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Mocellin S.,University of Padua | Goodwin A.,University of Sydney | Pasquali S.,Veneto Institute of Oncology IRCCS
Cochrane Database of Systematic Reviews

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the efficacy and acceptability of single agent CPAs for the prevention of primary breast cancer, in unaffected women, at an above average risk of developing breast cancer. Using a network meta-analysis, we also intend to rank single CPAs, based on their efficacy and acceptability (an endpoint that is defined as the inverse of CPA-related toxicity). © 2016 The Cochrane Collaboration. Source

Colombo C.,University of Milan | Verga U.,Fondazione Cagranda Instituto Of Ricovero E Cura A Carattere Scientifico Irccs | Mian C.,University of Padua | Ferrero S.,University of Milan | And 11 more authors.
Journal of Clinical Endocrinology and Metabolism

Context: The evaluation of basal calcitonin (bCT) and stimulated calcitonin (sCT) can be used for the diagnosis and follow-up of medullary thyroid cancer (MTC). Objective: The aim of this study was to evaluate the reliability of high-calcium (Ca) test and to identify gender-specific thresholds for MTC diagnosis. Patients: Patients with MTC in remission (n = 24) or in persistence (n = 18), RET gene mutations carriers (n = 14), patients with nodular goiter (n = 69), and healthy volunteers (n = 16) were submitted to pentagastrin and Ca (25 mg/kg) tests. Results: In all groups, the levels of calcitonin (CT) stimulated by either pentagastrin or Ca were significantly correlated. The prevalence of both C-cell hyperplasia (CCH) and MTC in women and men paralleled the increasing basal and peak CT levels in a gender-specific manner. Receiver operating characteristic plot analyses showed that the best levels of bCT to separate normal and CCH cases from MTC patients were above 18.7 pg/ml in females and above 68 pg/ml in males. Furthermore, Ca sCT above 184 pg/ml in females and above 1620 pg/ml in males had the highest accuracy to distinguish normal and CCH cases from patients with MTC. At the C-cell immunohistochemical examination, Ca sCT below 50 pg/ml corresponded to a mean number of 30 cells per 10 fields, whereas higher sCT associated with ameannumberof 400 cells per 10 fields, often displaying a diffuse and nodular distribution pattern. Conclusions: High-dose Ca test is a potent and well-tolerated procedure that can be applied worldwide at a low cost. Reference ranges for Ca sCT levels in different groups of patients and CT thresholds to diagnose CCH/MTC have been identified. Copyright © 2012 by The Endocrine Society. Source

Mazza E.,San Raffaele Scientific Institute | Brandes A.,IRCCS Institute of Neurological science | Zanon S.,San Raffaele Scientific Institute | Eoli M.,Unit of Molecular Neuro oncology | And 4 more authors.
Cancer Chemotherapy and Pharmacology

Purpose: Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. Methods: Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). Results: Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75 %, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75 %, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. Conclusion: The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified. © 2015 Springer-Verlag Berlin Heidelberg. Source

Lombardi G.,Medical Oncology | Corona G.,Italian National Cancer Institute | Bellu L.,Medical Oncology | Puppa A.D.,Neurological science | And 7 more authors.

Background. Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert a-ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine could predict the presence of IDH1/2 mutations in patients with glioma. Materials and Methods. All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry. Results. A total of 84 patients were enrolled: 38 with R132HIDH1mutatedand46withwild type.Amongthe38patientswith mutant IDH1, 21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma,urine, andplasma/urine ratio (Ratio_2HG).We found a significant difference in the Ratio_2HG between patients with andwithout an IDH1mutation (22.268.7 vs. 15.666.8; p,.0001).The optimal cutoff value for Ratio_2HGto identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high-grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma,we found a correlation between the Ratio_2HG value and the response to treatment. Conclusion. Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients. © AlphaMed Press 2015. Source

Richter S.,TU Dresden | Peitzsch M.,TU Dresden | Rapizzi E.,University of Florence | Lenders J.W.,Radboud University Nijmegen | And 15 more authors.
Journal of Clinical Endocrinology and Metabolism

Design, Setting, and Patients: PPGL tumor specimens from 233 patients, including 45 with SDHx mutations, were provided from eight tertiary referral centers for mass spectrometric analyses of Krebs cycle metabolites.Context: Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations.Objective: We assessed whether altered succinate dehydrogenase product-precursor relationships, manifested by differences in tumor ratios of succinate to fumarate or other metabolites, might aid in identifying and stratifying patients with SDHx mutations.Main Outcome Measure: Diagnostic performance of the succinate:fumarate ratio for identification of pathogenic SDHx mutations.Results: SDH-deficient PPGLs were characterized by 25-fold higher succinate and 80% lower fumarate, cis-aconitate, and isocitrate tissue levels than PPGLs without SDHx mutations. Receiveroperating characteristic curves for use of ratios of succinate to fumarate or to cis-aconitate and isocitrate to identify SDHx mutations indicated areas under curves of 0.94 to 0.96; an optimal cut-off of 97.7 for the succinate:fumarate ratio provided a diagnostic sensitivity of 93% at a specificityof 97% toidentify SDHX-mutated PPGLs. Succinate:fumarate ratios were higher in both SDHB-mutated and metastatic tumors than in those due to SDHD/C mutations or without metastases.Conclusions: Mass spectrometric-based measurements of ratios of succinate:fumarate and other metabolites in PPGLs offer a useful method to identify patients for testing of SDHx mutations, with additional utility to quantitatively assess functionality of mutations and metabolic factors responsible for malignant risk. Copyright © 2014 by the Endocrine Society. Source

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