Serial Monitoring of Circulating Tumour DNA for Early Detection of Recurrence in Colorectal Cancer
Colorectal cancer (CRC) 5-year survival remains poor. Advances in next-generation sequencing (NGS) technology may help introduce circulating tumour DNA (ctDNA) use into clinical practice. This thesis investigated the use of ctDNA surveillance following curative CRC resection. Methods were chosen for easy implementation in current clinical settings, such as automated DNA extraction and commercial panel-based single nucleotide variant analysis. Twenty-one patients with stages II-IV CRC were surveilled to 12 months. Circulating tumour DNA was detected in at least one sample per patient. Following primary tumour resection, 68 % saw a fall in ctDNA while 42 % saw a fall in carcinoembryonic antigen (CEA), for patients with stage II or III disease. Six patients experienced disease recurrence. Pre-operative ctDNA levels were comparable in both groups, with BRAF and KRAS mutations most frequent in those developing recurrence, but PIK3CA and TP53 mutations most frequent in those without recurrence. Three patients died of recurrence, all with stage III CRC and complete resection margins. None of these three patients received adjuvant chemotherapy and postoperative ctDNA increased despite falls in post-operative CEA, with ctDNA detection preceding recurrence diagnosis by a wider window than CEA detection (33-161 versus 0-28 days, respectively). In three patients alive with recurrence, post-operative ctDNA preceded recurrence diagnosis by 1-6 months, with CEA preceding recurrence diagnosis by 1 month in two patients and undetectable at all times in one patient. This thesis shows the potential utility of ctDNA in CRC surveillance for prognostication, decision making for adjuvant therapy, to highlight residual disease and as a potential substitute for patients with undetectable CEA.
History
Supervisor(s)
Alessandro Rufini; Anne ThomasDate of award
2024-11-20Author affiliation
Genetics & Genome BiologyAwarding institution
University of LeicesterQualification level
- Doctoral
Qualification name
- MD