Three discipline collaborative radiation therapy (3DCRT) special debate: Systemic radiotherapy using targeted isotopes is the best hope for advancing curative radiation therapy

Abstract

Radiation oncology is a highly multidisciplinary medical specialty, drawing significantly from three scientific disciplines—medicine, physics, and biology. As a result, discussion of controversies or changes in practice within radiation oncology involves input from all three disciplines. We have adopted a similar “team-science” approach to the traditional debates featured in this journal. This article is part of a series of special debates entitled “Three Discipline Collaborative Radiation Therapy (3DCRT)” in which each debate team includes three multidisciplinary team members with the hope that this format will be both engaging for the readership and foster further collaboration across the science and clinical practice of radiation oncology.

Radiation oncology has witnessed a technical revolution over the past several decades. The advent of advanced imaging and delivery techniques has dramatically improved our ability to target tumors with radiotherapy. However, local control of gross disease does not necessarily result in long-term success as a result of locoregional and/or distant microscopic disease. Traditional external beam and brachytherapy techniques are designed to eradicate disease and spare normal tissues through geometrical targeting. In contrast, systemic therapies are targeted on the cellular level, are not constrained to specific treatment locations or even by our ability to locate disease, and are therefore capable of eradicating tumor cells throughout the body. Systemic therapies are not new, having been around in some form for the better part of a century. However, the recent development and relative success of several new systemic therapies has breathed new life into this treatment technique, and it has rapidly become one of the most exciting areas of research and development in radiation oncology. How far can we hope to extend the application and capabilities of systemic therapy? Will emerging cellular delivery mechanisms, new imaging techniques, and the use of alpha emitting isotopes revolutionize systemic therapy? Can we expect a future in which systemic therapy provides the best hope for cure for a large number of disease sites, or will it continue to be limited to a relatively small number of unique treatment applications? This is the topic of the current 3DCRT debate.

Arguing for the proposition will be Drs Bridget Koontz, Marianne Koritzinsky, and Jacqueline Zoberi. Dr Koontz trained at Harvard Medical School and Duke University School of Medicine. She was a faculty member in the Duke University Department of Radiation Oncology for 14 years before serving as US Chief Medical Officer for GenesisCare from 2021 to 2023. Dr Koontz is currently the Medical Director of Radiation Oncology services at the AdventHealth Cancer Institute in Orlando, Florida. She also is an Affiliate Professor at East Carolina University and a Fellow of the American Society for Radiation Oncology. Dr Koritzinsky has a PhD in radiobiology from the University of Oslo (Norway) and completed postdoctoral training at the University of Maastricht (The Netherlands). She is a Senior Scientist at the Princess Margaret Cancer Centre in Toronto (Canada). The aim of her research program is to increase our understanding of molecular and cellular responses to altered metabolism in the tumor microenvironment. Dr Zoberi earned a PhD in medical physics from the University of Chicago and completed physics residency training at Washington University in Saint Louis, where currently she is a Professor of Radiation Oncology and Chief of Brachytherapy Physics. She is actively involved in multiple initiatives within AAPM, ASTRO, and ABS focused on brachytherapy, radiopharmaceutical therapy (RPT), and medical physics education.

Arguing against the proposition will be Drs Stephen Brown, Xuanfeng Ding, and Jeffrey Wong. Dr Brown is a Senior Scientist for the Department of Radiation Oncology at Henry Ford Health (HFH), Detroit, Michigan; Professor of Radiology, Michigan State University, East Lansing, Michigan; Professor of Oncology, Wayne State University, Michigan; and co-chair of Translational Oncology Research, Henry Ford Cancer Institute, HFH. His research focuses on early imaging predictors of tumor response, radiosensitizers, and minimizing normal tissue radiation injury. Dr Ding is Associate Professor and lead proton physicist at the proton therapy center at William Beaumont University Hospital, Corewell Health, Michigan. Dr Ding's research interests include proton arc technique, adaptive therapy, and motion management. In 2024, he received the John Laughlin Early-Career Scientist Award from the AAPM. He is past president of the Great Lakes Chapter of the AAPM. Dr Wong is a Professor in the Department of Radiation Oncology and the Department of Immunology and Theranostics at City of Hope in Los Angeles, California. His primary areas of research include the development of novel targeted radiopharmaceuticals for therapy of non-hematopoietic and hematopoietic malignancies and the development of targeted total marrow irradiation for bone marrow transplantation.

The first six authors contributed equally to this work. All authors were responsible for preparation of arguments, and/or were involved in writing and reviewing the manuscript.

Dr Koontz holds equity and leadership roles for Rythera Therapeutics and has served on advisory boards for Lantheus and Blue Earth Diagnostics.