Despite its clinical use and investigation in other countries, low dose radiation therapy (LDRT) in the treatment of osteoarthritis (OA) is minimally used in the United States (US). Numerous recent studies published outside the US have shown moderate to long-term pain relief and improvement of mobility after treatment with LDRT for joints affected by OA. Here, we review the most recent literature published on the use of LDRT in OA. We provide a brief outline on the epidemiology, pathophysiology, current treatments, and health care burden of OA within the US. We provide a brief history of the historic use of LDRT in the US as well as a history of LDRT within the modern era of radiation oncology, discuss criticisms of LDRT including recently published randomized trials questioning its benefit as well as the risk of secondary malignancy from LDRT, and provide an outline of treatment planning considerations and recommendations regarding dose and fractionation, energy, beam arrangements, and immobilization techniques. LDRT has been shown to be a cost-effective, noninvasive treatment with minimal side effects. Further investigation into the potential role in the treatment of OA with modern LDRT is recommended. 

http://www.redjournal.org/article/S0360301622003571/pdf

The Use of Low-Dose Radiotherapy in Osteoarthritis: A Review.

Malignant Tumor of Breast.

Osteoarthritis (OA) is the leading degenerative joint disease in the western world and leads, if left untreated, to a progressive deterioration of joint functionality, ultimately reducing quality of life. Recent data has shown, that especially OA of the ankle and foot are among the most frequently affected regions. Current research in OA points towards a complex involvement of various cell and tissue types, often accompanied by inflammation. Low-dose radiotherapy (LDRT) is widely used for the treatment of degenerative and inflammatory diseases. While the reported analgesic effects are well known, the underlying molecular mechanisms are only poorly understood. We therefore correlated a clinical approach, looking at pain reduction in 196 patients treated with LDRT with a pre-clinical approach, utilizing the K/BxN serum transfer mouse model using flow cytometry and multiplex ELISA for analysis. While an improvement of symptoms in the majority of patients was found, patients suffering from symptoms within the tarsi transversa show a significantly lower level of improvement. Further, a significant impact of therapy success was detected depending on whether only one or both feet were affected. Further, patients of younger age showed a significantly better outcome than older ones while needing fewer treatment series. When looking on a cellular level within the mouse model, a systemic alteration of immune cells namely a shift from CD8+ to CD4+ T cells and reduced numbers of DCs was observed. A general reduction of inflammatory cytokines was detected, with significant alterations in IL-4 and IL-17 levels, all of which could potentially be responsible for the highly effective clinical improvement in patients. Taken together our data indicate that LDRT can be regarded as a highly effective treatment option for patients suffering from OA of the foot and ankle, in terms of analgesic effects, especially in younger patients. Furthermore, the observed effects are mediated by an interplay of cellular and soluble immune factors, as observed in the K/BxN serum transfer model. With this interdisciplinary approach we aim to encourage the usage of LDRT as an additive treatment strategy not only as a last resort, but also earlier in the course of disease.

Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients

Background: Cardiovascular disease is the main cause of death among breast cancer survivors. Several chemotherapy drugs may cause cardiovascular toxicity. Our study aimed to assess the late effects of chemotherapy on left ventricular (LV) systolic and diastolic function in a group of female breast cancer survivors. Methods: Our study was a case-control study consisted of 60 breast cancer survivors who had undergone chemotherapy for more than 5 years and a control group of 49 women without breast cancer. All patients underwent echocardiography and left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), pulse-Doppler early transmitral peak flow velocity (E wave), early diastolic (e'), and left atrial (LA) diameter were calculated. Results: The mean LVEF and GLS were reduced in chemotherapy group (51.63±7.93% vs. 55.37±3.50%, P=0.002 and -17.99±3.27% vs. -19.25±2.27%, P=0.025). Also, the chemotherapy group had a larger left ventricular end-systolic internal diameter than the control group (1.74±0.44cm/m2 vs. 1.58±0.22cm/m2, P= 0.011). Logistic regression analysis showed among the different cardiovascular risk factors, chemotherapy had an association with decreasing LVEF. Conclusion: Breast cancer survivors might have an excess risk of having subclinical LV dysfunction over time. These findings present the potential benefits of echocardiographic assessment in breast cancer survivors.

Late consequences of chemotherapy on left ventricular function in women with breast cancer

The ongoing SARS-CoV-2 pandemic has resulted in over 6.3 million deaths and 560 million COVID-19 cases worldwide. Clinical management of hospitalized patients is complex due to the heterogeneous course of COVID-19. Low-dose radiation therapy is known to dampen localized chronic inflammation and has been suggested to be used to reduce lung inflammation in patients with COVID-19. However, it is unknown whether SARS-CoV-2 alters the radiation response and associated radiation exposure related risk.We generated gene expression profiles from circulating leukocytes of hospitalized patients with COVID-19 and healthy donors.The p53 signaling pathway was found to be dysregulated, with mRNA levels of p53, ATM, and CHK2 being lower in patients with COVID-19. Several key p53 target genes involved in cell cycle arrest, apoptosis, and p53 feedback inhibition were upregulated in patients with COVID-19 while other p53 target genes were downregulated. This dysregulation has functional consequences as the transcription of p53-dependant genes (CCNG1, GADD45A, DDB2, SESN1, FDXR, APOBEC) was reduced 24 hours after x-ray exposure ex vivo to both low (100 mGy) or high (2 Gy) doses.SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed patients with COVID-19. 

https://doi.org/10.1016/j.adro.2023.101215

Deficient Radiation Transcription Response in COVID-19 Patients

Background Osteoarthritis (OA), the most common degenerative joint disease, is associated with severe functional limitation and impairment of quality of life. Numerous reports have documented the clinical efficacy of low-dose radiotherapy (LD-RT) in the management of various inflammatory disorders, including OA. In this paper, we assessed the clinical literature involving the use of LD-RT in the treatment of OA, its dose-response features, possible underlying mechanistic features, and optimal therapeutic dose range. Methods We carried out a systematic review based on the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements and evaluated articles meeting the inclusion criteria for this review. Results A total of 361 articles were identified from databases, such as Scopus, PubMed, Embase, and Science Direct out of which 224 articles were duplicates and were discarded. Of the remaining 137 articles, 74 articles were un-related, 27 articles were review articles, eight were conference abstracts, three were letters, two were editorials, two were notes, and one was a book chapter. Finally, 20 articles met all the inclusion criteria and were included in this systematic review. Discussion Several single-arm retrospective/prospective studies showed advantages for LD-RT in the management of OA in terms of pain relief, improvement of mobility and function, and showed minimal side effects. Mechanistic considerations involve positive subcellular effects mediated by the activation of a nuclear factor erythroid 2-related transcription factor (Nrf2) mediated antioxidant response. Further research on both the short- and long-term effects of LD-RT on OA and other inflammatory disorders is recommended.

Low-dose radiation therapy for osteoarthritis and enthesopathies: a review of current data.

This study aimed to determine the association between cardiac dose distribution and strain and Tissue Imaging Doppler (TDI) echocardiographic indices during 1-year follow-up after Post-Mastectomy Radiotherapy (PMRT) in breast cancer patients In this prospective cohort study, patients with left breast cancer candidate for PMRT were included The patients treated radiation dose of 50 Gy in 25 fractions over 5 weeks Before the radiotherapy, and 6 and 12 months after it, the patients underwent echocardiography using strain and TDI methods The changes in echocardiographic indices and their association with cardiac radiation dose were evaluated In this study, 31 patients with mean age of 366 ± 46 years old and the cumulative doses of doxorubicin to 237 ± 5 mg/m2 were participated Correlation between cardiac dose during radiotherapy and changes in strain and TDI echocardiographic indices showed a significant inverse relation between minimum cardiac dose and 6-month TAPSE changes (p = 004, r = − 03), maximum cardiac dose and 6-month RV strain changes (p = 004, r = − 03) and 6 and 12-month S′ changes (p = 002, r = − 04 and p = 005, r = − 03), Cardiac V30 with 6 and 12-month E velocity changes (p = 005, r = − 03 and p = 002, r = − 04, respectively) and Heart V20 with 12-month E velocity changes (p = 004, r = − 03) Normal RV strain observed before starting the study in 12 patients (387%) was found to be abnormal after 6-month follow-up (p = 0004) Results of this study showed that, PMRT was associated with left heart diastolic dysfunction and right heart systolic dysfunction especially in the first 6 months after radiotherapy

Investigation of Association Between Cardiac Dose Distribution and Strain/Tissue Doppler Echocardiographic Indices During 1-Year Post-Mastectomy Radiation Therapy Follow-Up in Breast Cancer Patients

Nooshin Nazeminezhad

Papers

Low-dose radiation therapy for osteoarthritis and enthesopathies: a review of current data.

Investigation of Association Between Cardiac Dose Distribution and Strain/Tissue Doppler Echocardiographic Indices During 1-Year Post-Mastectomy Radiation Therapy Follow-Up in Breast Cancer Patients