Chinese expert consensus on selective internal radiation therapy with yttrium-90 for primary and metastatic hepatocellular carcinoma / 中华肝脏病杂志

Liver malignant tumors are one of the most common causes of cancer-related deaths in China. Selective internal yttrium-90 radioembolization therapy ((90)Y-SIRT) is a kind of promising local minimally invasive method, and its effectiveness and safety has been confirmed in clinical application over the past two decades. Moreover, it has been approved by the U.S. National Comprehensive Cancer Network and other international guidelines for the topical treatment of patients with liver malignancies. Taking into account the complexity of the (90)Y-SIRT and the need for multidisciplinary collaboration to improve the safety and success rate of treatment, the Nuclear Medicine Expert Committee of the Chinese society of Clinical Oncology, along with Beijing Nuclear Medicine Quality Control and Improvement Center invited experts from surgical oncology, interventional medicine, nuclear medicine, and other related fields to discuss and form a consensus on the clinical diagnosis, treatment and management, which mainly included definition, indications and contraindications, treatment procedures, postoperative follow-up, adverse reactions and complications, radiation safety management, etc. Herein, we provide the reference guidance to establish (90)Y-SIRT standardized management and treatment system various units for relevant practitioners.

Transarterial radioembolization for liver tumors as neoadjuvant therapy: three case reports / Radioembolização transarterial hepática como terapia neoadjuvante: relato de três casos

ABSTRACT Transarterial radioembolization (TARE) with yttrium-90 microspheres is a palliative locoregional treatment, minimally invasive for liver tumors. The neoadjuvant aim of this treatment is still controversial, however, selected cases with lesions initially considered unresectable have been enframed as candidates for curative therapy after hepatic transarterial radioembolization. We report three cases in which the hepatic transarterial radioembolization was used as neoadjuvant therapy in an effective way, allowing posterior potentially curative therapies.

RESUMO A radioembolização transarterial hepática com microesferas de ítrio-90 é uma modalidade paliativa de tratamento locorregional minimamente invasiva. O objetivo neoadjuvante deste tratamento ainda é controverso, mas casos selecionados de lesões consideradas inicialmente irressecáveis reenquadram-se como candidatos à terapia curativa após a radioembolização transarterial hepática. Relatamos três casos em que a radioembolização transarterial hepática foi utilizada como terapia neoadjuvante de forma efetiva possibilitando aplicação posterior de terapias potencialmente curativas.

Sinoviortesis con radioisótopos en hemofilia: Experiencia de un centro en Chile / Radionuclide synoviorthesis in hemophilia: experience in 107 patients

Background: In patients with hemophilia, radionuclide synoviorthesis, or the intra-articular injection of a radionuclide to decrease the synovial hypertrophy tissue, aims to decrease or avoid hemarthrosis. Aim: To evaluate the effectiveness of radionuclide synoviorthesis in hemophilia. Material and Methods: Observational retrospective study of the evolution of 107 male patients aged 3 to 54 years who were subjected to radionuclide synoviorthesis between 2007 and 2015. Results: Of 164 treated joints, in 65% treatment was successful, (defined as zero to two hemarthroses and absence of synovitis during the follow up period), in 17% it was partially successful (defined as two or less hemarthroses, but persistence of the synovitis) and failed in 18% of the procedures. No important complications were recorded. Conclusions: Radionuclide synoviorthesis has an overall 82% success rate, is minimally invasive, can be used at any age and is inexpensive We recommend its implementation in Chilean hemophilia treatment centers.

Evaluation of Early Response to Treatment of Hepatocellular Carcinoma with Yttrium-90 Radioembolization Using Quantitative Computed Tomography Analysis

OBJECTIVE: To identify an imaging predictor for the assessment of early treatment response to yttrium-90 transarterial radioembolization (TARE) in patients with hepatocellular carcinoma (HCC), using a quantitative assessment of dynamic computed tomography (CT) images. MATERIALS AND METHODS: Dynamic contrast-enhanced CT was obtained pre- and 4 weeks post-TARE in 44 patients (34 men, 10 women; mean age, 60 years) with HCC. Computer software was developed for measuring the percentage increase in the combined delayed-enhancing area and necrotic area (pD + N) and the percentage increase in the necrotic area (pNI) in the tumor-containing segments pre- and post-TARE. Local progression-free survival (PFS) was compared between patient groups using Cox regression and Kaplan-Meier analyses. RESULTS: Post-TARE HCC with pD + N ≥ 35.5% showed significantly longer PFS than those with pD + N < 35.5% (p = 0.001). The local tumor progression hazard ratio was 17.3 (p = 0.009) for pD + N < 35.5% versus pD + N ≥ 35.5% groups. HCCs with a high pNI tended to have longer PFS, although this difference did not reach statistical significance. CONCLUSION: HCCs with a larger pD + N are less likely to develop local progression after TARE.

Aspects of images in magnetic resonance of liver tumors treated with transarterial selective internal radiotherapy with yttrium-90 / Aspectos de imagens em exames de ressonância magnética de tumores hepáticos tratados com radioterapia interna seletiva transarterial com ítrio-90

ABSTRACT Transarterial selective internal radiation therapy with yttrium-90, also known as radioembolization, is a therapy based on the administration of resin or glass microspheres loaded with the radioisotope yttrium-90, via selective arterial catheterization of tumor-feeding vessels. It is classified as a type of locoregional therapy and its main goal is to treat patients with primary or secondary hepatic lesions that are unresectable and not responsive to other therapies. Since it is a new technology still restricted to very few hospitals in Brazil, but used in patients throughout the country, it is necessary to demonstrate the main aspects of hepatic lesions treated with selective internal radiation therapy found in magnetic resonance imaging, and to make specific considerations on interpretation of these images. The objective of this report is to demonstrate the main aspects of magnetic resonance imaging of unresectable primary or secondary hepatic lesions, in patients submitted to transarterial selective internal radiation therapy.

RESUMO A radioterapia interna seletiva transarterial com ítrio-90, também conhecida como radioembolização, é uma terapia baseada na administração de microesferas de resina ou vidro carregadas com o radioisótopo ítrio-90, via cateterismo arterial seletivo dos vasos nutridores do tumor. É classificada como um tipo de terapia locorregional e seu principal objetivo é tratar pacientes portadores de lesões hepáticas primárias ou secundárias irressecáveis e não responsivas a outras terapias. Por se tratar de uma nova tecnologia, portanto ainda restrita a pouquíssimos hospitais no Brasil (ainda que utilizada em todo país), é necessário demonstrar os principais aspectos de imagem das lesões hepáticas tratadas com radioterapia interna seletiva transarterial encontrados em exame de ressonância magnética, além de delinear considerações específicas de interpretação destas imagens. O objetivo deste relato é demonstrar os principais aspectos encontrados em ressonância magnética de lesões hepáticas irressecáveis, primárias ou secundárias, de pacientes submetidos à radioterapia interna seletiva transarterial.

Gastrectomy for the treatment of refractory gastric ulceration after radioembolization with 90Y microspheres

Transcatheter arterial radioembolization (TARE) with Yttrium-90 (90Y)-labeled microspheres has an emerging role in treatment of patients with unresectable hepatocellular carcinoma. Although complication of TARE can be minimized by aggressive pre-evaluation angiography and preventive coiling of aberrant vessels, radioembolization-induced gastroduodenal ulcer can be irreversible and can be life-threatening. Treatment of radioembolization-induced gastric ulcer is challenging because there is a few reported cases and no consensus for management. We report a case of severe gastric ulceration with bleeding that eventually required surgery due to aberrant deposition of microspheres after TARE.

Radioimmunotherapy-based treatment of cancer

The principle of cancer immunotherapy includes various methods of manipulations to influence immune responses against tumors in both humans and animals. This advanced technology of hybridoma production provided the necessary skills to efficiently produce highly specific monoclonal antibodies [mAb]. Radioactively-tagged antibodies which are applied in radioimmunotherapy [RIT], can target adjacent cells and may not require immune function. This study highlights the mechanism and the effect of action of radioimmunotherapic agents, especially two applied agents including [90]Yibritumomab tiuxetan and [131]I-tositumomab that are approved by Food and Drug Administration [FDA] for treatment of some cancers

Selective internal radiation therapy: 90 Y (yttrium) labeled microspheres for liver malignancies (primary and metastatic).

Selective Internal Radiation Therapy is a relatively new technique that irradiates malignant liver lesions using microscopic beads. It provides micro-embolization coupled with high-dose interstitial radiotherapy. Besides colorectal cancers, this therapy has shown benefit in patients with a variety of other tumors including carcinoid tumors, lung, breast, sarcoma, colon, hepatocellular and ocular melanoma. Its clinical benefit can be as much as 85%, survival can be doubled and patients with extensive colorectal metastases not amenable to resection or ablation can be offered a 32% chance of surviving for 18 months. Ongoing and future studies will refine our understanding of optimizing patient eligibility, dosage, frequency as well as novel applications.

Tratamiento de tumores neuroendocrinos (TNE) con péptidos análogos de la somatostatina marcados con radionucleidos / Treatment of neuroendocrine tumors (NET) with radiolabelled somatostatin analogues

Propósito. Los TNE avanzados tienen escasa respuesta a radioterapia o quimioterapia, el tratamiento sistémico con análogos de la SST radiactivos es una herramienta promisoria en su tratamiento. Presentamos nuestra experiencia, pionera en Latinoamérica, utilizando análogos de SST marcados con 90Y ó 177Lu. Material. Evaluamos 40 pacientes (50.3 años, rango 12-74) con TNE confirmados histológicamente y sobre-expresión de receptores de SST demostrada mediante imágenes. SPECT (111In-DOTATOC) ó PET/CT (68Ga-DOTATATE). Se evaluó respuesta clínica, laboratorio, imágenes con 111In-DOTATATE, post-terapia con 90Y ó 177Lu, 68Ga-DOTATATE PET/CT o TAC. Resultados. Observamos progresión de enfermedad en 10 (25.0 por ciento), remisión parcial en 25 (62.5 por ciento), enfermedad estable en 3 (7.5 por ciento) y remisión completa en 2 (5.0 por ciento). Hubo escasa toxicidad sin deterioro renal significativo. Observamos reducción tumoral y mejoría de calidad de vida en la mayoría de los pacientes. Conclusión. La terapia con radiopéptidos es un procedimento seguro y efectivo en el tratamiento de TNE avanzados.

Purpose. Advanced NETs have little response to radiotherapy or chemotherapy, systemic treatment with radioactive SST analogous is a promissory tool in its treatment. We present our pioneering experience in Latin America using analogous of SST labeled either with 90Y or 177Lu. Materials. We evaluated 40 patients (50.3 years, range 12-74) with histological proved NET and SST receptors over-expression demonstrated by SPECT or PET/CT images with 111In-DOTATOC or 68Ga-DOTATATE. We evaluated clinical response, laboratory test, images with 111In-DOTATATE, 90Y, 177Lu, and 68Ga-DOTATATE PET/CT or CT. Results. We observed progression of disease in 10 (7,5 percent), partial remission in 25 (62,5 percent), stable disease in 3 (7,5 percent) and complete remission in 2 (5,0 percent). There was little toxicity without significant renal deterioration. We observed tumor mass reduction and improvement of quality of life in most of the patients. Conclusion. The therapy with radiopeptides is a safe and effective procedure in the treatment of advanced NET.

90Yttrium-ibritumomab tiuxetan radioimmunotherapy for refractory follicular lymphoma

This paper aims to discuss the sequential use of rituximab and 90Yttrium-ibritumomab tiuxetan, a novel treatment approach in the management of refractory follicular non-Hodgkin's lymphoma. Radioimmunotherapy (RIT), which combines the benefits of targeted radiation therapy and monoclonal antibody, has significantly increased the response rate well in excess of 50%. This is explained by the inherent radiosensitive nature of lymphoma cells. We present a case of a 56-year-old male with refractory follicular lymphoma. The patient was referred for RIT, the first case in the Philippines. The patient was pretreated with two doses of rituximab followed by an intravenous infusion of 90Y-ibritumomab tiuxetan (Zevalin). Hematologic nadir was reached six weeks following administration of the radioimmunotherapy. During this time, the patient developed melena. Hematologic recovery was noted after three weeks. Re-evaluation with computed tomography three months after treatment showed significant reduction in the tumor bulk and resolution of lymphadenopathies. This report underscores the importance and evolving role of radioimmunotherapy in the management of refractory non-Hodgkin's lymphoma.

Pigmented villonodular synovitis managed by Yttrium 90 after debulking surgery

The goal of this study was to evaluate outcome of patients with pigmented villonodular synovitis [PVNS] managed by Yttrium90 [90Y] after debulking surgery. Seven patients [3 males and 4 females] with PVNS were studied retrospectively. Mean follow-up was 47.8 months [range 24-97 months]. Mean age was 44.8 years [range 20-68 years. Debulking surgeries via arthroscopic synovectomy were performed in 4 cases and in 3 cases via mini arthrotomy. After 90Y injection was applied. Magnetic resonance imaging [MRI] included measurement of synovial thickness in preoperative and at last control. Main musculoskeletal tumor society score was 26 [range, 23-29], main MTS rating was 70.4% [range, 38.5-86.2%]. Mean preoperative synovial thickness was 14.9mm range 20-12mm. Synovial thickness was completely disappeared at last MRI examination. There was diffuse joint effusion preoperatively, decreasing at last control. No cases of PVNS recurrence were found. Although we had a small number of cases, we believe that combination of debulking surgery with intra-articular injection of 90Y for PVNS of knee joint is an effective and safe treatment method

Targeted radionuclide therapy for patients with metastatic medullary thyroid carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effect of 90Y-DOTATOC and 131I-MIBG in treatment of metastatic medullary thyroid carcinoma (MTC).</p><p><b>METHODS</b>Twelve histologically confirmed patients with metastatic MTC were included. All patients underwent both 111In-DTPA-octreotide imaging and 131I/ 123I-meta-iodobenzylguanidine (MIBG) imaging. According to the results of the combined imaging, positive patients were selected to be treated with 90Y-DOTA-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) or 131I-MIBG, respectively. The therapeutic procedures of targeted internal radiation were performed with 3.33 GBq 90Y-DOTATOC at 6-week intervals, or 11.1 GBq 131I-MIBG with a minimum interval of three months.</p><p><b>RESULTS</b>The imaging procedure was positive in all 12 patients: 111In-DTPA-octreotide imaging in eight patients, 131I/ 123I-MIBG imaging in six patients. According to the results of combined imaging, we identified four patients to be treated with 90Y-DOTATOC, and five patients with 131 I-MIBG. After three to five sessions of treatment, three patients with partial remission and six with stable disease were observed. The effective rate was 3/9 (33.3%) and the overall tumor response rate was 9/9 (100%). No relevant toxicity was observed.</p><p><b>CONCLUSION</b>The combined imaging technique can be used to identify patients for effective radionuclide treatment. The treatment with 90Y-DOTATOC or 131I-MIBG is well tolerated and may improve the fate of patients with metastatic MTC.</p>

Labeling of CDTPA-dianhydride-coupled CD45 monoclonal antibody with yttrium-90 / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the methods for labeling CDTPA-coupled CD45 monoclonal antibody (mAb) with yttrium-90 ((90)Y) for potential acute myeloid therapy.</p><p><b>METHODS</b>CD45 mAb was labeled with (90)Y by CDTPA and the labeling rate, radiochemical purity, final specific activity, and immunological activity of the mAb were detected.</p><p><b>RESULTS</b>With the optimal molar ratio of CDTPA/Ab at 20:1, the labeling rate was 95%, radiochemical purity 99.8%, and final specific activity 1.9 mCi/mg. This conjugate was stable in vitro with comparable immunological activity in comparison with unlabeled CD45 mAb.</p><p><b>CONCLUSION</b>(90)Y-CDTPA-CD45 mAb possesses good properties as an ideal targetting therapeutic agent for acute leukemia.</p>

La Medicina Nuclear más allá de la imágenes / The Nuclear Medicine beyond the images

La Medicina Nuclear clínica se apoya tradicionalmente en tres grandes pilares básicos, estos son las imágenes, la terapia con radionucleidos y las técnicas "in vitro". En los últimos años, tanto con el desarrollo de las imágenes moleculares como con el surgimiento de nuevas aplicaciones terapéuticas con radionucleidos, se nos abren insospechadas oportunidades para que nuestra especialidad ocupe un valioso sitial en las nuevas aplicaciones oncológicas. En este artículo se revisa nuestra experiencia en dos novedosas áreas en las cuales hemos tenido la oportunidad de desarrollarlas en nuestro centro. Estas son la terapia con 90Y-DOTATOC en tumores con sobre-expresión de receptores de somatostatina[1] (carcinoides, neuroendocrinos y otros) y el uso de 90Y-Ibritumomab-Tiuxetan en Linfomas No Hodgkin de células B con presencia de antígeno CD20+[2].

Effect of beta radiation on TGF-beta1 and bFGF expression in hyperplastic prostatic tissues / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate the transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) expressions in benign prostatic hyperplasia (BPH) and the effect of beta-radiation.</p><p><b>METHODS</b>TGF-beta1 and bFGF expression was studied by means of an immunohistochemical method in nine normal prostatic (NP) tissues, 15 hyperplastic prostatic tissues and 35 hyperplastic prostatic tissues treated with 90Sr/90Y.</p><p><b>RESULTS</b>The TGF-beta1 expression in the epithelium and stroma of normal prostatic tissues was 68.2 % +/- 10.5 % and 29.7 % +/- 4.6 %, respectively, while it was 64.8 % +/- 9.3 % and 28.6 % +/- 4.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, TGF-beta1 expression in the epithelia and stroma of BPH treated with 90Sr/90Y increased significantly (P <0.01). The bFGF expression in epithelia and stroma of normal prostatic tissues was 17.4 % +/- 3.7 % and 42.5 % +/- 6.8 %, respectively, and was 46.3 % +/- 8.2 % and 73.2 % +/- 12.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, expressions of bFGF in the epithelia and stroma of BPH treated with a 90Sr/90Y prostatic hyperplasia applicator decreased significantly (P <0.01).</p><p><b>CONCLUSION</b>Exposure of beta-rays had noticeable effects on BPH tissues, enhancing TGF-beta1 expression and inhibiting bFGF expression.</p>

90Sr-90Y biokinetics at incorporation determine the radiation burden to bone marrow.

The decay characteristics of 90Sr-90Y ensure that the mother and daughter nuclides exist in radioactive equilibrium, unless they get discriminated on the basis of their chemical properties, as it happens during metabolism. Although bone is the ultimate organ of deposition, the two nuclides arrive at this target organ over different biokinetic pathways. As 90Y is not excreted, it goes through transient deposition in the liver before being secondarily deposited in bone. This leads to a temporary radioactive excess of 90Y in bone. Since the decay energy of 90Y is by a factor of about 4 higher than that of 90Sr, the initial radiation burden to the bone marrow is primarily due to 90Y. This was estimated in rats by implanting LiF thermoluminescence dosimeters (TLD) in the marrow cavity of the femur. By calibrating the TLD against a known source of 90Sr-90Y, the absorbed dose rates and cumulative doses were determined as a function of time after incorporation. Two routes of administration were employed and their influence on the radiation burden is also shown.

Sinovectomía radioactiva con yttrium 90 y rhenium 186, en artritis reumatoídea: seguimiento a largo plazo y efecto en la membrana sinovial / Radiation synovectomy with yttrium 90 and rhenium 186 in rheumatoid arthritis: long term follow up and effects on synovial membrane

Despite the progress in the treatment of rheumatoid arthritis (RA), many patients continue to suffer from persistent and painful synovitis. We assessed the clinical results of 64 intraarticular injections of Yttrium 90 in the knee and 56 injections of Rhenium 186 in the wrist in 71 patients with RA, older than 40 years, without relief of synovitis after six months of systemic or local treatment and with a radiological stage I or II of the joints. We obtained good results in 75 percent of knees and 100 of wrists during a follow up period of 8 to 60 months. A repeat histological examination of the synovial membrane of 14 joints in which good results were obtained disclosed a reduction in inflammation and transitory synovial cell hyperplasia that ended in a dense fibrosis. It is concluded that radiation synovectomy continues to be an effective therapy for selected patients with RA and synovitis. The observed histopathological changes may aid the interpretation of magnetic resonance imaging of the treated joints