Predictive role of intracranial PD-L1 expression in a real-world cohort of NSCLC patients treated with immune checkpoint inhibition following brain metastasis resection
© 2024. The Author(s)..
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: 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: 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: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:167 |
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| Enthalten in: |
Journal of neuro-oncology - 167(2024), 1 vom: 27. März, Seite 155-167 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wasilewski, David [VerfasserIn] |
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| Links: |
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| Themen: |
B7-H1 Antigen |
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| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 31.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s11060-024-04590-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368485064 |
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| 100 | 1 | |a Wasilewski, David |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Predictive role of intracranial PD-L1 expression in a real-world cohort of NSCLC patients treated with immune checkpoint inhibition following brain metastasis resection |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 31.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Brain metastasis | |
| 650 | 4 | |a Discordance | |
| 650 | 4 | |a NSCLC | |
| 650 | 4 | |a PD-L1 | |
| 650 | 4 | |a PFS | |
| 650 | 4 | |a Survival | |
| 650 | 7 | |a Immune Checkpoint Inhibitors |2 NLM | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 700 | 1 | |a Onken, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Höricke, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Bukatz, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Murad, Selin |e verfasserin |4 aut | |
| 700 | 1 | |a Früh, Anton |e verfasserin |4 aut | |
| 700 | 1 | |a Shaked, Zoe |e verfasserin |4 aut | |
| 700 | 1 | |a Misch, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Kühl, Anja |e verfasserin |4 aut | |
| 700 | 1 | |a Klein, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Ehret, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Kaul, David |e verfasserin |4 aut | |
| 700 | 1 | |a Radbruch, Helena |e verfasserin |4 aut | |
| 700 | 1 | |a Capper, David |e verfasserin |4 aut | |
| 700 | 1 | |a Vajkoczy, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Horst, David |e verfasserin |4 aut | |
| 700 | 1 | |a Frost, Nikolaj |e verfasserin |4 aut | |
| 700 | 1 | |a Bischoff, Philip |e verfasserin |4 aut | |
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