PhD Student Health-economic modelling of ctDNA based colorectal cancer treatment

Colorectal cancer (CRC) is one of the most prevalent tumor types in the Netherlands. As a PhD student, you will work on two projects: PROVENC3 (PROgnostic Value of Early Notification by ctDNA in Colon cancer stage 3) and DOLPHIN (DNA-testing Of Liquid biopsies for Patient care close to Home In the Netherlands) (project leaders Dr. V Coupé, Dr. Remond Fijneman, Dr. G Vink) which both focus on the potential of cell-free circulating tumor DNA (ctDNA) to guide CRC treatment.

The PROVENC3 project focuses on patients with stage III CRC. These patients are currently treated with surgery followed by systemic adjuvant chemotherapy. However, 8 out of 9 stage III patients receive futile adjuvant chemotherapy while suffering its side effects. ctDNA may be a promising biomarker to guide decisions who (not) to treat with adjuvant chemotherapy. As a PhD student, you will work on work package 3 of the PROVENC3 project (led by Dr. Veerle Coupé, Amsterdam UMC) in which you will develop a model-based evidence synthesis framework, bringing together data from the PROVENC3 prospective, observational study on the prognostic value of ctDNA testing in 300 stage III CRC patients, data from the Dutch Prospective Colorectal Cancer Cohort (PLCRC) and data from the National Cancer Registry. The modeling framework will include multi-state time-to-event models to capture the progressive disease process, evidence on the benefits and risks of treatment, quality of life data and costs. With the modeling framework, you will evaluate ctDNA-based selection strategies for adjuvant chemotherapy in terms of benefits, harms and cost-effectiveness.

The DOLPHIN project focuses on patients with metastatic CRC. These patients are currently monitored with CT scans to determine treatment response. ctDNA may be an alternative to CT-imaging as it is indicative of abundance of viable neoplastic cells. Our aim is to determine the optimal strategy to complement and/or partly replace CT-imaging with ctDNA-testing for treatment response monitoring (work package 1, led by Dr. Veerle Coupé, Amsterdam UMC). As a PhD student, you will analyze data from a prospective, observational study in which 400 metastatic CRC patients will undergo CT-imaging and ctDNA-testing every two months. Using advanced statistical modeling, you will analyze the longitudinal pattern of paired ctDNA-testing and CT-imaging data, in relation to clinical outcome. Based on these statistical analyses, you will build a decision-analytic model to evaluate a range of ctDNA-based monitoring strategies, thereby projecting long-term effects of monitoring on survival, costs and cost-effectiveness.

About the role
As a PhD student, your main tasks are:

• To perform a bottom-up costing study to estimate the costs of NGS-based ctDNA analysis (PROVENC3)
• To use multi-state survival models to estimate risk of recurrence and death based on ctDNA status (PROVENC3)
• To apply advanced survival modeling techniques to gain insight into the longitudinal pattern of paired ctDNA testing and CT-imaging data, in relation to overall survival (DOLPHIN)
• To integrate the survival models with data on quality of life and costs in a health-economic model, separately for PROVENC3 and DOLPHIN, programmed in e.g. R statistics or C++.
• To evaluate ctDNA-based selection strategies for adjuvant treatment in stage III CRC patients (PROVENC3) as well as a range of ctDNA-based monitoring strategies in metastatic CRC patients (DOLPHIN) in terms of benefits, harms and cost-effectiveness.
• To publish your research findings in biomedical, health-economic, and/or epidemiological journals.
• To write a PhD thesis for defense at the Vrije Universiteit Amsterdam.
• To assist in teaching activities in biostatistics courses for medical students.