Main Session
Sep
30
SS 33 - GI 2: Giving Radiation a Boost in Pancreatic Cancer and Responding to the Call for Esophageal Cancer
293 - Patient-Specific TP53-Mutant Circulating Tumor DNA as a Prognostic Biomarker for Detection of Minimal Residual Disease after Neoadjuvant Concurrent Chemoradiotherapy followed by Esophagectomy in Locally Advanced Esophageal Squamous Cell Carcinoma
Presenter(s)
Jason Chia-Hsien Cheng, MD, PhD, MS, FASTRO - National Taiwan University Hospital, Taipei, Taipei
F. M. Hsu1,2, S. L. Lu1,2, C. H. Hsu3,4, T. C. Huang3, J. C. Guo3, J. M. Lee5, P. M. Huang5, Y. L. Chang6, and J. C. H. Cheng1,4; 1Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, 2Department of Radiation Oncology, National Taiwan University Cancer Center, Taipei, Taiwan, 3Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, 4Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan, 5Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, 6Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
Purpose/Objective(s):
Neoadjuvant concurrent chemoradiotherapy (NeoCCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell carcinoma (LAESCC). However, patients (pts) without pathological complete response (pCR) face a high risk of disease recurrence. Adjuvant immunotherapy has demonstrated improved outcomes for pts with residual disease after NeoCCRT. Detecting minimal residual disease (MRD) after treatment might be crucial for selecting pts who would benefit most from adjuvant therapy. Given that TP53 mutation is the most frequently and diversely mutated gene in esophageal cancer, the present study investigated whether the quantification of circulating tumor DNA (ctDNA) with patient-specific TP53 mutations can serve as a prognostic biomarker to predict recurrences after trimodality therapy.Materials/Methods:
From 2019 to 2023, 50 pts diagnosed with TP53 mutant LAESCC and completed NeoCCRT followed by radical esophagectomy were enrolled. The plasma samples were obtained before NeoCCRT and after esophagectomy. The patient-specific TP53 mutation probes were designed for the detection and quantification of ctDNA by quantitative real-time polymerase chain reaction. The percentage of quantitative signals of patient-specific mutant TP53 to the wild-type TP53 (%ctDNA) was calculated for data analysis. The Mann-Whitney test, and Kaplan-Meier method analysis with the log-rank test were used for statistical analysis.Results:
Of the 50 pts, 17 pts achieved pCR while 33 pts did not. The mean and median values %ctDNA were 28.8% and 27%, respectively, before NeoCCRT and 24.2% and 18.9%, respectively, after surgery. No significant differences in %ctDNA were observed between pCR and non-pCR pts both before NeoCCRT (median 27% versus 26%, p=0.91) and after surgery (median 12.2% versus 22.4%, p=0.26). Notably, pts who experienced recurrence had significantly higher %ctDNA both before NeoCCRT (median 36.6% versus 18.2%, p=0.01) and after surgery (median 32.3% versus 5%, p<0.01). Using 10% as the threshold for detectable MRD, 19 pts (including 8 pts with pCR) were considered to have no MRD and 30 pts (one had not successfully assayed) were deemed to have MRD. Those with MRD had significantly worse recurrence-free survival after surgery compared to those without MRD in the entire cohort (median 11.3 months versus not reached, p<0.001) and among the non-pCR cohort (median 6.7 months versus not reached, p<0.001).Conclusion:
Detecting and quantifying patient-specific TP53 mutations in ctDNA is a promising prognostic tool for predicting recurrence in TP53-mutant LAESCC pts undergoing trimodality therapy. Pts without detectable MRD after surgery exhibited a low risk of recurrence. Further validation in larger, independent cohorts is warranted to confirm the clinical utility of this tool, which may be used to guide decisions for adjuvant therapy.