Non-Oncological Radiotherapy: A Review of Modern Approaches
Abstract
:1. Introduction
2. Search Strategy
3. Results
3.1. Heart
3.1.1. Ventricular Tachycardia
3.1.2. Atrial Fibrillation
3.2. Soft Tissue Disorders
3.2.1. Keloids
3.2.2. Dupuytren’s Disease
3.2.3. Peyronie’s Disease
3.3. Muscle-Skeletal Disorders
3.3.1. Osteoarthritis and Osteoarthrosis
3.3.2. Achillodynia
3.3.3. Heterotopic Ossification
3.4. Neurological Disorders
3.4.1. Epilepsy
3.4.2. Trigeminal Neuralgia
3.4.3. Brain Arteriovenous Malformations
3.4.4. Graves Ophthalmopathy
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Authors | Year | N pts | Diagnosis | End-Point | Dose tot/fx | Results |
---|---|---|---|---|---|---|
Cuculich PS [12] | 2017 | 5 | VT | Efficacy and safety of treatment | 25 Gy/1 fx | No complications during treatment. Fatigue after treatment (three patients), with no acute heart-failure. Marked reduction in the burden of ventricular tachycardia after treatment. |
Kurzelowski R [13] | 2022 | 2 | VT | Efficacy and safety of treatment | 25 Gy/1 fx | No problem in the first patient. The second one experienced acute side effects with an increase in VT that gradually improved at the end of the follow-up period. |
Wight J [14] | 2022 | 14 | VT | Efficacy and safety of treatment | 25 Gy/1 fx | VT was reduced in 59%, ATP was reduced in 39%, and shocks were reduced in 60%. |
Lee J [15] | 2021 | 7 | VT | Reduction of VT and safety of treatment | 25 Gy/1 fx | VT responded in all patients. After 6 months, VT burden was reduced by 85%. No high grade acute toxicity. |
Piccolo C [16] | 2022 | Phantom study | VT | Feasibility of Cyberknife on cardiac lesions by tracking as a single marker the lead tip of an implantable cardioverter defibrillator. | 25 Gy/1 fx | Tracking with a single marker is feasible considering adequate residual planning margins. The volumes could be further reduced by using additional markers. |
Bonaparte I [17] | 2021 | Dosimetric study | VT | STAR is efficacy in terms of BDT and MUs. | 25 Gy/1 fx | Several plans were evaluated for dosimetric considerations. |
Kovacs B [18] | 2021 | 57 | VT/FA | STAR’s effectivity and safety for structural VT/VF | 25 Gy/1 fx | Significant short-term reduction of sustained VT/VF-burden, but recurrences are common. |
Akdag O [19] | 2022 | Phantom study | VT | First experimental evidence for real-time cardiorespiratory motion-mitigated MRI-guided STAR on the 1.5 T Unity MRlinac aimed at simultaneously compensating cardiac and respiratory motions. | 25 Gy/1 fx | Cardiac motion was successfully mitigated using gating, which was demonstrated in the phantom and in-silico experiment. |
Kautzner J [20] | 2021 | 3 | VT | postmortem immunohistochemical was performed early and late after SBRT | 25 Gy/1 fx | Apoptosis and subsequent fibrosis was shown to be not immediate, thus the antiarrhythmic effects may be delayed after SBRT. |
Di Monaco A [21] | 2022 | 5 | AF | Side effects at 1 month after STAR | 25 Gy/1 fx25 Gy/1 fx | No acute treatment-related adverse events (>G1) |
Author | Year | N pts | Diagnosis | End Point | Dose | Results |
---|---|---|---|---|---|---|
Jiang [29] | 2018 | 29 | Keloids | Control rate | 18 Gy/3 fx | Response rate 91.9% |
Kim [30] | 2015 | 28 | Keloids | Control rate | 12–15 Gy/3 fx | Response rate 50% |
Shen [31] | 2015 | 568 | Keloids | Control rate | 18 Gy/3 fx | Response rate 90.41% |
Emad [32] | 2010 | 26 | Keloids | Control rate | 12 Gy/3 fx | Response rate 70.4% |
Malaker [33] | 2004 | 64 | Keloids | Control rate | 37.5 Gy/5 fx | Response rate 97% |
Lo [34] | 1990 | 199 | Keloids | Control rate | 2–20 Gy/1 fx | Response rate 87% for Dose > 9 Gy, 43% for Dose < 9 Gy. |
Borok [35] | 1988 | 250 | Keloids | Control rate | 4–16 Gy/various fx | Response rate 98% |
Van de Kar [36] | 2007 | 21 | Keloids | Control rate | 12 Gy/3–4 fx | Response rate 71.9% |
Arneja [37] | 2008 | 25 | Keloids | Control rate | HDR BT 5 Gy/3 fx | Response rate 92% |
Van Leeuwen [38] | 2014 | 67 | Keloids | Control rate | HDR BT 6 Gy/2 fx | Response rate 96.9% |
Jiang [39] | 2016 | 32 | Keloids | Control rate | HDR BT 6 Gy/3 fx | Response rate 94% |
Hafkamp [40] | 2017 | 29 | Keloids | Control rate | HDR BT 13 Gy/1 fx | Response rate 75.9% |
Kadhum [41] | 2017 | 698 | Dupuytren’s disease | Control rate | 21–42 Gy in 3–14 fx | Good ratio of regressions (6–20% depending on staging), stability (12–81%) and low ratio of progressions (13–65%, depending on staging). |
Seegenschmiedt [7] | 2015 | 1762 | Dupuytren’s disease | Control rate | 15–21 Gy in 5–7 fx, 30 Gy split in 2 series of 5fx with a 3 months interval | Stability of disease in 84% for N stage and 67% for N/I stage |
Betz [42] | 2010 | 135 | Dupuytren’s disease | Control rate | 30 Gy split in 2 series of 5 fx separated by a 6- to 8-week interval | Stability of disease in 59%, 10% improved, and 31% progressed. In stage N 87% and in stage N/I 70% remained stable or regressed |
Seegenschmiedt [8] | 2015 | 8732 | Peyronie’s disease | Pain, improvement | 10–20 Gy (2–10 fx) | Pain regression in 50–90%, Improvement of penile deviation in 30–70% |
Seinen [43] | 2015 | 155 RT alone, 815 Surgery + RT | Fibromatosis | Local control | 30–74 Gy | Local control in 78% of the patients treated with surgery and RT versus 85% in patients treated with RT alone |
Author | Year | N pts | Diagnosis | End Point | Dose | Results |
---|---|---|---|---|---|---|
Hautmann [45] | 2019 | 124 | epicondylitis humeri | pain relief | 6 Gy(1 Gy)–3 Gy (0.5 Gy) | complete response 64% at 24 months |
Rogers [46] | 2020 | 157 | epicondylitis, plantar fasciitis, and finger osteoarthritis | pain relief | 4 Gy (0.5 Gy)–8 Gy Orthovoltage | pain relief at rest and during activity and a corresponding objective improvement in handgrip strength in epicondylitis. Pain relief at rest, during activity and improvement in walking time were demonstrated in plantar fasciitis |
Hautmann [47] | 2020 | 86 | Humeral epicondylitis | pain relief | 3 Gy/2.5 Gy (0.5 Gy/fx); 6 Gy (1 Gy/fx) | |
Micke [48] | 2018 | 703 | Calcaneodynia, Achillodynia, Bursitis trochanterica, Shoulder Syndrome, Gonarthrosis | pain relief | 6 Gy (0.5–1 Gy) | At follow up, good response: Calcaneodynia 80.7%, Achillodynia 88.9%, Bursitis trochanterica 46.3%, Shoulder Syndrome 60%; only Gonarthrosis 29.2% |
Alvarez [49] | 2019 | 108 | OADD | pain relief | 6 Gy (1 Gy)–12 Gy | Overall, and with a follow-up of 8 months (range 1–31 months), 91% of patients experienced pain relief. The pain reported according to the VAS scale was 0–3 in 32.6% of the patients, 4–6 in 36.7% and greater or equal to 7 in 20.1% of treated patients. |
Mahler [50] | 2018 | 55 | knee osteoarthritis | pain relief | 6 Gy | At 3 months follow-up: no substantial beneficial effect on symptoms and inflammatory signs of LDRT in patients knee OA, compared with sham treatment |
Ott [51] | 2015 | 112 | Achillodynia | pain relief | 6 Gy/3 Gy | Pain control:Early 84% Middle-term 88% Long-term 95% |
Rudat [52] | 2021 | 666 | Heel Spur | pain relief | 3 Gy (Re-irradiation possible) | Good local control (>75%) and good response to reirradiation |
Hautmann [53] | 2014 | 110 | Heel Spur (Re-irradiation) | pain relief | 3 Gy (Re-irradiation possible) | 73.6% of Pain control after 24 months |
Niewald [54] | 2020 | 236 | Kneel and Hand Osteoarthritis | pain relief | 3 Gy/0.3 Gy | Good pain control with no difference between the two schemes |
Authors | Year | N pts | Diagnosis | End Point | Dose | Results |
---|---|---|---|---|---|---|
Rauch [60] | 2012 | 11 | Epilepsy | Tolerability and seizure frequency. | 26.3–58.3 Gy | Treatment led to an improvement in the frequency of seizures in 63%. |
Liang [61] | 2010 | 7 | Epilepsy | Seizure frequency | 12 Gy | Reduction of seizure frequency was 50% in two cases, 30% in one case, and 0% in two cases, and seizure frequency increased more than 100% in two cases. |
Bartolomei [62] | 2008 | 15 | Epilepsy | Seizure frequency | 24 Gy | A total of 60% pts were considered seizure free. All patients who were initially seizure free experienced a relapse of isolated aura (66%) or complex partial seizures (66%) during antiepileptic drug tapering. |
Barbaro [63] | 2009 | 28 | Epilepsy | Seizure frequency | 24 Gy high dose vs. 20 Gy low dose | At the 36-month follow-up evaluation, 67% of patients were free of seizures for the prior 12 months (high dose: 10/13, 76.9%; low dose 10/17, 58.8%) |
Smith [64] | 2011 | 169 | TN | Pain relief | 70–85 Gy, 90 Gy | A total of 79.3% experienced significant relief. A total of 19.0% had recurrent pain. Of 87 patients with idiopathic TN without prior procedures, 79 (90.8%) had initial relief. Among 28 patients treated with 70 Gy, 18 patients (64.3%) had significant relief. Of the patients with 90 Gy at the brainstem, 59 (79.0%) had significant relief. |
Rashid [65] | 2018 | 55 | TN | Pain relief | 90 Gy | After 30 months median follow-up, 69% of patients were pain free. |
Romanelli [66] | 2019 | 387 | TN | Pain relief | 60 Gy (80% isodose) | Pain relief rate at 6, 12, 18, 24, 30, and 36 months was, respectively, 92, 87, 87, 82, 78, and 76%. |
Lovo [67] | 2019 | 14 | TN | Pain relief | 140 Gy | A total of 90% pts reported some form of relief. A total of 60% reached the threshold of 50% pain relief, and for 40% the pain never improved. |
Kundu [68] | 2022 | 41 | TN | Pain relief | 90 Gy | There has been a significant improvement in the post-radiation pain score in 72% of patients. |
Starke [69] | 2016 | 2236 | AVM | Obliteration rate | 20.5 Gy (mean margin dose) | Overall obliteration rate was 64.7%. |
Ding [70] | 2017 | 232 | AVM | Obliteration rates, hemorrhage rate | 22.5 Gy | The actuarial obliteration rates at 5 and 10 years were 72% and 87%, respectively. Annual post-SRS hemorrhage rate was 1.0% |
Patibandla [71] | 2017 | 233 | AVM | Obliteration rates, hemorrhage rate in Grade III-IV AVMs | Mean dose 17.3 Gy | The actuarial obliteration rates at 3, 7, 10, and 12 years were 15%, 34%, 37%, and 42%, respectively. The annual post-SRS hemorrhage rate was 3.0% |
Matsuo [72] | 2014 | 51 | AVM | Obliteration rate | 15 Gy (80% isodose) | The actuarial obliteration rates at 3, 5, 10, and 15 years were 46.9%, 54.0%, 64.4%, and 68.0%, respectively |
Matthiesen [73] | 2012 | 211 | GO | Symptomatic improvement | 20 Gy/10 fx | A total of 84.2% pts reported a symptomatic improvement |
Kouloulias [74] | 2013 | 17 | GO | Symptomatic improvementand tolerability | 20 Gy/10 fx | Stabilization of the disease without recurrence was achieved in 12/17 patients. At the end of radiotherapy, the CAS regressed to 4.82 ± 2.24 (p < 0.001, Wilcoxon test). Extraocular motility and pain behind the globe were improved in 14/17 and 16/17 patients, respectively. Five patients developed recurrent signs and symptoms and they underwent surgical decompression |
Li Yim [75] | 2011 | 59 | GO | duration of symptoms, clinical activity score (CAS) | 20 Gy/12 fx (over 2 weeks) | Response (change in CAS) to orbital radiotherapy was statistically significant from 3.17 ± 1.75 standard deviation (SD) to 0.73 ± 0.92 SD (p < 0.001) |
Kahaly [76] | 2000 | 65 | GO | Symptomatic improvement and toxicity | A: 20 Gy/20 fx (over 20 weeks) B: 10 Gy/10 fx (over 2 weeks) C: 20 Gy/10 fx (over 2 weeks) | Response to therapy, defined as a significant amelioration of three objective parameters, was noted in 12 A (67%), 13 B (59%), and 12 C (55%) subjects (C vs. A, p = 0.007). Ophthalmic symptoms and signs regressed most in group A |
Cardoso [77] | 2012 | 18 | GO | Symptomatic improvement and Radiologic response | 10 Gy/10 fx (over 10 weeks) | Significant decrease in symptoms such as tearing (p < 0.001), diplopia (p = 0.008), and conjunctival hyperemia (p = 0.002). Magnetic resonance imaging showed decrease in ocular muscle thickness and in the intensity of the T2 sequence signal in the majority of patients |
NCT Number | Disease | Design | Location |
---|---|---|---|
NCT04722263 | Keloids | Single arm, interventional pilot study (15 patients). RT: 15 Gy in 3 fractions. | Montefiore Medical Center, New York, US |
NCT04853433 | Keloids | Single arm, interventional pilot study (15 patients). The primary endpoint will be toxicity. | Montefiore Medical Center, New York, US |
NCT04122313 | Dupuytren’s Disease | Prospective, Cohort study. Participants will be treated according to a standard treatment pathway, followed by post-operative radiation. RT: 15 Gy in 5 fx, followed by a 6–8 weeks break then a second identical course. Total dose: 30Gy. | University of Minnesota, US |
NCT04424628 | Gonarthrosis and Coxarthrosis | Non-inferiority study in which the investigators compare two low-dose radiotherapy schemes. Arm A will be treated at 3 Gy (0.5 Gy/fraction, 3 fractions/week), and patients in arm B will be treated at 6 Gy (1 Gy/fraction, 3 fractions/week). | GenesisCare, Malaga, Spain |
NCT02708810 | Trigeminal Neuralgia | To determine the feasibility of frameless Virtual Cone trigeminal neuralgia radiosurgery at a single institution prior to multi-institutional enrollment. | Hazelrig-Salter Radiation Oncology Center, Birmingham, Alabama, US |
NCT03995823 | Cerebral Arteriovenous Malformations | Prospective study including 50 patients with cerebral AVMs treated with GRKS to evaluate the sensitivity for nidus obliteration of MRI. | Department of Neurosurgery, Medical University of Vienna, Austria |
NCT04843683 | Cardiac Arrhythmias | Prospective, single-center, phase II trial that will be monitoring the safety and efficacy of using stereotactic ablative radiotherapy (SBRT) to treat arrhythmias. | University Health Network, Toronto, Canada |
NCT04392193 | Cardiac Arrhythmias | Proton Particle Therapy for Cardiac Arrhythmia Extracorporeal Energy Source Ablation of Cardiac Tissue: A First Stage Early Feasibility Study | Mayo Clinic, Rochester, Minnesota, US |
NCT04984265 | Cardiac Arrhythmias (Chagas) | SBRT in Chagas Disease Ventricular Tachycardia. A single 25 Gy dose will be delivered to the PTV. | University of Sao Paulo General Hospital, Sao Paulo, Brazil |
NCT04642963 | Cardiac Arrhythmias | Single arm, aimed at investigate safety requirements for clinical use. A single 25 Gy dose will be delivered to the PTV. | Medical University of Silesia, Katowice, Poland |
NCT04833712 | Cardiac Arrhythmias | The study aims to investigate the safety and preliminary efficacy of stereotactic radiotherapy for pulmonary vein isolation to treat refractory atrial fibrillation | Attikon University Hospital, Chaidari, Greece |
NCT04486339 | Cardiac Arrhythmias | Pulmonary Vein Isolation Using Stereotactic Radiotherapy System for the Treatment of Refractory Atrial Fibrillation | Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shangai, China |
NCT03867747 | Cardiac Arrhythmias | Radiosurgery for the Treatment of Refractory Ventricular Extrasystoles and Tachycardias (RAVENTA) | University Clinic Mannheim, Mannheim, Baden-Württemberg, Germany |
NCT04162171 | Cardiac Arrhythmias | Cohort Study—SBRT for VT Radioablation | Nova Scotia, Canada |
NCT04066517 | Cardiac Arrhythmias | STRA-MI-VT study is a spontaneous, open-label, not randomized, prospective clinical trial. The objective of the study is to evaluate the safety and efficacy of SBRT in strictly selected patients with refractory VT. | Istituto Europeo di Oncologia, IRCCS, Milan, Italy |
NCT04612140 | Cardiac Arrhythmias | Clinical trial: Patients with previously failed conventional RF catheter ablation will be randomized to radiosurgery (active treatment group) or repeated catheter ablation (control treatment group). | University Hospital Ostrava, Czechia |
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Nardone, V.; D’Ippolito, E.; Grassi, R.; Sangiovanni, A.; Gagliardi, F.; De Marco, G.; Menditti, V.S.; D’Ambrosio, L.; Cioce, F.; Boldrini, L.; et al. Non-Oncological Radiotherapy: A Review of Modern Approaches. J. Pers. Med. 2022, 12, 1677. https://doi.org/10.3390/jpm12101677
Nardone V, D’Ippolito E, Grassi R, Sangiovanni A, Gagliardi F, De Marco G, Menditti VS, D’Ambrosio L, Cioce F, Boldrini L, et al. Non-Oncological Radiotherapy: A Review of Modern Approaches. Journal of Personalized Medicine. 2022; 12(10):1677. https://doi.org/10.3390/jpm12101677
Chicago/Turabian StyleNardone, Valerio, Emma D’Ippolito, Roberta Grassi, Angelo Sangiovanni, Federico Gagliardi, Giuseppina De Marco, Vittorio Salvatore Menditti, Luca D’Ambrosio, Fabrizio Cioce, Luca Boldrini, and et al. 2022. "Non-Oncological Radiotherapy: A Review of Modern Approaches" Journal of Personalized Medicine 12, no. 10: 1677. https://doi.org/10.3390/jpm12101677