biostudies-literatureDong YChinese Academy of Medical Sciences Key lab of translational research on lung cancerNational Natural Science Foundation of ChinaBeijing Municipal Administration of Hospitals Incubating ProgramThe Capital health research and development of special fund5649https://www.ebi.ac.uk/biostudies/studies/S-EPMC9688065biostudies-literatureUnknown14(22)<h4>Introduction</h4>Recent studies exhibited the unstable prediction ability of blood-based tumor mutational burden (bTMB) when predicting the response of immune checkpoint inhibitors (ICIs) therapy in patients with non-small cell lung cancer (NSCLC). Circulating tumor DNA (ctDNA) abundance, usually represented by maximum somatic allele frequency (MSAF), was one possible confounding factor influencing bTMB ability in ICIs response prediction.<h4>Methods</h4>MSAF-adjusted bTMB (Ma-bTMB) was established and validated in patients with advanced NSCLC among Geneplus Cancer Genome Database (GCGD, <i>n</i> = 1679), Zhuo (<i>n</i> = 35), Wang (<i>n</i> = 45), POPLAR (NCT01903993, <i>n</i> = 211) and OAK (NCT02008227, <i>n</i> = 642) cohorts.<h4>Results</h4>MSAF demonstrated a modest positive correlation with bTMB and a negative one with survival benefit. Improved survival outcomes of ICIs therapy have been observed among patients with high-Ma-bTMB compared to those with low-Ma-bTMB in Zhuo and Wang cohorts. In addition, compared to low-Ma-bTMB, high-Ma-bTMB was associated with more positive clinical benefits from ICIs therapy than chemotherapy both in POPLAR and OAK cohorts. Further exploration suggested that Ma-bTMB could precisely identify more potential ICIs beneficiaries compared to bTMB and LAF-bTMB, complementary to PD-L1 expression.<h4>Conclusions</h4>We developed Ma-bTMB, a convenient, readily available, non-invasive predictive biomarker effectively differentiates beneficiaries of ICIs therapy in advanced NSCLC, warranting future clinical trials.CancersMaximum Somatic Allele Frequency-Adjusted Blood-Based Tumor Mutational Burden Predicts the Efficacy of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer.PMC9688065818718892018PT310358207258682141117PX20200452022-2-1023Duan JXia XYi XYi YDong YXie YZhu YHao SWang JYuan JZhuo MGuan YChen XYu ZBai HWang ZfalseMaximum Somatic Allele Frequency-Adjusted Blood-Based Tumor Mutational Burden Predicts the Efficacy of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer.<h4>Introduction</h4>Recent studies exhibited the unstable prediction ability of blood-based tumor mutational burden (bTMB) when predicting the response of immune checkpoint inhibitors (ICIs) therapy in patients with non-small cell lung cancer (NSCLC). Circulating tumor DNA (ctDNA) abundance, usually represented by maximum somatic allele frequency (MSAF), was one possible confounding factor influencing bTMB ability in ICIs response prediction.<h4>Methods</h4>MSAF-adjusted bTMB (Ma-bTMB) was established and validated in patients with advanced NSCLC among Geneplus Cancer Genome Database (GCGD, <i>n</i> = 1679), Zhuo (<i>n</i> = 35), Wang (<i>n</i> = 45), POPLAR (NCT01903993, <i>n</i> = 211) and OAK (NCT02008227, <i>n</i> = 642) cohorts.<h4>Results</h4>MSAF demonstrated a modest positive correlation with bTMB and a negative one with survival benefit. Improved survival outcomes of ICIs therapy have been observed among patients with high-Ma-bTMB compared to those with low-Ma-bTMB in Zhuo and Wang cohorts. In addition, compared to low-Ma-bTMB, high-Ma-bTMB was associated with more positive clinical benefits from ICIs therapy than chemotherapy both in POPLAR and OAK cohorts. Further exploration suggested that Ma-bTMB could precisely identify more potential ICIs beneficiaries compared to bTMB and LAF-bTMB, complementary to PD-L1 expression.<h4>Conclusions</h4>We developed Ma-bTMB, a convenient, readily available, non-invasive predictive biomarker effectively differentiates beneficiaries of ICIs therapy in advanced NSCLC, warranting future clinical trials.2022-01-01T00:00:00Z2022 Nov2025-04-05T14:41:10.22Z2025-04-05T14:41:10.22ZS-EPMC96880653642874410.3390/cancers14225649