Dose-Effect Relationships of 166Ho Radioembolization in Colorectal Cancer.

Radioembolization is a treatment option for colorectal cancer (CRC) patients with inoperable, chemorefractory hepatic metastases. Personalized treatment requires established dose thresholds. Hence, the aim of this study was to explore the relationship between dose and effect (i.e., response and toxicity) in CRC patients treated with 166Ho radioembolization. Methods: CRC patients treated in the HEPAR II and SIM studies were analyzed. Absorbed doses were estimated using the activity distribution on posttreatment 166Ho SPECT/CT. Metabolic response was assessed using the change in total-lesion glycolysis on 18F-FDG PET/CT between baseline and 3-mo follow-up. Toxicity between treatment and 3 mo was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5, and its relationship with parenchyma-absorbed dose was assessed using linear models. The relationship between tumor-absorbed dose and patient- and tumor-level response was analyzed using linear mixed models. Using a threshold of 100% sensitivity for response, the threshold for a minimal mean tumor-absorbed dose was determined and its impact on survival was assessed. Results: Forty patients were included. The median parenchyma-absorbed dose was 37 Gy (range, 12-55 Gy). New CTCAE grade 3 or higher clinical and laboratory toxicity was present in 8 and 7 patients, respectively. For any clinical toxicity (highest grade per patient), the mean difference in parenchymal dose (Gy) per step increase in CTCAE grade category was 5.75 (95% CI, 1.18-10.32). On a patient level, metabolic response was as follows: complete response, n = 1; partial response, n = 11; stable disease, n = 17; and progressive disease, n = 8. The mean tumor-absorbed dose was 84% higher in patients with complete or partial response than in patients with progressive disease (95% CI, 20%-180%). Survival for patients with a mean tumor-absorbed dose of more than 90 Gy was significantly better than for patients with a mean tumor-absorbed dose of less than 90 Gy (hazard ratio, 0.16; 95% CI, 0.06-0.511). Conclusion: A significant dose-response relationship in CRC patients treated with 166Ho radioembolization was established, and a positive association between toxicity and parenchymal dose was found. For future patients, it is advocated to use a 166Ho scout dose to select patients and yo personalize the administered activity, targeting a mean tumor-absorbed dose of more than 90 Gy and a parenchymal dose of less than 55 Gy.

Evaluation of the Safety and Feasibility of Same-Day Holmium-166 -Radioembolization Simulation and Treatment of Hepatic Metastases.

PURPOSE: To evaluate the safety and feasibility of same-day treatment, including the simulation procedure for assessment of intrahepatic and extrahepatic distribution of the microspheres, with holmium-166 (166Ho)-radioembolization. MATERIALS AND METHODS: This was a secondary analysis of patients included in the 4 prospective studies (HEPAR I, HEPAR II, HEPAR PLuS, and SIM) on 166Ho-radioembolization. The technical success rate of the same-day treatment protocol, defined as the number of patients who completed the same-day treatment, was measured. Total in-room time, duration of the scout procedure, time to imaging, and duration of the treatment procedure were recorded. Reasons for discontinuation or adjustment of treatment were identified. Adverse events that occurred during the treatment day were recorded. RESULTS: One hundred five of 120 scheduled patients completed the same-day treatment with 166Ho-radioembolization (success rate, 88%). After the simulation procedure, treatment was cancelled in 15 patients because of extrahepatic deposition (n = 8), suboptimal tumor targeting (n = 1), unanticipated vascular anatomy (n = 5), and dissection (n = 1). In another 14 patients, the treatment plan was adjusted. The median total procedure time (ie, simulation, imaging, and treatment) was 6:39 hours:minutes (range, 3:58-9:17 hours:minutes). Back pain was a major same-day treatment-related complaint (n = 28). CONCLUSION: 166Ho-radioembolization as a same-day treatment procedure is feasible in most selected patients, although treatment was adjusted in 12% of patients and cancelled in 12% of patients. This approach might be beneficial for a select patient population, such as patients needing a radiation segmentectomy.

Quality of life in patients with liver tumors treated with holmium-166 radioembolization.

Holmium-166 radioembolization is a palliative treatment option for patients with unresectable hepatic malignancies. Its influence on quality of life has not been evaluated yet. Since quality of life is very important in the final stages of disease, the aim of this study was to evaluate the effect of holmium-166 radioembolization on quality of life. Patients with hepatic malignancies were treated with holmium-166 radioembolization in the HEPAR I and II studies. The European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 questionnaires were used to evaluate quality of life at baseline, 1 week, 6 weeks and at 6, 9 and 12 months after treatment. The course of the global health status and symptom and functioning scales were analyzed using a linear mixed model. Quality of life was studied in a total of 53 patients with a compliance of 94%. Role functioning was the most affected functioning scale. Fatigue and pain were the most affected symptom scales. Changes in almost all categories were most notable at 1 week after treatment. A higher WHO performance score at baseline decreased global health status, physical functioning, role functioning and social functioning and it increased symptoms of fatigue, dyspnea and diarrhea. Quality of life in salvage patients with liver metastases treated with holmium-166 radioembolization was not significantly affected over time, although a striking decline was seen during the first week post-treatment. A WHO performance score > 0 at baseline significantly influenced quality of life.

Holmium-166 Microsphere Radioembolization of Hepatic Malignancies.

Holmium microspheres have recently become available in the European market as the third type of microspheres for radioembolization of unresectable liver malignancies. Holmium microspheres come with a dedicated administration system, and since these microspheres contain holmium-166 (166Ho) instead of yttrium-90, unique dosing and imaging possibilities have become available as well. In addition, a scout dose of 166Ho microspheres (Conformité Européenne mark is now granted and not pending anymore) can be used instead of 99mTc-macroaggragated albumin during the preparatory angiography procedure. So far, two prospective phase I and phase II clinical studies have been performed on 166Ho radioembolization in a population of liver metastases from mixed origins. These studies showed that a mean whole-liver dose of 60 Gy is safe and induces tumor response. Ongoing trials investigate the effect of 166Ho radioembolization in patients with neuroendocrine tumor metastases, hepatocellular carcinoma, and colorectal cancer metastases. Data derived from these studies will be used to refine the dosing schedule of 60 Gy to the whole liver and determine the optimal level of activity for each patient. This paper discusses several basics and provides an overview of relevant dosing aspects, technical aspects of performing holmium radioembolization, as well as a summary of completed and ongoing clinical studies and the upcoming developments regarding these microspheres.

Assessing the Learning Curve of Holmium Laser Enucleation of Prostate (HoLEP). A Systematic Review.

We systematically assessed the learning curve of Holmium laser enucleation of the prostate using the available literature to identify, as our primary outcome, the average number of cases required to reach competency. A computerized search of PubMed and Scopus for articles published from inception through to January 2018 was performed including 24 studies with a total of 5173 patients. Even though different outcome measures require varying case-loads to reach a plateau, Holmium laser enucleation of prostate has an acceptable learning curve with a proposed figure approximating 25-50 cases, with a structured mentorship programme aiding for faster progress.

Additional hepatic 166Ho-radioembolization in patients with neuroendocrine tumours treated with 177Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial).

BACKGROUND: Neuroendocrine tumours (NET) consist of a heterogeneous group of neoplasms with various organs of origin. At diagnosis 21% of the patients with a Grade 1 NET and 30% with a Grade 2 NET have distant metastases. Treatment with peptide receptor radionuclide therapy (PRRT) shows a high objective response rate and long median survival after treatment. However, complete remission is almost never achieved. The liver is the most commonly affected organ in metastatic disease and is the most incriminating factor for patient survival. Additional treatment of liver disease after PRRT may improve outcome in NET patients. Radioembolization is an established therapy for liver metastasis. To investigate this hypothesis, a phase 2 study was initiated to assess effectiveness and toxicity of holmium-166 radioembolization (166Ho-RE) after PRRT with lutetium-177 (177Lu)-DOTATATE. METHODS: The HEPAR PLUS trial ("Holmium Embolization Particles for Arterial Radiotherapy Plus 177 Lu-DOTATATE in Salvage NET patients") is a single centre, interventional, non-randomized, non-comparative, open label study. In this phase 2 study 30-48 patients with > 3 measurable liver metastases according to RECIST 1.1 will receive additional 166Ho-RE within 20 weeks after the 4th and last cycle of PRRT with 7.4 GBq 177Lu-DOTATATE. Primary objectives are to assess tumour response, complete and partial response according to RECIST 1.1, and toxicity, based on CTCAE v4.03, 3 months after 166Ho-RE. Secondary endpoints include biochemical response, quality of life, biodistribution and dosimetry. DISCUSSION: This is the first prospective study to combine PRRT with 177Lu-DOTATATE and additional 166Ho-RE in metastatic NET. A radiation boost on intrahepatic disease using 166Ho-RE may lead to an improved response rate without significant additional side-effects. TRIAL REGISTRATION: Clinicaltrials.gov NCT02067988 , 13 February 2014. Protocol version: 6, 30 november 2016.

(99m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹66Ho-microspheres.

PURPOSE: Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization. METHODS: This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with (166)Ho radioembolization. (99m)Tc-MAA-based and (166)Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after (166)Ho radioembolization. RESULTS: In the phantom study, (166)Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to -4.4 Gy) than (166)Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment (166)Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of (166)Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), (99m)Tc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and (99m)Tc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001). CONCLUSION: In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic (99m)Tc-MAA imaging. Pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after (166)Ho radioembolization.

In vivo dosimetry based on SPECT and MR imaging of 166Ho-microspheres for treatment of liver malignancies.

UNLABELLED: (166)Ho-poly(l-lactic acid) microspheres allow for quantitative imaging with MR imaging or SPECT for microsphere biodistribution assessment after radioembolization. The purpose of this study was to evaluate SPECT- and MR imaging-based dosimetry in the first patients treated with (166)Ho radioembolization. METHODS: Fifteen patients with unresectable, chemorefractory liver metastases of any origin were enrolled in this phase 1 study and were treated with (166)Ho radioembolization according to a dose escalation protocol (20-80 Gy). The contours of all liver segments and all discernible tumors were manually delineated on T2-weighted posttreatment MR images and registered to the posttreatment SPECT images (n = 9) or SPECT/CT images (n = 6) and MR imaging-based R2* maps (n = 14). Dosimetry was based on SPECT (n = 15) and MR imaging (n = 9) for all volumes of interest, tumor-to-nontumor (T/N) activity concentration ratios were calculated, and correlation and agreement of MR imaging- and SPECT-based measurements were evaluated. RESULTS: The median overall T/N ratio was 1.4 based on SPECT (range, 0.9-2.8) and 1.4 based on MR imaging (range, 1.1-3.1). In 6 of 15 patients (40%), all tumors had received an activity concentration equal to or higher than the normal liver (T/N ratio ≥ 1). Analysis of SPECT and MR imaging measurements for dose to liver segments yielded a high correlation (R(2) = 0.91) and a moderate agreement (mean bias, 3.7 Gy; 95% limits of agreement, -11.2 to 18.7). CONCLUSION: With the use of (166)Ho-microspheres, in vivo dosimetry is feasible on the basis of both SPECT and MR imaging, which enables personalized treatment by selective targeting of inadequately treated tumors.

Microbrachytherapy using holmium-166 acetylacetonate microspheres: a pilot study in a spontaneous cancer animal model.

PURPOSE: Holmium-166 acetylacetonate microspheres ((166)Ho-AcAc-MS) are proposed as an intratumoral radioablation device. This article presents a pilot study in housecats with unresectable liver cancer. Feasibility and tolerability of intratumoral administrations of (166)Ho-AcAc-MS was investigated. METHODS AND MATERIALS: Three cats with unresectable liver tumors of different histotype were included. One cat had hepatocellular carcinoma (HCC), one had cholangiocarcinoma (CC), and one had a malignant epithelial liver tumor (MELT) of unspecified histotype. (166)Ho-AcAc-MS were injected percutaneously under ultrasound guidance into the tumors. Followup consisted of physical examinations and hematologic and biochemical analyses. RESULTS: (166)Ho-AcAc-MS were administered to three liver tumor-bearing cats. The treatment was well tolerated and the clinical condition, that is body weight, alertness, mobility, and coat condition of the animals improved markedly. Most biochemical and hematologic parameters normalized shortly after treatment. Life of all cats was extended and associated with a good quality of life. The HCC cat that received 33-Gy tumor-absorbed dose was euthanized 6 months after the first administration owing to disease progression. The MELT cat received 99-Gy tumor dose and was euthanized 3 months posttreatment owing to bacterial meningitis. The CC cat received 333Gy and succumbed 4 months after the first treatment owing to the formation of a pulmonary embolism. CONCLUSIONS: Percutaneous intratumoral injection of radioactive (166)Ho-AcAc-MS is feasible in liver tumor-bearing cats. The findings of this pilot study indicate that (166)Ho-AcAc-MS may constitute safe brachytherapeutic microspheres and warrant studies to confirm the clinical utility of this novel brachytherapy device.

Radiosynoviorthesis of knees by means of 166Ho-holmium-boro-macroaggregates.

The aim of this study was to evaluate adverse and therapeutic effects of applicated holmium-boro-macroaggregates (HBMAs) in the radiosynoviorthesis (RSO) of knees in patients suffering from chronic synovitis. We started RSO of the knees by means of a new radiopharmaceutical (RF) HBMA in patients with gonarthrosis, rheumatoid arthritis, chronic synovitis, psoriatic arthritis, and gout arthropathy. Seventeen (17) intra-articular injections were performed in 15 patients who were receiving a mean activity of 972 MBq (range, 904-1057) of 166Ho-HBMA. Patient inclusion to the study followed a series of inclusion and exclusion criterions. The patients were hospitalized for 3 days. Side-effects were evaluated during their hospital stay and again after 6-8 weeks. Static scintigraphy of knee joints and measurements of blood radioactivity were performed. Therapeutic effects were evaluated after 6-8 weeks and at 6 months. In 2 hours and 2 days following the application, we proved, by means of knee and inguinal scintigraphy, only insignificant radiopharmaceutical leakage from the joint cavity to the inguinal lymph nodes in 4 patients. In the treated patients, no serious adverse effects occurred. Nine (9) patients were without complaints, 4 patients had slight knee exudation, and 2 patients had great exudation. Therapeutic effects were as follows: 2 patients were without pain, 9 were with lower pain, 3 were with the same pain, and 1 patient was with increased pain. Joint motion was improved in 7 patients, remained the same in 7 patients, and was impaired in 1 patient. Analgesics consumption was lower in 5 patients, the same in 9 patients, and greater in 1 patient. Knee exudation was absent in 2 patients, lower in 4 patients, the same in 6 patients, and greater in 3 patients. In 3 patients it was necessary to do surgical RSO. This RF can extend the range of clinically used radiopharmaceuticals for RSO and to supplement space between 90Y with high energy and 186Re with 169Er with lower beta energy. The energy of 166Ho is suitable for great and medium joints (i.e., knees, hips, shoulders, elbows, wrists, and ankles).

Effective local control of prostate cancer by intratumoral injection of (166)Ho-chitosan complex (DW-166HC) in rats.

PURPOSE: The aim of this study was to evaluate the therapeutic effect and morphological alterations resulting from (166)Ho-chitosan complex (DW-166HC) in an animal model of prostate cancer. METHODS: First, in a subcutaneous tumor model, 80 rats were randomly divided into four groups (n=20 in each group), and intratumoral injections of 0.05 ml (normal saline in group 1,( 165)Ho-chitosan complex solution in group 2, DW-166HC solution (10 mCi) in group 3, and DW-166HC solution (20 mCi) in group 4) were performed when the tumor measured approximately 1 cm along its long axis in each group. Further, in an orthotopic tumor model, 40 rats were similarly randomly divided into four groups (n=10 in each group), and intraprostatic injections of 0.05 ml [PBS in group 1,( 165)Ho-chitosan complex solution in group 2, DW-166HC solution (0.5 mCi) in group 3 and DW-166HC solution (1 mCi) in group 4] were performed at 1 week after implantation of the AIT cell line in the ventral prostate. RESULTS: In the subcutaneous tumor model, mean tumor weights of groups 3 and 4 were significantly lower than those of groups 1 and 2 at 2 and 4 weeks post injection (p<0.05). At 2 and 4 weeks after injection in the orthotopic tumor model, the mean weights of the prostate, including tumor, in groups 3 and 4 were also significantly lower than those in groups 1 and 2 (p<0.05). No adverse injury was seen in adjacent organs at histopathologic examination. CONCLUSION: Intratumoral injection of the beta-emitting radionuclide (166)Ho as a form of complex solution with chitosan appears to be a promising alternative therapeutic modality for the local control of prostate cancer.

Our first clinical experience with radiosynoviorthesis by means of (166)Ho-holmium-boro-macroaggregates.

BACKGROUND: In this paper, we evaluate the therapeutic and adverse effects of the application of 166-holmium-boro-macroaggregates (HMBA) in radiosynovectomy (RSO) of the knees. We assessed the efficacy and safety of (166)Ho-HBMA in a prospective clinical trial in patients suffering from chronic synovitis. MATERIAL AND METHODS: An effective component of radiopharmaceutical (166)Ho-boro-macroaggregates is radionuclide (166)Ho which has both beta-emission and gamma-emission. The physical half-life time of 166 Ho is 26.8 hours. After application of the radiopharmaceutical into a joint cavity, the effect of beta-emission causes radiation necrosis of pathologically changed (inflamed) synovial membrane. From 15th April 2005, we have started RSO of knees by means of new radiopharmaceutical (166)Ho-boro-macroaggregates in patients with gonarthrosis, rheumatoid arthritis, chronic synovitis, psoriatic arthritis, gout arthropathy. Seventeen intra-articular injections were performed in fifteen patients receiving a mean activity of 972 MBq (range: 904-1,057 MBq) (166)Ho-HMBA. The patients were hospitalized for three days. Side effects were evaluated during hospital stay and after 6-8 weeks. Static scintigraphy of knee joints and measurements of blood radioactivity were performed. Therapeutic effects were evaluated after 6-8 weeks. RESULTS: In 2 hours and 2 days after application, we proved, by means of knee and inguinal scintigraphy, only insignificant radiopharmaceutical leakage from the joint cavity to the inguinal lymph nodes in four patients. In treated patients, no serious adverse effects occurred. Nine patients were without complaints; 4 patients had slight knee exsudation and 2 patients had great exsudation. Therapeutic effects after 6-8 weeks were as follows: 2 patients were without pain, 9 with lower pain, 3 with the same pain and 1 patient with increased pain. Joint motion was improved in 7 patients, remained the same in 7 patients and was impaired in 1 patient. Analgesics consumption was lower in 5 patients, the same in 9 patients and greater in 1 patient. Knee exsudation was absent in 2 patients, lower in 4 patients, the same in 6 patients and greater in 3 patients. CONCLUSIONS: We proved only insignificant radiopharmaceutical leakage from the joint cavity to the inguinal lymph nodes. Six patients had early slight or great radiation synovitis. The possible cause could be rather high applicated activity. One can take into consideration its reduction. Therapeutic effects can be precisely evaluated after a longer time interval than was possible for us (6-8 weeks after RSO). (166)Ho-boro-macroaggregates can extend the scale of clinically used radiopharmaceuticals for RSO. This paper is presented in the scope of the first stage of clinical evaluation of synovectomy application of holmium-boro-macroaggregates.

Radiation synovectomy with holmium-166 ferric hydroxide macroaggregate in equine metacarpophalangeal and metatarsophalangeal joints.

OBJECTIVES: To evaluate the effects of radiation synovectomy (RSYN) with holmium-166 ferric hydroxide macroaggregate (Ho-166 FHMA) on synovium and synovial fluid in normal metacarpo- and metatarsophalangeal joints of horses and to determine intraarticular distribution of radioactivity after Ho-166 FHMA treatment. STUDY DESIGN: Either Ho-166 FHMA or nonradioactive Ho-165 FHMA was injected into metacarpo- or metatarsophalangeal joints. ANIMALS: Six adult mixed-breed horses without any clinical evidence of metacarpo- or metatarsophalangeal joint disease. METHODS: Joints were injected with a single high dose of Ho-166 FHMA (mean, 1,000 MBq/joint) or a nonradioactive Ho-165 FHMA preparation (controls). Clinical examination, arthroscopy, synovial fluid analyses, and histologic studies were performed to detect effects of RSYN. Scintigraphy was used to localize intraarticular distribution of Ho-166 FHMA. RESULTS: Ho-166 FHMA treatment induced joint inflammation leading to regional edema, effusion, and scar tissue formation. Scintigraphy revealed the highest intensity of radioactivity in the proximal plantar joint pouch, at which the Ho-166 FHMA treatment caused multifocal necrosis. In the dorsal joint pouch, however, arthroscopic study and histologic analysis showed very little effect of RSYN. There was no regeneration of synovium evident within 2 months. Synovial fluid protein concentration was significantly (P <.01) elevated, and some residual radioactivity remained for 5 days after Ho-166 FHMA injection. CONCLUSIONS: Injection of a single high dose of Ho-166 FHMA caused multifocal necrosis of synovium and deep, soft-tissue injury in equine fetlock joints. CLINICAL RELEVANCE: Inflamed equine joints with synovial lining hyperplasia could benefit from Ho-166 FHMA-induced radiation synovectomy if excessive scar tissue formation can be avoided.

166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials.

Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation.

Radiation synovectomy with (166)Ho-ferric hydroxide: a first experience.

UNLABELLED: Radiation synovectomy (RS) is indicated when conventional pharmacologic treatment of chronic synovitis has not relieved its symptoms. The use of radionuclides that are bound to ferric hydroxide (FH) particles has been shown to be effective and safe for this procedure. (166)Ho-FH macroaggregates offer promising properties for RS but there is a lack of clinical data. We investigated the efficacy and safety of (166)Ho-FH in a prospective clinical trial in patients suffering from chronic synovitis. METHODS: Twenty-four intraarticular injections were performed in 22 patients receiving a mean activity of 1.11 GBq (range, 0.77-1.24 GBq) (166)Ho-FH. Blood activity measurements and monitoring of activity distribution were performed by whole-body gamma-camera imaging for control of leakage 3 and 24 h after injection of (166)Ho-FH. The patients were evaluated clinically before RS, 1 wk and 1 mo after the treatment, and thereafter in 3-mo intervals by assessing joint effusion, pannus, local pain, range of motion, and the patient's satisfaction. RESULTS: In 18 of 24 treatments, no leakage to nontarget organs was visible, whereas small amounts of activity could be detected in the local inguinal lymph nodes in 6 patients and to the lungs and to the liver in 1 patient (<0.1%). In all cases leakage to the lymph nodes was <1%. Leakage to the blood was negligible. Clinically, 17 patients (71%) exhibited a complete or partial response. CONCLUSION: RS with (166)Ho-FH was safe and effective in patients with chronic synovitis of different origin. Controlled clinical trials are necessary to evaluate the therapeutic efficacy and safety compared with the treatment with other radionuclides and glucocorticosteroids.

Does the Holmium:Yag laser cause osteonecrosis?

Some authors have reported a few cases of paraarticular osteonecrosis following arthroscopic knee surgery in which laser was used to assist in the treatment of cartilage and meniscal pathology. We performed a prospective randomized clinical study to determine if osteonecrosis occurs after arthroscopic laser surgery. Fifty-five patients with cartilage problems in their knee joints were randomized into two groups: the laser group included 30 patients and the conventionally instrumented group consisted of 25 patients. Power settings for the Holmium:YAG laser were 0.5 to 1.5 joules per pulse and 5 and 25 Hertz. Total energy used for the procedures was 1 to 2 K joules. Magnetic resonance imaging was performed on all patients preoperatively and postoperatively (in third, sixth, and thirteenth months). None of the patients had osteonecrosis following arthroscopic laser surgery. When the Holmium:YAG laser is used at an optimal dosage (optimal joule and Hertz) with an optimal technique (keeping the handpiece at an appropriate angle and distance) and for an optimal time (avoiding overtreatment), it does not cause osteonecrosis.