Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Pierer, K.
ctDNA analysis in colorectal cancer (CRC) patients under regorafenib.
[ Diplomarbeit/Master Thesis (UNI) ] Universität Graz; 2020.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Heitzer Ellen
- Altmetrics:
- Abstract:
- The continuous monitoring of cancer patients is of great importance in order to adapt therapies as quick as possible and thus guarantee the best treatment success. Treatment selection is usually performed from tissue biopsies, which comes with high costs and burdens the patient. Furthermore, the biopsy is only a snapshot of a specific site of the tumor and does not provide any information regarding tumor heterogeneity or metastatic lesions. The so-called liquid biopsy, which refers to the analysis of circulating tumor DNA (ctDNA) from blood, might overcome this limitation by enabling a continuous, minimally invasive monitoring of the tumor genome over the entire course of the disease. The main aim of this thesis was to investigate a possible pertinence of ctDNA as a prognostic and/or early predictive marker in the treatment of mCRC patients receiving regorafenib. To this end, available follow-up plasma samples from patients with non-resectable, pretreated and metastatic colorectal cancer recruited to the RELAIS study (regorafenib's liquid biopsy) were analyzed. We leveraged existing mutation data established from a custom gene panel performed prior to therapy initiation and tracked known mutations in follow-up samples using deep sequencing. We hypothesized that changing levels of ctDNA assessed with deep sequencing correlate with response to regorafenib. Moreover, we hypothesized that early changes of ctDNA from baseline to the fist follow up might be used to predict a response or clinical outcome. However, a statistical evaluation was not possible due to the fact that the majority of patients did not respond to regorafenib and only two patients had a partial response. Moreover, the sample size of available patients was small, and many patients lacked continuous follow-up samples. Yet, the majority of patients had increased ctDNA levels at the time of progression, an assessment of ctDNA during treatment revealed mixed responses. While some patients had decreased level of ctDNA at the first follow-up, other demonstrated elevated levels with a correlation of disease control or progression. Although the hypothesis that ctDNA changes could predict treatment response could not be confirmed, our data indicated a prognostic significance of ctDNA levels at baseline. Moreover, the additional data from untargeted sequencing approaches that were applied to the same cohort, indicated that the integration of various genetic alterations is a promising approach and could improve monitoring in late stage CRC.