Radiotherapy for painful benign skeletal disorders

Rhee

2021

JAD

Our research team recently published two relevant papers. In one study, we have seen the acute effect of low-dose ionizing irradiation (LDIR) did not reduce the amyloid-β (Aβ) protein concentration in brain tissue, yet significantly improved synaptic degeneration and neuronal loss in the hippocampus and cerebral cortex. Surprisingly, in another study, we could see late effect that the LDIR-treated mice showed significantly improved learning and memory skills compared with those in the sham group. In addition, Aβ concentrations were significantly decreased in brain tissue. Furthermore, the pro-inflammatory cytokine tumor necrosis factor-α was decreased and the anti-inflammatory cytokine transforming growth factor-β was increased in the brain tissue of 5xFAD mice treated with LDIR. Definitive clinical results for the safety and efficacy of LDIR have not yet been published and, despite the promising outcomes reported during preclinical studies, LDIR can only be applied to patients with Alzheimer’s disease dementia when clinical results are made available. In addition, in the case of LDIR, additional large-scale clinical studies are necessary to determine the severity of Alzheimer’s disease dementia, indications for LDIR, the total dose to be irradiated, fraction size, and intervals of LDIR treatment. The purpose of this review is to summarize the mechanism of LDIR based on existing preclinical results in a way that is useful for conducting subsequent clinical research.

Section: Introductonmentioning

confidence: 99%

Clinical Approach of Low-Dose Whole-Brain Ionizing Radiation Treatment in Alzheimer’s Disease Dementia Patients1

Rhee

2021

JAD

“…Second, we had insufficient data about patients’ long-term pain response, as patients were not routinely re-assessed over the following years. However, previous analyses rather have shown that pain response is augmented with increasing duration and that the full analgesic effect of low-dose radiotherapy is most pronounced at later time points [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Low-dose radiotherapy for painful osteoarthritis of the elderly: A multicenter analysis of 970 patients with 1185 treated sites

et al. 2021

Purpose Painful osteoarthritis is common in elderly patients, and low-dose radiotherapy has been demonstrated to provide effective symptomatic treatment. We examined the analgesic effects of low-dose radiotherapy for osteoarthritis in the elderly aiming to reveal potential differences in the response rates relating to increasing age. Methods A retrospective analysis was performed at two university hospitals including elderly patients (≥ 65 years) undergoing radiotherapy for osteoarthritis between 2008 and 2020. Pain intensity and response were quantified using the numerical rating scale (NRS) and the Pannewitz score. Age groups were defined for young old (65–74 years), older old (75–84 years), and oldest old patients (≥ 85 years). Results In all, 970 patients with 1185 treated sites and a median age of 76 years were analyzed. Mean NRS was 66 at baseline (t0), 53 after radiotherapy (t1), and 44 at first follow-up (t2) (p < 0.001 for t0–t1, t1–t2, and t0–t2). At t1, 1.5% exhibited a Pannewitz score of 0 (no pain), 58.5% of 1–2 (less pain), 36.1% of 3 (equal pain), and 3.9% of 4 (worse pain), while at t2, pain response shifted towards 6.9% (0), 58.6% (1–2), 28.1% (3), and 6.3% (4). Pain response did not differ between age groups at t1 (p = 0.172) or t2 (p = 0.684). In addition, pain response after re-irradiation (n = 384 sites) was 61.0% and was comparable between age groups (p = 0.535). Conclusion Low-dose radiotherapy results in pain reduction in about two-thirds of treated sites with no difference relating to increasing age, showing that radiotherapy is an effective analgesic treatment for osteoarthritis even at advanced ages.

“…In the context of atherosclerosis long term effects of LMDIR, in terms of lesions size, stability and composition are unknown. A clinical study demonstrated that repeated LMDIR with a nal dose of 3 Gy could have bene cial long term effects on painful skeletal disorder (Juniku et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Low to moderate dose 137 Cs (γ) radiation enhances M2 type macrophages function at short term associated with reduced inflammation at long term exposure in ApoE (-/-) mice

Rey,

Ebrahimian,

Gloaguen

et al. 2024

Preprint

Effects of low doses of ionizing radiation on atherosclerosis are still a source of many uncertainties, and in particular whether these effects generate anti or pro-inflammatory responses. Furthermore, the delay of occurrence of such effects upon irradiation are unknown. Atheroprone ApoE(−/−) mice were exposed to single doses of 0, 0.05, 0.5 and 1 Gy of 137Cs (γ) at 10.35 mGy.min− 1 dose rate. Short term (24 hours) effects on bone marrow-derived macrophage polarization and long term (100 days) consequences on atherosclerotic plaques were investigated. We found a significant dose-dependent increase of Chil3 and Retnla anti-inflammatory markers gene expression in M0 and M2 type macrophages upon 24 hours exposure and no effects on M1 types. These effects were associated with a dose-dependent increase of IL-10 and a reduction of IL-1beta secretions in M0 and M2 and an increase of IL-6 in M1 type macrophages. Circulating pro-inflammatory Ly6CHigh monocytes were reduced at 24 hours and anti-inflammatory Ly6Clow monocytes were notably increased in the spleen 100 days upon irradiation. Long term exposures to any doses did not affect atherosclerotic plaque size determined by OilredO. However, a tendency in plaque stability, determined by collagen and alpha-smooth muscle actin increase was observed, associated with a significant reduction of plaque macrophage content at 1Gy. Taking together these findings show an increase of anti-inflammatory behavior of M2 macrophages with low to moderate doses of ionizing radiation at short term after irradiation, at long term these changes could influence atheromatous plaques after irradiation with decreased macrophages contents. These results suggest that the mechanisms that lead to on atheroprotective response after low and moderate doses of ionizing radiation would involve early effects on circulating monocytes and the macrophages polarization towards an anti-inflammatory profile.