Feasibility of circulating tumour DNA (ctDNA) analysis using automated capillary blood sampling

Aging of the general population results in an increasing number of patients who
need to be cared for by a decreasing number of health care professionals. To
ensure sustainable and patient-centred health care in the near future, we need
to rebalance hospital-based and home-based care. Following surgery of a primary
tumour or metastases thereof, patients are offered blood-based follow-up in the
hospital, which is necessary to detect recurrence but represents a major burden
on the current health care system. The more recently discovered, highly
specific circulating tumour-derived DNA fragments (ctDNA) have high potential
as a new biomarker and clinical implementation of ctDNA in CRC patient care is
expected in the future. However, feasibility of ctDNA detection in blood
collected through automated capillary sampling had not yet been investigated.


The adoption of home-based oncology care offers several societal and economic
advantages, especially in the long-term. Firstly and most importantly, bringing
this type of care closer to a patient*s home has the advantage of patient
empowerment and the potential to increase quality of life and satisfaction
during oncological follow-up. Additionally, it has the capacity to make
surveillance strategies more cost-effective. Follow-up after curative treatment
of cancer consists of several years of surveillance and multiple blood and
imaging tests. The outpatient clinic visits with blood testing account for a
substantial part of the expenses in oncological follow-up. A previous study has
already shown that the lancet sampling technique for chronic care patients
reduces the overall societal costs per patient. Novel, painless techniques like
the TAP, an automated capillary sampling device, continue to gain interest of
manufacturers and, therefore, expenses are expected to drop in the future.
Additional to reducing healthcare costs, home-based sampling will alleviate
hospital pressure and reduce the demand on healthcare workers, particularly
important in times of ever-increasing healthcare demands.

Finally, it provides benefits on an environmental level by reducing the need
for patients to travel to healthcare facilities. For now, CEA is still the
standard of care biomarker investigated in patients who have been treated for
colorectal cancer. However, it remains a relatively non-specific serum
biomarker that is elevated in various malignancies, but may also be elevated in
the case of inflammation, other liver diseases, smoking, and so on.
Furthermore, ctDNA has the potential to reflect comprehensive genomic
information and overcome intratumor heterogeneity. The current project aims to
determine the feasibility of ctDNA detection in small volumes of capillary
blood to ensure this promising new biomarker can be implemented in future
home-based surveillance strategies for cancer patients. Although this project
proposes to use patients with colorectal liver metastases (CRLM) for proof of
principle to leverage experiences gained in the MIRACLE and CASA studies,
results will be highly relevant for other cancers currently lacking reliable
blood-based tumour markers as well. Ultimately this will pave the way for
homebased, patient-centred follow up after surgical removal of cancerous
lesions irrespective of tumour type, which will reduce the burden on the health
care system while improving patient satisfaction.

The primary objective of the study is to determine the technical feasibility of
ctDNA detection in small volumes of capillary blood. This will be investigated
through determining the agreement between ctDNA measurements in venous
(standard blood collection) versus capillary blood through automated capillary
blood sampling. We will consider a Kappa >0.75 as sufficient agreement.

This proof-of-concept study aims to determine technical feasibility of ctDNA
detection in small volumes of capillary blood in 35 patients. Venous blood from
the same patients will be used as reference

There is no specific benefit to the participants from participating. Potential
risks associated with participation are low
to mild discomfort and/or temporary superficial hematomas of the skin after
venipuncture and use of the TAP device on the upper arm.

The burden on test subjects is minimal. A participating patient will perform
one extra blood sample (TAP) under the supervision of a researcher at the
outpatient clinic. Furthermore, an extra blood tube will be filled during a
standard blood collection at the blood collection station. This will happen at
a time when the patient has to go to the blood test anyway for a blood test for
the regular treatment process. The time a patient will spent on this study is
about 10-15 minutes in total. The current pilot study has the potential to
enable future blood collection at home for a much larger group than patients
with colon cancer and the results will therefore be more widely applicable.