A Conversation Between Elisabeth de Vries and Johannes Czernin

Abstract

Johannes Czernin, editor in chief of The Journal of Nuclear Medicine, initiated in 2019 a series of recorded discussions with leaders in nuclear medicine and molecular imaging. For this issue, he talked with Elisabeth de Vries, MD, PhD, a professor of Medical Oncology at University Medical Center Groningen (The Netherlands). She is involved in patient care, teaching, and research, including clinical trials. A primary focus of her multifaceted work is on international collaboration to improve cancer treatment and on interdisciplinary translational research for applications in personalized medicine. These interests include improving cancer care by defining tumor response criteria and defining the scope of clinical benefit from cancer drugs, clinical and translational research in breast cancer and neuroendocrine tumors, and translational oncology and early drug development using molecular imaging to visualize tumor-specific targets and the effects of immunotherapy. Dr. de Vries is known internationally for her organizational work to improve quality and effectiveness in cancer treatment. She is currently cochair of the Response Evaluation Criteria in Solid Tumors (RECIST) Committee on behalf of the European Organization for Research and Treatment of Cancer (EORTC) and chairs the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale working group (2016–current) and the ESMO Cancer Medicines Committee (2018–current). In 2002, she was appointed a member of the Royal Netherlands Academy of Arts and Sciences. She received the ESMO Award in 2009 and is a fellow of the European Academy of Cancer Sciences. Dr. Czernin: Dr. de Vries, you are a medical oncologist, and you served as the head of the Department of Medical Oncology at the University of Groningen. But you are also a key figure in molecular imaging and imaging biomarker development and validation. What ignited your interest in molecular imaging? Dr. de Vries: I have always combined lab research with clinical research, and I have always tried to bridge the gap between preclinical research and clinical applications. We have a good PET Center here in my hospital, and I was very eager to see whether we could make tracers that would be of interest to get answers for our patients in the clinic. I am involved in tracer development and in deciding which tracers we would like to use, how to conduct informative animal experiments, and how we translate these to the clinic. Dr. Czernin: So would you call yourself something like a ‘‘translational relevantist’’? Someone who bridges the gap between preclinical science and clinical need? Dr. de Vries: Beautiful words. I’m also aware that I can’t do anything on my own. I have tremendous input from a multidisciplinary team including pharmacologists and radiopharmacists. And nuclear medicine physicians are critically important partners for clinical translation. Dr. Czernin: Before we get back to imaging I would like to mention your international leadership in clinical trials design. Many of the trials were unrelated to imaging, but for others imaging parameters were used as predictive or intermediate endpoint biomarkers. Dr. de Vries: I like to be involved in smart clinical trial design to get meaningful answers, preferably without the need to enroll too many patients. I also believe strongly that not only pharma but also academia should design clinical studies. I do not really know how I became cochair of RECIST (https://recist.eortc.org/). I guess I was asked because of my training as an oncologist and my interest in imaging. The RECIST Working Group comprises representatives of the EORTC, the National Cancer Institute (NCI) in the United States, and the Canadian Cancer Trials Group, as well as several pharmaceutical companies. Its mission is to ensure that RECIST undergoes continued testing, validation, and updating. I am also involved in the ESMO Magnitude of Clinical Benefit Scale committee. In The Netherlands we already had criteria to determine drug effectiveness. In 2013 ESMO decided to try to develop a scale (https://www.esmo.org/Guidelines/ESMO-MCBS) to determine the impact of newly registered cancer drugs on patients. Initially the scale was considered to be especially relevant for patients in Eastern Europe, where access to important drugs may be difficult. However, we are now seeing worldwide interest in the scale, because all countries have difficulties in prioritizing cancer drugs, which are often quite expensive. Dr. Czernin: Did you assess drug cost effectiveness? Dr. de Vries: No, here we currently don’t take cost into account. We look only at aspects such as disease-free survival, overall survival, toxicity, and quality of life. Dr. Czernin: You emphasized your focus on smart clinical trials to limit the number of patients needed for enrollment. This can be done through patient stratification and also response assessments, 2 key requirements for true precision oncology, which is currently almost exclusively understood in the context of genomics. The NCI Molecular Analysis for Therapy Choice (MATCH) trial and other trials in which specific cancer mutations were identified and matched to targeted drugs provided disappointing results, with only a small number of patients ending up with matching therapies. Outcomes may not have been improved. Was part of the mistake to believe that many cancers have a single oncogene addiction? Elisabeth de Vries, MD, PhD