On Wednesday the 24th of June, Henrik Ditzel and Julia Sidenius Johansen invited the DCCC ctDNA research center members to join an online meeting under the clinical focus area 4 (CFA4) about monitoring ctDNA levels to predict therapy response.
The purpose of the meeting was to keep all members updated on projects relevant to this clinical area.
The projects seek to investigate whether monitoring ctDNA levels during treatment is a better measure of treatment efficacy compared to standard imaging methods and other circulating biomarkers. Furthermore, the meeting supports the formation of a strong network. An important goal for the DCCC ctDNA research center is to ensure formation of new projects and collaborations across Denmark. This is a place to meet fellow researchers and doctors, who could complement your project or benefit from learning from you.
At this meeting, Professor Lars Dyrskjøt gave a short introduction to some methods for ctDNA detection and covered the following methods:
- ddPCR based on clonal mutations from tumors: May be used both retrospectively and prospectively
- Tumor informed targeted sequencing: Primarily used retrospectively
- Cancer type specific targeted sequencing: May be used retrospectively and prospectively
- Whole exome sequencing and whole genome sequencing may be used to detect new mutations when ctDNA levels are high: Used both retrospectively and prospectively
If you want to know more about specific methods, please reach out to the ctDNA network at an upcoming meeting or make direct contact. (See the planned meetings and workshops here)
An important topic, discussed at all the meetings this week, was funding applications. Not only in relation to the fall-call from the ctDNA center, but also funding in general. For the next round of funding from the ctDNA center the deadline is 23 October 2020. The guidelines for funding through the ctDNA center are found here: https://ctdna.dk/projekter/projects/apply-for-funding. The application and evaluation process will be a bit different for this round but the requirements will not change. The bar was set high for the first round, and this will not change. Receiving funding from the ctDNA center is to receive a sign of approval from peer researchers and thus an argument for funding from other agencies. More information about the new application and evaluation process will come later.
At this meeting, three projects were introduced: TOMBOLA, PACTO, and Be To-Ovar.
TOMBOLA (Treatment Of Metastatic Bladder cancer at the time Of biochemical reLApse following radical cystectomy) Professor Lars Dyrskjøt:
The TOMBOLA trial is a non-randomized phase II study covering multiple CFAs. The intervention occurs after surgery (CFA2) and during surveillance(CFA3) and with a primary endpoint (ctDNA decrease) during treatment (CFA4). The aim of the study is to investigate whether an earlier detection of relapse and following earlier onset of treatment will result in treatment that is more effective, measured by a decrease in ctDNA levels. For each patient included, four patient specific ddPCR assays are run. Prior to trial onset, the group has focused on optimization, SOP and protocols – if you would like inspiration for your own SOP or protocols, please contact the group. At the next meeting we hope to see the first data from the project.
PACTO (A multinational, randomized, phase II study of the combination of nab-paclitaxel and gemcitabine with or without IL-6R inhibitor, tocilizumab, as first-line treatment in patients with locally advanced or metastatic pancreatic cancer” (NCT02767557))
The PACTO study is a trial investigating the effects of chemotherapy in combination with anti-IL-6R inhibitor in patients with locally advanced and metastatic pancreatic cancer. It is a multinational, randomized phase II study. The project includes patients from Herlev (initiating hospital), Hillerød, Roskilde and Oslo.
The patients are followed with CT scans and blood samples before, during and after treatment to investigate whether plasma ctDNA and ctDNA KRAS mutation can predict treatment response and prognosis. The project has almost included all patients.
Clinical Professor Anders Jakobsen:
The BeTo-Ovar project is a phase II protocol monitoring on the basis of ctDNA.