E Seregni

Istituto Nazionale Tumori "Fondazione Pascale", Napoli, Campania, Italy

Are you E Seregni?

Claim your profile

Publications (173)435.69 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Differentiated thyroid cancer is a rare malignancy, but leaves numerous survivors for life-long follow-up. The cornerstone in current guidelines for follow-up is by measuring the thyroid specific tumour marker, thyroglobulin in serum. Most patients can be followed by this method, but some thyroid cancer patients have antithyroglobulin antibodies in serum, both at diagnosis and after treatment, where follow-up is commenced. These antibodies interfere technically in the immunological methods for measuring thyroglobulin, and the antithyroglobulin antibody positive patients are thus eliminated from following current guidelines. In recent years studies have indicated that following the concentration of antithyroglobulin antibodies in serum may be a surrogate marker for recurrence of the thyroid carcinoma. This has recently resulted in publication of an expert position paper, providing a flow scheme for these particular patients. The current review summarises the literature which is the basis for the paper.
    Current Medicinal Chemistry 08/2014; · 3.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up for DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous thyrotropin (TSH) is recommended by current clinical guidelines to detect occult disease with maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation. Use of these highly sensitive Tg assays has not yet been incorporated into clinical guidelines but they will, we believe, be used by physicians caring for patients with DTC. The aim of this clinical position paper is, therefore, to offer advice on the various aspects and implications of using these highly sensitive Tg assays in the clinical care of patients with DTC.
    European Journal of Endocrinology 04/2014; · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter (90Y) and a medium-energy beta/gamma emitter (177Lu) in patients with metastatic NET refractory to conventional therapy. Methods A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [177Lu]DOTA-TATE (5.55 GBq) and [90Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [177Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Results Administration of tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment Conclusion The results of our study indicates that combined [90Y]DOTA-TATE and [177Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach.
    European journal of nuclear medicine and molecular imaging 02/2014; 41(2). · 5.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract This study evaluated the effects of 10-day broccoli (250 g/day) intake on dietary markers and markers of inflammations in young male smokers. A dietary intervention study with a repeated measures crossover design was conducted. Circulating levels of carotenoids, folate, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 6 receptor (IL-6sR) and adiponectin were measured. Broccoli intake significantly increased plasma levels of folate (+17%) and lutein (+39%), while no significant effect was observed for TNF-α, IL-6, IL-6sR or adiponectin. Plasma CRP decreased by 48% (post-hoc analysis, p < 0.05) following broccoli diet; this resulted to be independent from the plasma variations in lutein and folate. An inverse correlation between lycopene, TNF-α and IL-6sR was observed at baseline. In conclusion, broccoli consumption may reduce CRP levels in smokers, consistent with epidemiologic observations that fruit and vegetable intake is associated with lower circulating CRP concentrations.
    International Journal of Food Sciences and Nutrition 09/2013; · 1.20 Impact Factor
  • Journal of Clinical Oncology 07/2013; · 17.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 06/2013; 57(2):146-152. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Even though the presence of anti-thyroglobulin antibodies (TgAb) represents a significant problem in the follow-up of differentiated thyroid cancer (DTC) patients, the current guidelines on the management of DTC that have been published in recent years contain no paragraphs concerning the methods to be used for detecting such antibody-related interference in thyroglobulin (Tg) measurement, or how to manage TgAb-positive patients in whom Tg cannot be used reliably as a tumor marker. Aim: An international group of experts from the European Thyroid Association - Cancer Research Network who are involved in the care of DTC patients met twice to form a consensus opinion on how to proceed with treatment and follow-up in TgAb-positive DTC patients based on the available evidence in the literature. Here we will report on the consensus opinions that were reached regarding technical and clinical issues. Result: This clinical opinion paper provides an overview of the available evidence and the resulting consensus recommendations. The current literature does not provide sufficient data for giving evidence-based answers to many questions arising in the care of TgAb-positive DTC patients. Where insufficient evidence was available, a thorough discussion by a group of physician-scientists, all of whom have a distinguished track record in thyroid cancer care, was held to arrive at a consensus expert opinion. The questions and answers discussed were then summarized into an algorithm for the management of TgAb-positive patients. Conclusion: We were able to define 26 consensus expert recommendations and a resulting algorithm for the care of TgAb-positive DTC patients.
    Thyroid: official journal of the American Thyroid Association 05/2013; · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prostate carcinoma is the most common non-cutaneous cancer in developed countries and represents the second leading cause of death. Early stage androgen dependent prostate carcinoma responds well to conventional therapies, but relatively few treatment options exist for patients with hormone-refractory prostate cancer. One of the most suitable targets for antibody-mediated approaches is prostate specific membrane antigen (PSMA) which is a well known tumour associated antigen. PSMA is a type II integral cell-surface membrane protein that is not secreted, and its expression density and enzymatic activity are increased progressively in prostate cancer compared to normal prostate epithelium, thereby making PSMA an ideal target for monoclonal antibody imaging and therapy. To obtain a small protein that can better penetrate tissue, we have engineered a single-chain variable fragment (scFv) starting from the variable heavy and light domains of the murine anti-PSMA monoclonal antibody D2B. scFvD2B was analysed in vitro for activity, stability, internalisation ability and in vivo for targeting specificity. Maintenance of function and immunoreactivity as well as extremely high radiolabelling efficiency and radiochemical purity were demonstrated by in vitro assays and under different experimental conditions. Despite its monovalent binding, scFvD2B retained a good strength of binding and was able to internalise around 40% of bound antigen. In vivo we showed its ability to specifically target only PSMA expressing prostate cancer xenografts. Due to these advantageous properties, scFvD2B has the potential to become a good theranostic reagent for early detection and therapy of prostate cancers.
    European journal of cancer (Oxford, England: 1990) 02/2013; · 4.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intra-arterial radioembolization using microspheres labeled with the high-energy beta-emitter yttrium-90 (90Y) is an innovative therapeutic strategy for primary and secondary hepatic malignancies. An accurate imaging workup plays a pivotal role in correctly selecting patients for treatment, to avoid severe complications and in assessment of the post-administration microsphere distribution. Nuclear medicine imaging modalities are an integral part of a complex multidisciplinary approach. In particular, hepatic perfusion imaging with 99mTc-macroaggregated albumin particles (99mTc-MAA), which identifies extrahepatic accumulation of radiopharmaceutical and lung shunt, is necessary to correctly select patients who may benefit from the treatment. Furthermore, 99mTc MAA SPECT-based dose planning may optimize RE efficacy, overcoming the limitations of empirical methods to determine the activity to be administered. Quantitative assessment of the post-administration intrahepatic microsphere distribution with SPECT or PET is important for evaluation of toxicity and efficacy and can be used for the prediction of patient response and for patient-specific therapeutic dose optimization. Finally, [18F]FDG PET/CT imaging is important in the assessment of early response after RE and in predicting patient outcome. This review provides a comprehensive overview of multimodality imaging in the complex management of patients undergoing RE for liver tumors.
    Clinical and Translational Imaging. 01/2013;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim: Our goal was to limit liver toxicity and to obtain good efficacy by developing a dosimetric treatment planning strategy. While several dosimetric evaluations are reported in literature, the main problem of the safety of the treatment is rarely addressed. Our work is the first proposal of a treatment planning method for glass spheres, including both liver toxicity and efficacy issues. Methods: Fifty-two patients (series 1) had been treated for intermediated/advanced hepatocellular carcinoma (HCC) with glass spheres, according to the Therasphere® prescription of 120 Gy averaged on the injected lobe. They were retrospectively evaluated with voxel dosimetry, adopting the local deposition hypothesis. Regions of interest on tumor and non tumor parenchyma were drawn to determine the parenchyma absorbed dose, averaged also on non irradiated voxels, excluding tumor voxels. The relationship between the mean non tumoral parenchyma absorbed dose D and observed liver decompensation was analyzed. Results: Basal Child-Pugh strongly affected the toxicity incidence, which was 22% for A5, 57% for A6, 89% for B7 patients. Restricting the analysis to our numerically richest class (basal Child-Pugh A5 patients), D median values were significantly different between toxic (median 90 Gy) and non toxic treatments (median 58 Gy) at a Mann-Withney test, (P=0.033). Using D as a marker for toxicity, the separation of the two populations in terms of area under ROC curve was 0.75, with 95% C.I. of [0.55-0.95]. The experimental Normal Tissue Complication Probability (NTCP) curve as a function of D resulted in the following values: 0%, 14%, 40%, 67% for D interval of [0-35] Gy, [35-70] Gy, [70-105] Gy, [105-140] Gy. Discussion. A limit of about 70 Gy for the mean absorbed dose to parenchyma was assumed for A5 patients, corresponding to a 14% risk of liver decompensation. This result is applicable only to our administration conditions: glass spheres after a decay interval of 3.75 days. Different safety limit (40 Gy) are published for resin spheres, characterized by higher number of particle per GBq (more uniform irradiation, bigger biological effect for the same absorbed dose). Conclusion: As result of this study we suggest a constraint of about 70 Gy mean absorbed dose to liver non tumoral parenchyma, corresponding to about 15% probability of radioinduced liver decompensation while still aiming at achieving an absorbed of several hundreds of Gy to lesions.
    The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 12/2012; 56(6):503-8. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid carcinomas derived from follicular cells comprise papillary (PTC), follicular (FTC), poorly-differentiated (PDTC), and undifferentiated anaplastic (ATC) carcinomas. PTC, the most frequent thyroid carcinoma histotype, is associated with gene rearrangements that generate RET/PTC and TRK oncogenes and with BRAF-V600E and RAS gene mutations. These last two genetic lesions are also present in a fraction of PDTCs. The ERK1/2 pathway, downstream of the known oncogenes activated in PTC, has a central role in thyroid carcinogenesis. In this study, we demonstrate that the BRAF-V600E, RET/PTC, and TRK oncogenes upregulate the ERK1/2 pathway's attenuator cytoplasmic dual-phase phosphatase DUSP6/MKP3 in thyroid cells. We also show DUSP6 overexpression at the mRNA and protein levels in all of the analysed PTC cell lines. Furthermore, DUSP6 mRNA was significantly higher in PTC and PDTC in comparison to normal thyroid tissues both in expression profile datasets and in patients' surgical samples analysed by real-time RT-PCR. Immunohistochemical and Western blot analyses showed that DUSP6 was also overexpressed at the protein level in most PTC and PDTC surgical samples tested, but not in ATC, and revealed a positive correlation trend with ERK1/2 pathway activation. Finally, DUSP6 silencing reduced the neoplastic properties of four PTC cell lines, thus suggesting that DUSP6 may have a pro-tumourigenic role in thyroid carcinogenesis.
    Endocrine Related Cancer 11/2012; · 5.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recently, in Italy, the reimbursement for the use of rhTSH in preparing patients for radiometabolic treatment of iodine-avid metastases from differentiated thyroid cancer has been made possible. Intramuscular administration of rhTSH increases the radioiodine uptake and thyroglobulin production by thyroid cells. In addition to the previous indications on the use of rhTSH (mainly: serum thyreoglobulin assay with or without 131I scintigraphy and ablation with 131I of remnants in low risk patients), the reimbursement is now allowed for the treatment with radioiodine of iodine-avid loco-regional and distant metastases, in subjects with inability to reach adequate TSH levels and/or severe clinical conditions which could be potentially worsened by other concurrent diseases (history of stroke or transient ischemic attack, severe cardiac disease, renal failure or major psychiatric disorders). The Italian Medicines Agency (AIFA) approved this use (and added this hormone in the special list of drugs regulated by the D.Lgs 648/96) on the basis of a series of scientific evidences, proposed by a "team of experts". In the present paper we illustrate the scientific background of the use of rhTSH (clinical usefulness, economic considerations, aspects related to a better quality of life) that allowed the modification of the reimbursement and how it was made possible in the Italian legislative context.
    The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 10/2012; 56(5):476-84. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: an increased frequency of primary hyperparathyroidism (PHP) has been reported in patients with treated breast cancer (BC). PHP has been found in about 7% of BC patients after surgery and radio-, chemio- or hormonal therapy. The aim of this work was evaluate the frequency of PHP in untreated BC patients. Subjects and Methods: we evaluated 186 women with BC and 233 women with thyroid cancer (TC, n=122) or benign thyroid diseases (BTD, n=111). In all patients serum calcium, albumin, PTH and 25-OHvitD were measured before any treatment. Results: Serum calcium concentrations were significantly higher in BC than in TC and BTD groups (median values 9.5 mg/dl, 9.3 mg/dl and 9.3 mg/dl, respectively), but, according to a logistic regression model, calcium was not significantly different between the 3 groups when age was taken into account. In all patients, serum calcium was in the normal range, indicating that no case of overt PHP was present. Five patients (1 in BC, 2 in TC and 2 in BDT groups) had serum calcium close to the upper limit of normal range, high PTH and low 25-OHvitD, indicating a possible PHP with hypercalcemia masked by concomitant 25-OHvitD deficiency. Conclusions: in untreated BC group, no patient had overt PHP and 1/186 (0.5%) presented a possible PHP masked by 25-OHvitD deficiency, a PHP frequency much lower than that observed in treated BC patients. These data suggest that the treatments of BC may be responsible for the increased frequency of PHP reported in previous studies.
    Journal of endocrinological investigation 08/2012; · 1.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The established treatment for differentiated thyroid carcinoma (DTC) is founded on total thyroidectomy and subsequent administration of radioiodine (131I) to ablate the thyroid remnant and to treat the metastatic disease. In the case of metastatic or recurrent disease, further cycles of 131I therapy are often necessary. The condition for maximizing the effectiveness of the treatment is to have an adequate stimulation from TSH, which must be >25-30 mIU/L. This elevation is achieved either discontinuing the hormone suppression therapy for an appropriate period, or administering recombinant human TSH (rhTSH). The latter has shown good clinical efficacy in patients with residual thyroid gland and is nowadays commonly employed since it is easy to use and allows to avoid the side effects of hypothyroidism. It thus represents a good alternative to thyroid hormone withdrawal for the remnant ablation, while is still open the question if its efficacy on the management of metastatic disease is superimposable to thyroid hormone withdrawal. To this purpose, a Panel of expert reviewed the literature, assessing the advantages and disadvantages for the patient, as well as the impact in terms of cost and benefit to the National Health Service. The work of the Panel concluded with a proposal for the use of rhTSH in selected patients with metastatic DTC, in which is considered the efficacy and safety of the product and is examined its use in terms of costs; this proposal was accepted by the Italian Drug Agency resulting in an update of the indications for rhTSH.
    Minerva medica 06/2012; 103(3):209-18. · 1.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To reduce the sequelae of craniospinal irradiation (CSI) in children under 10 (≥3) years old and to improve the prognosis for high-risk medulloblastoma in adolescents, we adjusted postoperative chemotherapy and CSI doses to patients' stage and age. From 1986 to 1995, 73 patients entered the study. Children under 10 and adolescents with metastases, residual disease (RD) or stage >T3 received postoperative IV vincristine and high-dose (HD) ± intrathecal (IT) methotrexate, while standard-risk adolescents were given IV vincristine and IT methotrexate. Chemotherapy was followed by CSI (19.8 Gy for children <10; 36 Gy for adolescents), with a 54-Gy posterior fossa boost. Maintenance chemotherapy with lomustine and vincristine was administered for a year afterwards. A total of 39 children were under 10 of whom 20 had metastases. Response to chemotherapy was recorded in 70%, but 5-year EFS and OS were only 48 and 56%, respectively. Results were significantly worse for metastatic cases, patients under 10, those with RD, and those staged without MRI (unavailable early in the study). Efforts to preserve survivors' quality of life did not pay off, and most patients over 30 still depended on their parents' income and had severe cognitive/endocrine disabilities. In conclusion, despite a very high response rate with this preradiation HD methotrexate schedule, the outcome for high-risk medulloblastoma patients did not improve (especially when lower CSI doses were used) and patients still developed severe morbidities.
    Journal of Neuro-Oncology 02/2012; 108(1):163-71. · 3.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Oncogene-induced senescence (OIS) is a growth arrest triggered by the enforced expression of cancer-promoting genes and acts as a barrier against malignant transformation in vivo. In this study, by a combination of in vitro and in vivo approaches, we investigate the role of OIS in tumours originating from the thyroid epithelium. We found that expression of different thyroid tumour-associated oncogenes in primary human thyrocytes triggers senescence, as demonstrated by the presence of OIS hallmarks: changes in cell morphology, accumulation of SA-β-Gal and senescence-associated heterochromatic foci, and upregulation of transcription of the cyclin-dependent kinase inhibitors p16(INK4a) and p21(CIP1). Furthermore, immunohistochemical analysis of a panel of thyroid tumours characterised by different aggressiveness showed that the expression of OIS markers such as p16(INK4a), p21(CIP1) and IGFBP7 is upregulated at early stages, and lost during thyroid tumour progression. Taken together, our results suggest a role of OIS in thyroid carcinogenesis.
    Endocrine Related Cancer 09/2011; 18(6):743-57. · 5.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bone pain in advanced stages of cancer significantly decreases the patient's quality of life having a great impact on physical, physiological and social functioning. About 65% of patients with prostate or breast cancer will experience symptomatic skeletal metastases. Bone pain sustained by osseous metastases represents the most frequent kind of pain and its clinical presentation and characteristics differ from other type of neoplastic pain (i.e., neuropathic or visceral ones). Pathophysiology of bone pain is not yet completely understood but a general mechanism including infiltration of bone tissue associated with osteolysis and release of biological active molecules able to stimulate peripheral nervous terminals, seems to be principally involved. In oncological practice, painful skeletal metastases are managed by different multidisciplinary modalities which include the use of systemic analgesics (i.e., bisphosphonates), antineoplastic agents (i.e., hormones and chemotherapeutics), external beam radiotherapy, interventional radiology and radiopharmaceuticals. In this review we will discuss the state of the art of palliative therapy of bone pain with particular emphasis to the current approved radiopharmaceuticals, focusing on indications, patient selection, efficacy and toxicity. Some remarks on new or under developing strategies in systemic metabolic radiopharmaceutical therapy will be reported.
    The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 08/2011; 55(4):411-9. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypothyroidism remains a common late effect after irradiation of the neck/mediastinum for Hodgkins lymphoma (HL). We evaluated the protective effect of TSH suppression during neck/mediastinum irradiation. From 1998 to 2001, 14 consecutive euthyroid children were given, before and until the end of their radiotherapy on neck/mediastinum, L-thyroxine at TSH-suppressive doses. The 14 patients had adequate TSH suppression during irradiation in 8, inadequate in 6. The 8-year hypothyroidism-free-survival after irradiation was 75 ± 15% for the former group, 0% for the latter (P = 0.009). TSH suppression could have a protective effect on thyroid function as shown in a small group of patients with HL.
    Pediatric Blood & Cancer 07/2011; 57(1):166-8. · 2.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Activating mutations of RET, a gene encoding two isoforms of a tyrosine kinase receptor physiologically expressed in several neural crest-derived cell lineages, are associated with the inherited forms of medullary thyroid carcinoma (MTC). The identification and characterization of novel RET mutations involved in MTC is valuable, as RET gene testing plays a crucial role in the management of these patients. In an MTC patient, we have identified a germline c.1996A>G transition in heterozygosis leading to K666E substitution. In addition, the conservative S904S (c.2712C>G) and the non-conservative functional G691S (c.2071G>A) polymorphisms have been identified. Through functional studies, we demonstrate for the first time that K666E is a gain-of-function mutation with oncogenic potential, based on its ability to transform NIH3T3 cells. It was not possible to define whether K666E is a de novo or inherited RET variant in the patient, as the family history was negative for MTC, and the carrier status of family members could not be tested. Our results, together with a recent report of co-segregation of the mutation in three MTC families, suggest that K666E is a causative MTC mutation. As we have shown that the same patient allele carries both K666E and G691S variants, the latter known to increase downstream RET signaling, a possible role for the G691S polymorphism has also been investigated. We have demonstrated that, although RET-G691S is not oncogenic per se, it enhances the transforming activity of the RET-K666E mutant, thus suggesting a modifier role for this functional polymorphism.
    Endocrine Related Cancer 06/2011; 18(4):519-27. · 5.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In most centres, the choice of the optimal activity to be administered in selective intra-arterial radioembolization with microspheres is nowadays based on empirical models which do not take into account the evaluation of tumour and non tumour individual absorbed dose, despite plenty of published data which showed that local efficacy is correlated to tumour absorbed dose, and that the mean absorbed dose is a toxicity risk factor. A pitfall of the crudest, empirical tumour involvement method are 20 deaths in a single centre which adopted it to administer the whole liver, or the need of systematic 25% subjective reduction of activity prescribed with body surface area method. In order to develop a possibly safer and more effective strategy based on real individual dosimetry, we examine first external beam liver radiation therapy results. The half century experience has something to be borrowed: the volume effect, according to which the smaller the fraction of the irradiated liver volume, the higher the tolerated dose. Different tolerance for different underlying disease or previous non radiation treatment is to be expected. Radiobiological models experience also has to be inherited, but not their dose reference values. Then we report the published dosimetric experience about (90)Y microsphere radioembolization of primary and metastatic liver tumours. In addition we also present original data from our growing preliminary experience of more refined (99m)Tc MAA SPECT based calculations in hepatocarcinoma patients. This overcame the mean dose approach in favour of the evaluation of dose distribution at voxel level. An insight into dosimetry issues at microscopic level (lobule level) is also provided, from which the different radiobiological behaviour between resin and glass spheres can be understood. For tumour treatment, an attenuation corrected (99m)Tc- SPECT based treatment planning strategy can be proposed, although quantitative efficacy thresholds should be differentiated according to the kind of pathology and previous treatment. For non tumour liver parenchyma, data in favour of a relationship between absorbed dose and dangerous effects are encouraging. Unfortunately in hepato-cellular carcinoma, some confounding factors may hamper the adequate estimation of the risk of toxicity. First there is a lack of consensus about the exact definition of toxicity after (90)Y microsphere radioembolization. Second, for HCC patients, progression of both cancer and cirrhosis can simulate a radioinduced toxicity, making the analysis more complex.
    The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 04/2011; 55(2):168-97. · 1.72 Impact Factor

Publication Stats

2k Citations
435.69 Total Impact Points

Institutions

  • 2014
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1994–2013
    • CRO Centro di Riferimento Oncologico di Aviano
      • Division of Nuclear Medicine
      Aviano, Friuli Venezia Giulia, Italy
  • 2012
    • Azienda Ospedaliera SS Arrigo e Biagio e Cesare Arrigo
      Alessandria, Piedmont, Italy
  • 1992–2009
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      • s.c. Medicina Nucleare
      Milano, Lombardy, Italy
  • 1996–2005
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 1996–1999
    • University of Milan
      • Istituto di Scienze Dermatologiche
      Milano, Lombardy, Italy