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Milano, Italy

Lannering B.,Gothenburg University | Rutkowski S.,University of Hamburg | Doz F.,University of Paris Descartes | Pizer B.,Alder Hey Childrens Hospital | And 20 more authors.
Journal of Clinical Oncology | Year: 2012

Purpose: To compare event-free survival (EFS), overall survival (OS), pattern of relapse, and hearing loss in children with standard-risk medulloblastoma treated by postoperative hyperfractionated or conventionally fractionated radiotherapy followed by maintenance chemotherapy. Patients and Methods: In all, 340 children age 4 to 21 years from 122 European centers were postoperatively staged and randomly assigned to treatment with hyperfractionated radiotherapy (HFRT) or standard (conventional) fractionated radiotherapy (STRT) followed by a common chemotherapy regimen consisting of eight cycles of cisplatin, lomustine, and vincristine. Results: After a median follow-up of 4.8 years (range, 0.1 to 8.3 years), survival rates were not significantly different between the two treatment arms: 5-year EFS was 77% ± 4% in the STRT group and 78% ± 4% in the HFRT group; corresponding 5-year OS was 87% ± 3% and 85% ± 3%, respectively. A postoperative residual tumor of more than 1.5 cm2 was the strongest negative prognostic factor. EFS of children with all reference assessments and no large residual tumor was 82% ± 2% at 5 years. Patients with a delay of more than 7 weeks to the start of RT had a worse prognosis. Severe hearing loss was not significantly different for the two treatment arms at follow-up. Conclusion: In this large randomized European study, which enrolled patients with standard-risk medulloblastoma from more than 100 centers, excellent survival rates were achieved in patients without a large postoperative residual tumor and without RT treatment delays. EFS and OS for HFRT was not superior to STRT, which therefore remains standard of care in this disease. © 2012 by American Society of Clinical Oncology. Source

Massimino M.,Fondazione IRCCS | Massimino M.,Pediatric Oncology Unit | Gandola L.,Fondazione IRCCS | Barra S.,Istituto Tumori | And 21 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: The protocols of the 1990s omitted or delayed irradiation, using upfront chemotherapy to spare the youngest children with ependymoma the sequelae of radiotherapy (RT). We treated 41 children under the age of 3 years with intracranial ependymoma between 1994 and 2003. Patients and Methods: After surgery, chemotherapy was given as follows: regimen I with four blocks of vincristine, high-dose methotrexate 5 g/m2, and cyclophosphamide 1.5 g/m2 alternating with cisplatin 90 mg/m2 plus VP16 450 mg/m2 for 14 months; subsequently, regimen II was used: VEC (VCR, VP16 300 mg/m2, and cyclophosphamide 3 g/m2) for 6 months. Radiotherapy was planned for residual tumor after the completion of chemotherapy or for progression. Results: We treated 23 boys and 18 girls who were a median 22 months old; 14 were given regimen I, 27 were given regimen II; 22 underwent complete resection, 19 had residual tumor. Ependymoma was Grade 2 in 25 patients and Grade 3 in 16; tumors were infratentorial in 37 patients and supratentorial in 4. One child had intracranial metastases; 29 had progressed locally after a median 9 months. Event-free survival was 26% at 3 and 5 years and 23% at 8 years. One child died of sepsis, and another developed a glioblastoma 72 months after RT. Progression-free survival was 27% at 3, 5, and 8 years, and overall survival was 48%, 37%, and 28% at 3, 5, and 8 years, respectively. Of the 13 survivors, 6 never received RT; their intellectual outcome did not differ significantly in those children than in those without RT. Conclusions: Our results confirm poor rates of event-free survival and overall survival for up-front chemotherapy in infant ependymoma. No better neurocognitive outcome was demonstrated in the few survivors who never received RT. © 2011 Elsevier Inc. Source

Numico G.,Medical Oncology | Russi E.G.,S. Croce General Hospital | Colantonio I.,S. Croce General Hospital | Lantermo R.A.,S. Croce General Hospital | And 7 more authors.
Anticancer Research | Year: 2010

Background: Overexpression of epidermal growth factor receptor (EGFR) is related to poor prognosis in patients with head and neck cancer (HNC) treated with surgery or radiotherapy. We assessed the relationship between EGFR status and outcome in patients treated with concurrent chemoradiotherapy. Patients and Methods: Among 149 patients with unresectable HNC treated with chemoradiotherapy, immunohistochemistry was performed on 122 available tumor specimens. The following factors were included in the analysis: age at diagnosis, gender, performance status, site of primary tumor, T- and N-stage, grading, pretreatment, treatment protocol and EGFR staining. Results: Overall, 43/122 (35%) were considered positive. At a median follow-up of 45 months, 5-year survival did not differ between positive and negative cases (42.1% vs. 48.0% respectively: hazard ratio for death 1.23; 95% confidence interval 0.70 to 2.17, p=0.45) nor was 5-year progression-free survival and 5-year locoregional control. Only when a smaller subgroup of tumors showing the strongest EGFR expression was considered, was any difference in 5-year overall survival detected (33.6% vs. 50.1%, p=0.009). Conclusion: EGFR appears to have no prognostic value when chemoradiotherapy is used. Possibly a small subgroup of cases with stronger positivity and worse prognosis can be identified. Source

Volinia S.,University of Ferrara | Volinia S.,Ohio State University | Galasso M.,University of Ferrara | Costinean S.,Ohio State University | And 48 more authors.
Genome Research | Year: 2010

We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most connected miRNAs. hsa-miR-103/106 were downgraded in cancer, whereas hsa-miR-30 became most prominent. Cancer networks appeared as built from disjointed subnetworks, as opposed to normal tissues. A comparison of these nets allowed us to identify key miRNA cliques in cancer. We also investigated miRNA copy number alterations in 744 cancer samples, at a resolution of 150 kb. Members of miRNA families should be similarly deleted or amplified, since they repress the same cellular targets and are thus expected to have similar impacts on oncogenesis. We correctly identified hsa-miR-17/92 family as amplified and the hsa-miR-143/145 cluster as deleted. Other miRNAs, such as hsa-miR-30 and hsa-miR-204, were found to be physically altered at the DNA copy number level as well. By combining differential expression, genetic networks, and DNA copy number alterations, we confirmed, or discovered, miRNAs with comprehensive roles in cancer. Finally, we experimentally validated the miRNA network with acute lymphocytic leukemia originated in Mir155 transgenic mice. Most of miRNAs deregulated in these transgenic mice were located close to hsa-miR-155 in the cancer network. © 2010 by Cold Spring Harbor Laboratory Press. Source

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