Back to the Future: Revitalizing Radiation Therapy for Non-Malignant Conditions

In the past several decades, the field of radiation therapy has been focused on radiation as a cancer treatment. However, a growing body of evidence has demonstrated radiation’s effectiveness in treating non-malignant conditions, sparking renewed interest. We interviewed two experts in the field of non-malignant radiation therapy to provide some insights in this field and provide a general overview of how to treat two different non-malignant conditions. The ASTRO 2025 annual meeting will address non-malignant radiation therapy indications in depth, with Dr. Keole’s Presidential Symposium highlighting this field.

Dr. Schuster, expert in connective tissue disorders

Jessica Schuster, MD, Associate Professor at the University of Wisconsin, has built a practice caring for patients with connective tissue disorders such as Dupuytren’s contracture and other non-malignant diseases. Her interest was sparked in residency when she was able to work with her attending, Dr. Elizabeth Weiss, who had trained in Germany where radiation for non-malignant reasons is routine. Dr. Wiess had a whole cohort of patients who were treated for early stage plantar and palmar fibromatosis, "I found it fascinating that there were things that radiation did well but weren’t cancer" recalls Dr. Schuster. This early exposure led to a longitudinal investigation of non-malignant radiation cases which revealed a crucial insight: patients treated with radiation therapy for benign conditions were overwhelmingly satisfied with their choice (Schuster et al. PRO 2015). What was equally striking, however, was that "most patients reported they had to do their own research to find radiation as an option." This highlights a significant gap in awareness and referral patterns that Dr. Schuster and many in the field are eager to address.

To build your practice in non-malignant diseases, Dr. Schuster recommends ensuring your online profiles and practice websites clearly list the non-malignant diseases you are willing to treat, as most patients still discover radiation treatment as an option through their own research. Additionally, proactively reaching out to colleagues in orthopedics and primary care can be helpful. Offering to share supporting literature and give educational talks can increase the more traditional physician to physician referrals. The outlook for radiation therapy in non-malignant diseases is optimistic. "I think you’re going to see a continued upward trend where there will be  more mainstream referrals" predicts Dr. Schuster. As awareness grows among both medical professionals and patients, radiation therapy is poised to become a more recognized and utilized treatment option for a wider range of non-malignant conditions.

Brief Overview of Radiation Treatment for Dupuytren's Contracture

Dupuytren’s contracture is a condition that causes fibrous tissue to form in the palm of the hand, leading to finger contractures and progressive loss of function. Recent literature suggests microtraumas from activities like rowing, biking, or rock climbing may serve as inciting events or exacerbate the condition. Dupuytren’s contracture is a clinical diagnosis, however an MRI can be used to assess the extent and depth of the disease, especially when there's uncertainty. The treatment for Dupuytren's contracture, or its foot counterpart Ledderhose disease, is generally delivered with electrons (often 6MeV), with bolus utilized to ensure optimal dose distribution.

• Dose: The standard dose, based on German protocols, is 3 Gy delivered in 5 fractions, followed by a 8-12-week break, and then another 3 Gy in 5 fractions.
• Target: For hands, the target typically involves all palpable nodules and cords, generally encompassing two-thirds of the palm. For feet, the target extends a couple of centimeters anterior/posterior (heel/toe) and 1-2 cm laterally.
• Immobilization: For hands, a custom-indexed sponge ensures precise positioning on the treatment board. For feet, the patient lies prone with their feet positioned close to perpendicular to allow for en face electrons.
• Further literature:
  • De Haan et al. Radiotherapy for Ledderhose disease: Results of the LedRad-study, a prospective multicentre randomised double-blind phase 3 trial. Radiotherapy and Oncology 2023
  • Schuster et al. Patient-reported outcomes after electron 4 radiation treatment for early-stage palmar and 5 plantar fibromatosis. PRO 2015
  • Guidelines from Germany, where radiation for non-oncologic indications is common – Deutsche Gesellschaft für Radioonkologie (DEGRO)

Dr. Thomas, expert in CNS disorders

Evan Thomas, MD, PhD, Chief Medical Officer and Founder of Renaissance Institute of Precision Oncology and Radiosurgery, is an expert in the field of high dose radiation therapy for non-malignant conditions – including radiation for essential tremor. His interest in the non-malignant CNS space was sparked by the lack of other available treatments for these patients. “For these conditions, once the patients are severe enough, they are orphaned by the medical system in terms of care” says Dr. Thomas. We now have excellent, non-invasive options for these patients for whom medications have failed and cannot, or do not want, invasive procedures. “What’s interesting is that radiation treatments for benign conditions have been around a lot longer than radiation for a lot of brain cancers. We were treating Parkinson’s and essential tremor long before we were offering SRS for brain metastases.” Dr. Thomas has focused on taking his CNS expertise to allow him to offer “sub-millimetric precision ablations in the brain or spine – be it for pain conditions such as spinal nerve ablations, psychiatric conditions such as OCD, or movement disorders such as essential tremor.” To build a practice in high dose radiation therapy for CNS disorders, Dr. Thomas says “starting from a background of a CNS specialist is important, understanding functional neuroanatomy is critical.” He recommends seeking out a movement disorder clinic to join in weekly meetings, discussing radiosurgery as a treatment option and providing education to other providers. Dr. Thomas echoes Dr. Schuster’s optimism: “The low dose applications are going to be exploding, in part due to the accessibility of these treatments to any radiation oncologist.” He goes on to state “I would like to see academies or other learning platforms, where we can teach other radiation oncologists interested in the field and grow the space.

Brief Overview of Radiation Treatment for Essential Tremor

Essential tremor is the most common movement disorder, with the tremor usually occurring in the bilateral upper extremities when the patient is trying to use their hands. These tremors tend to progress over time and can impact daily life. The most important part of radiation therapy for essential tremor is patient selection. For this group of patients medical therapy is no longer effective and surgical management is not an option or not desired. The treatment involves a one-time ablative dose of radiation using a linear accelerator with sub-millimetric precision.

• Dose: The standard dose ranges between 130-150 Gy for a point Dmax
• Target: Target is the ventral intermediate nucleus of the thalamus, located using MRI tractography
• Immobilization: Either invasive (screws) head frame or frameless mask with robust motion tracking
• Further literature:
  • McLaughlin et al. Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response. Translational Psychiatry 2023

Bilski et al. Stereotactic radiosurgery in the treatment of essential tremor – a systematic review. Front Neurol 2024.Modern radiation techniques allow for effective treatment of many non-malignant diseases, either taking advantage of anto-proliferative and anti-inflammatory properties of lower doses or taking advantage of the precision available with current imaging and radiation techniques. This increasing application of radiation for non-malignant disease is driven by the desire for non-invasive options, improved patient quality of life, and the ability to precisely target affected tissues while minimizing damage to healthy surrounding areas. Be sure to attend the Presidential Symposium at the ASTRO Annual Meeting on Sunday, September 28, 8:45 to 12:00 Pacific time to learn more.