Observational studyJournal of translational medicine2021
High lymphocyte population-related predictive factors for a long-term response in non-small cell lung cancer patients treated with pemetrexed: a retrospective observational study.
Observational study in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Maintenance therapy for metastatic non-squamous non-small cell lung cancer: efficacy and biomarker analysis of pemetrexed discontinuation.Translational lung cancer research · 2026Article
- Clinical efficacy of Atezolizumab/Bevacizumab combined with TACE in treating BCLC stage C hepatocellular carcinoma.Frontiers in oncology · 2026Article
- Targeting lung cancer: synergistic therapeutic strategy of cuproptosis and immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- A Review of the Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Nonhematologic Malignancies.Diagnostics (Basel, Switzerland) · 2024Review
- Clinical significance of the advanced lung cancer inflammation index in patients with limited-stage small cell lung cancer treated with chemoradiotherapy.Scientific reports · 2024Article
- Clinical application of immunogenic cell death inducers in cancer immunotherapy: turning cold tumors hot.Frontiers in cell and developmental biology · 2024Review
- Association between changes in thioredoxin reductase and other peripheral blood biomarkers with response to PD-1 inhibitor-based combination immunotherapy in non-small cell lung cancer: a retrospective study.Translational lung cancer research · 2022Article
- From targeted therapy to a novel way: Immunogenic cell death in lung cancer.Frontiers in medicine · 2022Review
- Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma.Cancer cell international · 2021Article
- Neutrophils in the era of immune checkpoint blockade.Journal for immunotherapy of cancer · 2021Review
- Baseline Neutrophil-to-Lymphocyte Ratio Predicts Overall Survival in PD-L1-positive Advanced Triple-negative Breast Cancer With Immune-checkpoint-inhibitor Treatment.Cancer diagnosis & prognosisArticle
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRegimens combining pemetrexed (PEM) and immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed death-ligand 1 (PD-L1) are widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSq-NSCLC). Recently, PEM was shown to induce immunogenic cell death (ICD) and to enhance immune-regulatory genes. Some patients demonstrate an extremely long-term response to PEM. It is possible that the continued response in these patients is dependent on not only the pharmacological induction of cytotoxic cell death but also antitumor immunity. However, factors that can predict outcomes associated with long-term PEM administration using blood test results have not yet been elucidated. We investigated the clinical characteristics and predictive factors in patients with advanced NSq-NSCLC who underwent long-term PEM maintenance therapy.
methodsIn total, 504 patients with advanced NSq-NSCLC who received PEM combination therapy/monotherapy (n = 414) or paclitaxel (PTX) combination therapy (n = 90) between January 2010 and November 2019 were recruited; 381 patients were retained for the final analysis. Patients treated with PEM (n = 301) were divided into subgroups according to the total cycles of PEM (≥ 17 [n = 25] for the long-term administration group and ≤ 16 [n = 276] for the intermediate/short-term group) and compared with another population (n = 80) treated with PTX combination regimen. We investigated clinical features and predictive biomarkers, focusing on immune-regulatory factors, absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), and PD-1 and PD-L1 expression, to predict long-term response to PEM.
resultsThe long-term PEM administration group exhibited a higher ALC and a lower NLR than the shorter-term group did. Both these markers displayed greater association with progression-free survival and overall survival in the PEM combination therapy group than in the PTX combination therapy group. Increased PD-1 lymphocytes were associated with the long-term PEM response group, as PD-L1 expression in tumors was associated with a high incidence of immune-related adverse effects following ICI administration.
conclusionsALC, NLR, and PD-1 expression are PEM-mediated predictive biomarkers that are indirectly related to tumor immunity and can provide useful predictive information on the long-term response to PEM in patients with NSq-NSCLC.
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