In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 3544-3544
Abstract:
3544 Background: ‘Watch and Wait’ policy has currently led to growing interest for organ-preservation after neoadjuvant chemoradiation (nCRT) to improve quality of life. However, how to predict and select patients who may achieve clinical complete response is still an unsolved issue. We conducted a pilot study to evaluate the potential role of ctDNA as a biomarker to predict treatment outcome and improve risk stratification in locally advanced rectal cancer (LARC). Methods: In this study, we recruited 119 patients with LARC receiving nCRT. 595 serial plasma samples were collected at d0, d15, d25 of radiotherapy as well before and 7 days post surgery. The level of ctDNA was calculated by dynamic monitoring the mutant allele frequency of somatic mutations in plasma. Plasma and tissue samples were subjected to targeted-NGS using a 422 cancer-related genes panel. We followed up patients with concomitant CT until disease progression or death. Results: Detected mutation of TP53 and APC gene in pre-treatment samples was negatively correlated with patients’ response to nCRT. Alterations in homologous recombination and adherens junction pathways were associated with a better response (P 〈 0.05). Detection of pre-treatment mutations in any time points during nCRT was significantly (P = 0.03) decreased from TRG3 to TRG0 group (33%, 29%, 22% and 4%, respectively); while detection of acquired mutations showed an opposite trend (P = 0.04). A predictive model based on support vector machine was developed for prediction of pCR achieving a mean AUC of 0.85 assessed by repeated cross validation. Further, detection of pre-treatment mutations after completion of nCRT was significantly associated with worse disease-free survival (DFS) (P 〈 0.05). Through tracking clonal extinction, persistence and emergence, patients were grouped into four evolutionary subtypes with distinct TRG and DFS. Conclusions: Our data showed the prognostic value of ctDNA on DFS. Dynamic monitoring of ctDNA can be used to predict TRG and prognosis in LARC patients receiving nCRT. ctDNA sequencing depicts the evolutionary trajectories of sensitive and resistant clones during nCRT in LARC. CtDNA could potentially be used to guide patient selection for W & W strategy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.3544
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
