F Fossati-Bellani

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Lombardy, Italy

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Publications (96)423.92 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Despite the excellent survival rate of Wilms tumor (WT) patients, only approximately one-half of children who suffer tumor recurrence reach second durable remission. This underlines the need for novel markers to optimize initial treatment. We investigated 77 tumors using Illumina 370CNV-QUAD genotyping BeadChip arrays and compared their genomic profiles to detect copy number (CN) abnormalities and allelic ratio anomalies associated with the following clinicopathological variables: relapse (yes vs. no), age at diagnosis (≤ 24 months vs. >24 months), and disease stage (low stage, I and II, vs. high stage, III and IV). We found that CN gains at chromosome region 1q21.1-q31.3 were significantly associated with relapse. Additional genetic events, including allelic imbalances at chromosome arms 1p, 1q, 3p, 3q, and 14q were also found to occur at higher frequency in relapsing tumors. Interestingly, allelic imbalances at 1p and 14q also showed a borderline association with higher tumor stages. No genetic events were found to be associated with age at diagnosis. This is the first genome wide analysis with single nucleotide polymorphism (SNP) arrays specifically investigating the role of genetic anomalies in predicting WT relapse on cases prospectively enrolled in the same clinical trial. Our study, besides confirming the role of 1q gains, identified a number of additional candidate genetic markers, warranting further molecular investigations.
    Genes Chromosomes and Cancer 03/2012; 51(7):644-53. · 3.55 Impact Factor
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    ABSTRACT: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase predominantly expressed in the developing nervous system. Recently, mutated ALK has been identified as a major oncogene associated with familial and sporadic neuroblastomas (NBL). Yet, a direct correlation between endogenous expression level of the ALK protein, oncogenic potential, and clinical outcome has not been established. We investigated ALK genetic mutations, protein expression/phosphorylation, and functional inhibition both in NBL-derived cell lines and in 34 localized and 48 advanced/metastatic NBL patients. ALK constitutive phosphorylation/activation was observed in high-ALK expressing cells, harboring either a mutated or a wild-type receptor. No activation was found in cell lines with low expression of wild-type ALK. After 72 hours of treatments, small molecule ALK inhibitor CEP-14083 (60 nmol/L) induced growth arrest and cell death in NBL cells overexpressing wild-type (viability: ALK(high) 12.8%, ALK(low) 73%, P = 0.0035; cell death: ALK(high) 56.4%, ALK(low) 16.2%, P = 0.0001) or mutated ALK. ALK protein expression was significantly up-regulated in advanced/metastatic compared with localized NBLs (ALK overexpressing patients: stage 1-2, 23.5%; stage 3-4, 77%; P < 0.0001). Interestingly, protein levels did not always correlate with ALK genetic alterations and/or mRNA abundance. Both mutated and wild-type ALK receptor can exert oncogenic activity in NBL cells. However, wild-type ALK receptor requires a critical threshold of expression to achieve oncogenic activation. Overexpression of either mutated or wild-type ALK defines poor prognosis patients. Alternative mechanisms other than direct mutations and/or gene amplification regulate the ALK level of expression in NBL cells. Wild-type ALK is a potential therapeutic target for advanced/metastatic NBLs.
    Cancer Research 09/2009; 69(18):7338-46. · 8.65 Impact Factor
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    ABSTRACT: Research has identified a growing use of complementary and alternative medicines (CAM) in the pediatric oncology setting and health care professionals should consider how they might interact with and/or be used in lieu of conventional treatment. The present study was designed to establish the prevalence of CAM usage at an Italian pediatric oncology department, and the reasons why patients used these unconventional therapies. This was an observational study involving parents whose children were treated for tumors at the pediatric oncology unit of the Istituto Nazionale Tumori in Milano. Data were collected on their sociodemographic variables and their use of CAM by means of a self-administered questionnaire. We distributed 145 questionnaires and 97 of them (67%) were returned. Judging from this survey, 12.4% of the children used at least one type of CAM and homoeopathy was the most often used. Benefits were reported by 83% of parents. The most common reasons for using CAM were to reduce the side-effects of conventional therapies. The oncologists taking care of the patients were notified of the child's use of CAM in only one case. CAM were used not as a substitute but in addition to conventional treatments. In almost all cases, oncologists were not informed that a child was using CAM, posing a risk of any interaction with pharmacological treatments being inadequately understood.
    Pediatric Blood & Cancer 07/2009; 53(4):599-604. · 2.35 Impact Factor
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    ABSTRACT: Tumor size is a key prognostic variable for soft tissue sarcomas (STS), and a tumor diameter of 5 cm is generally used as a cutoff for risk grouping purposes. This study aimed to investigate the prognostic effect of tumor size on overall survival and whether such an effect was influenced by the patient's size, expressed as body-surface area (BSA), in a series of 553 pediatric patients with localized STS. Multivariable Cox models were used in which the effect of tumor size was adjusted for patients age, tumor site, histologic subtype, and Intergroup Rhabdomyosarcoma Study grouping, and the interaction between size and BSA was included. Tumor size was confirmed as a significant prognostic factor. Interaction between size and BSA meant that, for a given tumor size, the mortality increased from the larger to the smaller BSA. Conversely, the mortality risk associated with a patient with a BSA of 1.75 m(2) and a 5-cm tumor was the same as for a 0.6 m(2) child with a 2.8-cm tumor. Tumor and body size are jointly informative on outcome. The risk associated with a given tumor size is not the same in patients of different body size, so it may be wrong to use the same 5-cm cutoff for tumor size in risk stratification.
    Journal of Clinical Oncology 01/2009; 27(3):371-6. · 18.04 Impact Factor
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    ABSTRACT: With a view to improving the prognosis for patients with metastatic medulloblastoma, we tested the efficacy and toxicity of a hyperfractionated accelerated radiotherapy (HART) regimen delivered after intensive sequential chemotherapy. Between 1998 and 2007, 33 consecutive patients received postoperative methotrexate (8 g/m(2)), etoposide (2.4 g/m(2)), cyclophosphamide (4 g/m(2)), and carboplatin (0.8 g/m(2)) in a 2-month schedule, then HART with a maximal dose to the neuraxis of 39 Gy (1.3 Gy/fraction, 2 fractions/d) and a posterior fossa boost up to 60 Gy (1.5 Gy/fraction,2 fractions/d). Patients with persistent disseminated disease before HART were consolidated with two myeloablative courses and circulating progenitor cell rescue. Patients were classified as having M1 (n = 9), M2 (n = 6), M3 (n = 17), and M4 (n = 1) disease. Seven patients younger than 10 years old who achieved complete response after chemotherapy received a lower dose to the neuraxis (31.2 Gy). Twenty-two of the 32 assessable patients responded to chemotherapy; disease was stable in five patients and progressed in five patients. One septic death occurred before radiotherapy. Eight patients experienced relapse after a median of 12 months. Fourteen of the 33 patients underwent consolidation therapy after HART. With a median 82-month survivor follow-up, the 5-year event-free, progression-free, and overall survival rates were 70%, 72%, and 73%, respectively. No severe clinical complications of HART have emerged so far. HART after intensive postoperative chemotherapy, followed by myeloablative chemotherapy in selected cases, proved feasible in children with metastatic medulloblastoma. The results of our treatment compare favorably with other series treated using conventional therapies.
    Journal of Clinical Oncology 01/2009; 27(4):566-71. · 18.04 Impact Factor
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    ABSTRACT: The WT1 gene plays a crucial role in urogenital and gonadal development. Germline WT1 alterations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms tumor (WT), frequently occurring in combination. We report on a novel WT1 nonsense mutation (c.1105C>T), introducing a premature stop codon in exon 8 (p.Q369X), in a young XY male patient who presented with bilateral cryptorchidism, nystagmus, mild proteinuria and WT, but no sign of severe nephropathy. Although the majority of congenital urogenital abnormalities are not due to constitutional defects of the WT1 gene, our findings provide a rational for considering WT1 mutational analysis as one of the screening options in newborns with congenital defects of the urogenital tract due to the associated high risk of WT.
    Pediatric Nephrology 01/2009; 24(7):1413-7. · 2.94 Impact Factor
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    ABSTRACT: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa (+/- carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few exceptions. A salvage therapy for medulloblastoma after CSI still needs to be sought.
    International journal of radiation oncology, biology, physics 12/2008; 73(5):1358-63. · 4.59 Impact Factor
  • Pediatric Blood & Cancer 07/2008; 50(6):1290-1; author reply 1291-2. · 2.35 Impact Factor
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    ABSTRACT: Patients with diffuse pontine gliomas have a median survival of less than one year and represent a challenge for pediatric oncologists, prompting them to attempt experimental therapies. From 1987 to 2005, 62 children with diffuse pontine glioma, not amenable to curative surgery, were treated according to four successive pilot protocols: (1) concomitant chemo-radiotherapy (etoposide, cytarabine, ifosfamide, cisplatin, and dactinomycin); (2) intensive high-dose courses chemotherapy (cisplatin/etoposide, cyclophosphamide/vincristine/methotrexate) and a subsequent course of myeloablative thiotepa followed by radiation and maintenance chemotherapy; (3) cisplatin/etoposide followed by isotretinoin before, during and after focal irradiation; and (4) iv vinorelbine before, during, and after irradiation. Considering all patients, 77% experienced a transient response to treatment, always detectable after radiotherapy. The progression-free survival (PFS) rate was 25 +/- 6% at one year, median PFS was seven months; overall survival (OS) was 45 +/- 6%, median OS was eleven months: no statistical differences in the four studies in terms of outcome were detected. Despite improved diagnostic, therapeutic, and supportive tools in pediatric neuro-oncology, little has been achieved for patients with diffuse pontine tumors.
    Journal of Neuro-Oncology 06/2008; 87(3):355-61. · 3.12 Impact Factor
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    ABSTRACT: For many years the precise genetic etiology of the majority of Wilms' tumors has remained unexplained. Recently, the WTX gene, mapped to chromosome Xq11.1, has been reported to be lost or mutated in approximately one-third of Wilms' tumors. Moreover, in female cases, the somatically inactivated alleles were found to invariantly derive from the active chromosome X. Consequently, WTX has been proposed as a 'one-hit' tumor suppressor gene. To provide further insights on the contribution of WTX to the development of the disease, we have examined 102 Wilms' tumors, obtained from 43 male and 57 female patients. Quantitative PCR analyses detected WTX deletions in 5 of 45 (11%) tumors from males, whereas loss of heterozygosity at WTX-linked microsatellites was observed in 9 tumors from 50 informative females (19%). However, in the latter group, using a combination of HUMARA assay and bisulfite-modified DNA sequencing, we found that the deletion affected the active chromosome X only in two cases (4%). Sequence analyses detected an inactivating somatic mutation of WTX in a single tumor, in which a strongly reduced expression of the mutant allele respect to the wild-type allele was observed, a finding not consistent with its localization on the active chromosome X. Overall, a functional somatic nullizygosity of the WTX gene was ascertained only in seven of the Wilms' tumors included in the study (approximately 7%). Our findings indicate that previously reported estimates on the proportion of Wilms' tumors due to WTX alterations should be reconsidered.
    Oncogene 05/2008; 27(33):4625-32. · 7.36 Impact Factor
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    ABSTRACT: Brain necrosis or other subacute iatrogenic reactions has been recognized as a potential complication of radiotherapy (RT), although the possible synergistic effects of high-dose chemotherapy and RT might have been underestimated. We reviewed the clinical and radiologic data of 49 consecutive children with malignant brain tumors treated with high-dose thiotepa and autologous hematopoietic stem cell rescue, preceded or followed by RT. The patients were assessed for neurocognitive tests to identify any correlation with magnetic resonance imaging (MRI) anomalies. Of the 49 children, 18 (6 of 25 with high-grade gliomas and 12 of 24 with primitive neuroectodermal tumors) had abnormal brain MRI findings occurring a median of 8 months (range, 2-39 months) after RT and beginning to regress a median of 13 months (range, 2-26 months) after onset. The most common lesion pattern involved multiple pseudonodular, millimeter-size, T1-weighted unevenly enhancing, and T2-weighted hyperintense foci. Four patients with primitive neuroectodermal tumors also had subdural fluid leaks, with meningeal enhancement over the effusion. One-half of the patients had symptoms relating to the new radiographic findings. The MRI lesion-free survival rate was 74%+/-6% at 1 year and 57%+/-8% at 2 years. The number of marrow ablative courses correlated significantly to the incidence of radiographic anomalies. No significant difference was found in intelligent quotient scores between children with and without radiographic changes. Multiple enhancing cerebral lesions were frequently seen on MRI scans soon after high-dose chemotherapy and RT. Such findings pose a major diagnostic challenge in terms of their differential diagnosis vis-à-vis recurrent tumor. Their correlation with neurocognitive results deserves further investigation.
    International Journal of Radiation OncologyBiologyPhysics 04/2008; 70(4):1011-9. · 4.52 Impact Factor
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    ABSTRACT: Hypothyroidism is one of the earliest endocrine effects of craniospinal irradiation (CSI). The effects of radiation also depend on circulating thyroid-stimulating hormone (TSH), which acts as an indicator of thyrocyte function and is the most sensitive marker of thyroid damage. Hence, our study was launched in 1998 to evaluate the protective effect of TSH suppression during CSI for medulloblastoma/primitive neuroectodermal tumor. From Jan 1998 to Feb 2001, a total of 37 euthyroid children scheduled for CSI for medulloblastoma/primitive neuroectodermal tumor underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of CSI. From 14 days before and up to the end of CSI, patients were administered l-thyroxine at suppressive doses; every 3 days, TSH suppression was checked to ensure a value <0.3 mum/ml. During follow-up, blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was considered an increased TSH level greater than normal range. CSI was done using a hyperfractionated accelerated technique with total doses ranging from 20.8-39 Gy; models were used to evaluate doses received by the thyroid bed. Of 37 patients, 25 were alive a median 7 years after CSI. They were well matched for all clinical features, except that eight children underwent adequate TSH suppression during CSI, whereas 17 did not. Hypothyroidism-free survival rates were 70% for the "adequately TSH-suppressed" group and 20% for the "inadequately TSH-suppressed" group (p = 0.02). Thyroid-stimulating hormone suppression with l-thyroxine had a protective effect on thyroid function at long-term follow-up. This is the first demonstration that transient endocrine suppression of thyroid activity may protect against radiation-induced functional damage.
    International Journal of Radiation OncologyBiologyPhysics 10/2007; 69(2):404-10. · 4.52 Impact Factor
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    ABSTRACT: The aim of the study was to determine the activity and toxicity of melphalan as a single agent given in up-front therapy for patients with newly-diagnosed Ewing's family tumours with bone/bone marrow metastases. Nineteen patients were enrolled from 2001 to 2004. The treatment consisted of up-front therapy with melphalan (two courses of 50 mg/m2, 3 weeks apart). The overall rate of response to melphalan (complete response+partial response, according to the RECIST criteria) was 78%. Transient grade 3-4 neutropenia, thrombocytopenia and anaemia were recorded in 97%, 81% and 28% of melphalan courses, respectively. No other relevant toxicities were recorded. Melphalan proved to be active in up-front treatment at non-myeloablative doses, and its toxicity was predictable and manageable. The schedule adopted did not interfere with any further intensive chemotherapy or myeloablative treatment in the majority of cases.
    European Journal of Cancer 04/2007; 43(5):885-90. · 5.06 Impact Factor
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    ABSTRACT: Neither hormone-related nor genetics risk factors have been associated with the development of highly proliferative HER2-positive breast carcinomas. Because the majority of HER2-positive tumors present the amplification of the oncogene, we asked whether genomic instability triggered by irradiation might be involved in the induction of HER2-overexpressing breast carcinomas. Sixty-six infiltrating breast carcinomas from patients treated with radiation therapy for Hodgkin's lymphoma or other pediatric solid tumors and a control series of 61 consecutive sporadic breast tumors were analyzed by immunohistochemistry for HER2 expression with HercepTest. A panel of antibodies against estrogen receptor, progesterone receptor, c-kit, cytokeratin 5/6, p53, and ki67 antigen was also used to identify differentiation subsets and molecular characteristics of the analyzed breast carcinomas. Although no differences between the two tumor series were found with respect to HER2 expression scored 2+ and 3+, the percentage of 3+ HER2-positive tumors was significantly higher in patients irradiated during breast maturation compared with patients irradiated after breast maturation (35.3% versus 12.5%, P = 0.046). In the latter group, 52.5% of the breast carcinomas showed basal-like differentiation (estrogen receptor, progesterone receptor, and HER2 negative) versus only 5.9% in the group irradiated during breast development (P < 0.0001). Analysis adjusted for age confirmed the significant increase in basal-like tumor development in patients irradiated within 4 years of menarche, but also showed that the differences between patients irradiated before and after puberty in HER2 3+ tumor frequencies are due to age-related differences in HER2 3+ tumor onset. Together, our data indicate that the development of HER2-positive tumors correlates with timing rather than type of carcinogenic hits and provide clear evidence that radiation is a risk factor for breast carcinomas showing basal-like differentiation.
    Clinical Cancer Research 02/2007; 13(1):46-51. · 7.84 Impact Factor
  • American Journal of Medical Genetics Part A 02/2007; 143(1):85-8. · 2.30 Impact Factor
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    ABSTRACT: We have previously suggested the transcription factor gene POU6F2 as a novel tumor suppressor involved in Wilms tumor (WT) predisposition. Since WT arises from pluripotent embryonic renal precursors, in this study we analyzed the expression of the murine homolog Pou6f2 during kidney embryogenesis and compared it to that of Wt1, the homolog of WT1, a known WT related gene involved in mesenchyme to epithelium conversion. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) performed for Pou6f2 on kidney specimens from embryos, pups, and adult mice, showed that the Pou6f2 mRNA was more abundant in the earliest analyzed phase of kidney organogenesis (E13) than in more advanced fetal stages and in adult animal. In situ RT-PCR demonstrated that Pou6f2 expression parallels the centripetal differentiation of renal morphogenesis. In addition, in E18 kidney, most structures exhibiting Pou6f2 expression stained positively in immunohistochemistry for the Wt1 protein. Finally, quantitative real-time RT-PCR revealed an overexpression (≥80 times) of POU6F2 compared with normal kidney in 5 of 22 (23%) WTs. The finding of a highly regulated temporal and spatial Pou6f2 expression during renal organogenesis, of its coexpression with Wt1 and of POU6F2 overexpression in a subset of WTs are consistent with a role of POU6F2 in kidney development and provide further support to its involvement in WT.
    Journal of Pediatric Hematology/Oncology 11/2006; 28(12):791-797. · 0.97 Impact Factor
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    ABSTRACT: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial. We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue. Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere in 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively. Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.
    International Journal of Radiation OncologyBiologyPhysics 04/2006; 64(4):1031-7. · 4.52 Impact Factor
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    ABSTRACT: Prior to 1990s, papillary thyroid carcinomas (PTCs) in childhood/adolescence underwent a standard therapeutic approach (total thyroidectomy plus elective neck dissection, followed by radioactive iodine (RAI) ablation), with an overall survival of about 100%. The aim of this study is to outline the possibility of a conservative approach (hemithyroidectomy plus selective neck dissection of clinically involved nodes, followed by TSH-suppressive therapy) in a selected group of patients. From 1968 to 2001, 42 pediatric PTC patients were treated at our institution. Absence of distant metastases and a tumor clinically limited to one lobe were both present in 28 cases that underwent a radical (20 cases) or a conservative (8 cases) surgical approach at the thyroid level. At cervical node level, 10 patients underwent a radical and 32 a conservative surgical approach. Clinicopathologic features at onset, type of therapy (radical vs. conservative), post-operative complications, and outcome till May 31, 2004 were recorded. The impact of the type of surgery on outcome was evaluated. Overall and progression-free survival (PFS) curves were found to be independent of the type of therapy (radical vs. conservative) in subgroups of patients matched for extent of disease at onset. Post-operative complications occurred only with radical surgical approaches. Childhood and adolescence PTCs show a high rate of spread but an excellent outcome independent of the type of therapy (radical vs. conservative). Taking into account the marked responsiveness to TSH-suppression and the complications after radical therapy, in selected cases, a conservative approach should be considered, reserving more aggressive therapies in case of metastases or relapse.
    Pediatric Blood & Cancer 04/2006; 46(3):307-13. · 2.35 Impact Factor
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    ABSTRACT: Survival rates are reportedly excellent for papillary thyroid carcinomas (PTCs) in childhood/adolescence, despite their strong tendency to spread. The aim of this study was to verify this assumption in a single-institution series spanning a 30-year period with a very long follow-up. From 1968 to 2001, 74 cases of thyroid carcinoma were collected. The papillary histological type was confirmed in 42 cases with available slides; we recorded the sex, age at diagnosis, age of menarche, tumor side and size, TNM/pTNM classification, multicentricity, vascular invasion, type of surgery, post-operative complications, post-surgical therapies and outcome up to May 31, 2004. The female/male ratio was 2.2; pT4, pN1 and M1 cases were 52%, 95%, and 12% (four in lungs and one in bone), respectively. Total thyroidectomy was performed in 33 patients, hemithyroidectomy in 8, and a biopsy in 1 inoperable case. Nine patients (21%) relapsed, six in the cervical lymph nodes and three in the lungs. After a median follow-up of 189 months, all patients were alive, two of them with evidence of disease. Overall and progression-free survival curves were independent of sex, age, TNM/pTNM classification, or type of surgery. Overall survival was also independent of recurrence. Unlike its adult counterpart, PTC of childhood and adolescence is a cancer with a high frequency of spread, but an excellent outcome irrespective of sex, age at diagnosis, TNM/pTNM classification, type of surgery, recurrence. Since pediatric PTCs proved highly responsive to hormone manipulation, it is worth considering a different therapeutic approach from adult cases.
    Pediatric Blood & Cancer 04/2006; 46(3):300-6. · 2.35 Impact Factor
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    ABSTRACT: This study aims to describe the clinical features and outcome of pediatric patients with head and neck rhabdomyosarcoma (RMS), which can be divided into parameningeal, orbital, or nonorbital, nonparameningeal. This is a retrospective single-institution analysis. The study was performed at the Istituto Nazionale Tumori, Milan, Italy. The study considered 142 consecutive patients < 21 years treated from 1973 to 2003. Patients were treated using a multimodality approach: complete conservative surgery was performed at diagnosis in only two patients, all patients received chemotherapy, and most (91%) also had radiotherapy. Disease-free survival and overall survival were estimated according to the Kaplan-Meier method. For the series as a whole, the 5-year disease-free and overall surival rates were 49% and 57%, respectively. The 5-year overall survival rate improved over the years from 38% before 1980 to 78% after 1990; it was 44% for parameningeal, 79% for orbital, and 77% for nonorbital, nonparameningeal RMS. The treatment of head and neck RMS is complex and necessarily multidisciplinary. Complete surgery is rarely feasible in the head and neck region. This study confirms that orbital RMS has a favourable outcome, whereas therapeutic results are generally unsatisfactory in parameningeal cases, although recent progress in radiotherapeutic techniques and in the efficacy of chemotherapy would suggest clear improvements in survival.
    The Journal of otolaryngology 03/2006; 35(1):53-9. · 0.50 Impact Factor

Publication Stats

2k Citations
423.92 Total Impact Points


  • 1998–2012
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      • • s.c. Medicina Oncologica 1
      • • s.c. Pediatria Oncologica
      Milano, Lombardy, Italy
  • 2009
    • Istituto di Cura e Cura a Carattere Scientifico Basilicata
      Rionero in Vulture, Basilicate, Italy
  • 2008
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1981–2007
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 2006
    • University of Milan
      Milano, Lombardy, Italy
  • 1972
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy