Method for comprehensive treatment of knee osteoarthritis of 0-2 x-ray stages according to kellgren-lawrence using low-dose radiation therapy with megavoltage radiation

Abstract

FIELD: radiotherapy; rheumatology.SUBSTANCE: used in the treatment of patients with osteoarthritis of the knee joint in stages 0–2 according to Kellgren Lawrence using low-dose radiation therapy with megavoltage radiation. The method includes a course of taking SYSADOA drugs: glucosamine 500 mg and chondroitin sulfate 400 mg. The administration of drugs is combined with local exposure to the knee joint area of low-dose radiation therapy (LDRT). In this case, before irradiation, the patient undergoes topography on a computed tomography scanner using 1.25–2.5 mm slices. For this, the patient is placed on his back with the knee joint flexed at an angle of up to 5° with fixation in a vacuum mattress, contoured using CTV – clinical target volume: separately the bones that form the knee joint and soft tissues, cartilage, ligaments. The indentation on the PTV is determined to be 3 mm. Next, LDRT is performed using megavolt radiation on a linear accelerator on the contoured zones with a single focal dose of 0.45 Gy. A total of 10 sessions are carried out with an interval of 48 hours up to a total dose of 4.5 Gy. At the same time, the linear accelerator complies with the stated conditions of depth, PDD, homogeneity and symmetry.EFFECT: method effectively relieves pain and helps improve the functional state of the joint.1 cl, 1 dwg, 1 ex

Description

[0001] The invention relates to medicine, in particular, to radiotherapy, internal medicine and rheumatology and can be used in the treatment of patients with osteoarthritis of the knee joint in 0-2 radiographic stages according to Kellgren Lawrence.

[0002] The mechanism of cartilage wear in osteoarthritis (OA) is multifaceted and complex, involving degeneration, inflammation, and impaired cartilage regeneration. Initially, the process occurs at the biochemical level (the metabolic stage of OA). Normally, cartilage tissue is constantly renewed through the synthesis of type II collagen and proteoglycans, particularly aggrecan, by chondrocytes (Wang et al. MRI Biomarkers for Post-Traumatic Cartilage Repair. Journal: AJR, 2024). However, with OA, there is a shift in the balance of repair and catabolism processes towards the predominance of the latter, while the activity of matrix metalloproteinases (MMP-1, MMP-3, MMP-13) and aggrecanases (ADAMTS-4, ADAMTS-5), which break down collagen and proteoglycans, increases, the rate of anabolic processes decreases significantly, as a result, chondrocytes are no longer able to compensate for the loss of matrix due to aging, oxidative stress and inflammation (Robinson WH, Lepus CM., Wang Q.Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis / / Nat. Rev. Rheumatol. - 2016. Vol. 12 (10). P. 580-592). As catabolic changes accumulate, the morphological stage of OA occurs (Li X. Cartilage T2 Assessment: Differentiation of Normal Hyaline Cartilage and Reparative Tissue After Arthroplasty. Osteoarthritis and Cartilage. 2013). With the progression of OA, irreversible changes occur in the components of the joint, which can lead to disability; in advanced stages, endoprosthetics of the affected joint is required.

[0003] Currently, there is a wide range of treatment options for knee OA, including, in addition to SYSADOA, non-steroidal anti-inflammatory drugs, hyaluronic acid and growth factor injections, synovial fluid prostheses, chondrocyte and osteochondral complex transplantation.

[0004] Local exposure of the joint to low doses of ionizing radiation (DOR less than 1 Gy) activates anti-inflammatory processes. First of all, low-dose radiotherapy (LDRT) affects the synthesis of inflammatory mediators (increased synthesis of RvEl-3 and RvDl-3), due to the induction of anti-inflammatory cytokines TGF-β1 and IL-10, adhesion of monocytes to endothelial cells decreases, expression of E-selectin on the surfaces of endothelial cells is inhibited, apoptosis is induced and proteolytic release of L-selectin from leukocytes occurs (Deloch L., Derer A., ​​Hueber AJ Low-dose radiotherapy ameliorates advanced arthritis in hTNF-alpha tg mice by particularly positively impacting on bone metabolism / / Front Immunol. 2018. Vol. 9. P. 1834). Partial blockade of Toll-like receptors occurs, and freely circulating DAMPs are subject to biodegradation.This occurs due to a decrease in the activity of inducible NO synthase (iNOS), which, in turn, activates heme oxygenase and reduces the production of ROS (the duration of the process is 21-30 days after irradiation) with final phagocytosis by M2 macrophages. This process leads to a local anti-inflammatory response, as well as a decrease in synovial fluid (Lodermann B., Wunderlich R., Frey S. Low dose ionizing radiation leads to a NF-kappa B dependent decreased secretion of active IL-lbeta by activated macrophages with a discontinuous dose-dependency / / Int. J. Radiat. Biol. 2012. Vol. 88 (10). P. 727-734).

[0005] With low-dose irradiation, the analgesic effect is due both to the direct effect of ionizing radiation on nerve endings with temporary blocking of signaling pathways, and indirectly by activating the anti-inflammatory response described above, which leads to a weakening of inflammatory changes, a decrease in interstitial pressure, and an increase in the concentration of potassium ions (Deloch L., Fuchs J., Rückert M. Low-dose irradiation differentially impacts macrophage phenotype in dependence of fibroblast-like synoviocytes and radiation dose / / J. Immunol. Res. 2019. Vol. 2019).

[0006] The closest in technical essence to the proposed invention is a method for treating osteoarthrosis, which consists in exposing the knee joint to an X-ray beam in orthovoltage mode. Orthovoltage X-ray therapy is performed from two opposite fields on the area of ​​​​the tibiofemoral joint (Makarova M.V. Shubin A.M. Radiation therapy for osteoarthritis of the knee joint, features of topography for orthovoltage X-ray therapy / / Radiology - practice. 2017. Vol. 66, No. 6.-Pp. 15-26). The disadvantage of the above-mentioned method is its non-conformal spatial dose distribution. Thus, to achieve a total focal dose of 4.8 Gy, the dose to the skin will be 13.5 Gy, which does not cause deterministic radiation effects, but can potentially adversely affect the condition of the skin in the long term, which limits the indications for its use.

[0007] The technical result of the proposed invention is effective, lasting relief of pain, a reduction in the duration of morning stiffness, and an improvement in the functional state of the joint.

[0008] This technical result is achieved by implementing a treatment plan tailored to each patient. Before irradiation, the patient undergoes topometry on a specialized CT scanner using thin slices (1.25-2.5 mm). For this, the patient is placed supine with a slight knee flexion angle of up to 5° and secured in a vacuum mattress. The irradiation volume is selected and defined by contouring the CTV (clinical target volume) and PTV (planning treatment volume).

[0009] In the case of radiation treatment of OA, the concept of GTV (gross tumor volume) is not applicable, so only GTV and PTV were used to describe the irradiation volumes. For a detailed assessment of the volumetric distribution of the dose, the bones that form the knee joint are separately contoured: 1) the distal metaepiphysis of the femur, 2) the proximal metaepiphysis of the tibia, 3) the patella, 4) the joint cavity of the tibiofemoral joint (menisci, cruciate ligaments, articular cartilages of the femur and tibia, synovial membrane), 5) the joint space of the patellofemoral joint (the posterior surface of the patella, its cartilage, synovial membrane), 6) the popliteal anatomical region, limited from above by the tendons of the biceps femoris (from the outside) and the semimembranosus and semitendinosus muscles (from the inside), and from below it is limited by the head of the gastrocnemius muscle with the popliteal vessels with their branches contained in it.The clinical irradiation volume included anatomical zones potentially involved in the inflammatory process—delineated zones 1–5. Zone 6 was defined as the risk area, with a 3 mm margin on the PTV. Next, NDLT was performed with megavoltage radiation on a linear accelerator under the following conditions: dose calculation for the average plane, according to ICRU protocol 50, a single focal dose of 0.45 Gy, with a total of 10 sessions at 48-hour intervals for a total dose of 4.5 Gy. Depth d. max =1.5 cm, PDD~70% at 5 cm. Homogeneity ≤ ± 3%, symmetry ≤ ± 2%. NDLT is carried out against the background of treatment with SYSADOA glucosamine (500 mg) and chondroitin (400 mg) sulfate, the treatment regimen: 1 capsule 3 times a day for 3 weeks, from the fourth week, 1 capsule 2 times a day up to 12 weeks. After a break of 8 weeks, a repeat course in the same regimen was prescribed for 12 weeks.

[0010] Figure 1 shows the clinical volume of irradiation with the inclusion of anatomical zones that may be involved in the inflammatory process - outlined zones 1-5.

[0011] Example of the method implementation. The patient is 55 years old, diagnosis: left-sided osteoarthritis of the knee joint, stage I, complicated by synovitis. Functional insufficiency stage I. Before treatment, complaints of constant pain in the left knee joint up to 7 points on the visual analogue scale (VAS), a comprehensive assessment according to WOMAC: pain syndrome (WOMAC A) 76 mm, morning stiffness (WOMAC B) 68 mm, functional insufficiency of the joint (WOMAC C) 51 mm. An ultrasound examination (US) revealed synovitis of the left knee joint (the presence of increased accumulation of fluid in the joint cavity, superior recess, as well as thickening of the synovial membrane up to 4.5 mm with increased vascularization). The patient was treated according to the method described above.Immediately after the end of the treatment course, the pain syndrome level according to VAS decreased by 4 points and amounted to 3 points, according to the comprehensive WOMAC assessment: WOMAC A - 33 mm, WOMAC B - 42 mm, WOMAC C - 39 mm, according to ultrasound data, the amount of fluid in the joint cavity decreased, the thickness of the synovial membrane was 3.2 mm. After 6 months. The pain syndrome level according to VAS was 2 points, according to the comprehensive WOMAC assessment: WOMAC A - 25 mm, WOMAC B -29 mm, WOMAC C - 16 mm. According to the control ultrasound examination, synovitis is not detected. Analysis of clinical and instrumental data allowed us to evaluate the overall treatment results as significant improvement. The patient's ability to work was restored. A follow-up examination of the patient after 6 months showed the sustainability of the achieved effect. During this time, the patient did not receive additional treatment.

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