Publications (56) View all
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Article: Combined Imaging With 18F-FDG-PET/CT and 111In-Labeled Octreotide SPECT for Evaluation of Thymic Epithelial Tumors.
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ABSTRACT: PURPOSE: This study aimed to test the role of combined imaging with F-FDG-PET/CT and In-octreotide SPECT in characterizing thymic epithelial tumors (TETs). METHODS: We evaluated 20 patients with newly diagnosed TETs who had undergone concomitant F-FDG-PET/CT and In-octreotide SPECT. Thymic epithelial tumors were classified by World Health Organization (WHO) as low-risk thymomas (5), high-risk thymomas (4), and thymic carcinomas (11, among which 6 neuroendocrine tumors). Patients were staged according to Masaoka system. F-FDG-PET/CT was performed and SUVmax of primary tumors was recorded. In-octreotide SPECT of the thorax was performed, and tumor-to-background ratio was determined on the 24-hour coronal sections. RESULTS: All patients showed increased F-FDG uptake in mediastinal lesions. SUVmax were significantly correlated with WHO classification (r = 0.66, P < 0.01) and with Masaoka stage (r = 0.60, P < 0.01). SUVmax of low-risk thymomas (mean [SD], 2.87 [0.83]) were significantly lower than those of high-risk thymomas (mean [SD], 7.21 [1.73], P < 0.01) and of thymic carcinomas (mean [SD], 9.39 [5.80], P < 0.05), whereas no significant difference was found between high-risk thymomas and thymic carcinomas. SUVmax of all high-risk thymomas and thymic carcinomas was 4.5 or greater. All primary tumors were detected by In-octreotide SPECT, and tumor-to-background ratios ranged between 1.67 and 10.10. No statistically significant correlation was found between tumor-to-background ratios and WHO classification (r = 0.24, P = 0.36) and Masaoka stages (r = 0.31, P = 0.23). However tumor-to-background ratios of thymic neuroendocrine tumors (mean [SD], 5.71 [3.09]) were significantly higher than those of all other TETs with SUVmax of 4.5 or greater (mean [SD], 2.41 [0.56]; P < 0.05). CONCLUSIONS: F-FDG-PET/CT scan allows to differentiate high-risk epithelial tumors and thymic carcinomas from low-risk thymomas, whereas In-octreotide SPECT may identify neuroendocrine tumors among those showing high F-FDG uptake.Clinical nuclear medicine 03/2013; · 3.92 Impact Factor -
Article: Hodgkin's lymphoma emerging radiation treatment techniques: trade-offs between late radio-induced toxicities and secondary malignant neoplasms.
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ABSTRACT: BACKGROUND: Purpose of this study is to explore the trade-offs between radio-induced toxicities and second malignant neoplasm (SMN) induction risk of different emerging radiotherapy techniques for Hodgkin's lymphoma (HL) through a comprehensive dosimetric analysis on a representative clinical model. METHODS: Three different planning target volume (PTVi) scenarios of a female patient with supradiaphragmatic HL were used as models for the purpose of this study. Five treatment radiation techniques were simulated: an anterior-posterior parallel-opposed (AP-PA), a forward intensity modulated (FIMRT), an inverse intensity modulated (IMRT), a Tomotherapy (TOMO), a proton (PRO) technique. A radiation dose of 30 Gy or CGE was prescribed. Dose-volume histograms of PTVs and organs-at-risk (OARs) were calculated and related to available dose-volume constraints. SMN risk for breasts, thyroid, and lungs was estimated through the Organ Equivalent Dose model considering cell repopulation and inhomogeneous organ doses. RESULTS: With similar level of PTVi coverage, IMRT, TOMO and PRO plans generally reduced the OARs' dose and accordingly the related radio-induced toxicities. However, only TOMO and PRO plans were compliant with all constraints in all scenarios. For the IMRT and TOMO plans an increased risk of development of breast, and lung SMN compared with AP-PA and FIMRT techniques was estimated. Only PRO plans seemed to reduce the risk of predicted SMN compared with AP-PA technique. CONCLUSIONS: Our model--based study supports the use of advanced RT techniques to successfully spare OARs and to reduce the risk of radio-induced toxicities in HL patients. However, the estimated increase of SMNs' risk inherent to TOMO and IMRT techniques should be carefully considered in the evaluation of a risk-adapted therapeutic strategy.Radiation Oncology 01/2013; 8(1):22. · 2.32 Impact Factor -
Article: In Regard to Boomsma et al.
International journal of radiation oncology, biology, physics 01/2013; 85(1):11. · 4.59 Impact Factor -
Article: Development of multivariate NTCP models for radiation-induced hypothyroidism: a comparative analysis.
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ABSTRACT: BACKGROUND: Hypothyroidism is a frequent late side effect of radiation therapy of the cervical region. Purpose of this work is to develop multivariate normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RHT) and to compare them with already existing NTCP models for RHT. METHODS: Fifty-three patients treated with sequential chemo-radiotherapy for Hodgkin's lymphoma (HL) were retrospectively reviewed for RHT events. Clinical information along with thyroid gland dose distribution parameters were collected and their correlation to RHT was analyzed by Spearman's rank correlation coefficient (Rs). Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). Models were tested against external published data on RHT and compared with other published NTCP models. RESULTS: If we express the thyroid volume exceeding X Gy as a percentage (Vx(%)), a two-variable NTCP model including V30(%) and gender resulted to be the optimal predictive model for RHT (Rs = 0.615, p < 0.001. AUC = 0.87). Conversely, if absolute thyroid volume exceeding X Gy (Vx(cc)) was analyzed, an NTCP model based on 3 variables including V30(cc), thyroid gland volume and gender was selected as the most predictive model (Rs = 0.630, p < 0.001. AUC = 0.85). The three-variable model performs better when tested on an external cohort characterized by large inter-individuals variation in thyroid volumes (AUC = 0.914, 95%CI 0.760-0.984). A comparable performance was found between our model and that proposed in the literature based on thyroid gland mean dose and volume (p = 0.264). CONCLUSIONS: The absolute volume of thyroid gland exceeding 30 Gy in combination with thyroid gland volume and gender provide an NTCP model for RHT with improved prediction capability not only within our patient population but also in an external cohort.Radiation Oncology 12/2012; 7(1):224. · 2.32 Impact Factor -
Article: The impairment of the High Mobility Group A (HMGA) protein function contributes to the anticancer activity of trabectedin.
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ABSTRACT: Trabectedin (Ecteinascidin-743 or ET-743) is a novel antitumour agent of marine origin with potent antitumour activity both in vitro and in vivo. It interacts with the minor groove of DNA, interfering with transcriptional activity and DNA repair pathways. Here, we report a novel mechanism by which trabectedin exerts its cytotoxic effects on carcinoma cells. It is based on its ability to impair the function of the High-Mobility Group A (HMGA) proteins. These proteins have a key role in cell transformation, and their overexpression is a common feature of human malignant neoplasias, representing a poor prognostic index often correlated to anti-cancer drug resistance. They bind the minor groove of DNA, alter chroma-tin structure and, thus, regulate the transcription of several genes by enhancing or suppressing the activity of transcription factors. We first report that trabectedin has a higher cytotoxic effect on thyroid and colon carcinoma cells expressing abundant levels of HMGAs in comparison with cells not expressing them. Then, we have shown that trabectedin treatment displaces HMGA proteins from the HMGA-responsive promoters, including ATM promoter, impairing their transcriptional activity. Finally, we report a synergism between Ionising Radiations and trabectedin treat- A v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e j c a n c e r . i n f o Please cite this article in press as: D'Angelo D. et al., The impairment of the High Mobility Group A (HMGA) protein function contributes to the anticancer activity of trabectedin, Eur J Cancer (2012), http://dx.doi.org/10.1016/j.ejca.2012.10.014 ment restricted to the HMGA-overexpressing cancer cells. This result might have important clinical implications since it would suggest the use of trabectedin for the treatment of neopla-sias expressing abundant HMGA levels that are frequently associated to chemoresistance and poor prognosis.European Journal of Cancer 11/2012; · 5.54 Impact Factor
