Carlo Chiesa

Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study.

Yttrium‐90 radioembolization (Y90RE) is a novel approach to radiation therapy for hepatocellular carcinoma (HCC), never tested in phase 2 studies. Fifty‐two patients with intermediate (n.17) to advanced (n.35) HCC were prospectively recruited to assess, as the primary endpoint, efficacy of Y90RE on time‐to‐progression (TTP). Secondary endpoints were tumor response, safety, and overall survival (OS). All patients were Eastern Cooperative Oncology Group (ECOG) score 0‐1, Child‐Pugh class A‐B7. Y90RE treatments aimed at a lobar delivery of 120 Gy. Retrospective dosimetric correlations were conducted and related to response. Fifty‐eight treatments were performed on 52 patients. The median follow‐up was 36 months. The median TTP was 11 months with no significant difference between portal vein thrombosis (PVT) versus no PVT (7 versus 13 months). The median OS was 15 months (95% confidence interval [CI], 12‐18 months) with a nonsignificant trend in favor of non‐PVT versus PVT patients (18 versus 13 months). Five complete responses occurred (9.6%), and the 2 year‐progression rate was 62%. Objective response was 40.4%, whereas the disease control rate (78.8%) significantly affected survival (responders versus nonresponders: 18.4% versus 9.1%; P = 0.009). Tumor response significantly correlated with absorbed dose in target lesions (r = 0.60, 95% CI, 0.41‐0.74, P < 0.001) and a threshold of 500 Gy predicted response (area under the curve, 0.78). Mortality at 30‐90 days was 0%‐3.8%. Various grades of reduction in liver function occurred within 6 months in 36.5% of patients, with no differences among stages. On multivariate analysis, tumor response was the sole variable affecting TTP (P < 0.001) and the second affecting survival (after Child‐Pugh class). Conclusion: Y90RE is an effective treatment in intermediate to advanced HCC, particularly in the case of PVT. Further prospective evaluations comparing Y90RE with conventional treatments are warranted. (HEPATOLOGY 2013)

Radiation dose to technicians per nuclear medicine procedure: comparison between technetium-99m, gallium-67, and iodine-131 radiotracers and fluorine-18 fluorodeoxyglucose

Abstract.The aim of this study was to determine the non-extremity gamma dose received by a technician while performing an ordinary nuclear medicine procedure or a static (i.e. without blood sampling) fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) study. The dose per patient was measured by means of a commercial electronic pocket Geiger Mueller dosimeter, worn in the upper left pocket of the overalls. This was previously tested by exposure to known point sources of technetium-99m, gallium-67, iodine-131 and fluorine-18 in the air. A further test was performed with 99mTc, 131I and 18F sources inserted in a water phantom to simulate the condition of high scattering degradation of the primary radiation due to the patient’s tissues. Subsequently, the dose was measured by two technicians for a total of 314 clinical cases, covering the most common nuclear medicine procedures, including 44 static, two-level FDG PET studies with repositioning of the patient on the couch between the transmission and the emission scan and seven whole-body PET studies. The dose read by the dosimeter was corrected for environmental background and for detector efficiency measured with sources in the air. For a limited subset of cases, the time spent close to patients was also measured. Doses were then estimated by a crude non-absorbing point source approximation and by using experimental dose rates. A comparison between experimental and estimated doses, as well as with previously published data, completed the work. For most of the conventional procedures, the measured dose per procedure proved to be within the range 0.2–0.4 μSv, except for equilibrium angiocardioscintigraphy (1.0±0.5 μSv) and 99mTc-sestamibi single-photon emission tomography (1.7±1.0 μSv). Comparison with data published in the last 20 years shows that our values are generally lower. The current more favourable working conditions are a result of technological improvements (for instance two-head gamma cameras capable of whole-body studies), and safer shielding and distance from patients. Two-level PET gave 11.5±4.4 μSv and whole-body PET 5.9±1.2 μSv. In a subset of patients these values could be subdivided into the separate contributions from each phase of the procedure. They were: 0.11±0.04 μSv for daily quality assurance, 2.9±3.0 μSv for two transmission scans, 0.3±0.1 μSv for syringe preparation, 2.8±1.8 μSv for injection and escorting the patient to the waiting room, 1.7±1.5 μSv for a whole-body emission scan, 7.7±5.2 μSv for two emission scans, and 0.8±0.2 μSv for patient departure. The higher value from PET by comparison with conventional procedures is attributable to the higher specific gamma constant of 18F, as well as the longer time required for accurate positioning.

Sentinel node in breast cancer procedural guidelines.

ContentProcedure guidelines for scintigraphic detection of sentinel node in breast cancer are presented.AuthorsThe paper was written by several experts in this field on behalf of the European Association of Nuclear Medicine Oncology and Dosimetry committees and approved by the Executive Committee.

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds

Primary liver cancers (i.e. hepatocellular carcinoma or cholangiocarcinoma) are worldwide some of the most frequent cancers, with rapidly fatal liver failure in a large majority of patients. Curative therapy consists of surgery (i.e. resection or liver transplantation), but only 10–20% of patients are candidates for this. In other patients, a variety of palliative treatments can be given, such as chemoembolization, radiofrequency ablation or recently introduced tyrosine kinase inhibitors, e.g. sorafenib. Colorectal cancer is the second most lethal cancer in Europe and liver metastases are prevalent either at diagnosis or in follow-up. These patients are usually treated by a sequence of surgery, chemotherapy and antibody therapy [Okuda et al. (Cancer 56:918–928, 1985); Schafer and Sorrell (Lancet 353:1253–1257, 1999); Leong et al. (Arnold, London, 1999)]. Radioembolization is an innovative therapeutic approach defined as the injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous intra-arterial techniques. Advantages of the use of these intra-arterial radioactive compounds are the ability to deliver high doses of radiation to small target volumes, the relatively low toxicity profile, the possibility to treat the whole liver including microscopic disease and the feasibility of combination with other therapy modalities. Disadvantages are mainly due to radioprotection constraints mainly for 131I-labelled agents, logistics and the possibility of inadvertent delivery or shunting [Novell et al. (Br J Surg 78:901–906, 1991)]. The Therapy, Oncology and Dosimetry Committees have worked together in order to revise the European Association of Nuclear Medicine (EANM) guidelines on the use of the radiopharmaceutical 131I-Lipiodol (Lipiocis®, IBA, Brussels, Belgium) and include the newer medical devices with 90Y-microspheres. 90Y is either bound to resin (SIR-Spheres®, Sirtex Medical, Lane Cove, Australia) or embedded in a glass matrix (TheraSphere®, MDS Nordion, Kanata, ON, Canada). Since 90Y-microspheres are not metabolized, they are not registered as unsealed sources. However, the microspheres are delivered in aqueous solution: radioactive contamination is a concern and microspheres should be handled, like other radiopharmaceuticals, as open sources. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients undergoing such treatment.

EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry.

IntroductionThe level of administered activity in radionuclide therapy is often limited by haematological toxicity resulting from the absorbed dose delivered to the bone marrow. The purpose of these EANM guidelines is to provide advice to scientists and clinicians on data acquisition and data analysis related to bone-marrow and whole-body dosimetry.Materials and methodsThe guidelines are divided into sections “Data acquisition” and “Data analysis”. The Data acquisition section provides advice on the measurements required for accurate dosimetry including blood samples, quantitative imaging and/or whole-body measurements with a single probe. Issues specific to given radiopharmaceuticals are considered. The Data analysis section provides advice on the calculation of absorbed doses to the whole body and the bone marrow. The total absorbed dose to the bone marrow consists of contributions from activity in the bone marrow itself (self-absorbed dose) and the cross-absorbed dose to the bone marrow from activity in bone, larger organs and the remainder of the body.ConclusionAs radionuclide therapy enters an era where patient-specific dosimetry is used to guide treatments, accurate bone-marrow and whole-body dosimetry will become an essential element of treatment planning. We hope that these guidelines will provide a basis for the optimization and standardization of the treatment of cancer with radiopharmaceuticals, which will facilitate single- and multi-centre radionuclide therapy studies.

EANM procedure guideline for treatment of refractory metastatic bone pain

IntroductionBone pain is a common symptom of metastatic disease in cancer, experienced with various intensities by about 30% of cancer patients, during the development of their disease, up to 60–90% in the latest phases.DiscussionIn addition to other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy, bone-seeking radiopharmaceuticals are also used for the palliation of pain from bone metastases. Substantial advantages of bone palliation radionuclide therapy include the ability to simultaneously treat multiple sites of disease with a more probable therapeutic effect in earlier phases of metastatic disease, the ease of administration, the repeatability and the potential integration with the other treatments.ConclusionThe Therapy, Oncology and Dosimetry Committees have worked together to revise the EANM guidelines on the use of bone-seeking radiopharmaceuticals. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients undergoing such treatment.

Joint Practice Guidelines for Radionuclide Lymphoscintigraphy for Sentinel Node Localization in Oral/Oropharyngeal Squamous Cell Carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee.

EANM Dosimetry Committee guidance document: good practice of clinical dosimetry reporting

Many recent publications in nuclear medicine contain data on dosimetric findings for existing and new diagnostic and therapeutic agents. In many of these articles, however, a description of the methodology applied for dosimetry is lacking or important details are omitted. The intention of the EANM Dosimetry Committee is to guide the reader through a series of suggestions for reporting dosimetric approaches. The authors are aware of the large amount of data required to report the way a given clinical dosimetry procedure was implemented. Another aim of this guidance document is to provide comprehensive information for preparing and submitting publications and reports containing data on internal dosimetry. This guidance document also contains a checklist which could be useful for reviewers of manuscripts submitted to scientific journals or for grant applications. In addition, this document could be used to decide which data are useful for a documentation of dosimetry results in individual patient records. This may be of importance when the approval of a new radiopharmaceutical by official bodies such as EMA or FDA is envisaged.

High-Dose Yttrium-90–Ibritumomab Tiuxetan With Tandem Stem-Cell Reinfusion: An Outpatient Preparative Regimen for Autologous Hematopoietic Cell Transplantation

PURPOSE To develop high-dose myeloablative therapy for CD20(+) non-Hodgkins lymphoma (NHL) as a safe and widely applicable regimen. PATIENTS AND METHODS Patients with relapsed/refractory (n = 25) or de novo high-risk (n = 5) NHL received one myeloablative dose of yttrium-90 ((90)Y)-ibritumomab tiuxetan after five chemotherapy courses, including three cycles of anthracycline- or platinum-containing regimens, one cycle of cyclophosphamide (4 to 7 g/m(2)), and one cycle of cytarabine (12 to 24 g/m(2)). The only exclusion criteria were CNS lymphoma and Eastern Cooperative Oncology Group performance status of more than 3. Primary end points were overall survival (OS) and event-free survival (EFS). Secondary end points included safety and applicability of high-dose (90)Y-ibritumomab tiuxetan. To minimize hematologic toxicity, stem cells were reinfused at days 7 and 14 after (90)Y-ibritumomab tiuxetan. RESULTS Thirteen patients received (90)Y-ibritumomab tiuxetan 0.8 mCi/kg, and 17 patients received 1.2 mCi/kg. At 1.2 mCi/kg, the radiation absorbed by critical nonhematologic organs approached the protocol-defined upper safety limit, defining this as the recommended dose for subsequent studies. Hematologic toxicity was mild to moderate and of short duration. Infections occurred in 27% of patients (none had a severity grade greater than 3). After a median observation time of 30 months (range, 22 to 48 months), no myeloid secondary malignancy or chromosomal abnormality was observed, the OS rate was 87%, and the EFS rate was 69%. CONCLUSION High-dose (90)Y-ibritumomab tiuxetan seems to be an innovative myeloablative regimen with unprecedented short-term toxicity and wide applicability. Further studies are required to assess its long-term safety and role in the management of CD20(+) NHL.

The evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy

Molecular radiotherapy (MRT) has demonstrated unique therapeutic advantages in the treatment of an increasing number of cancers. As with other treatment modalities, there is related toxicity to a number of organs at risk. Despite the large number of clinical trials over the past several decades, considerable uncertainties still remain regarding the optimization of this therapeutic approach and one of the vital issues to be answered is whether an absorbed radiation dose–response exists that could be used to guide personalized treatment. There are only limited and sporadic data investigating MRT dosimetry. The determination of dose–effect relationships for MRT has yet to be the explicit aim of a clinical trial. The aim of this article was to collate and discuss the available evidence for an absorbed radiation dose–effect relationships in MRT through a review of published data. Based on a PubMed search, 92 papers were found. Out of 79 studies investigating dosimetry, an absorbed dose–effect correlation was found in 48. The application of radiobiological modelling to clinical data is of increasing importance and the limited published data on absorbed dose–effect relationships based on these models are also reviewed. Based on National Cancer Institute guideline definition, the studies had a moderate or low rate of clinical relevance due to the limited number of studies investigating overall survival and absorbed dose. Nevertheless, the evidence strongly implies a correlation between the absorbed doses delivered and the response and toxicity, indicating that dosimetry-based personalized treatments would improve outcome and increase survival.