ArticleBMC medicine2022
Increased blood-based intratumor heterogeneity (bITH) is associated with unfavorable outcomes of immune checkpoint inhibitors plus chemotherapy in non-small cell lung cancer.
Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- The prognostic role of circulating DNA markers in patients with lung malignancies: a systematic review and meta-analysis.Biomarkers in medicine · 2025Pooled it
- Prognostic value of lung immune prognostic index in non-small cell lung cancer patients receiving immune checkpoint inhibitors: a meta-analysis.Pathology oncology research : POR · 2024Pooled it
- Tumor-Informed ctDNA in Guiding First-Line Immunochemotherapy in Advanced Non-Small Cell Lung Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Trial
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- Prognostic value of diabetes-related clinical indices in patients with non-small cell lung cancer and comorbid type 2 diabetes receiving immune checkpoint inhibitor therapy.Acta diabetologica · 2026Article
- Proteogenomic characterization of pulmonary large-cell neuroendocrine carcinoma identifies molecular features and therapeutic strategy.Science advances · 2026Article
- ITHindex: An integrated web-based platform for intratumor heterogeneity evaluation.PLOS digital health · 2026Article
- Intratumoral heterogeneity as a potential biomarker for immunotherapy response and postoperative recurrence in NSCLC.Frontiers in immunology · 2026Article
- Molecular features influencing clinical outcome of advanced HER2-positive gastric cancer receiving trastuzumab plus chemotherapy.Annals of medicine · 2025Article
- Monoclonal antibody immune therapy response instrument for stratification and cost-effective personalized approaches in 3PM-guided pan cancer management.The EPMA journal · 2025Review
- The association of immune-inflammation indices at multiple time points with treatment response and survival in advanced non-small cell lung cancer patients receiving immune checkpoint inhibitors.World journal of surgical oncology · 2025Article
- Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese Population.Research (Washington, D.C.) · 2025Article
- From Chaos to Opportunity: Decoding Cancer Heterogeneity for Enhanced Treatment Strategies.Biology · 2023Review
- Blood tumor mutational burden and dynamic changes in circulating tumor DNA predict response to pembrolizumab treatment in advanced non-small cell lung cancer.Translational lung cancer research · 2023Article
- Targeting immune cell types of tumor microenvironment to overcome resistance to PD-1/PD-L1 blockade in lung cancer.Frontiers in pharmacology · 2023Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe combination of immune checkpoint inhibitors (ICIs) and chemotherapy has been the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with driver-gene negative. However, efficacy biomarkers for ICIs-based combination therapy are lacking. We aimed to identify potential factors associated with outcomes of ICIs plus chemotherapy at baseline and dynamic changes in peripheral blood.
methodsWe collected plasma samples of 51 advanced NSCLC patients without EGFR/ALK/ROS1 alteration at baseline and/or after two treatment cycles of ICIs plus chemotherapy. A blood-based intratumor heterogeneity (bITH) score was calculated based on the allele frequencies of somatic mutations using a 520-gene panel. bITH-up was defined as a ≥ 10% increase in bITH score from baseline, with a second confirmatory measurement after treatment.
resultsAt baseline, the number of metastatic organs and lung immune prognostic index (LIPI) were significantly associated with shorter progression-free survival (PFS) of ICIs plus chemotherapy, while bITH and other common molecular biomarkers, including ctDNA level, blood-based tumor mutational burden (bTMB), and PD-L1 expression, had no effect on PFS. LRP1B mutation at baseline was significantly associated with favorable outcomes to ICIs plus chemotherapy. There were 37 patients who had paired samples at baseline and after two cycles of treatment, with the median interval of 53 days. Intriguingly, patients with bITH-up had significant shorter PFS (HR, 4.92; 95% CI, 1.72-14.07; P = 0.001) and a lower durable clinical benefit rate (0 vs 41.38%, P = 0.036) than those with bITH-stable or down. Case studies indicated that bITH was promising to predict disease progression.
conclusionsThe present study is the first to report that increased bITH is associated with unfavorable outcomes of ICIs plus chemotherapy in advanced NSCLC patients.
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