1. Circulating Tumor DNA (ctDNA) Dynamics Predict Early Response to Treatment in Metastasized Gastroesophageal Cancer (mGEC) After 2 Weeks of Systemic Treatment.
- Author
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Tatalovic, Stefan, Doleschal, Bernhard, Kupferthaler, Alexander, Grundner, Stephan, Burghofer, Jonathan, Webersinke, Gerald, Schwendinger, Simon, Jukic, Emina, Zschocke, Johannes, Danhel, Lorenz, Kirchweger, Antonia, Havranek, Lukas, Shalamberidze, Demetre, Rezaie, Daniel, Biebl, Matthias, Rumpold, Holger, and Kirchweger, Patrick
- Subjects
RISK assessment ,STOMACH tumors ,RESEARCH funding ,CANCER relapse ,POLYMERASE chain reaction ,DNA ,TUMOR markers ,TREATMENT effectiveness ,ESOPHAGEAL tumors ,DESCRIPTIVE statistics ,BODY fluid examination ,METASTASIS ,CANCER chemotherapy ,NUCLEIC acids ,EXTRACELLULAR space ,PROGRESSION-free survival ,CONFIDENCE intervals ,OVERALL survival ,SENSITIVITY & specificity (Statistics) ,DISEASE risk factors - Abstract
Simple Summary: This pioneering study investigates the prognostic value of circulating tumor DNA (ctDNA) as a biomarker for monitoring treatment response in metastatic gastroesophageal cancer (mGEC). Despite advancements in personalized and multimodal treatments, the prognosis for mGEC remains poor, with low survival rates. ctDNA has emerged as a promising tool for non-invasive cancer monitoring, but its clinical implementation has not yet been fully realized. This study marks a pioneering effort in evaluating ctDNA kinetics using a serial liquid biopsy method that is easy to implement and clinically applicable. The study found that ctDNA changes within the first two weeks of chemotherapy were significantly associated with treatment response, with a 57.1% decline in ctDNA levels correlating with a better prognosis. This method was able to predict treatment response 80% faster than the current gold standard, computed tomography (CT), providing early insight into the effectiveness of systemic chemotherapy. Despite advances in personalized and multimodal treatment in recent years, the prognosis of metastasized gastroesophageal cancer (mGEC) is still poor. Circulating tumor DNA (ctDNA) has evolved as a promising new biomarker for treatment monitoring but has failed to reach clinical implementation yet. This study shows the immediate prognostic impact of ctDNA kinetics using an easily implementable clinical applicable method of serial liquid biopsies. Additionally, this personalized method enables early response to treatment evaluation 80% faster than current gold standard computed tomography (CT) after only 2 weeks of systemic chemotherapy. mGEC is associated with poor overall survival (OS) of approximately 4–10 months. CtDNA is emerging as a promising prognostic biomarker with high potential for early relapse detection. However, until now, there was little knowledge on serial ctDNA detection and its impact on early treatment evaluation and prognosis in mGEC. Methods: ctDNA detection (ddPCR) was carried out serially in 37 matched tissue (NGS) patients with mGEC prior to systemic treatment initiation and every two weeks thereafter until restaging (n = 173 samples). The results have been correlated with response to treatment (restaging CT), overall survival (OS), and progression-free survival (PFS). Results: The pretherapeutic detection rate was 77.8%. Response to treatment assessment was correct in 54.2% (pretherapeutically pos./neg.) and 85.7% (dynamics at week 4). Moreover, a decline in ctDNA (MAF in %) below 57.1% of the pretherapeutic value after 2 weeks of systemic treatment was accompanied by a sensitivity of 57.1% and a specificity of 90% (AUC = 0.73) for correct restaging assessment (response evaluation by CT after 3 months) evaluating 76.5% of patients correctly after only 2 weeks. In contrast to mere pretherapeutic ctDNA positivity (p = 0.445), a decline in ctDNA dynamics to under 57.1% of its initial value was significantly associated with OS (4.1 (95% Cl 2.1–6.1) vs. 13.6 (95% CI 10.4–16.6) months, p < 0.001) and PFS (3.2 (1.9–4.5) vs. 9.5 (95% CI 5.5–13.5) months, p = 0.001) after two weeks of treatment. Additionally, the change in detectability from positive pretherapeutic levels to negative during treatment was associated with similar survival as for patients who were always regarded as ctDNA-negative (9.5 (95%Cl 0.4–18.5) vs. 9.6 (95%Cl 1.3–17.9)). The absence of becoming undetectable was associated with worse survival (4.7 months). Conclusions: ctDNA is a promising additional biomarker allowing for early evaluation of response to treatment and saving unevaluated treatment time for patients with mGEC, and could allow for an early change in treatment with anticipated prognostic benefit in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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