Circulating tumor DNA predicts outcome in metastatic gastroesophageal cancer.
Gastric Cancer
; 25(5): 906-915, 2022 09.
Article
en En
| MEDLINE
| ID: mdl-35763187
ABSTRACT
BACKGROUND:
Circulating tumor DNA (ctDNA) has predictive and prognostic value in localized and metastatic cancer. This study analyzed the prognostic value of baseline and on-treatment ctDNA in metastatic gastroesophageal cancer (mGEC) using a region-specific next generation sequencing (NGS) panel.METHODS:
Cell free DNA was isolated from plasma of patients before start of first-line palliative systemic treatment and after 9 and 18 weeks. Two NGS panels were designed comprising the most frequently mutated genes and targetable mutations in GEC. Tumor-derived mutations in matched metastatic biopsies were used to validate that the sequencing panels assessed true tumor-derived variants. Tumor volumes were calculated from baseline CT scans and correlated to variant allele frequency (VAF). Survival analyses were performed using univariable and multivariable Cox-regression analyses.RESULTS:
ctDNA was detected in pretreatment plasma in 75% of 72 patients and correlated well with mutations in metastatic biopsies (86% accordance). The VAF correlated with baseline tumor volume (Pearson's R 0.53, p < 0.0001). Detection of multiple gene mutations at baseline in plasma was associated with worse overall survival (OS, HR 2.16, 95% CI 1.10-4.28; p = 0.027) and progression free survival (PFS, HR 2.71, 95% CI 1.28-5.73; p = 0.009). OS and PFS were inferior in patients with residual detectable ctDNA after 9 weeks of treatment (OS HR 4.95, 95% CI 1.53-16.04; p = 0.008; PFS HR 4.08, 95% CI 1.31-12.75; p = 0.016).CONCLUSION:
Based on our NGS panel, the number of ctDNA mutations before start of first-line chemotherapy has prognostic value. Moreover, residual ctDNA after three cycles of systemic treatment is associated with inferior survival.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
/
Neoplasias Esofágicas
/
ADN Tumoral Circulante
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Gastric Cancer
Asunto de la revista:
GASTROENTEROLOGIA
/
NEOPLASIAS
Año:
2022
Tipo del documento:
Article
País de afiliación:
Países Bajos