Coreline Burggraaff obtained her PhD on 9 September at VU University Amsterdam her dissertation entitled ‘18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation’. Prof. Dr. JM Zijlstra-Baalbergen and Prof. Dr. Ir. HCW de Vet acted as supervisors. Co-promoters were Prof. Dr. OS Hoekstra and Prof. Dr. R. Boellaard. Burggraaff is currently working as a resident internal medicine and will start differentiation hematology on 1-1-2023.
What was the aim of your PhD research?
The goal was to validate interim 18F-FDG PET as a biomarker of response during treatment in patients with diffuse large B-cell lymphoma (DLBCL), as well as to determine optimal response criteria (visually using the Deauville 5-point scale or quantitatively using ΔSUVmax criteria) and timing (after how many cycles R-CHOP) from interim 18F-FDG PET. By setting up an international PETRA (PET Re-Analysis) consortium1 enough patient data and PET scans from DLBCL studies could be collected and reanalyzed to answer these questions.
What do you want the clinical doctor to know about your research?
In addition to baseline staging and response evaluation after first-line treatment, the value of the interim 18F-FDG PET validated. In a large meta-analysis of individual patient data, we showed that interim 18F-FDG PET has a high negative predictive value of more than 80% when using the visual Deauville and quantitative ΔSUVmax criteria for response assessment in DLBCL. This has led to interim 18F-FDG PET-guided treatment is included in the current Dutch guideline for DLBCL.2
What was the most frustrating part of your research?
Establishing the contracts – the so-called data sharing policy documents for the PETRA database – with the various international studies. A lot of time has been spent in contact with the various legal offices to get these documents correct. And that despite the fact that ‘letters of intent’ had already been signed by the principal investigators themselves before the start of the project and we were able to use a sample policy document via another individual data meta-analysis project from the epidemiology department. After this hurdle had been overcome, we could finally get started with the research (patient data and scans).
Which moment/insight brought about a breakthrough?
The annual meetings of the PETRA consortium in Amsterdam provided many new ideas for the research among all those present, as well as greater motivation to provide data, analyze it and meet the deadlines. The ever-growing enthusiasm of this expert group of haematologists, nuclear medicine physicians, researchers and epidemiologists has led to the interim 18F-FDG PET research was successfully completed and has also led to new projects.
What is the follow-up question arising from your research?
Currently, the PETRA database is being used from the interim 18F-FDG PET study was designed and used for a follow-up study on baseline predictive value 18F-FDG PET factors (so-called radiomics factors). In addition, further research is being conducted into the validation of the metabolic tumor volume (MTV) and how the positive predictive value of end-of-treatment 18F-FDG PET can be improved. Recently, the PETRA consortium has proposed a new prognostic index (consisting of MTV, age and stage) with a better predictive value compared to the well-known IPI score.3
What will you take away from your PhD research? What are your next steps?
What I take with me is the importance of good multidisciplinary collaboration, in which knowledge of and interest in each other’s profession really helps to be able to offer better research and therefore better patient care. As of January 1, 2023 I will start differentiation hematology at the Amsterdam UMC, location VUmc. In the future, as an internist-haematologist, I hope to continue to develop my research experience, both in daily clinical patient care and in the research itself.
References:
- www.petralymphoma.org
- www.hematologienederland.nl/wp-content/uploads/2021/10/Richtlijn-DLBCL-_NVvH.pdf
- Mikhael GN, Heymans MW, Eertink JJ, et al. Proposed New Dynamic Prognostic Index for Diffuse Large B-Cell Lymphoma: International Metabolic Prognostic Index. J Clin Oncol. Rev. 2022;40:2352–6