Jiguang Jia1, Bin Huang1, Zhengling Zhuang1, Sen Chen2. 1. 1 Department of Orthopedics, Xiangyang No.1 People's Hospital, Hubei University of Medicine - China. 2. 2 Department of Orthopedics, Renmin Hospital of Wuhan University - China.
Abstract
PURPOSE: Bone metastases from non-small cell lung cancer (NSCLC) are common, and current prognostic stratification methods are challenging to predict outcomes. The aim of the study is to examine circulating tumor DNA as a potential biomarker to gauge overall survival. METHODS: Late stage NSCLC patients associated with bone metastasis were recruited for the study. Circulating tumor DNA was quantified using droplet digital polymerase chain reaction, a sensitive assay that is capable to pick up low mutant DNA frequencies. KRAS and EGFR genes were serially profiled at monthly intervals to ascertain their variations in different patients during monitoring. These were correlated to overall survival as an endpoint measure. RESULTS: Analysis of circulating tumor DNA and tumor tissues samples yielded a 94.7% overall agreement for KRAS and EGFR mutations. Higher circulating tumor DNA quantities of more than 1.4-fold were also detected in patients with bone metastases. To gauge the prognostic utility of circulating tumor DNA for these patient groups, circulating tumor DNA quantities as well as the patients' genotypes were used to stratify patients in the survival analysis. Hazard ratios for patient groups with and without bone metastasis was 1.63. Patients groups separated by circulating tumor DNA quantity and molecular profile were 1.51 and 1.58, respectively. The results showed that circulating tumor DNA was a useful marker to identify patients with better survival outcomes. CONCLUSION: The good overall concordance in genetic profiling and circulating tumor DNA measurements associated with NSCLC patients with bone metastases supports plasma-based testing. This study presents exploratory evidence of the prognostic role of circulating tumor DNA that can be of value in the management of the disease.
PURPOSE:Bone metastases from non-small cell lung cancer (NSCLC) are common, and current prognostic stratification methods are challenging to predict outcomes. The aim of the study is to examine circulating tumor DNA as a potential biomarker to gauge overall survival. METHODS: Late stage NSCLCpatients associated with bone metastasis were recruited for the study. Circulating tumor DNA was quantified using droplet digital polymerase chain reaction, a sensitive assay that is capable to pick up low mutant DNA frequencies. KRAS and EGFR genes were serially profiled at monthly intervals to ascertain their variations in different patients during monitoring. These were correlated to overall survival as an endpoint measure. RESULTS: Analysis of circulating tumor DNA and tumor tissues samples yielded a 94.7% overall agreement for KRAS and EGFR mutations. Higher circulating tumor DNA quantities of more than 1.4-fold were also detected in patients with bone metastases. To gauge the prognostic utility of circulating tumor DNA for these patient groups, circulating tumor DNA quantities as well as the patients' genotypes were used to stratify patients in the survival analysis. Hazard ratios for patient groups with and without bone metastasis was 1.63. Patients groups separated by circulating tumor DNA quantity and molecular profile were 1.51 and 1.58, respectively. The results showed that circulating tumor DNA was a useful marker to identify patients with better survival outcomes. CONCLUSION: The good overall concordance in genetic profiling and circulating tumor DNA measurements associated with NSCLCpatients with bone metastases supports plasma-based testing. This study presents exploratory evidence of the prognostic role of circulating tumor DNA that can be of value in the management of the disease.
Entities:
Keywords:
Bone metastases; Circulating tumor DNA; KRAS; NSCLC; T790M
Authors: Pieter A Boonstra; Thijs T Wind; Michel van Kruchten; Ed Schuuring; Geke A P Hospers; Anthonie J van der Wekken; Derk-Jan de Groot; Carolien P Schröder; Rudolf S N Fehrmann; Anna K L Reyners Journal: Cancer Metastasis Rev Date: 2020-09 Impact factor: 9.264