The Prognostic and Predictive Roles of Ataxia–Telangiectasia Mutated (ATM) Expression in Patients with Metastatic Non-Small-Cell Lung Cancer Receiving Pembrolizumab Monotherapy Alone or in Combination with Chemotherapy
<b><b>Background/Objectives:</b></b> This study investigated the prognostic and predictive significance of Ataxia–Telangiectasia Mutated (ATM) expression in patients with metastatic non-small-cell lung cancer (NSCLC) who were treated with pembrolizumab. <b>Methods:</...
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2025-04-01
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| author | Jamshid Hamdard Harun Muğlu Ahmet Bilici Elif Kuzucular Özgür Açıkgöz Ömer Fatih Ölmez Oktay Olmuşçelik Özcan Yıldız |
| author_facet | Jamshid Hamdard Harun Muğlu Ahmet Bilici Elif Kuzucular Özgür Açıkgöz Ömer Fatih Ölmez Oktay Olmuşçelik Özcan Yıldız |
| author_sort | Jamshid Hamdard |
| collection | DOAJ |
| description | <b><b>Background/Objectives:</b></b> This study investigated the prognostic and predictive significance of Ataxia–Telangiectasia Mutated (ATM) expression in patients with metastatic non-small-cell lung cancer (NSCLC) who were treated with pembrolizumab. <b>Methods:</b> A retrospective analysis was conducted on 49 patients with metastatic NSCLC who received first-line pembrolizumab, either as a single agent or in combination with chemotherapy. ATM expression in archival pathology specimens was assessed using immunohistochemistry, where nuclear staining was considered to be positive. ATM expression was categorized into low- and high-expression groups based on staining intensity and the percentage of positive cells. Subsequently, the prognostic and predictive value of ATM expression was evaluated. <b>Results:</b> In terms of demographics, the mean age was 62.7 ± 9.5, most patients (91.8%) were male, and the majority (75.5%) had adenocarcinoma. The objective response rate (ORR) was 69.4%, and ATM expression was high in 75.5% of patients. Patients with low ATM expression had significantly longer progression-free survival (PFS) compared to those with high expression (51 vs. 5.7 months, <i>p</i> = 0.004). In multivariate analysis, ATM expression was the only independent prognostic factor for PFS, showing that patients with high ATM expression had a shorter overall survival (OS) compared to those with low expression (51 vs. 8.9 months, <i>p</i> = 0.013), which was statistically significant (HR 2.41, <i>p</i> = 0.034). Logistic regression analysis showed that ATM expression, as well as the presence of bone metastasis and the absence of liver metastasis, was significantly associated with a response to treatment (<i>p</i> = 0.006; OR: 0.06; 95% CI: 0.008–0.45). <b>Conclusions:</b> The findings of this study concerning ATM expression as a biomarker should be interpreted cautiously due to inherent limitations, including its retrospective design, the semi-quantitative nature of immunohistochemistry for ATM assessment, the small sample size with uneven clinical characteristics, and the relatively short follow-up period, which collectively impact generalizability. Despite these limitations, lower ATM expression was associated with better prognosis and pembrolizumab treatment response, suggesting that it may be a valuable biomarker for predicting these factors. |
| format | Article |
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| issn | 2075-4418 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-b7f4c673e8c447e8a09005e6c474d35f2025-08-20T02:17:24ZengMDPI AGDiagnostics2075-44182025-04-01158104810.3390/diagnostics15081048The Prognostic and Predictive Roles of Ataxia–Telangiectasia Mutated (ATM) Expression in Patients with Metastatic Non-Small-Cell Lung Cancer Receiving Pembrolizumab Monotherapy Alone or in Combination with ChemotherapyJamshid Hamdard0Harun Muğlu1Ahmet Bilici2Elif Kuzucular3Özgür Açıkgöz4Ömer Fatih Ölmez5Oktay Olmuşçelik6Özcan Yıldız7Medical Oncology Department, Faculty of Medicine, Medipol University, İstanbul 34214, TürkiyeMedical Oncology Department, Faculty of Medicine, Medipol University, İstanbul 34214, TürkiyeMedical Oncology Department, Faculty of Medicine, Medipol University, İstanbul 34214, TürkiyeMedical Pathology Department, Faculty of Medicine, Medipol University, İstanbul 34214, TürkiyeMedical Oncology Department, Faculty of Medicine, Medipol University, İstanbul 34214, TürkiyeMedical Oncology Department, Faculty of Medicine, Medipol University, İstanbul 34214, TürkiyeInternal Medicine Department, Faculty of Medicine, Medipol University, İstanbul 34214, TürkiyeMedical Oncology Department, Faculty of Medicine, Medipol University, İstanbul 34214, Türkiye<b><b>Background/Objectives:</b></b> This study investigated the prognostic and predictive significance of Ataxia–Telangiectasia Mutated (ATM) expression in patients with metastatic non-small-cell lung cancer (NSCLC) who were treated with pembrolizumab. <b>Methods:</b> A retrospective analysis was conducted on 49 patients with metastatic NSCLC who received first-line pembrolizumab, either as a single agent or in combination with chemotherapy. ATM expression in archival pathology specimens was assessed using immunohistochemistry, where nuclear staining was considered to be positive. ATM expression was categorized into low- and high-expression groups based on staining intensity and the percentage of positive cells. Subsequently, the prognostic and predictive value of ATM expression was evaluated. <b>Results:</b> In terms of demographics, the mean age was 62.7 ± 9.5, most patients (91.8%) were male, and the majority (75.5%) had adenocarcinoma. The objective response rate (ORR) was 69.4%, and ATM expression was high in 75.5% of patients. Patients with low ATM expression had significantly longer progression-free survival (PFS) compared to those with high expression (51 vs. 5.7 months, <i>p</i> = 0.004). In multivariate analysis, ATM expression was the only independent prognostic factor for PFS, showing that patients with high ATM expression had a shorter overall survival (OS) compared to those with low expression (51 vs. 8.9 months, <i>p</i> = 0.013), which was statistically significant (HR 2.41, <i>p</i> = 0.034). Logistic regression analysis showed that ATM expression, as well as the presence of bone metastasis and the absence of liver metastasis, was significantly associated with a response to treatment (<i>p</i> = 0.006; OR: 0.06; 95% CI: 0.008–0.45). <b>Conclusions:</b> The findings of this study concerning ATM expression as a biomarker should be interpreted cautiously due to inherent limitations, including its retrospective design, the semi-quantitative nature of immunohistochemistry for ATM assessment, the small sample size with uneven clinical characteristics, and the relatively short follow-up period, which collectively impact generalizability. Despite these limitations, lower ATM expression was associated with better prognosis and pembrolizumab treatment response, suggesting that it may be a valuable biomarker for predicting these factors.https://www.mdpi.com/2075-4418/15/8/1048non-small-cell lung cancerATM expressionpembrolizumabprogression-free survivaloverall survival |
| spellingShingle | Jamshid Hamdard Harun Muğlu Ahmet Bilici Elif Kuzucular Özgür Açıkgöz Ömer Fatih Ölmez Oktay Olmuşçelik Özcan Yıldız The Prognostic and Predictive Roles of Ataxia–Telangiectasia Mutated (ATM) Expression in Patients with Metastatic Non-Small-Cell Lung Cancer Receiving Pembrolizumab Monotherapy Alone or in Combination with Chemotherapy Diagnostics non-small-cell lung cancer ATM expression pembrolizumab progression-free survival overall survival |
| title | The Prognostic and Predictive Roles of Ataxia–Telangiectasia Mutated (ATM) Expression in Patients with Metastatic Non-Small-Cell Lung Cancer Receiving Pembrolizumab Monotherapy Alone or in Combination with Chemotherapy |
| title_full | The Prognostic and Predictive Roles of Ataxia–Telangiectasia Mutated (ATM) Expression in Patients with Metastatic Non-Small-Cell Lung Cancer Receiving Pembrolizumab Monotherapy Alone or in Combination with Chemotherapy |
| title_fullStr | The Prognostic and Predictive Roles of Ataxia–Telangiectasia Mutated (ATM) Expression in Patients with Metastatic Non-Small-Cell Lung Cancer Receiving Pembrolizumab Monotherapy Alone or in Combination with Chemotherapy |
| title_full_unstemmed | The Prognostic and Predictive Roles of Ataxia–Telangiectasia Mutated (ATM) Expression in Patients with Metastatic Non-Small-Cell Lung Cancer Receiving Pembrolizumab Monotherapy Alone or in Combination with Chemotherapy |
| title_short | The Prognostic and Predictive Roles of Ataxia–Telangiectasia Mutated (ATM) Expression in Patients with Metastatic Non-Small-Cell Lung Cancer Receiving Pembrolizumab Monotherapy Alone or in Combination with Chemotherapy |
| title_sort | prognostic and predictive roles of ataxia telangiectasia mutated atm expression in patients with metastatic non small cell lung cancer receiving pembrolizumab monotherapy alone or in combination with chemotherapy |
| topic | non-small-cell lung cancer ATM expression pembrolizumab progression-free survival overall survival |
| url | https://www.mdpi.com/2075-4418/15/8/1048 |
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