Circulating Tumor DNA for Prediction of Complete Pathological Response to Neoadjuvant Radiochemotherapy in Locally Advanced Rectal Cancer (NEORECT Trial)

循环肿瘤 DNA 预测局部晚期直肠癌新辅助放化疗的完全病理反应(NEORECT 试验)

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作者:Tatiana Mögele, Michael Höck, Florian Sommer, Lena Friedrich, Sebastian Sommer, Maximilian Schmutz, Amadeus Altenburger, Helmut Messmann, Matthias Anthuber, Thomas Kröncke, Georg Stüben, Martin Trepel, Bruno Märkl, Sebastian Dintner, Rainer Claus

Conclusions

In conclusion, the NEORECT trial establishes the feasibility of ctDNA-based personalized monitoring for rectal cancer patients undergoing nCRT. However, the utility of ctDNA in enhancing pCR prediction for a W&W strategy warrants further investigation. Larger studies integrating multi-gene analyses and expanded clinical datasets are essential in the future.

Methods

In the prospective single-center NEORECT trial, the plasma of forty rectal cancer patients was collected before, during, and after nCRT and before TME. Informative somatic mutations were identified in tissue biopsies by NGS and subsequently used for ctDNA quantification by dPCR.

Results

The results identified three distinct ctDNA patterns: increase, decrease, and absence. Remarkably, undetectable DNA was observed in good responders, while a tenfold ctDNA increase was associated with the emergence of new metastases. Despite these insights, ctDNA alone demonstrated low specificity, with no significant correlation to pCR or long-term prognosis. A multimodal approach incorporating routinely available clinical parameters remains inadequate for accurately predicting pCR prior to TME. Conclusions: In

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