Radiotherapy CT-based contouring atlas for non-malignant skeletal and soft tissue disorders: a practical proposal from Spanish experience.

OBJECTIVE: Interest in low-dose radiotherapy (LD-RT) for the symptomatic treatment of nonmalignant conditions, including inflammatory and degenerative disorders of the joints and para-articular soft tissues, has increased substantially in recent years. In the present document, we provide a CT-based contouring atlas to help identify and delineate the most common osteoarticular regions susceptible to LD-RT. METHODS: The clinical efficacy of LD-RT is supported by a large body of evidence. However, there is no consensus on the parameters for contouring the planning target volume (PTV). Moreover, 3D simulation and planning should be the standard of care even for nonmalignant disorders. For this reason, the present guidelines were prepared to help guide PTV contouring based on CT images, with the same quality criteria for patient immobilization, treatment simulation, planning and delivery as those routinely applied for cancer radiotherapy. RESULTS: PTV for radiotherapy requires precise identification of the target areas based on CT and other imaging techniques. Using a series of cases treated at our institution, we have defined the PTVs for each location on the simulation CT to establish the relationship between the image and the anatomical structures to be treated. We also specify the immobilization systems used to ensure treatment accuracy and reproducibility. CONCLUSIONS: This comprehensive atlas based on CT images may be of value to radiation oncologists who wish to use LD-RT for the symptomatic treatment of degenerative or inflammatory osteoarticular diseases. ADVANCES IN KNOWLEDGE: The recommendations and contouring atlas described in this article provide an eminently practical tool for LD-RT in non-malignant conditions, based on the same quality criteria recommended for all modern radiotherapy treatments in Spain.

[Joint DGN, OGNMB and SGNM S1 guideline for radiosynoviorthesis]. / Gemeinsame Handlungsempfehlung (S1-Leitlinie) von DGN, OGNMB und SGNM ­ Radiosynoviorthese ­ Stand: 9/2019 ­ AWMF-Registernummer: 031-023.

This recommendation is intended to provide a guideline for radiosynoviorthesis (RSO) in the effective local treatment of chronic inflammatory (non-infectious) joint diseases. It was developed in an interdisciplinary manner and describes the general objectives, definitions, clinical background information, indication and contraindications of this radionuclide therapy. The requirements to be met by a treatment center, the results of pretherapeutic examinations as well as recommendations on how the treatment should be carried out. Here, organizational and technical issues have been considered. Furthermore, information on the surveillance and follow-up of the treated patients can be found. In general, treatment and follow-up should be done in in close cooperation of the participating disciplines.

Low Dose Radiation Therapy, Particularly with 0.5 Gy, Improves Pain in Degenerative Joint Disease of the Fingers: Results of a Retrospective Analysis.

Low-dose radiation therapy (LDRT) has been successfully established for decades as an alternative analgesic treatment option for patients suffering from chronic degenerative and inflammatory diseases. In this study, 483 patients were undergoing LDRT for degenerative joint disease of the fingers and thumb at the University Hospital Erlangen between 2004 and 2019. Radiotherapy was applied according to the German guidelines for LDRT. Several impact factors on therapeutic success, such as the age and gender, the number of affected fingers, the single and cumulative dose, as well as the number of series, were investigated. In summary, 70% of the patients showed an improvement of their pain following LDRT. No significant impact was found for the factors age, gender, the number of series or the cumulative dosage. Patients with an involvement of the thumb showed a significantly worse outcome compared to patients with an isolated affection of the fingers. In this cohort, patients receiving a single dose of 0.5 Gy reported a significantly better outcome than patients receiving 1.0 Gy, strongly suggesting a reduction in the total dose. In summary, LDRT is a good alternative treatment option for patients suffering from degenerative and inflammatory joint disease of the fingers.

Individual dose planning in radiosynoviorthesis treatment: Step by step.

Radiosynoviorthesis (RSO) is a minimally invasive treatment aiming for the necrosis of the pannus tissue by the use of radionuclide. The method suggested here starts with the segmentation of the joint effusion, synovial thickness, and area of the synovial membrane using the 3D Slicer software. The last step is the estimated value of the activity to be injected without considering the leakage of the radiopharmaceutical into the articular cavity. It includes the S-values obtained by Monte Carlo simulation coupled with the calculated therapeutic distance (ST90).

Using synovial volume measurement by MRI to evaluate the effect of 32P Radiation synovectomy on hemophilic arthropathy patients.

OBJECTIVE: To evaluate the potential of synovial membrane volume measurement by MRI in monitoring the effect of radiation synovectomy on patients of Hemophilic Arthropathy (HA). METHODS: We studied 63 diseased joints of 42 HA patients who received hospitalized services at the Hemophilia Diagnosis and Treatment Center of Henan Provincial People's Hospital from May 2011 to January 2015. Unenhanced and enhanced MR scanning of each diseased joint was performed simultaneously. The volumes of synovial membrane of 21 joints from 16 patients before and after being treated with 32P radiation synovectomy (PRS) were measured and compared using image post-processing software and workstation. Two sample matching t test was conducted to analyze the synovial membrane volumes of the same joint measured by unenhanced and enhanced MR, as well as change of MR enhancement ratio after treatments. RESULTS: The synovial membrane volumes measured by unenhanced versus enhanced MR scanning showed no statistical significance. Significant reduction (t = 7.831, p < 0.001) of the synovial membrane volume after treatment (2479.45±46.48 mm3 versus 2983.30±42.87 mm3 before treatment) was observed. MR enhancement ratio of synovial membrane decreased after treatment (0.92±0.06 after vs 1.17±0.07 before treatment) with statistical significance. CONCLUSION: The synovial membrane volume and MR enhancement ratio can be used to monitor patient response to PRS treatment.

Low-Dose Radiation Therapy for Benign Painful Skeletal Disorders: The Typical Treatment for the Elderly Patient?

PURPOSE: To prospectively evaluate the short-term and long-term efficacy of low-dose radiation therapy (RT) for calcaneodynia, achillodynia, painful gonarthrosis, and painful bursitis trochanterica in elderly patients aged ≥70 years. METHODS AND MATERIALS: Between October 2011 and October 2013, patients aged ≥70 years with painful degenerative disorders of joints were recruited for a prospective trial. Single doses of 0.5 to 1.0 Gy and a total dose of 6.0 Gy per series were used. Pain was measured before and right after RT (early response) with a 10-point visual analogue scale. Additionally, pain relief was measured with the 4-point pain scale according to "von Pannewitz" immediately on completion of RT and during follow-up. We defined a good response as complete pain relief and markedly improved. RESULTS: A total of 166 evaluable patients with a mean age of 76.6 years (range, 70-90 years) with calcaneodynia (n=51), achillodynia (n=8), painful gonarthrosis (n=80), and painful bursitis trochanterica (n=27) were recruited. The mean visual analogue scale value before treatment was 6.38 and immediately upon completion of RT was 4.49 (P<.001). Concerning the von Pannewitz status immediately on completion of RT, 6 patients were free of pain, 56 were much improved, 47 reported slight improvement, and 57 experienced no change. After a median follow-up of 29 months, 109 patients could be reached for evaluation of follow-up results. Thirty-three patients were free of pain, 21 had marked improvement, 18 had some improvement, and 37 experienced no change. Therefore, a good response immediately on completion of RT could be achieved in 62 of 166 patients, and with the follow-up in 54 of 109 patients (P=.001). CONCLUSIONS: Low-dose RT is a very effective treatment for the management of painful degenerative disorders of joints in the elderly. Low-dose RT offers a low-risk, genuinely conservative, noninvasive therapeutic alternative for elderly patients.

[Radiotherapy indications for non-malignant diseases in 2014]. / Indications non oncologiques de la radiothérapie : quelles indications en 2014 ?

This review updates the radiotherapy indications for non-malignant diseases, except those treated by radiosurgery. Since the last 2005 review, there have been no major changes in the indications: the prevention of heteropic bone formation and keloids remain classical indications, while the treatment of macular degeneration or the prevention of coronary restenosis are now past history. Nevertheless, the radiation treatment for benign diseases should have the same criteria as for malignant diseases: information of the patient on risks, benefits and treatment quality.

Ionizing radiation induces cellular senescence of articular chondrocytes via negative regulation of SIRT1 by p38 kinase.

Radiotherapy is increasingly used in the treatment of joint diseases, but limited information is available on the effects of radiation on cartilage. Here, we characterize the molecular mechanisms leading to cellular senescence in irradiated primary cultured articular chondrocytes. Ionizing radiation (IR) causes activation of ERK, in turn generating intracellular reactive oxygen species (ROS) with induction of senescence-associated beta-galactosidase (SA-beta-gal) activity. ROS activate p38 kinase, which further promotes ROS generation, forming a positive feedback loop to sustain ROS-p38 kinase signaling. The ROS inhibitors, nordihydroguaiaretic acid and GSH, suppress phosphorylation of p38 and cell numbers positive for SA-beta-gal following irradiation. Moreover, inhibition of the ERK and p38 kinase pathways leads to blockage of IR-induced SA-beta-gal activity via reduction of ROS generation. Although JNK is activated by ROS, this pathway is not associated with cellular senescence of chondrocytes. Interestingly, IR triggers down-regulation of SIRT1 protein expression but not the transcript level, indicative of post-transcriptional cleavage of the protein. SIRT1 degradation is markedly blocked by SB203589 or MG132 after IR treatment, suggesting that cleavage occurs as a result of binding with p38 kinase, followed by processing via the 26 S proteasomal degradation pathway. Overexpression or activation of SIRT1 significantly reduces the IR-induced senescence phenotype, whereas inhibition of SIRT1 activity induces senescence. Based on these findings, we propose that IR induces cellular senescence of articular chondrocytes by negative post-translational regulation of SIRT1 via ROS-dependent p38 kinase activation.

Hemophilic pseudotumor--is there a role of radiotherapy? Literature review and a case report.

We share the literature and management of an adult with moderate hemophilia a presented with a calcaneal pseudotumor and non healing ulcer by radiation therapy, factor VIII and cryoprecipitate supplement. Numerous literatures so far have quoted the satisfactory role of radiotherapy in hemophilic pseudotumor. We found it to be of great help as our case responded with radiotherapy, factor VIII and cryoprecipitate supplement and has a satisfactory 2 years follow up.

Radiation therapy for preventing recurrence of neurogenic heterotopic ossification.

Radiation therapy is commonly used to prevent heterotopic ossification, and the dose-dependent effects of this treatment have been well documented in patients after total hip arthroplasty (THA). However, the efficacy and dose requirement of radiation therapy to prevent heterotopic ossification of nonsurgical origin have not been studied. The purpose of this retrospective case-control study was to determine the effects of prophylactic radiation therapy on severe heterotopic ossification recurrence, postoperative range of motion (ROM), and wound healing in patients with heterotopic ossification secondary to neurologic deficits. Selection was not blinded, and higher risk patients were generally assigned to the treatment group. Standard doses of radiation therapy did not adequately lower recurrence rates; in fact, there was a higher incidence of heterotopic ossification formation necessitating revision in the treatment group (15.0%) compared to the control group (5.1%). Moreover, patients who received radiation therapy were not more successful at maintaining intraoperative ROM over time. There was a similar incidence of delayed wound healing between groups (12.8% in the control group and 12.5% in the treatment group), and no other negative side effects or complications were observed. These results suggest that the 700 cGy dose of radiation therapy typically used for the prophylaxis of heterotopic ossification associated with THA does not effectively prevent the recurrence of neurogenic heterotopic ossification in high-risk patients. Further studies are needed to determine whether higher doses of radiation therapy will provide more effective prophylaxis for heterotopic ossification.

Radiation exposure of hemophiliacs after radiosynoviorthesis with 186Re colloid.

UNLABELLED: Very limited data are available in the literature on the doses of unwanted radiation that patients receive following treatment with radiosynoviorthesis (RSO). OBJECTIVE: The aim of this study was to assess the radiation exposure after RSO with (186)Re colloid in hemophiliacs. METHODS: This study involved 12 hemophiliacs who were treated for hemophilic joint disease with 14 RSOs by using (186)Re colloid. Whole-body scintigrams were performed 1, 6, and 24 hours and 3 and 7 days after RSO. Measurements, using a whole-body counter, were done immediately after scintigraphy, with the treated joint protected with a lead shield. The cumulative activity of (186)Re in the body and in the lymph nodes was calculated. The distribution of (186)Re in the body was determined by using the values for small colloids as proposed by the International Commission on Radiological Protection (ICRP) Publication 53. The computer code, OLINDA/EXM (Vanderbilt University, Nashville, TN), was used for the calculation of the internal dose. A constant distance of 1 m between the ankle joint and body organs, and of 0.33 m between the elbow or shoulder joint and body organs, was used to calculate the contribution of gamma radiation to the effective radiation dose. RESULTS: The mean effective dose received by hemophiliacs after RSO with (186)Re colloid was 28 +/- 9 microSv/MBq of the activity injected into the joint. The patients received 0.8-3.7 mSv (1.9 +/- 0.8 mSv) owing to the leakage of (186)Re from the treated joint and its retention in the body. The highest doses were established in the spleen (26.0 +/- 10.7 mGy), the liver (17.6 +/- 7.2 mGy), and red marrow (3.0 +/- 0.8 mGy). The contribution of gamma radiation to the effective dose was less than 0.1 mSv in RSO of the ankle, 0.4 mSv in the elbow, and 0.6 mSv in the shoulder-joint treatment. The activity of (186)Re in the regional lymph nodes was noted in 4 of the 14 treatments. In these cases, the estimated average dose received by individual lymph nodes was 14.7 +/- 1.9 Gy. CONCLUSIONS: RSO with (186)Re colloid is a safe treatment method. The effective dose received by patients after RSO by using (186)Re colloid is low, as are the radiation doses to the most exposed organs. If (186)Re is retained in the regional lymph nodes, the lymph node radiation dose would be high.

[Can hand radiation absorbed dose from radiosynomicronvectomy be high?].

Preparing and injecting radiopharmaceuticals containing beta emitting radionuclides, for radiosynovectomy (RS), implies the risk of exceeding the upper limit of skin and hand radiation absorbed dose, of 500 mSv/year to both technologists, who prepare and to doctors, who inject these radiopharmacuticals. A high number of RS treatments per day lack of effective radiation protection devices and skin contamination, increase the skin radiation absorbed dose. Pronounced dosimetric and radiation protection data for radionuclides used for RS, like yttrium-90, erbium-169, rhenium-186, dysprosium-165 and holmium-166, indicate the risk and the rationale for minimizing skin radiation doses to the hands of technologists and to doctors. Hands and skin radiation exposure is mainly due to direct beta radiation from yttrium-90 containing syringes. However skin contamination, may increase this dose independently of the radionuclide used for RS. Using a syringe shield with 5 mm perspex and holding the syringe by forceps, especially for the fixation of the needle to the syringe, beta radiation exposure to the finger tips may be reduced effectively. The use of radiation-resistant gloves reduces beta radiation dose to the skin only slightly, but offers a much better protection than Latex gloves for radioactive contamination. In this article we report measurements performed by us, underlining aspects of the most effective syringe shielding applied for RS. For reducing hands beta radiation exposure during RS the following are proposed: a) To use radiation protection devices, like manipulators and perspex syringe shields and b) Special training of the personnel for the proper handling of doses and for the removal of possible contamination from beta-emitting radionuclides and c) To use beta radiation personal ring dosimeters.

Efficacy of synovectomy in haemophilic patients with 153Sm-hydroxyapatite

Introduction - We preconized the use of 153Sm-Hydroxyapatite (HYP) in the synoviorthesis of haemophilic patients (pts) by physical, chemical and biological characteristics. The real efficacy is beeing confirmed by the actual experience over the previous results. These are the first results with 153Sm-HYP in our literature review. Material and Methods - Fiftheen pts. were treated, all males, with ages between 15 and 31 years (average = 22,8 years old), with an intraarticular injection of 185MBq (5mCi) of 153Sm-HYP, totalizing 29 joints: 12 knees, 11 elbows, 4 ankles and 2 shoulders. The 153Sm, produced by IPEN/CNEN - São Paulo, targeted hydroxyapatite particles with a diameter between 1-10µm, radiochemical purity superior to 95 percent and stability of 96,6 percent 1440min after the labeling process. The intraarticular punction was made after local antiseptic, aspirating synovial fluid, injecting 0,5 ml of radioactive solution and flushing the tract with a saline with a total volume no greater than 1,5 ml. The images were obtained 2 and 24h after injection in all pts in a large field of view gamma-camera. The clinical evaluation was made before and one year after it, using objective (range of motion, joint tenderness, degree of joint effusion) and subjective criteria (joint pain by visual scale and joint aspect). The response were graded: 1 - Excellent (E); 2 - Good (G); 3 - Mild (M); 4 - Bad (B); 5 - Worse (W). The reduction in clotting factor use and heamarthroses were others aspects evaluated. Results - The scintigrafies showed homogeneous distribution of the material in joints (2h) and no articular scape (24h). The was a reduction of 34 percent in the clotting factor use and of 51,4 percent in haemarthroses including the poor responses in knees. The results by patients were: 53,3 percent E, 20 percent G, 13,3 percent M, 13,3 percent B, 0 percent W and by joints were 47,75 with excellent and good responses and 84,75 percent when included the mild group. The...

Stability of radioactive colloids for radiation synovectomy: influence of X-ray contrast agents, anaesthetics and glucocorticoids in vitro.

AIM: This in-vitro study investigated the influence of the contrast agents iothalamate (Conray) and special preparations of iotrolan (Isovist) and iopromide (Ultravist) without ethylenediaminetetraacetic acid (EDTA), the anaesthetic Scandicain and the glucocorticoid triamcinolone on the stability of 90Y-, 169Er- and 186Re-radiocolloids used for radiation synovectomy. METHODS: Vials of 1 ml of synovial fluid and 0.02 ml of radiocolloid suspension (0.56-3.6 MBq) were mixed with 0.06, 0.6 and 1.0 ml of each contrast agent. In an additional series, 0.1 ml of Scandicain and 0.1 ml of triamcinolone were tested. Thin layer chromatography and ultrafiltration/centrifugation were performed between 1 h and 15 days after incubation with negative and positive controls. RESULTS: Within 24 h, 0.6 and 1.0 ml of Conray had mobilized 5-20% of the 90Y and 169Er out of the colloids. No interference between 186Re-colloids and Conray was visible before the ninth day after incubation. Iotrolan and iopromide without EDTA had no effect on the stability at shorter incubation periods of up to 6 days. The addition of Scandicain did not produce low-molecular 90Y or 169Er in the presence of synovial fluid. The fraction of low-molecular 186Re reached 4% after 24 h. Triamcinolone did not have any effect on stability in the presence of synovial fluid. CONCLUSION: The disintegration of the radioactive colloids can be attributed to either the formation of EDTA complexes or radiolytic effects. The volume of the injected contrast agent should be as small as possible to confirm correct intra-articular distribution.

Estimation of the carcinogenic risk of radiotherapy of benign diseases from shoulder to heel.

BACKGROUND AND PURPOSE: To estimate risk on fatal tumour induction in patients by radiotherapy of benign diseases at various body sites, including heterotopic ossification, omarthritis, gonarthrosis, heel spurs and hidradenitis suppurativa. MATERIAL AND METHODS: The carcinogenic risk is estimated by applying the effective dose concept from the ICRP with the average risk factor of 10% per Sv for high dose and high dose rate. Although, the concept of effective dose for the present study has limitations, its use is considered acceptable for a fairly rough risk estimate. The organ doses are calculated using a Monte Carlo radiation transport code and anthropomorphic mathematical phantoms. Special risk modifying factors like patient's age at exposure and gender are taken into account. RESULTS: For the treatment of heterotopic ossification, omarthritis, gonarthrosis, heel spurs and hidradenitis suppurativa the effective dose is in the range of 5-400 mSv. For an average-aged population, the estimated number of radiation-induced fatal tumours due to these treatments is assessed to be between 0.5 and 40 persons per 1000 patients treated. At higher ages the risks are reduced. CONCLUSIONS: The range of effective doses found for the various types of treatment at various body sites is large. There are several possibilities to optimise the treatment protocols resulting in reduced effective doses and related radiation risks.

Should lidocaine be avoided for local anesthesia in radiation synovectomy?

AIM: Leakage is of major concern when performing radiation synovectomy. Although post-treatment immobilization was provided, extra-articular leakage of radioactivity has occasionally been observed in patients receiving local anesthesia in the course of radiation synovectomy. This study was performed to uncover any unfavourable effect of lidocaine on stability of (166)Ho-FHMA (ferrum hydroxide macroaggregate). METHODS: The radiopharmaceutical was investigated in bovine serum albumin (BSA) solutions (5, 10 mg/ml) at pH 6, 7 and 8. Furthermore, the tracer was incubated for 0, 2, 24, 48 and 120 hours in synovial fluid. In both series the influence of lidocaine-HCl 2% (500, 1000 microl) has been evaluated. RESULTS: In BSA test solutions, amount of lidocaine added [df(2), F=7.82, p-level: 0.00] and pH [df(2), F=7.82, p-level: 0.00] significantly influenced in vitro stability of (166)Ho labeled FHMA (n=72). This finding was confirmed in synovial fluid [df(2), F=3.82, p-level: 0.03] (n=60). CONCLUSION: In an experimental design mimicking normal and inflammatory conditions in the joint, addition of a few milliliters of lidocaine-HCl followed by a shift towards lower pH-values in synovial fluid may endanger stability of the carrier-tracer complex (166)Ho-FHMA and thereby enhance extra-articular leakage.

[166Dy]Dy/166Ho hydroxide macroaggregates: an in vivo generator system for radiation synovectomy.

Radiation synovectomy is an effective treatment in patients suffering from inflammatory-rheumatoid and degenerative joint diseases. The aim of this work was to examine the feasibility of preparing dysprosium-166 (166Dy)/holmium-166(166Ho) hydroxide macroaggregates ([166Dy]Dy/166Ho-HM) as an in vivo generator for radiation synovectomy evaluating whether the stability of 166Dy-HM and 166Ho-HM complexes is maintained when the daughter 166Ho is formed. The Monte Carlo (MCNP4B) theoretical depth dose profile for the in vivo [166Dy]Dy/166Ho generator system in a joint model was calculated and compared with that produced by 90Y, 153Sm and 166Ho. 166Dy was obtained by neutron irradiation of enriched 164Dy2O3 in a Triga Mark III reactor. Macroaggregates were prepared by reaction of [166Dy]DyCl3 with 0.5 M NaOH in an ultrasonic bath. [166Dy]Dy/166Ho-HM was obtained with radiochemical purity >99.5% and with the majority of particles in the 2-5 microm range. In vitro studies demonstrated that the radio-macroaggregates are stable in saline solution and human serum without a significant change in the particle size over 14 d, suggesting that no translocation of the daughter nucleus occurs subsequent to beta- decay of 166Dy. Biological studies in normal rats demonstrated high retention in the knee joint even 7 d after [166Dy]Dy/166Ho-HM administration. The Monte Carlo (MCNP4B) theoretical depth dose profiles in a joint model, showed that the in vivo [166Dy]Dy/166Ho generator system would produce 25% and 50% less radiation dose to the articular cartilage and bone surface, respectively, than that produced by 90Y or pure 166Ho in a treatment with the same therapeutic dose to the synovium surface. Despite that 153Sm showed the best depth dose profile sparing doses to healthy tissues, the use of 166Dy could provide the advantage of being applied in patients that cannot be reached within a few hours from a nuclear reactor and to produce less radiation exposure to the medical personnel during the radiopharmaceutical administration.

Lipoma arborescens; successfully treated by yttrium-90 radiosynovectomy.

Although radiosynovectomy (RS) applications have been carried out for many years, clinical indications of this non-invasive procedure is thought to be limited probably due to the lack of information of clinicians. Clinicians' preferential indication for RS is the treatment-resistant synovitis of individual joints, i.e. despite systemic pharmacotherapy and intra-articular steroid injections. We present here a case of "lipoma arborescens" treated by yttrium-90, which is a rare intra-articular lesion characterized by villous proliferation of the synovial membrane and hyperplasia of subsynovial fat. The results of clinical, biochemical and hematological examinations, magnetic resonance (MR) imaging, arthroscopy and histological analysis have shown that the etiology was lipoma arborescens in a female patient, aged 36 having swelling and sometimes associating pain at her right knee for 4 years. We have applied to our patient's right knee RS with 185 MBq yttrium-90 colloid together with 40 mg of methylprednisolone acetate, although in our literature survey we have not met any similar case being treated with such indication. Even a year after the application, the patient has absolutely benefited from the treatment clinically, and this was also confirmed by comparative MR images (pre- and post-treatment). Consequently, we consider that Y-90 treatment might be applicable in suitable cases with lipoma arborescens.