatment to CNS, and primary (BM present at diagnosis) BM were associated, at a statistically significant level, with an increased probability of achieving IC disease control in our cohort. These results suggest that specific clinical parameters may potentially influence IC outcomes in NSCLC patients with BM.There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.

Highlights

  • The central nervous system (CNS) is a frequently metastasized site in non-small cell lung cancer (NSCLC) [1,2,3]

  • Brain metastases (BM) constitute an adverse prognostic factor for NSCLC [4,5,6] and despite the improvements made in diagnosis, staging, and treatment for NSCLC patients with brain metastases (BM) and non-oncogenic driven tumors, prognosis remains poor with an average overall survival ranging from 5 to 9 months [7,8]

  • We initially examined the effect of age, number of BM, and the diameter of the largest BM as continuous variables on IC disease control (PR or SD) (DC) rates

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Summary

Introduction

The central nervous system (CNS) is a frequently metastasized site in non-small cell lung cancer (NSCLC) [1,2,3]. A retrospective study by Hendriks et al [24] analyzed 255 patients with BM due to NSCLC treated with ICIs and 73 out of these 255 patients were categorized as having active BM. In their analysis, they reported an IC ORR of 27.3% in the subgroup of patients with active BM. In a similar retrospective study, our research group demonstrated an IC ORR of 24% in individuals with advanced NSCLC and active BM, whereas the presence of neurological symptoms due to BM and the administration of steroids did not affect IC response rates [25]

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