Abstract 179P
Background
For unresectable locally advanced esophageal squamous cell carcinoma (ESCC) patients, definitive concurrent chemoradiotherapy (dCRT) stands as the standard treatment. Despite recent advancements in radiotherapy (RT) techniques and therapeutic regimens, the overall prognosis remains unfavorable. Therefore, effective predictive methods hold promise in providing risk-stratified and response-adapted treatment plans for individuals.
Methods
Fifty-one patients who underwent definitive radiotherapy (dRT) were included from a prospective real-world study on comprehensive treatment of ESCC (NCT05543057). Tumor biopsies were collected before treatment. Blood samples for ctDNA analysis were collected after the whole dRT process. A tumor-informed MRD detection strategy was employed to analyze the cfDNA samples. Exome sequencing was performed on DNA from tumor biopsies and buffy coats to obtain a list of somatic mutations for each case. 40 mutations were selected for analysis in the matched cfDNA samples. We applied Mutation Capsule technology to profile the tumor-specific mutations in cfDNA. Plasma samples with two or more ctDNA mutations were defined as MRD positive. For the MRD positive samples, the sample-level ctDNA fraction was evaluated.
Results
In the dRT cohort, 45% (23/51) of them exhibited disease progression during a median follow-up period of 19 months. A significant difference was observed in the ctDNA fractions between the disease progression group and the progression-free groups at the post-dRT time point (P<0.0001). Of the 51 cases, 26 (51%) were MRD positive and 25 (49%) were MRD negative in the post-dRT blood. Notably, none of the MRD negative patients (0/25) showed progression. Conversely, 88% (23/26) of the MRD-positive patients encountered disease progression. The post-dRT MRD status accurately forecasted prognosis by detecting residual cancer cells with a sensitivity of 100% (23/23) and a specificity of 89% (25/28).
Conclusions
In summary, we present an MRD profiling solution that precisely identified a subgroup of ESCC patients who might progress after dRT. These findings highlight MRD profiling's potential as an invaluable tool in predicting ESCC patient prognosis.
Clinical trial identification
NCT05543057.
Editorial acknowledgement
Legal entity responsible for the study
Wen-Yang Liu.
Funding
This work was supported by grants from the CAMS Innovation Fund for Medical Sciences (CIFMS) [grant number 2023-I2M-C&T-B-088]; and the Beijing Hope Run Special Fund of Cancer Foundation of China [grant number LC2022A16].
Disclosure
All authors have declared no conflicts of interest.