Posts in category: News

About Me

Hello everyone, my name is Nastaran Riahi. I am a PhD Candidate in Oncology at the University of Antwerp and a Clinical Researcher at Universal Diagnostics (UDX).

When I joined UDX five years ago as a cancer researcher, I was captivated by a simple, powerful idea: could a routine blood test help us detect cancer and its precursors early enough to change someone’s story? That question led me to pursue my  PhD at the University of Antwerp within the ENDEAVOR project, under the supervision of Prof. Dr. Krishnadath, who leads this European initiative. ENDEAVOR is a five-year, EU-funded collaboration bringing together 15 academic partners, two general hospitals, and UDX as an industry partner. Our shared goal is to translate that “simple blood test” idea into practical tools for people living with Barrett’s esophagus (BE).

Why Barrett’s Esophagus and Why Now?

Esophageal cancer is one of the deadliest cancers worldwide because it’s often found late and behaves aggressively. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two most common histological subtypes of EC. Over four decades, the frequencies of EAC and BE, the known precursor lesion for EAC, have sharply increased in North America and Europe. Despite early detection and endoscopic therapy, the patient’s clinical course remains difficult to predict. That uncertainty means many patients undergo frequent, invasive endoscopies. Since no other modality of surveillance is currently available. We can do better.

ENDEAVOR’s goals

ENDEAVOR aims to build smarter risk-stratification for BE: helping clinicians see earlier and more precisely, who is likely to progress and who will respond well to treatment. The vision is personalized prevention, directing the right treatment at the right time and tailoring follow-up so patients avoid unnecessarily invasive procedures while remaining cancer-free.

My Project in a Nutshell

My PhD focuses on whether a multi-omics approach combining DNA methylation signals in blood with genetic mutations identified in tissue can predict how BE patients respond to endoscopic therapy and who is at the highest risk for EAC. In practical terms, I analyze cell-free DNA (cfDNA) from blood samples taken before and after endoscopy treatment, using targeted methylation sequencing developed at UDX. Then, with the ENDEAVOR collaborator, I integrate those data with matched tissue mutation profiles. The hope is to create a robust set of biomarkers that distinguishes responders from non-responders to treatment and guides clinical decisions.

Why Methylation?

Among many potential biomarkers, aberrant DNA methylation has emerged as one of the most promising for monitoring BE and detecting EAC early. By reading methylation changes in cfDNA, we may capture a real-time picture of tumor biology from a simple blood draw. Pairing that with mutation data can reveal how genetics and epigenetics work together during disease progression and how they respond to treatment.

How We’re Doing It

• 1. Who we study: In the pilot study, approximately 50 patients with high-grade dysplasia (HGD)/ early EAC are at the highest risk for progression.
• 2. When we sample: Two time points, before treatment and after completion (e.g., after endoscopic mucosal resection (EMR)and/ or endoscopic submucosal dissection (ESD) and before radiofrequency ablation (RFA)), to see how molecular signals shift with therapy.
• 3. What we measure:
  • A) At UDX, we perform hybrid-capture targeted methylation sequencing on cfDNA and process results with proprietary signal-processing and machine-learning tools for precise, fragment-level scoring.
  • B) Partner performs exome sequencing on matched tissue within ENDEAVOR to map somatic mutations.
  • C) We then integrate both layers to build prediction models for treatment response and risk.

The Role of UDX

UDX is a Spanish diagnostics company building blood tests that can “read” cancer and precancer signals at their earliest stages. Our platform, already used in colorectal cancer detection programs, brings three things to ENDEAVOR:

1. Targeted methylation assay development and sequencing,
2. Advanced signal processing at the read/fragment level, and
3. Machine-learning pipelines for risk stratification.

What Success Looks Like

If we get this right, patients could have access to:

• 1. A minimally invasive blood test that helps forecast who will respond to endoscopic therapy and who may need closer monitoring or alternative strategies.
• 2. Sharper risk-stratification to personalize surveillance intervals, reducing unnecessary procedures for many, while focusing attention where it matters most.
• 3. A path to earlier intervention, when treatments can be most effective and lives most changed.

A Personal Note

As a clinical researcher, I’m motivated by the patients behind every tube, dataset, and model. ENDEAVOR lets me work at the intersection of academia and industry, combining the methodological discipline of a university PhD with the translational power of UDX’s technology. It’s a privilege to work alongside clinicians, bioinformaticians, and scientists across Europe who share a simple aim: to make care predictive, patient-centered, and more precise for people with Barrett’s esophagus.

Nastaran Riahi

About Me

Hello everyone, my name is Henrik Maltzman. I am foremost a physician at Karolinska University Hospital in Sweden, with special focus on removing early cancer and precancerous lesions in the gastrointestinal tract using endoscopy. With techniques such as ESD (Endoscopic Submucosal Dissection) we can locally resect tumors that previously would have required more invasive surgical procedures. I am also a PhD student as of last year, honestly a bit late blooming since I am already 40 years old. Because of my role also as a clinician I’m involved in the Endeavor team in two different ways – as part of the research team and also in the clinical management of patients.

Barrett’s Esophagus & ENDEAVOR

Barrett’s esophagus is a condition in the lower esophagus affecting up to 5% of the general population, caused by acid reflux. As such, it can barely be called a disease but rather a risk factor for esophageal cancer. The hallmark for Barrett’s is a change in the type of cells in the esophageal mucosa from the ordinary squamous epithelium (not much unlike the cells in the mouth or throat) to cells resembling the normal small intestine. This cell change is called intestinal metaplasia in our medical language, and the presence of such cells is the basis of the diagnosis of Barrett’s.

It is important to emphasize that most patients with Barrett’s have a low overall risk of developing esophageal cancer or precancerous lesions (see Figure 1 for an example of Barrett’s esophagus with an early cancer).

Figure 1. Barrett’s esophagus with early cancer at 2 o’clock position.

As the numbers of patients are vast, this poses a clinical dilemma for us as doctors – which patients should we monitor closer and which could we see more seldom? The same problem applies to patients that have an early cancer removed by us. The absolute majority of these patients will have an excellent prognosis and a low risk of new events. However about 10 % can have a more aggressive disease and either develop new tumors in the remaining Barrett’s, or even metastasis. How do we know which patients to prioritize and follow more closely?

The latter question is currently being addressed in our Endeavor trial, and I am proud to be part of the research team. In the project, we are looking at specific genetic abnormalities that could indicate a worse outcome after endoscopic removal of a Barrett’s tumor. In my clinical practice, I see patients like this every week. Apart from the obvious concerns of being diagnosed with cancer, these patients also face the burden of frequent follow-up endoscopies, radiological exams, and other interventions. If the Endeavor study could find ways of individualizing this follow-up based on the patient’s genetic risk, this could be of great importance for many of my patients that are often elderly and suffer from other medical conditions.

My other research

In my own research, I am studying various themes in upper gastrointestinal cancer from an endoscopic perspective. The main part of my doctoral thesis is outside of the Endeavor umbrella. It encompasses the whole spectrum of what we do in endoscopy – from detection of early dysplastic changes in conditions such as Barrett’s all the way to treating advanced gastric cancer in patients that are too frail to withstand normal surgery. By combining clinical research and my work as a clinician, I hope to make a meaningful impact on both patient care and the broader medical field. People like me will probably never be top-tier academic researchers, but our strength is that we know very well what is relevant to actual patients and in real life problems in the clinical realm. Together with the preclinical and lab oriented scientists, we can forge an alliance to withstand the challenges of treating Barrett’s and other conditions in the upper gastrointestinal tract.

Henrik Maltzman

Members of the Endeavor consortium meet eachother monthly via Teams to discuss the latest status of the Endeavor study, including the to do’s, challenges, and progress. Once a year, we can also meet live to put our heads together, which contributes immensely to the progress of the study!

Over the weekend of 10 – 13 April 2025, the consortium met in beautiful Ireland. Consortium partners were present both live and online (via Teams). Members of our PPI panel also joined us, providing useful feedback and giving us an insight into their views on the project and the PhD projects arising from the Endeavor study (see more in the PPI section on the website soon).

What was discussed? Find a brief overview below of the most important topics:

• • The Endeavor study will consist of a pilot study to test the flow and afterwards a larger study (RCT). The meeting mainly focused on the current status of the pilot study (the status of ethics committee approval at all recruiting sites, the challenges that have occurred so far, the expected start date, the flow for taking and processing biological samples etc).
  • In addition, several partners presented their plan of action for the conduct of the pilot study and the follow-up study, specifically for their part of the project.
  • Also, we discussed the steps required for a smooth start of the follow-up RCT study.
  • We will work with an electronic case report form (to enter patient data) and electronic questionnaires for the patients. These were reviewed together, with members of our PPI panel also giving their feedback.
  • Our Endeavor PhD students (7 in total) also presented their projects to our PPI panel in a short pitch in plain English. The patients gave meaningful insights and feedback to help the PhD students further along the way of their project.

Thanks to this annual consortium (and PPI) meeting, we are several steps closer again to the start of our pilot study! Hope you will follow along.

PhD student Martin Wyckmans (from the University of Antwerp, Belgium) has performed a study in collaboration with the Endeavor Chief Investigator Prof. Dr. Sheila Krishnadath. The research was presented via a poster on February 13th in Liège, Belgium at the Belgian Week of Gastroenterology (BWGE) during the Belgian Society of Gastrointestinal Endoscopy (BSGIE) session.

What was the study about? For the Endeavor study ‘brushes’ will be used to obtain cellular samples of the esophagus during endoscopy. This technique is called ‘brush cytology’. When performing brush cytology, the brush bristles exit a protective sheath and are, per standard protocol, retracted back into the sheath after sampling. This study compared the cellular yield of samples where the brush was retracted back into the sheath versus samples where the brush was not retracted back into the sheath after sampling.

Results? There was more cellular yield when not retracting the brush. As diagnostic accuracy depends on the cellular yield, this small-scale study points towards better diagnostic performance of brush cytology by not restracting the brush into the sheath after sampling during endoscopy.

Why is this important? Improving how we sample tissue of the esophagus will lead to better results for the ENDEAVOR project. By sharing this study with other researchers, research methods of other studies can be improved. This will lead to better science in a wide range of projects!

We held our first Endeavor PPI panel on Thursday the 5^th of September! Barrett’s Esophagus and Esophageal cancer patients from Ireland and Sweden were introduced to the project and already gave very valuable feedback regarding the questionnaires that will be used, among others. Barrett’s Esophagus experts Prof. Dr. Sheila Krishnadath, Prof. Dr. Magnus Nilsson and Prof. Jacintha O’Sullivan were present as well to guide the meeting and answer any specific questions. The info gathered from this interesting meeting will be implemented into the project in order to make it as patient-friendly as possible!

We are thrilled to announce that the pilot study of our Endeavor trial now has an NCT number: NCT06523374. Another step closer to the start of our project! Read more about our project on clinicaltrials.gov

From April 25^th to April 28^th  2024 the Endeavour EU consortium members gathered live for the first time. It were three intensive days full of brainstorming to shape and further concretize the Endeavor trial. Great progress has been made and we hope to start the pilot/test phase of the project at the end of 2024!