Radiotherapy has long been associated with the treatment of malignant tumors, yet its application in nonmalignant (benign) diseases predates many contemporary oncologic uses and has played a critical role in shaping the broader field of radiation medicine.1 As of 2025, roughly 130 years have elapsed since the first experimental clinical applications of X‑rays and radium for non‑malignant conditions, and a review of this period may provide insights both into medical innovation and the trade‑offs inherent in using potentially harmful agents for nonmalignant indications.2

Since the discovery of X-rays by Wilhelm Conrad Röntgen in 1895 and the subsequent identification of radioactivity by Henri Becquerel and Marie Curie, the medical community has explored the therapeutic potential of ionizing radiation not only for cancer but also for a wide array of noncancerous conditions.3

Early enthusiasm for this novel modality led to the rapid adoption of radiotherapy for a broad spectrum of nonmalignant disorders, including skin diseases, inflammatory and degenerative musculoskeletal conditions, endocrine disorders, and even infectious diseases, often with anecdotal or empirical justification and little understanding of the long-term risk.2,4

Over the first half of the 20th century, radiotherapy for benign disease expanded rapidly as therapeutic sources (eg radium, orthovoltage X‑ray machines) became more available and better understood; in these early years of radiotherapy more nonmalignant than malignant diseases were treated.2,5 Clinicians reported successes in treating conditions such as plantar fasciitis, ankylosing spondylitis, keloids, and heterotopic ossification, and many more other, even very obscure, indications6. However, dosimetry was rudimentary, long‑term follow‑up often was lacking, and the potential risks of ionizing radiation, particularly the induction of secondary cancers or late tissue damage, were not fully appreciated.2,7

By mid‑century, accumulating evidence of late adverse effects, combined with the development of non‐radiation therapies, led to a reappraisal and in many settings a sharp decline in the use of radiotherapy for non‐malignant conditions.1,2 Regulatory oversight increased, and radiation protection principles became more formalized. But improvements in technology (for example, better imaging, beam‑shaping, more precise delivery) coupled with a deeper understanding of radiation biology have in recent decades enabled a selective revival of interest in non‑malignant radiotherapy, especially for conditions where conventional therapies fail.8

Despite this decline, the therapeutic rationale for radiotherapy in nonmalignant conditions never disappeared entirely. Advances in radiation technology, including the development of linear accelerators, improved beam collimation, image-guided delivery, and more accurate dosimetry, have allowed for renewed interest in select benign indications.1,2,9 Moreover, an improved understanding of the radiobiological mechanisms underpinning the anti-inflammatory and antifibrotic effects of low-dose radiation10 has contributed to a cautious resurgence of this modality, particularly in Europe, where it is now used under clear clinical protocols for conditions such as painful osteoarthritis,11 Dupuytren´s disease,12 and prophylaxis against heterotopic ossification following endoprosthetic surgery.13

Today, however, the use of radiotherapy for benign diseases is actively discussed and varies significantly amongst countries due to differing regulatory frameworks, cultural perceptions of radiation risk, and levels of evidence supporting efficacy.14 In Germany, for instance, it continues to be a standard therapeutic option for certain indications, whereas in the United States and the United Kingdom, it is used far more sparingly.15

Currently, at least 50,000 patients are treated with radiotherapy annually in Germany for “benign” or “nonmalignant diseases” or “functional disorders.”16 Based on the results of a research report on radiation protection from the German Society for Radiation Oncology (DEGRO),17 in 2016, more than 250,000 completed treatment cycles were performed for benign diseases (including benign tumors) in Germany. Depending on the type of and geographical location (originally eastern or western Germany and nowadays more rural and urban locations), the indications for radiation therapy for benign disorders comprise between 10 and 60% of patients, as various patterns of care (PCS) studies in Germany have shown in the past.9,16,18 Of the more than 300 active radiotherapy facilities in Germany today, there is not a single 1 that does not offer radiotherapy for benign diseases.1,2

This development over the past decades can undoubtedly be regarded as a “renaissance” of a therapy that was hardly considered relevant almost 40 years ago, but then experienced an unexpected upswing at the beginning of the 1990s, particularly with the opening of the “Iron Curtain” between East and West Germany.1,2,9,19 It was clinical experience and knowledge gained over many years “in the East” that, since 1989, has been increasingly subjected to modern scientific debate and justification,20,21 culminating in demands for randomized clinical trials to be conducted in order to improve the evidence base.21, 22, 23 The independent development has been promoted since 1995 by the establishment of a national society for radiation therapy in Germany (German Society for Radiation Oncology, DEGRO) and systematic continuing education and training in the field.2 The indications commonly used today for nonmalignant diseases, which differ greatly from the original applications, were established between 1996 and 2010 in the specialist groups through a consensus process and jointly developed guidelines within the scientific society.9,24, 25, 26, 27, 28, 29

Today's challenges lie in reconciling historical experience with contemporary standards of evidence-based medicine, balancing the demonstrated clinical benefits with the ethical imperative to minimize harm.24,25,30

In light of 130 years of experience, tracing the arc of radiotherapy for non‑malignant disease offers more than pure historical interest. It provides insights into how medical innovation, risk management, evidence standards, and ethical principles evolve together. Such a historical overview31 can help us understand past missteps, guide present practice, and shape future research, especially in defining indications, optimizing dose/fractionation schedules, and ensuring long‑term monitoring of outcomes and risks. Our review will touch cornerstones and landmarks of the long and widely branched history of radiotherapy and also looks at important pioneers and martyrs of the field, so that we can learn from their thinking, research and experience.