The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors.
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ABSTRACT:
SUBMITTER: Jin Y
PROVIDER: S-EPMC7596978 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors.
Jin Ying Y Chen Dong-Liang DL Wang Feng F Yang Chao-Pin CP Chen Xu-Xian XX You Jin-Qi JQ Huang Jin-Sheng JS Shao Yang Y Zhu Dong-Qin DQ Ouyang Yu-Ming YM Luo Hui-Yan HY Wang Zhi-Qiang ZQ Wang Feng-Hua FH Li Yu-Hong YH Xu Rui-Hua RH Zhang Dong-Sheng DS
Molecular cancer 20201030 1
A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13. ...[more]
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Project description:Immune checkpoint inhibitors (ICIs), represented by anti-CTLA-4 or anti-PD-1/anti-PD-L1 pathway antibodies, have led to a revolution in cancer treatment modalities. ICIs have unique clinical benefits, such as effectiveness against a broad range of tumor types, strong overall impact on survival, and persistent responses after the cessation of therapy. However, only a subset of patients responds to these therapies, and a small proportion of patients even experience rapid progression or an increased risk of death. Therefore, it is imperative to optimize patient selection for treatment. This review focuses on the mechanisms of tumor escape from immune surveillance, the composition and activity of a preexisting immune infiltrate, the degree of tumor foreignness (as reflected by the mutational burden, expression of viral genes, and driver gene mutations), and host factors (including peripheral blood biomarkers, genetic polymorphisms, and gut microbiome) to summarize current evidence on the biomarkers of responses to ICIs and explore the future prospects in this field.
| S-EPMC6086110 | biostudies-literature
Project description:BackgroundThe use of circulating tumor DNA (ctDNA) to reflect clinical benefits of advanced non-small cell lung cancer (NSCLC) patients during immune checkpoint inhibitor (ICI) therapy remains controversial. This study aimed to determine the association of pre-treatment and early dynamic changes of ctDNA with clinical outcomes in advanced NSCLC patients treated with ICIs.MethodsElectronic databases (PubMed, Embase, Web of Science, and Cochrane) were systematically searched to include relevant studies published in English up to November 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS) and the secondary outcome was objective response rate (ORR) with RECIST criteria.ResultsA total of 1017 patients from 10 studies were identified. The baseline ctDNA levels (detected versus not detected) showed no significant association with clinical outcomes regarding OS (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.93-1.51), PFS (HR, 0.98; 95% CI, 0.80-1.21), and ORR (odds ratio [OR], 0.89; 95% CI, 0.54-1.46). Interestingly, when taken early longitudinal assessment of ctDNA into consideration, the early reduction of the concentration of ctDNA was associated with significant improvements of OS (HR, 0.19; 95% CI, 0.10-0.35), PFS (HR, 0.30; 95% CI, 0.22-0.41) and ORR (OR, 0.07; 95% CI, 0.03-0.18). Further subgroup analyses revealed that the reduction magnitude did not significantly impact the association between ctDNA and clinical outcomes, suggesting that both patients with decreased ctDNA or a ≥50% reduction of ctDNA was associated with improved OS, PFS and ORR.ConclusionEarly reduction of ctDNA was associated with improved OS, PFS and ORR in advanced NSCLC patients treated with ICIs.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, CRD42021226255.
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Project description:Immunotherapy has recently changed the treatment of several cancers. We performed a literature-based meta-analysis of randomised controlled trials to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in metastatic gastric cancer. The main outcome was overall survival. Based on age (cut-off agreed at 65 years), tumour location (gastric vs. gastro-oesophageal junction), programmed death-ligand 1 (PD-L1) status, sex and Eastern Cooperative Oncology Group (ECOG) status (1 vs. 0), we scheduled a subgroup analysis for the overall survival. Three studies were included in the analysis for a total of 1456 cases (811 cases were in the experimental group and 645 cases in the control group). The pooled analysis showed improved overall survival in the experimental arm in the absence of statistical significance (hazard ratio (HR) = 0.87, 95% CI: 0.64-1.18; p = 0.37). The subgroup of patients with PD-L1-positive tumours (HR = 0.82 vs. 1.04) and gastro-oesophageal junction cancer (HR = 0.82 vs. 1.04) showed a statistically significant advantage of overall survival. This study supports the efficacy of immune checkpoint inhibitors in the subgroup of patients with metastatic gastric cancer with PD-L1-positive and gastro-oesophageal junction tumour location. Future studies are needed with the aim of identifying reliable predictive biomarkers of ICI efficacy.
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Project description:PurposeImmunotherapy is regarded as the most promising treatment for cancer. However, immune checkpoint inhibitors (ICIs) are not effective for all patients. Herein, we conducted a systematic review and meta-analysis to explore whether tumor mutational burden (TMB) can be used as a potential prognostic biomarker for cancer patients treated with ICIs.MethodsWe systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to December 28, 2020. All cohort studies and clinical trials that reported hazard ratios (HRs) for overall (OS) and progression-free survival (PFS), as well as the corresponding 95% confidence intervals (CIs) of high and low TMB patients, were included. All statistical analyses were performed using the R software.ResultsPooled results from a total of 32 studies with 6,131 participants showed significantly increased OS (HR: 0.61, 95% CI: 0.53-0.71; P <0.01) and PFS (HR: 0.51, 95% CI: 0.44-0.60; P <0.01) for the high TMB group receiving ICIs as compared to the low TMB group. Particularly, results were found to be more significant in studies with larger sample sizes (≥30), Western patients, higher TMB cutoff values (≥20 mut/Mb), anti-PD-1 therapy, and when the sample source was tissue and tumor type was either melanoma, small cell lung cancer, or gastric cancer.ConclusionTMB is a promising independent prognostic biomarker for cancer patients receiving ICIs, which could provide a new potential therapeutic strategy for high TMB patients who have failed traditional therapy. Furthermore, consistency in the key aspects of TMB assessment is expected in the future.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42021229016.
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Project description:Immune checkpoint inhibitors (ICIs) combined with platinum-containing chemotherapy are recommended as the standard first-line treatment for non-small cell lung cancer (NSCLC). However, specific prognostic markers for this combination therapy are yet to be identified. Evaluation of circulating tumor cells (CTCs) and cell surface programmed death-ligand 1 (PD-L1) exhibits potential in predicting the efficacy of the aforementioned combination therapy. Thus, the present study aimed to evaluate the prognostic value of CTC PD-L1 testing and other clinical characteristics in patients with NSCLC treated with combination therapy as first-line treatment. In total, 40 patients with advanced NSCLC were included in the present study, and all patients underwent CTC PD-L1 testing at initial diagnosis to determine the association between CTC PD-L1 and tissue PD-L1. The prognostic value of CTC PD-L1 and the baseline characteristics of 26 patients with NSCLC were analyzed, and the prognostic values of changes in CTC PD-L1 and baseline characteristics during 6 months of treatment were further explored. Results of the present study demonstrated that there was no association between CTC PD-L1 and tissue PD-L1 levels. After 6 months of combination therapy, tumor shrinkage, CYFA19 levels and treatment maintenance were associated with progression-free survival (PFS) of patients. Notably, CTC PD-L1 and tissue PD-L1 levels, TNM stage, nutritional score, inflammation score and other blood indicators were not associated with PFS. In conclusion, the evaluation of CTCs and CTC PD-L1 suggested that undetectable CTCs at 6 months of NSCLC treatment are associated with a good prognosis. In addition, negative CTC PD-L1 expression may change to positive CTC PD-L1 expression in line with disease progression, and this may be indicative of poor prognosis.
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