Radiotherapy, long established as a key modality in oncology, also has an important but more discreet role in the management of selected benign, non-neoplastic diseases. In this context, ionising radiation is used not to eradicate a tumour, but to modulate pathological biological processes such as inflammation, aberrant vascular proliferation, fibroblast activation, or ectopic bone formation. Typical examples include arteriovenous malformations, trigeminal neuralgia, Graves’ orbitopathy, keloid scars, heterotopic ossification, selected benign gynecological and dermatologic conditions, and, more recently, refractory cardiac arrhythmias. In many of these indications, radiation is considered when conventional medical or surgical treatments have failed, are contraindicated, or would carry an unacceptably high morbidity.
The doses, fractionation schemes, and techniques used for benign diseases differ substantially from those employed in cancer care. Treatments are usually hypofractionated at relatively low total doses, aiming to achieve durable symptom control or functional improvement while minimising late toxicity.
From a pathophysiological perspective, the benefit of radiation in benign conditions is linked to its anti-proliferative, anti-inflammatory and pro-remodelling effects, rather than to cytotoxic tumour cell kill. Low to moderate doses can inhibit fibroblast proliferation and collagen deposition, reduce endothelial cell activation and neovascularisation, and modulate immune cell function. These mechanisms underlie the use of radiotherapy in conditions such as keloids, Dupuytren disease, or prophylaxis of heterotopic ossification, where the goal is to prevent or attenuate excessive tissue responses rather than remove a mass.
Muskuloskeletal Diseases
Kim et al presented results at ASTRO 2025 showing that a single course of low-dose radiation therapy may offer a safe, effective option for people with painful mild to moderate knee osteoarthritis (OA) who are not ready for or cannot tolerate surgery and stronger medications.
In this randomized, sham-controlled trial of 114 patients across three Korean centers, participants were assigned to one of three groups: 3 Gy, 0.3 Gy, or sham radiation, all delivered in six sessions. Only acetaminophen was allowed as rescue medication during the first 4 months so that the true effect of radiation would not be masked by stronger analgesics.
At 4 months, 70% of patients in the 3 Gy group met responder criteria for meaningful improvement in pain, function, and overall condition, compared with 42% in the placebo group (P = 0.014). The 0.3 Gy group (58.3% responders) did not differ significantly from placebo. Patients in the 3 Gy arm were also more likely to report clinically important improvements in combined scores for pain, stiffness, and physical function (56.8% vs 30.6%; P = 0.024). No radiation-related side effects were observed, and the radiation doses were less than 5% of typical cancer regimens.
Martin et al. reported results from the DEPART trial at ASTRO 2025, a multicenter randomized study evaluating low-dose radiotherapy (LDRT) for early Dupuytren’s disease (DD). Because DD has a proliferative phase before fixed contractures develop, the trial tested whether LDRT could be used safely as a preventative or adjuvant approach, focusing here on toxicity and quality of life (QOL) compared with observation.
In total, 404 hands (202 Observation, 202 LDRT) were randomized across 12 centers in Australia and the Netherlands. Patients in the LDRT arm received 30 Gy in 10 fractions with a 4–12 week mid-course break. Adverse events (AEs) were prospectively graded (CTCAE v4.0), and QOL was assessed using QuickDASH, URAM, and pain scores up to 60 months, with p<0.01 considered significant.
AEs occurred in 4 patients in the observation arm and 158 in the LDRT arm, predominantly grade 1 (96.6%) dermatitis, reduced sweating, and localized edema. Fourteen AEs were grade 2; only one dermatitis persisted to 18 months. No grade 3+ toxicities were seen, and only 2.5% of hands had any persistent AE at 24 months. QOL scores were low at baseline, changed little over time, and did not differ significantly between arms at 36 months (e.g., QuickDASH 18.4 Obs vs 12.1 LDRT; pain 2.0 Obs vs 1.1 LDRT).
The authors concluded that randomized trials of radiotherapy for benign disease are feasible and that LDRT for early DD is well tolerated, with mostly mild, self-limiting AEs and no meaningful negative impact on QOL. Longer follow-up will determine whether LDRT also translates into improved long-term disease control.
Karimi et al. reported a retrospective study, published in 2024 in the International Journal of Radiation Oncology, Biology, Physics, evaluating low-dose radiotherapy as a treatment for painful heel spurs. The analysis included 100 patients (27 men, 73 women; mean age 70.7 years, range 37–101) who received 3 Gy of radiotherapy, with outcomes assessed over a 20-year follow-up.
More than 70% of patients experienced marked symptom improvement, with reduced need for NSAIDs and preservation of a largely normal gait, although some reported mild limitations in mobility and daily activities. Importantly, no skin changes, tumor induction, or significant radiogenic side effects were observed in the treated area. The authors concluded that low-dose radiotherapy is a safe and effective option for heel spur–related pain and may merit broader consideration in orthopedic practice, while underscoring the value of further research to refine long-term outcomes and optimal treatment protocols.
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Neurological Diseases
de Haan et al. published a PRISMA-guided systematic review in 2025 in Radiotherapy and Oncology evaluating stereotactic radiotherapy (SRT) for medically refractory Parkinson’s disease tremor. Six studies comprising 193 patients were included, all using single-fraction SRT with prescribed doses between 85–165 Gy (most commonly 130–140 Gy), frequently targeting the ventral intermediate nucleus (VIM).
Across studies, 71%–100% of patients showed tremor improvement, with tremor severity reduced by 38%–67% and complete tremor elimination reported in 0%–70% of cases. Medication reduction after one year occurred in 6%–75% of patients. Tremor recurrence ranged from 3%–24%, and adverse events were reported in about 7% of patients. Quality of life outcomes were inconsistently captured, with only one study finding no significant QoL benefit. The authors concluded that SRT is a promising non-invasive option for refractory PD tremor with substantial tremor reduction and relatively low toxicity, but emphasized the need for standardized reporting of treatment parameters and outcomes to strengthen the evidence base and clarify long-term efficacy.
Ortholan et al. published an open, prospective, single-center study in 2023 in The Journal of Headache and Pain comparing outcomes of LINAC-based radiosurgery for medically refractory classical trigeminal neuralgia using 5-mm vs 6-mm shot sizes (95 cases, 93 patients). The target was the intracisternal segment of the trigeminal nerve. The 6-mm shot delivered a higher mean maximum dose (D0.035) to the brainstem (21.3 vs 12.6 Gy, p<0.001) and provided better pain control, with pain-free rates of 90.2% and 87.8% at 12 and 24 months, compared with 73.6% at both time points for the 5-mm group (p=0.045).
However, hypoesthesia was more frequent with the 6-mm cone (47.0% and 58% at 12 and 24 months vs 11.3% and 30.8% with 5 mm, p=0.002). Stratifying by cone size and brainstem dose showed hypoesthesia rates of 11.3%, 33.5%, and 76.0% at 12 months for 5 mm (Dmax<25 Gy), 6 mm (Dmax<25 Gy), and 6 mm (Dmax>25 Gy), respectively, while pain recurrence tended to be lowest in the high-dose 6-mm group. The authors concluded that a 6-mm shot improves pain control but increases trigeminal nerve dysfunction, particularly when brainstem Dmax exceeds 25 Gy, underscoring the importance of dose constraints in treatment planning.
Skin Diseases
Tsai-Ling Tsai, Helen H. W. Chen, and Wei-Ting Hsueh reported a retrospective case series in 2025 in Therapeutic Radiology and Oncology describing their institutional experience with postoperative brachytherapy for resectable keloids. Ten keloid lesions in six patients at National Cheng-Kung University Hospital were treated with surgical excision followed by superficial mould brachytherapy to 20 Gy in 4 fractions, usually started within 2 weeks after surgery.
All lesions achieved excellent local control with no recurrences and good cosmetic outcomes. Median VSS, VAS, and JSW scores all improved markedly (from 11→1, 5→0, and 11→1, respectively; all P=0.002), reflecting substantial reductions in pain and scar severity. The only toxicity observed was Grade 1 acute radiation dermatitis in all patients, with no Grade 3 or higher acute or late effects, leading the authors to conclude that 20 Gy in 4 fractions of postoperative brachytherapy is a highly effective and well-tolerated option for keloid managem
Goutos and Ogawa published a narrative review in 2017 in Scars, Burns & Healing examining the role of brachytherapy as adjuvant radiation for keloid scars. They reviewed the English-language literature up to June 2017 (PubMed, Embase, Web of Science) using the terms “brachytherapy” and “keloid,” outlining how techniques have evolved from early low–dose rate interstitial brachytherapy (first reported in 1976) to contemporary high–dose rate interstitial and superficial (surface) approaches.
High–dose rate interstitial brachytherapy was found to compare favourably with conventional external beam radiotherapy in terms of keloid recurrence and relief of symptoms such as pain and pruritus, while more recently introduced superficial brachytherapy also appears to offer promising outcomes relative to external beam treatment. The authors concluded that brachytherapy is a valid and increasingly popular adjuvant radiotherapy option for keloid scars, but emphasized the need for randomized controlled trials and careful discussion of long-term risks, including secondary carcinogenesis, as part of shared decision-making in clinical practice.