表 1.
检测ctDNA和bTMB的不同研究的比较
Comparison of the different studies testing ctDNA and bTMB
| Author, Year | Design | Population | Treatment | Method(s)/panel | Main findings/Threshold |
| R/P: retrospective/prospective design; NSCLC: non-small cell lung cancer; UM: uveal melanoma; MSI: microsatellite instability; CRC: colorectal cancer; ddPCR: droplet-digital polymerase chain reaction; bi-PAP: bidirectional pyrophosphorolysis activated polymerization; NGS: next generation sequencing; PFS: progression free survival; OS: overall survival; ICI: immune checkpoint inhibitor; CTx: chemotherapy; AF: allele fraction; qPCR: quantitative polymerase chain reaction; TTP: time to progression; TEC-Seq: targeted error corrected sequencing; VAF: variant allele fraction; bTMB: blood tumor mutational burden; CAPP-Seq: cancer personalized profiling by deep sequencing; DCB: durable clinical benefits; ctDNA: circulating tumor DNA; bTMB: blood tumor mutational burden. | |||||
| Cabel, 2017[2] | P | NSCLC (n=10), UM (n=3), MSI-high CRC (n=2) | Nivolumab | ddPCR, bi-PAP, NGS monogene, 39 genes panel | ctDNA levels undetectable at 8 weeks associated with longer PFS and OS |
| Goldberg, 2018[3] | P | Metastatic NSCLC (n=28) | ICI, not further specified, CTx | NGS 24 genes panel | ctDNA diminution associated with prolonged survival; threshold ctDNA response as a > 50% decrease in AF from baseline |
| Giroux, 2018[4] | P | Stage Ⅲb/Ⅳ NSCLC (n=15) | Nivolumab | NGS 22 genes panel | 9% increase of ctDNA at first tumor evaluation correlated with absence of clinical benefit, shorter PFS and poorer OS |
| Passiglia, 2019[5] | R | Stage Ⅳ NSCLC (n=45) | Nivolumab | qPCR unknow | cfDNA increase > 20% at 6 weeks associated with worse OS and shorter TTP |
| Guibert, 2019[6] | R | Stage Ⅲb/Ⅳ, progressive NSCLC (n=65) | ICI | NGS 36 genes panel | Early changes (increase vs decrease) in the ctDNA AF were correlated with PFS |
| Anagnostou, 2019[7] | R | Metastatic NSCLC (n=24) | ICI | TEC-Seq NGS 58 genes panel | Reduction in ctDNA to undetectable levels was associated with longer PFS and OS |
| Stage Ⅰ-Ⅲ NSCLC (n=14) | Neo-adjuvant nivolumab | Reduction in ctDNA to undetectable levels was associated with major or partial pathological response | |||
| Zhang, 2020[8] | R | Advanced lung cancer (n=333) Other solid tumors (n=645) | Durvalumab±tremelimumab | NGS 73 genes panel | Pretreatment VAF was inverse correlated with OS; ctDNA increased during treatment was correlated with poor OS |
| Gandara, 2018[10] | R | Advanced NSCLC: OAK (n=273) +POPLAR (n=583) | Atezolizumab | F1CDx 324 genes | bTMB is positively associated with PFS threshold 16 Mut/mb |
| MYSTIC, 2020[11] | R | Metastatic NSCLC: MYSTIC (n=809) | Durvalumab+ tremelimumab | GuardantOMNI 500 genes | bTMB is positively associated superior ORR, PFS and OS; threshold 20 Mut/mb |
| Wang, 2019[12] | R | Advanced NSCLC (Line 1: n=48; Line 2: n=50) | ICI, non-specified | NCC-GP150 150 genes | bTMB is positively associated with superior ORR and PFS; threshold 6 Mut/mb |
| Nabet, 2020[13] | R | Advanced NSCLC (n=99) | ICI | CAPP-Seq 270 genes | High blood based TMB, ctDNA decreased after one infusion, low CD8 are associated with good DCB; threshold 14 Mut/mb |