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AIM: Since the second half of the 1980s, (131)I-MIBG has been widely used for treatment of patients with malignant pheochromocytoma. In 1991, at the International Meeting in Rome, it was agreed that (131)I-MIBG therapy induces significant tumor responses in about 30-50% of cases, long-term stabilization of disease in several cases and significant reduction of cathecolamine-related symptoms in almost all patients. Nevertheless, more than 20 years later, its therapeutic use in malignant phaeochromocytoma has not yet been standardized. Aim of the present study was to compare the use of low versus intermediate activity of MIBG to achieve better results in a shorter time with higher activities. METHODS: Two different modalities of (131)I-MIBG therapy were performed: before 2001, 12 patients (Group 1) received a fixed activity of 5.55 GBq/session. From 2001 to 2009, 16 patients (Group 2) were treated with 9.25-12.95 GBq/session. RESULTS: As expected, the overall response rate in Group 2 are slightly better. The most important result of increasing the single session activity was the shorter median time to achieve a significant response (7 versus 19 months), which was obtained with a lower median cumulative activity (11 versus 22 GBq) in a lower median number of sessions (2 versus 7). CONCLUSIONS: We demonstrated that intermediate single session activity shortened to one third the global treatment time, with similar efficacy and a moderate increment of toxicity. Consequently, the increase of (131)I-MIBG activity, without reaching myeloablative levels, can be recommended for standard treatment of pheochromocytoma and paraganglioma patients.

This paper analyzes the available data on the dosimetric approach and describes the use of dosimetry in the Division of Nuclear Medicine of the National Cancer Institute in Milan. Dosimetry is rarely performed when planning radio-iodine activity, although most of the available guidelines do mention this possibility, without giving any well defined indication. Aim of the present research was to validate the usefulness of dosimetry in the management of metastatic thyroid cancer. Benua (1962) set the limit of blood absorbed dose at 2 Gy to avoid hematological toxicity. Maxon (1983) determined at 80 Gy the dose to achieve complete destruction of a metastatic lesion. Dorn (2003) combined red marrow and lesion dosimetry showing that high activity administrations with less that 3 Gy to the red marrow are a safe and more effective with respect to fixed activities administrations. Lee (2008) reported 50% responses with high activity administrations based on blood dosimetry, in 47 patients which were unsuccessfully previously treated with fixed activities. Sgouros (2005) and Song (2006) introduced key parameters as Biological Effective Dose and Uniform Equivalent Dose in order to describe the effects of continuous low dose rate irradiation and non uniform activity uptake, typical of nuclear medicine treatments.Red marrow and lesion dosimetry (planar view) were performed during the treatment, without changing the fixed activity schema.This experience demonstrate first of all, that dosimetry is feasible in the clinical routine, and that it can provide the clinician with important information, no matter its often quoted limited numerical accuracy. A total of 17/20 lesion doses below 80 Gy have been detected. Three/17 (doses between 40 and 80 Gy) disappeared in the follow-up scintigram. Two/17 were undetectable at computed tomography or nuclear magnetic resonance. These data suggest that repetition of treatment on a lesion drastically reduces its uptake, with a loss of therapeutic efficacy along the sequence of fixed activity administrations.The usefulness of dosimetry should not be assessed only on the basis of patient survival or therapeutic efficacy; the possibility to avoid useless treatments should also be considered. According to the authors, individualized dosimetry could improve the management of metastatic differentiated thyroid cancer. Even post-therapeutic dosimetry, as performed at this institution, has a significant impact on clinical decision-making. The question for the future is how to include dosimetry into the patient management framework.

Iodine-131 metaiodobenzylguanidine (I-131 MIBG) has been used for the diagnosis and treatment of malignant pheochromocytomas (PHEO) and paragangliomas (PGL) since 1980's. Despite increasing amount of experience with iodine-131 (I-131) MIBG therapy, many important questions still exist. In this article, we will discuss the current problems learned from clinical experience in diagnosis and therapy of PHEO/PGL with I-131 MIBG, and present a sample case to emphasize the critical aspects for an optimal treatment strategy.

Aims and background Neuroblastoma is the most common solid extracranial tumor in children. The median age of onset is 2 years, with more than 95% of patients younger than 10 years at diagnosis. As neuroblastoma is rare in adolescents and exceedingly rare in adults, few series are reported in the literature. In the present study, we analyzed the outcomes and clinical characteristics of a mono-institutional series. Methods We describe 27 consecutive patients over 12 years of age (range, 12–69) with previously untreated neuroblastoma treated at our Institution between 1982 and 2001. Results Overall survival at 5 and 10 years was 40% and 20%, respectively, and progression-free survival at 5 and 10 years was 18%. In the present series, there was a long interval between the onset of signs/symptoms and diagnosis, and between recurrence/progression and death. None had MYCN amplification. Conclusions The passive course of the disease in most of our patients did not reflect a more favorable outcome compared with younger patients, thus suggesting a possible genetically different subset of neuroblastoma in older patients. Free full text available at www.tumorionline.it

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors. Knowledge about such neoplasms ameliorated in the last 10-15 years with the discovery of increasing number of germ line mutations even in apparently sporadic cases. Seemingly, genetic tests are going to be an integral part of diagnostic procedures. Standard therapies (advanced surgery, radiometabolic therapy, chemotherapy and radiotherapy) have revealed suboptimal results in tumor size reduction and survival. Currently, there is no standard therapeutic protocol and thus some patients end up with overtreatment while others are undertreated. An effective molecular target therapy aiming at permanent control of these highly complex neoplasms should be the aim of future efforts. In clinical setting investigatory trials with multiple drug therapies targeting a variety of different parallel pathways should be available. Successful management requires a multidisciplinary teamwork.

45 patients with neuroendocrine tumours (22 neuroblastomas, 10 phaeochromocytomas, 3 para-gangliomas, 6 medullary thyroid carcinomas and 4 carcinoids) underwent 131I-MIBG therapy.All patients, with the exception of 5 phaeochromocytoma cases with nonoperable disease, had previously been treated with conventional therapies. Patients had a previous diagnostic scintigraphy with 131I-MIBG (activity 20-44.4 MBq) or with 123I-MIBG (activity 74-222 MBq). The therapeutic activity for adults ranged from 3.7 to 7.4 GBq of 131I-MIBG; for children from 2.7 to 5.5 GBq. All treatments were repeated at not less than 4-weekly intervals. The neuroblastoma patients were divided into two groups: the first included 14 patients with advanced metastatic disease not responding to previous treatments; the second included 8 patients with documented residual neuroblastoma tissue that could not be surgically removed after first-line therapy.In neuroblastoma patients with advanced disease resistant to previous therapies 2 out of 14 showed a partial response, 9 stable disease and 3 progression of cancer. In neuroblastoma patients with residual disease (7 evaluable out of 8) we obtained 3 partial responses; a stable response was observed in 3 patients. The results of MIBG therapy in the group of phaeochromocytoma patients (9 evaluable out of 10) consisted of 3 partial responses, 5 stable disease and 1 progression. Evaluation of the response carried out on the basis of biochemical parameters increased the responses and MIBG therapy showed good effectiveness in controlling the functional symptoms. In the group of paraganglioma patients we observed 1 complete, 1 partial and 1 stable response. In patients with medullary thyroid carcinoma a partial response was observed in 1 patient with mediastinal metastases and 2 disease stabilisations were seen in another 2 patients. Patients with carcinoids who underwent MIBG therapy showed 3 disease stabilisations. The overall toxicity was acceptable, especially considering that the majority of our patients had had previous myelotoxic treatments (chemotherapy and/or radiotherapy, alone or in combination).On the basis of our experience we can conclude that 131I-MIBG therapy is effective and also well tolerated.