Cristina Ferrari

Late effects of chemotherapy and radiotherapy in osteosarcoma and Ewing sarcoma patients: the Italian Sarcoma Group Experience (1983-2006).

Patients with osteosarcoma and Ewing sarcoma have achieved longer survival over the past decades, but late side effects of chemotherapy and radiotherapy have become important concerns.

Prognostic role of nuclear factor/IB and bone remodeling proteins in metastatic giant cell tumor of bone: A retrospective study

Giant cell tumor of bone (GCTb) represents 5% of bone tumors, and although considered benign, 5% metastasize to the lung. The expression of proteins directly or indirectly associated with osteolysis and tumor growth was studied on 163 samples of GCTb. Of these, 33 patients developed lung metastasis during follow‐up. The impact of tumor–host interaction on clinical aspects was evaluated with the aim of finding specific markers for new biological therapies, thus improving clinical management of GCTb. Protein expression was evaluated by immunohistochemical analysis on Tissue Microarray. The majority of GCTb samples from patients with metastatic disease were strongly positive to RANKL and its receptor RANK as well as to CAII and MMP‐2 and to pro‐survival proteins NFIB and c‐Fos. Kaplan–Meier analysis indicated a significant difference in metastasis free survival curves based on protein staining. Interestingly, the statistical correlation established a strong association between all variables studied with a higher τ coefficient for RANK/RANKL, RANK/NFIB, and RANKL/NFIB pairs. At multivariate analysis co‐overexpression of NFIB, RANK and RANKL significantly increased the risk of metastasis with an odds ratio of 13.59 (95%CI 4.12–44.82; p < 0.0005). In conclusion, the interconnection between matrix remodeling and tumor cell activity may identify tumor–host endpoints for new biological treatments.

Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic) of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [64Cu]CuCl2. To evaluate the potential theranostic role of [64Cu]CuCl2 in GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [64Cu]CuCl2 to simulate single- and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy.

18F-FDG PET/CT role in staging of gastric carcinomas: comparison with conventional contrast enhancement computed tomography.

AbstractThe purpose of the report was to evaluate the role of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging gastric cancer comparing it with contrast enhancement computed tomography (CECT).This retrospective study included 45 patients who underwent performed whole body CECT and 18F-FDG PET/CT before any treatment. We calculated CECT and 18F-FDG PET/CT sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) for gastric, lymphnode, and distant localizations; furthermore, we compared the 2 techniques by McNemar test. The role of 18F-FDG PET/CT semiquantitative parameters in relation to histotype, grading, and site of gastric lesions were evaluated by ANOVA test.Sensitivity, specificity, accuracy, PPV and NPV of CECT, and 18F-FDG PET/CT for gastric lesion were, respectively, 92.11%, 57.14%, 86.66%, 92.11%, 57.14% and 81.58%, 85.71%, 82.22%, 96.88%, 46.15%. No differences were identified between the 2 techniques about sensitivity and specificity. No statistical differences were observed between PET parameters and histotype, grading, and site of gastric lesion. The results of CECT and 18F-FDG PET/CT about lymphnode involvement were 70.83%, 61.90%, 66.66%, 68%, 65% and 58.33%, 95.24%, 75.55%, 93.33%, 66.67%. The results of CECT and 18F-FDG PET/CT about distant metastases were 80%, 62.86%, 66.66%, 38.10%, 91.67% and 60%, 88.57%, 82.22%, 60%, 88.57%. 18FDG PET/CT specificity was significantly higher both for lymphnode and distant metastases.The 18F-FDG PET/CT is a useful tool for the evaluation of gastric carcinoma to detect primary lesion, lymphnode, and distant metastases using 1 single image whole-body technique. Integration of CECT with 18F-FDG PET/CT permits a more valid staging in these patients.

18 F-FDG PET/CT contribution to diagnosis and treatment response of rhino-orbital-cerebral mucormycosis

OBJECTIVE Mucormycosis is an infection caused by mycetes mucorales, emerged as a life-threatening infection associated with severe morbidity and high mortality. Conventional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) are usually performed to assess mucormycosis extension, but they may present insufficiencies in their performance. CASE PRESENTATION We present the case of a 13 years old patient with diagnosis of rhino-orbital-cerebral mucormycosis (RCM) who performed head MRI and [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) both for the infection spread assessment and for the early evaluation of response to systemic amphotericin-B treatment. CONCLUSION This case suggests that (18)F-FDG PET/CT could be considered as a valuable tool for the initial staging of RCM when compared with MRI and should be performed as soon as possible after the first clinical suspicion of this disease. In addition (18)F-FDG PET/CT may also be useful for the assessment of response to treatment.

18F-FDG PET/CT in suspected recurrences of epithelial malignant pleural mesothelioma in asbestos-fibers-exposed patients (comparison to standard diagnostic follow-up)

This retrospective study evaluated the role of 18-fluorine-labeled 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with previous occupational or environmental exposure to asbestos, with histopathological diagnosis of epithelial malignant pleural mesothelioma and suspected recurrences, comparing the data from 18F-FDG PET/CT and computed tomography with contrast enhancement (CECT). 18F-FDG PET/CT has greater sensitivity than CECT in identifying local extent, lymph nodes, and metastasis. 18F-FDG PET/CT whole-body explorations are useful to monitor the follow-up and evaluate the metabolic response to chemo- and radiotherapy, modifying the scheduled treatment plan.

Myeloma bone and extra-medullary disease: Role of PET/CT and other whole-body imaging techniques

Multiple myeloma (MM) is the second most common hematological malignancy. Although it can affect different organs, the bone compartment stands out both in terms of prevalence and clinical impact. Despite the striking advances in MM therapy, bone disease can remarkably affect the patients quality of life. The occurrence and extension of bone marrow and extra-medullary involvement should be carefully assessed to confirm the diagnosis, to locate and whenever possible prevent dreadful complications such as pathological fractures and spinal cord compression, and to establish suitable therapeutic measures. Many imaging techniques have been proposed for the detection of MM skeletal involvement. With the development of more sophisticated imaging tools, it is time to use the right technique at the right time. Based on the review of the literature and our own experience, this article discusses advantages and disadvantages of the different imaging methods in the work-up of MM patients, with particular emphasis on the role that PET/CT can play. It is emphasized that whole body low-dose computed tomography should be the preferred imaging technique at baseline. However, bone marrow infiltration and extra-medullary manifestations are better detected by whole body magnetic resonance imaging. Positron emission tomography/computed tomography, on the other hand, combines the benefits of the two mentioned imaging procedures and is particularly useful not only for the detection of osteolytic lesions unrevealed by conventional X-ray, but also in the assessment of prognosis and therapeutic response.

124Iodine: A Longer-Life Positron Emitter Isotope—New Opportunities in Molecular Imaging

124Iodine (124I) with its 4.2 d half-life is particularly attractive for in vivo detection and quantification of longer-term biological and physiological processes; the long half-life of 124I is especially suited for prolonged time in vivo studies of high molecular weight compounds uptake. Numerous small molecules and larger compounds like proteins and antibodies have been successfully labeled with 124I. Advances in radionuclide production allow the effective availability of sufficient quantities of 124I on small biomedical cyclotrons for molecular imaging purposes. Radioiodination chemistry with 124I relies on well-established radioiodine labeling methods, which consists mainly in nucleophilic and electrophilic substitution reactions. The physical characteristics of 124I permit taking advantages of the higher PET image quality. The availability of new molecules that may be targeted with 124I represents one of the more interesting reasons for the attention in nuclear medicine. We aim to discuss all iodine radioisotopes application focusing on 124I, which seems to be the most promising for its half-life, radiation emissions, and stability, allowing several applications in oncological and nononcological fields.

Osteosarcoma of the pelvis: a monoinstitutional experience in patients younger than 41 years.

AIMS AND BACKGROUND Information is scarce on systemic treatment of pelvic osteosarcoma because most chemotherapy protocols for osteosarcoma include patients with extremity tumors and aged up to 30-40 years. METHODS Data on patients <41 years of age with high-grade pelvic osteosarcoma were prospectively collected. Patients received two chemotherapy protocols consisting of methotrexate, cisplatin, doxorubicin (MAP) and standard-dose or high-dose ifosfamide. RESULTS Forty patients between 11 and 36 years were included. The most frequent histological subtype was osteoblastic followed by chondroblastic (37.5%). Complete surgical remission was achieved in 65% of patients. Eighteen patients had MAP/standard-dose ifosfamide, 22 MAP/high-dose ifosfamide. Primary chemotherapy was given to 25 patients and 6 (24%) of them had a good histological response. Median follow-up was 32 months (range, 4-134). Five-year overall survival was 27.5%: 33% in localized and 0 in metastatic patients ( P = 0.02); 45% in patients with complete surgical remission and 0 for patients without complete surgical remission (P = 0.001). Local recurrence rate was 46%. In patients with complete surgical remission, 5-year overall survival was 32% with MAP/standard-dose ifosfamide and 59% with MAP/high-dose ifosfamide regimen (P = 0.3). CONCLUSIONS Local control is the major issue in the treatment of pelvic osteosarcoma. Poor pathological response and high incidence of chondroblastic variant indicate different characteristics between pelvic and extremity osteosarcoma. Chemotherapy with MAP and high-dose ifosfamide might be beneficial in patients with pelvic osteosarcoma and warrants further investigation.

Endovascular treatment of brain arteriovenous malformations ruptured during pregnancy — A report of two cases

Acutely ruptured brain arteriovenous malformations (AVMs) are a known etiology of hemorrhagic stroke during pregnancy. The aim of this paper is to report two cases of patients which presented with ruptured AVMs during pregnancy and were successfully treated with endovascular techniques. Peculiar issues related to the application of this treatment strategy in this category of patients will be discussed as well. To the best of our knowledge, this therapeutic approach in cerebral AVMs ruptured during pregnancy has not been described yet.