Chromosomal alterations and liquid biopsies as monitoring and prognostic biomarkers in metastatic colorectal cancer
Final Report Abstract
Metastases are the leading cause of mortality in colorectal cancer patients. In recent years, the analysis of circulating tumor DNA (ctDNA) from blood samples has emerged as a promising tool for personalised treatment options and treatment monitoring in those patients. This project utilized two independent datasets to investigate, on the one hand, the biological and clinical determinants of ctDNA levels and, on the other, how ctDNA dynamics compare to radiological tumor volume as predictive markers for treatment response and prognosis. In the first part of the study, we analyzed data from 150 patients with non-metastatic colon cancer from the PLCRC cohort. Our findings revealed that ctDNA levels are influenced by tumor size, chromosomal instability, and specific gene expression patterns. Notably, certain genomic alterations, such as loss of chromosome 10p or 10q, were associated with increased ctDNA levels. The second part of the study used an independent dataset from the CAIRO5 trial, which included patients with metastatic CRC. Here, we compared ctDNA measurements with radiological tumor volume (TTV) assessments. The results demonstrated that both ctDNA and TTV independently correlate with prognosis. While radiological imaging offers a macroscopic view of tumor burden, ctDNA dynamics can provide an early indication of treatment response and an additional molecular perspective. Combining both modalities improved the predictive accuracy for overall survival and early recurrence risk. These findings highlight the potential of liquid biopsies as a valuable addition to imaging in clinical practice. Integrating both approaches could enhance disease monitoring and enable more personalized treatment strategies.
Publications
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Age-dependent benefit of neoadjuvant treatment in adenocarcinoma of the esophagus and gastroesophageal junction: a multicenter retrospective observational study of young versus old patients. International Journal of Surgery, 109(12), 3804–3814.
Rompen, Ingmar F.; Crnovrsanin, Nerma; Nienhüser, Henrik; Neuschütz, Kerstin; Fourie, Lana; Sisic, Leila; Müller-Stich, Beat P. & Billeter, Adrian T.
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Clinical Characteristics and Oncological Outcomes of Surgically Treated Early-Onset Gastric Adenocarcinoma - a Retrospective Cohort Study. Journal of Cancer, 14(9), 1470-1478.
Rompen, Ingmar F.; Nienhüser, Henrik; Crnovrsanin, Nerma; Musa, Julian; Haag, Georg Martin; Longerich, Thomas; Fiedler, Timon; Müller-Stich, Beat P.; Sisic, Leila & Billeter, Adrian T.
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Perioperative chemotherapy with 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) for esophagogastric adenocarcinoma: ten years real-life experience from a surgical perspective. Langenbeck's Archives of Surgery, 408(1).
Sisic, Leila; Crnovrsanin, Nerma; Nienhueser, Henrik; Jung, Jin-On; Schiefer, Sabine; Haag, Georg Martin; Bruckner, Thomas; Schneider, Martin; Müller-Stich, Beat P.; Büchler, Markus W. & Schmidt, Thomas
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584P Genomic and transcriptomic characterization of peritoneal, lung and liver metastases of colorectal carcinoma reveals site-specific differences. Annals of Oncology, 35, S472.
Crnovrsanin, N.; Lakbir, S.; de Wit, R.; Ketelaars, S.; Kok, N.; Snaebjornsson, P.; Meijer, G.; Abeln, S. & Fijneman, R.
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Abstract 3786: Genomic and transcriptomic characterization of peritoneal, lung and liver metastases of colorectal carcinoma reveals site-specific differences. Cancer Research, 84(6_Supplement), 3786-3786.
Crnovrsanin, Nerma; Lakbir, Soufyan; Wit, Renske d.; Ketelaars, Steven L.; Kok, Niels F.; Snaebjornsson, Petur; Meijer, Gerrit A.; Abeln, Sanne & Fijneman, Remond J.
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Definition and Predictors of Early Recurrence in Neoadjuvantly Treated Esophageal and Gastroesophageal Adenocarcinoma: a Dual-Center Retrospective Cohort Study. Annals of Surgical Oncology, 32(3), 1617-1627.
Rompen, Ingmar F.; Billeter, Adrian T.; Crnovrsanin, Nerma; Sisic, Leila; Neuschütz, Kerstin J.; Musa, Julian; Bolli, Martin; Fourie, Lana; Kraljevic, Marko; Al-Saeedi, Mohammed; Nienhüser, Henrik & Müller-Stich, Beat P.
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Inhibition of the renin–angiotensin system in patients with upper gastrointestinal adenocarcinoma. British Journal of Surgery, 111(1).
Wirsik, Naita M.; Stengel, Svenja; Jung, Jin-On; Sisic, Leila; Crnovrsanin, Nerma; Nienhüser, Henrik; Schleussner, Nikolai; Hamm, Alexander; Büchler, Markus W. & Schmidt, Thomas
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Is neoadjuvant chemotherapy followed by surgery the appropriate treatment for esophagogastric signet ring cell carcinomas? A systematic review and meta-analysis. Frontiers in Surgery, 11.
Schiefer, Sabine; Crnovrsanin, Nerma; Kalkum, Eva; Vey, Johannes A.; Nienhüser, Henrik; Rompen, Ingmar F.; Haag, Georg M.; Müller-Stich, Beat; Billmann, Franck; Schmidt, Thomas; Probst, Pascal; Klotz, Rosa & Sisic, Leila
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Optimal Treatment Strategies for cT2 Staged Adenocarcinoma of the Esophagus and the Gastroesophageal Junction. Annals of Surgery, 280(5), 799–807.
Wirsik, Naita M.; Kooij, Cezanne D.; Dempster, Niall; Crnovrsanin, Nerma; Donlon, Noel E.; Uzun, Eren; Bhanot, Kunal; Nienhüser, Henrik; Polette, Daniela; Kewani, Kammy; Grimminger, Peter; Reim, Daniel; Seyfried, Florian; Fuchs, Hans F.; Gisbertz, Suzanne S.; Germer, Christoph-Thomas; Ruurda, Jelle P.; Klevebro, Fredrik; Schröder, Wolfgang ... & Bruns, Christiane J.
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Prognostic Relevance of the Proximal Resection Margin Distance in Distal Gastrectomy for Gastric Adenocarcinoma. Annals of Surgical Oncology, 31(10), 6900-6908.
Rompen, Ingmar F.; Schütte, Isabel; Crnovrsanin, Nerma; Schiefer, Sabine; Billeter, Adrian T.; Haag, Georg Martin; Longerich, Thomas; Czigany, Zoltan; Schmidt, Thomas; Billmann, Franck; Sisic, Leila & Nienhüser, Henrik
