Maximum Somatic Allele Frequency-Adjusted Blood-Based Tumor Mutational Burden Predicts the Efficacy of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer

Dong, Yingyue; Zhu, Yongfa; Zhuo, Minglei; Chen, Xiaomin; Xie, Yinpeng; Duan, Jianchun; Bai, Hua; Hao, Shiguang; Yu, Zicheng; Yi, Yuting; Guan, Yanfang; Yuan, Jie; Xia, Xuefeng; Yi, Xin; Wang, Jie; Wang, Zhijie

doi:10.3390/cancers14225649

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…The predictive efficacy was further validated with the retrospective cohort (OS: HR = 0.20, 95% CI: 0.05-0.84; PFS: HR = 0.30, 95% CI: 0.13-0.70) [57,65]. This biomarker was further validated with the cohorts of the Geneplus Cancer Genome Database and other retrospective cohorts [66].…”

Section: Blood Tmb (Btmb)mentioning

confidence: 99%

Biomarkers for Immunotherapy in Driver-Gene-Negative Advanced NSCLC

Huang,

Chau,

Bai

et al. 2023

IJMS

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Outcome improvement in patients with driver-gene-negative advanced non-small cell lung cancer (NSCLC) has been significantly enhanced through targeting the immune system, specifically the PD-L1/PD-1 axis. Nevertheless, only a subset of patients with advanced NSCLC may derive benefits from immuno-monotherapy or immunotherapy combined with chemotherapy. Hence, in order to identify patients who will gain the maximum advantage from immunotherapy, it is crucial to investigate predictive biomarkers. This review provides a summary of the currently identified biomarkers associated with the extent of benefit from immuno-monotherapy or immunotherapy combined with chemotherapy in patients with advanced NSCLC. These biomarkers can be categorized into three groups: tumor-related, tumor-microenvironment-related, and host-factor-related.Tumor-related factors include PD-L1 expression, tumor mutational burden and specific genetic mutations, while tumor-microenvironment-related factors include extracellular vesicles and T-cell receptors, and host-related factors include systemic inflammation, circulating fatty acid profile, and the microbiome.

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Section: Blood Tmb (Btmb)mentioning

confidence: 99%

Biomarkers for Immunotherapy in Driver-Gene-Negative Advanced NSCLC

Huang,

Chau,

Bai

et al. 2023

IJMS

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“…MSAF considered that those frequencies' participation correspond to the abundance of ctDNA in cfDNA. Unfortunately, MSAF does not consider clonal hematopoiesis; thus, in many cases, TFE is more often recommended [45,46]. On the other hand, Schrock et al observed in NSCLC patients that a lower MSAF level was associated with a higher risk of missing important genomic alterations in the plasma, such as exon 19 deletion and p.Thr790Met substitution in the EGFR gene [47].…”

Section: Cfdna and Ctdna Differentiationmentioning

confidence: 99%

Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients

Galant,

Nicoś,

Kuźnar-Kamińska

et al. 2024

Cancers

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Despite the different possible paths of treatment, lung cancer remains one of the leading causes of death in oncological patients. New tools guiding the therapeutic process are under scientific investigation, and one of the promising indicators of the effectiveness of therapy in patients with NSCLC is variant allele frequency (VAF) analysis. VAF is a metric characterized as the measurement of the specific variant allele proportion within a genomic locus, and it can be determined using methods based on NGS or PCR. It can be assessed using not only tissue samples but also ctDNA (circulating tumor DNA) isolated from liquid biopsy. The non-invasive characteristic of liquid biopsy enables a more frequent collection of material and increases the potential of VAF analysis in monitoring therapy. Several studies have been performed on patients with NSCLC to evaluate the possibility of VAF usage. The research carried out so far demonstrates that the evaluation of VAF dynamics may be useful in monitoring tumor progression, remission, and recurrence during or after treatment. Moreover, the use of VAF analysis appears to be beneficial in making treatment decisions. However, several issues require better understanding and standardization before VAF testing can be implemented in clinical practice. In this review, we discuss the difficulties in the application of ctDNA VAF analysis in clinical routine, discussing the diagnostic and methodological challenges in VAF measurement in liquid biopsy. We highlight the possible applications of VAF-based measurements that are under consideration in clinical trials in the monitoring of personalized treatments for patients with NSCLC.

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Prospect of immunotherapy alone in patients with advanced NSCLC with high btmb: a review and a meta-analysis

Zhao,

Qiu,

Yang

et al. 2023

Holist Integ Oncol

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Lung cancer is the most prevalent cancer in the world, and the main treatment for advanced non-small cell lung cancer is immunotherapy combined with chemotherapy. In recent years, bTMB has received increasing attention as an emerging metric for monitoring the efficacy of tumour immunotherapy in terms of its operability, accessibility and real-time nature. We envisaged whether immunotherapy alone could be used to reduce the side effects of chemotherapy in patients with high bTMB lung cancer. We thus did a meta-analysis in order to show that immunotherapy alone is feasible in patients with high bTMB NSCLC.Methods This study aims to compare the efficacy of PD- 1/PD-L1 inhibitors (namely, atezolizumab, pembrolizumab, nivolumab, or tislelizumab) versus chemotherapy in NSCLC patients. The search for relevant studies was conducted in three major databases (i.e., PubMed, Embase, and Medline) up until January 2023. Specifically, we identified studies that reported risk ratios (HRs) for reporting progression-free survival (PFS) or overall survival (OS), or objective remission rates (ORs) for immunotherapy alone versus chemotherapy in high bTMB and low bTMB patient groups. Given that NSCLC represents the predominant type of lung cancer, we exclusively focused on this subtype. Our analysis encompassed a meta-analysis of the identified literature, incorporating heterogeneity analysis and sensitivity analysis. The quality of the evidence is evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to ascertain the reliability and robustness of the findings.Result-We conducted a meta-analysis of seven randomised controlled trials including 4,755 patients with advanced non-small cell lung cancer (NSCLC) evaluated the efficacy of PD- 1 or PD-L1 monotherapy compared to chemotherapy alone. All patients were randomized to receive either PD- 1/PD-L1 treatment alone or chemotherapy alone as a control. In the high bTMB patient group, PD- 1/PD-L1 monotherapy resulted in significant improvements in overall survival (HR = 0.55, 95% CI 0.49–0.61, p = 0.77) and progression-free survival (HR = 0.74, 95% CI 0.68–0.81, p = 0.78) compared to chemotherapy alone. Conversely, in the low bTMB patient group, PD- 1 monotherapy or PD-L1 monotherapy failed to demonstrate significant improvements in overall survival (HR = 0.82, 95% CI 0.73–0.92, p = 0. 13) and progression-free survival (HR = 1.22, 95% CI 1.22- 1.45, p = 0.003) in advanced NSCLC. Conclusion Our analysis suggests that monotherapy with immunotherapy is a feasible option for patients with advanced NSCLC and high bTMB. However, the results have to be construed with caution because of the small sample size and the potential bias in the studies included. Therefore, further research with larger sample sizes and rigorous study designs is necessary to confirm the observed benefits of immunotherapy in this patient population.

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Maximum Somatic Allele Frequency-Adjusted Blood-Based Tumor Mutational Burden Predicts the Efficacy of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer

Cited by 5 publications

References 33 publications

Biomarkers for Immunotherapy in Driver-Gene-Negative Advanced NSCLC

Biomarkers for Immunotherapy in Driver-Gene-Negative Advanced NSCLC

Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients

Prospect of immunotherapy alone in patients with advanced NSCLC with high btmb: a review and a meta-analysis

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