Predictive role of intracranial PD-L1 expression in a real-world cohort of NSCLC patients treated with immune checkpoint inhibition following brain metastasis resection.

Brain metastasis Discordance NSCLC PD-L1 PFS Survival

Journal

Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335

Informations de publication

Date de publication:
15 Feb 2024
Historique:
received: 30 12 2023
accepted: 27 01 2024
medline: 15 2 2024
pubmed: 15 2 2024
entrez: 15 2 2024
Statut: aheadofprint

Résumé

Emerging evidence suggests that treatment of NSCLC brain metastases with immune checkpoint inhibitors (ICIs) is associated with response rates similar to those of extracranial disease. Programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) serves as a predictive biomarker for ICI response. However, the predictive value of brain metastasis-specific (intracranial) PD-L1 TPS is not established. We investigated the role of intra- and extracranial PD-L1 TPS in NSCLC patients treated with ICI following brain metastasis resection. Clinical data from NSCLC patients treated with ICI following brain metastasis resection (n = 64) were analyzed. PD-L1 TPS of brain metastases (n = 64) and available matched extracranial tumor tissue (n = 44) were assessed via immunohistochemistry. Statistical analyses included cut point estimation via maximally selected rank statistics, Kaplan-Meier estimates, and multivariable Cox regression analysis for intracranial progression-free survival (icPFS), extracranial progression-free survival (ecPFS), and overall survival (OS). PD-L1 expression was found in 54.7% of brain metastases and 68.2% of extracranial tumor tissues, with a median intra- and extracranial PD-L1 TPS of 7.5% (0 - 50%, IQR) and 15.0% (0 - 80%, IQR), respectively. In matched tissue samples, extracranial PD-L1 TPS was significantly higher than intracranial PD-L1 TPS (p = 0.013). Optimal cut points for intracranial and extracranial PD-L1 TPS varied according to outcome parameter assessed. Notably, patients with a high intracranial PD-L1 TPS (> 40%) exhibited significantly longer icPFS as compared to patients with a low intracranial PD-L1 TPS (≤ 40%). The cut point of 40% for intracranial PD-L1 TPS was independently associated with OS, icPFS and ecPFS in multivariable analyses. Our study highlights the potential role of intracranial PD-L1 TPS in NSCLC, which could be used to predict ICI response in cases where extracranial tissue is not available for PD-L1 assessment as well as to specifically predict intracranial response.

Sections du résumé

BACKGROUND BACKGROUND
Emerging evidence suggests that treatment of NSCLC brain metastases with immune checkpoint inhibitors (ICIs) is associated with response rates similar to those of extracranial disease. Programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) serves as a predictive biomarker for ICI response. However, the predictive value of brain metastasis-specific (intracranial) PD-L1 TPS is not established. We investigated the role of intra- and extracranial PD-L1 TPS in NSCLC patients treated with ICI following brain metastasis resection.
METHODS METHODS
Clinical data from NSCLC patients treated with ICI following brain metastasis resection (n = 64) were analyzed. PD-L1 TPS of brain metastases (n = 64) and available matched extracranial tumor tissue (n = 44) were assessed via immunohistochemistry. Statistical analyses included cut point estimation via maximally selected rank statistics, Kaplan-Meier estimates, and multivariable Cox regression analysis for intracranial progression-free survival (icPFS), extracranial progression-free survival (ecPFS), and overall survival (OS).
RESULTS RESULTS
PD-L1 expression was found in 54.7% of brain metastases and 68.2% of extracranial tumor tissues, with a median intra- and extracranial PD-L1 TPS of 7.5% (0 - 50%, IQR) and 15.0% (0 - 80%, IQR), respectively. In matched tissue samples, extracranial PD-L1 TPS was significantly higher than intracranial PD-L1 TPS (p = 0.013). Optimal cut points for intracranial and extracranial PD-L1 TPS varied according to outcome parameter assessed. Notably, patients with a high intracranial PD-L1 TPS (> 40%) exhibited significantly longer icPFS as compared to patients with a low intracranial PD-L1 TPS (≤ 40%). The cut point of 40% for intracranial PD-L1 TPS was independently associated with OS, icPFS and ecPFS in multivariable analyses.
CONCLUSION CONCLUSIONS
Our study highlights the potential role of intracranial PD-L1 TPS in NSCLC, which could be used to predict ICI response in cases where extracranial tissue is not available for PD-L1 assessment as well as to specifically predict intracranial response.

Identifiants

DOI: 10.1007/s11060-024-04590-w PMID: 38358406
pubmed: 38358406
doi: 10.1007/s11060-024-04590-w
pii: 10.1007/s11060-024-04590-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

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Auteurs

David Wasilewski (D)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany. david.wasilewski@charite.de.
Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany. david.wasilewski@charite.de.
German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany. david.wasilewski@charite.de.

Julia Onken (J)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Berlin Institute of Health (BIH) Charité, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Paul Höricke (P)

Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Jan Bukatz (J)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Selin Murad (S)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Anton Früh (A)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Berlin Institute of Health (BIH) Charité, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Zoe Shaked (Z)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Martin Misch (M)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Anja Kühl (A)

Berlin Institute of Health (BIH) Charité, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Oliver Klein (O)

Berlin Institute of Health (BIH) Charité, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Felix Ehret (F)

Department of Radiation Oncology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

David Kaul (D)

Department of Radiation Oncology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Helena Radbruch (H)

Institute of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

David Capper (D)

German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Berlin Institute of Health (BIH) Charité, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Institute of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Peter Vajkoczy (P)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

David Horst (D)

Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Nikolaj Frost (N)

Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Philip Bischoff (P)

German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Berlin Institute of Health (BIH) Charité, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.

Classifications MeSH