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Objective To characterize neurological involvement in multisystem inflammatory syndrome in children (MIS-C) related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods Retrospective analysis of the clinical, electroencephalographic, CSF and neuroradiological parameters recorded in seven children (3 males, aged 3–10 years) affected by MIS-C with acute neurological involvement. Results All cases presented acute encephalopathy with drowsiness, irritability, mood deflection and diffuse EEG slowing with periodic posterior complexes. Focal neurological signs, normal brain MRI and CSF, were present in four patients; these patients received intravenous methylprednisolone at 30 mg/kg/day for 3 days. In all cases, the clinical picture rapidly improved in the first three days, and all neurological symptoms and EEG abnormalities disappeared within 10 and 30 days respectively. The severity and duration of the EEG abnormalities was proportional to the extent of the neurological involvement. Conclusions Patients with MIS-C may present acute encephalitis characterized by rapid-onset encephalopathy and EEG abnormalities (slow wave activity and/or epileptic abnormalities), in some cases associated with focal neurological signs that disappear with immunomodulatory therapy. The detection through neurological evaluation of sentinel neurological signs and distinctive EEG patterns documentable at disease onset will allow timely diagnosis and treatment of these cases.

PROCEDURE The survival of children with rhabdomyosarcoma (RMS) has gradually improved as a result of the adoption of multidisciplinary treatments. Dedicated skills and facilities are indispensable and more readily available at reference centers. In this study, we examined the role of centers' experience (based on the number of patients treated) in their management of patients with RMS. METHODS We analyzed 342 patients with localized RMS enrolled in the European RMS 2005 protocol from October 2005 to December 2016 at 31 Italian centers that are part of the Soft Tissue Sarcoma Committee (STSC). We grouped the centers by the number of patients each one enrolled (Group 1: >40; Group 2: 10; and Group 3

ObjectivesAnthracycline cardiotoxicity is an important side-effect in long-term childhood cancer survivors. We evaluated the incidence of and factors associated with anthracycline cardiotoxicity in a population of patients diagnosed with bone or soft tissue sarcoma.Materials and methodsWe retrospectively enrolled patients diagnosed with bone or soft tissue sarcoma, from 1995 to 2011, treated with anthracycline chemotherapy at our Centre and with a follow-up echocardiography carried out ⩾3 years from cardiotoxic therapy completion. Cardiac toxicity was graded using Common Terminology Criteria for Adverse Events version 4.0.ResultsA total of 82 patients were eligible. The median age at treatment was 11.9 years (1.44–18). We evaluated the median cumulative anthracycline dose, age at treatment, sex, thoracic radiotherapy, hematopoietic stem cell transplantation, and high-dose cyclophosphamide treatment as possible risk factors for cardiotoxicity. The median cumulative anthracycline dose was 390.75 mg/m2(80–580). Of the 82 patients, 12 (14.6%) developed cardiotoxicity with grade ⩾2 ejection fraction decline: four patients were asymptomatic and did not receive any treatment; six patients were treated with pharmacological heart failure therapy; one patient with severe cardiomyopathy underwent heart transplantation and did not need any further treatment; and one patient died while waiting for heart transplantation. The median time at cardiac toxicity, from the end of anthracycline frontline chemotherapy, was 4.2 years (0.05–9.6). Cumulative anthracycline dose ⩾300 mg/m2(p 0.04) was the only risk factor for cardiotoxicity on statistical analyses.ConclusionsIn our population, the cumulative incidence of cardiotoxicity is comparable to rates in the literature. This underlines the need for primary prevention and lifelong cardiac toxicity surveillance programmes in long-term childhood cancer survivors.

The term congenital hypopigmentary disorders refers to a wide group of heterogeneous hereditary diseases, clinically characterized by inborn pigmentary defects of the iris, hair, and/or skin. They include Gray Hair Syndromes (GHSs), a rare group of autosomal recessive genodermatosis hallmarked by inborn silvery gray hair. GHSs encompass Griscelli, Chediak–Higashi, Elejalde, and Cross syndromes, which are all characterized by a broad spectrum of severe multisystem disorders, including neurological, ocular, skeletal, and immune system impairment. In this manuscript, we describe in detail the clinical, trichoscopic, and genetic features of a rare case of Griscelli syndrome; moreover, we provide an overview of all the GHSs known to date. Our report highlights how an accurate clinical examination with noninvasive methods, like trichoscopy, may play a crucial rule in diagnosis of rare and potentially lethal genetic syndromes such as Griscelli syndrome, in which timely diagnosis and therapy may modify the clinical course, quality of life, and likelihood of survival.

Lipoblastomas are rare benign mesenchymal tumors that arise from embryonal fat cells.They are usually discovered in infants and children under 3 years of age, and mostly occur in the trunk (from 10 to 60%, depending on the study) and extremities (from 40 to 45%), while head and neck localizations are rare, with only five cases described to date.We report on three cases of lipoblastomas in infants younger than 4 years, with unusual localizations: one intra-abdominal, discovered during a laparotomy for an intussusception; one pelvic, misdiagnosed as an ovarian mass; and one gluteal with a pelvic extension.All children underwent magnetic resonance imaging as preoperative workup. All tumors were completely resected with free surgical margins and ultrasonographic follow-up was uneventful for all patients.

Introduction: Rhabdomyosarcoma is a soft tissue malignant musculoskeletal tumor frequent in children. Biliary duct localization is extremely rare, but it is the most common cause of malignant obstructive jaundice in pediatric patients. Methods: This report describes a series of 10 patients under 18 years of age with biliary tract rhabdomyosarcoma who were enrolled, from 1979 to 2004, in 3 consecutive Italian pediatric cooperative protocols that had been drawn up by the Soft Tissue Sarcoma Committee of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP). Results: Considering initial and delayed surgery, tumor resection was achieved in 7 cases, 3 complete with free margins (2 liver transplants) and 4 with microscopic residual disease. Chemotherapy was given to all patients and radiotherapy to 3. At present, 5 patients survive in complete remission 90-200 months after diagnosis while 4 died of disease progression or relapse and 1 of liver transplant-related complications. Conclusions: Better outcomes in this series were associated with the feasibility of conservative surgery due to the favorable location of the tumor, in particular in the common bile duct. Chemotherapy and radiotherapy might obviate the need for demolitive surgery or liver transplant, which were linked to worse outcomes in our series.

Background Rhabdomyosarcoma (RMS) occurring at nonparameningeal head and neck (NPM-HN) sites carries a better prognosis than parameningeal RMS and some other sites. We analyzed the treatments administered and results obtained in patients with localized NPM-HN RMS, included in the protocols coordinated by the Italian Soft Tissue Sarcoma Committee (STSC), in an effort to identify prognostic factors that could facilitate the tailoring of treatment. Methods Sixty-six patients up to 18 years of age with previously untreated, localized NPM-HN RMS were prospectively registered in three consecutive protocols: RMS79, RMS88, and RMS96. Primary surgery was recommended when complete tumor resection was deemed feasible without mutilations. In other cases, only a biopsy was performed, followed by chemotherapy and delayed surgery and/or radiotherapy (RT). Results NPM-HN RMS showed favorable characteristics: 72.7% were

Many types of dorsal neoplasm of early infancy are described in literature ranging from benign to aggressive. Some are more common while others quite unusual. Here, we describe a newborn with a lumbosacral soft tissue mass. Positivity of S-100 and vimentin was compatible with the neural cell line and the high proliferation rate of major activity cells (biopsy Ki67 20%) suggests an aggressive nature. An exclusively surgical approach was chosen and no clinical or radiological signs of recurrence have been observed after 2 years of follow-up. This case is atypical for location, histological pattern, radiological aspect, and clinical behavior. Diagnosis is hard to define and limited to a mesenchymal neoplasia with myxoid tracts. The described aspects raise concerns about clinical and therapeutic approach, classification, and radiological follow-up of sacral tissue masses in newborns.

Background Gastrointestinal (GI) carcinomas are very rare in the pediatric and adolescent age range. We report the clinical features, treatment, and outcome of a series of children and adolescents with GI carcinoma prospectively registered in the Italian Tumori Rari in Eta Pediatrica (TREP) project. Methods The TREP project developed diagnostic and therapeutic guidelines based on recommendations currently in use for adults. Clinical data were centrally registered and reviewed. Results Fifteen patients were registered over the years 2000–2016. Most of the tumors were colorectal carcinomas (12 cases). All but one patient had advanced-stage disease (American Joint Committee on Cancer stages III–IV), and the majority of patients had aggressive histological subtypes, i.e. poorly differentiated (G3) (five patients), mucinous (four patients), and signet ring (two patients) adenocarcinomas. Surgery was performed in 13 of 15 patients, and was radical in nine of 13 patients. Only one patient received postoperative radiotherapy. All patients received chemotherapy, with the addition of bevacizumab in two cases. Nine patients were still alive at the time of the present report, but two of them had only just completed their treatment program and one patient is still on treatment. Six patients died due to disease progression. Conclusions This prospective report on pediatric GI tract carcinomas confirms the rarity and biological aggressiveness of these diseases in pediatric and adolescent age. Further prospective studies are needed to explore the distinct biology of tumor in this age group in order to find new therapeutic targeted agents.

Background The management of children with cancer during the end-of-life (EOL) period is often difficult and requires skilled medical professionals. Patients with tumors of the central nervous system (CNS) with relapse or disease progression might have additional needs because of the presence of unique issues, such as neurological impairment and altered consciousness. Very few reports specifically concerning the EOL period in pediatric neuro-oncology are available. Procedure Among all patients followed at our center during the EOL, we retrospectively analyzed data from 39 children and adolescents with brain tumors, in order to point out on their peculiar needs. Results Patients were followed-up for a median time of 20.1 months. Eighty-two percent were receiving only palliative therapy before death. Almost half the patients (44%) died at home, while 56% died in a hospital. Palliative sedation with midazolam was performed in 58% of cases; morphine was administered in 51.6% of cases. No patient had uncontrolled pain. Conclusions The EOL in children with advanced CNS cancer is a period of active medical care. Patients may develop complex neurological symptoms and often require long hospitalization. We organized a network-based collaboration among the reference pediatric oncology center, other pediatric hospitals and domiciliary care personnel, with the aim to ameliorate the quality of care during the EOL period. In our cohort, palliative sedation was widely used while no patients died with uncontrolled pain. A precise process of data collection and a better sharing of knowledge are necessary in order to improve the management of such patients. Pediatr Blood Cancer 2014;61:2004–2011. © 2014 Wiley Periodicals, Inc.

Patients with diffuse intrinsic pontine glioma (DIPG) have a very poor prognosis. Only radiotherapy (XRT) has proven to be effective in delaying the disease progression. Several chemotherapy schedules have been applied so far, but none demonstrated significant improvements in progression and survival. We retrospectively analyzed the clinical data of children diagnosed with DIPG at our center (Pediatric Hospital “Regina Margherita,” Turin, Italy) between 1999 and 2013. Progression-free survival (PFS) and overall survival (OS) were used to describe the outcomes. Twenty-four children were included in our report. Patients diagnosed before March 2003 (n = 12) were treated with XRT and vincristine (VCR); the remaining 12 patients received XRT and temozolomide (TMZ). Progression-free survival was 18.8 % at 1 year (SE = 7.6 %), while overall survival was 44.1 % at 1 year (SE = 9.9 %). Median PFS was 8.1 months, whereas median OS was 11.2 months. No statistically significant difference in PFS or OS was evidenced between the two treatment groups. Radiotherapy followed by VCR or TMZ allows obtaining results that are in line with previous reports, with no advantages over other similar treatment schedules. DIPGs are challenging tumors with a dismal outcome. Further research and newer therapies are urgently needed in order to achieve improvements in survival.

Pazopanib is an oral multikinase inhibitor that has proved effective in adults treated for relapsing soft tissue sarcoma and synovial sarcoma in particular. Two cases are reported here of pediatric patients with pretreated relapsing synovial sarcoma whose tumors showed a prolonged response to pazopanib given on compassionate grounds. These results suggest that new agents found effective in adult patients might achieve similar results in adolescents with the same disease. Facilitating the availability of new drugs for children and adolescents is a major challenge for pediatric oncologists.

Ependymomas are glial tumours representing approximately 5-10% of all intracranial tumours and are the third most common primary brain tumour in childhood. Only a few karyotypic studies on paediatric ependymomas have been published and no specific chromosomal aberration has been specifically related to this type of cancer. We performed cytogenetic analysis of an ependymoma in an 11-year-old boy. Our patient showed a complex karyotype, characterized by a near-tetraploidy and a sole structural unbalanced aberration: der(2)t(2;11)(q11.2;q13.1), which has not been described before. We here discuss such cytogenetic findings, comparing our data with those reported in the literature.

Hepatoblastoma (HB) is the most common liver cancer in infants younger than 3 years. Its onset has been associated with other genetic syndromes and some genetic and biochemical markers has been identified recently in this neoplasia. Nevertheless the patients have a poor prognosis and the resection or transplantation remains the only effective therapeutic approach. The identification of non-invasive markers may represent an innovative approach and may contribute to a more accurate histological classification of this tumor. We previously demonstrated that some microRNAs are helpful in discriminating HB from hepatocellular carcinoma. In this study, we describe the involvement of the two forms of microRNA-483 (-3p and -5p) in a selected cohort of HB patients who underwent surgical resection or liver transplantation. Differently from other liver diseases we observed that the quantitative expression of the two forms did not significantly changed among patients. Furthermore, 3p/5p ratio was different between HB and non-HB samples, being positive in the latter and negative in HB samples. Influence of concomitant treatments in the expression of miR-483 (i.e. chemotherapy, and immunosuppressive drugs) was also evaluated and no changes were found in the follow-up. In conclusion the expression and function of miR-483-3p/5p in HB still remains unclear and further studies are needed to elucidate the possible mechanisms that regulate the different strand selection between the two forms of microRNA-483 in patients affected by HB. We deem that the analysis of microRNA-483 different forms could be useful for the molecular identification of HB patients and the discrimination with non-HB patient.

A case of Schinzel-Giedion syndrome, a rare malformation syndrome, is described. In addition to the classic features of the syndrome, the patient had a malignant sacrococcygeal teratoma and agenesis of the corpus callosum. So far, this patient is the fifth case with a sacrococcygeal tumor and the eighth with anomalies of the corpus callosum. According to this occurrence of uncommon tumors, risk of malignancy could be a component of Schinzel-Giedion syndrome.

Background Pediatric nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) may rarely occur in visceral tissues, and little is known about their clinical history. The present study retrospectively analyzed a group of patients prospectively registered in Italian pediatric protocols conducted between 1979 and 2004. Methods Inclusion criteria for the study were as follows: a pathological diagnosis of “adult-type NRSTS,” arising at visceral sites (lung-pleurae, liver, kidney, and mesentery-bowel); age under 18 years; no previous treatment except for primary surgery; available clinical data; and written consent. Results Thirty cases with visceral NRSTS were collected and analyzed. Sites of origin were as follows: mesentery-bowel in 12 cases, lung-pleurae in 11, liver in 5, and kidney in 2. According to the Intergroup Rhabdomyosarcoma Study (IRS) surgical grouping system, patients were classified as follows: nine IRS group I, three group II, 12 group III, and six group IV. Patients were treated with a multimodal approach including surgery, radiotherapy, and/or chemotherapy, according to their characteristics. For the series as a whole, the 5-year event-free and overall survival rates were 33.3% and 40.0%, respectively. The IRS group (reflecting the feasibility of initial complete resection) emerged as the main prognostic factor. Survival rates also correlated with tumor size and local invasiveness, histological subtype, and tumor sites (the worst outcome was seen for tumors arising in the lung and pleurae). Conclusions This study confirmed that visceral NRSTS are aggressive tumors carrying a worse prognosis than pediatric NRSTS arising in soft tissues of the extremities. Local treatment remains the main challenge for these tumors.

The management of children with cancer during the end-of-life (EOL) period is often difficult and requires skilled medical professionals. Patients with tumors of the central nervous system (CNS) with relapse or disease progression might have additional needs because of the presence of unique issues, such as neurological impairment and altered consciousness. Very few reports specifically concerning the EOL period in pediatric neuro-oncology are available.Among all patients followed at our center during the EOL, we retrospectively analyzed data from 39 children and adolescents with brain tumors, in order to point out on their peculiar needs.Patients were followed-up for a median time of 20.1 months. Eighty-two percent were receiving only palliative therapy before death. Almost half the patients (44%) died at home, while 56% died in a hospital. Palliative sedation with midazolam was performed in 58% of cases; morphine was administered in 51.6% of cases. No patient had uncontrolled pain.The EOL in children with advanced CNS cancer is a period of active medical care. Patients may develop complex neurological symptoms and often require long hospitalization. We organized a network-based collaboration among the reference pediatric oncology center, other pediatric hospitals and domiciliary care personnel, with the aim to ameliorate the quality of care during the EOL period. In our cohort, palliative sedation was widely used while no patients died with uncontrolled pain. A precise process of data collection and a better sharing of knowledge are necessary in order to improve the management of such patients.

Background. In this study we retrospectively evaluated if18F-FDG-PET/CT provided incremental diagnostic information over CI in a group of hepatoblastoma patients performing restaging.Procedure. Nine patients (mean age: 5.9 years; range: 3.1–12 years) surgically treated for hepatoblastoma were followed up by clinical examination, serumα-FP monitoring, and US. CI (CT or MRI) and PET/CT were performed in case of suspicion of relapse. Fine-needle aspiration biopsies (FNAB) were carried out for final confirmation if the results of CI, PET/CT, and/orα-FP levels were suggestive of relapse. PET/CT and CI findings were analyzed for comparison purposes, using FNAB as reference standard.Results.α-FP level was suggestive of disease recurrence in 8/9 patients. Biopsy was performed in 8/9 cases. CI and PET/CT resulted to be concordant in 5/9 patients (CI identified recurrence of disease, but18F-FDG-PET/CT provided a better definition of disease extent); in 4/9 cases, CI diagnostic information resulted in negative findings, whereas PET/CT correctly detected recurrence of disease.18F-FDG-PET/CT showed an agreement of 100% (8/8) with FNAB results.Conclusions.18F-FDG-PET/CT scan seems to better assess HB patients with respect to CI and may provide incremental diagnostic value in the restaging of this group of patients.

Summary Background Prognostic factors have been studied in patients with rhabdomyosarcoma in general, but little is known about prognostic factors in the subgroup of patients with bladder/prostate rhabdomyosarcoma (BP-RMS) requiring salvage surgery after failure of chemotherapy ± radiotherapy to achieve local control. We reviewed the 28-year Italian experience with BP-RMS requiring salvage surgery after failure of nonsurgical management indicated by evidence of disease persistence after chemotherapy ± radiotherapy. Our hypothesis was that the same variables identified as prognostic factors in the general population with RMS could have prognostic value in this subgroup. Method Between 1986 and 2014, 108 patients with a histological diagnosis of BP-RMS were registered into three consecutive protocols. Patients undergoing salvage surgery after failure of chemotherapy ± radiotherapy and follow-up >5 years were considered for study. Variables related to the patient, to treatment, and to the surgical specimen were compared using the log-rank test in patients who achieved and failed to achieve 5-year progression-free survival (5-yr PFS). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated for significant variables. Results Of the 108 patients enrolled in the protocols, 33 (30.6%) underwent salvage surgery and 26 matched study criteria. Seventeen patients were disease-free after a median follow-up of 125 months (range 65.5–311.7 months), 5-yr PFS 65.4%. Nine events were registered after a median follow-up of 5.4 months (range 1.9–27.5 months). Among the variables assessed (Table), only an undifferentiated histology proved to be significantly associated with a poorer 5-yr PFS, whereas a tumor size above 5 cm in the removed specimen approached significance. The OR (95% CI) for failure of 5-yr PFS was 28 (2.4–326.8) and 8.3 (1.03–67.1), respectively. Conclusion 5-yr PFS proved unrelated to excision margins of the surgical specimen, that is on whether there was evidence of microscopic residues left behind during surgery. These data suggest that the outcome is more influenced by the biological properties of the tumor. If small foci of differentiated cells are left behind, these probably do not compromise final prognosis. In our patients requiring salvage bladder-prostate surgery after failure of chemotherapy ± radiotherapy, long-term progression-free survival seemed unrelated to patient/tumor characteristics at presentation and preoperative management. Regarding the characteristics of the removed specimen, instead, an undifferentiated tumor histology and a diameter of the removed tumor >5 cm negatively influenced prognosis, whereas the presence of positive excision margins did not. PFS >5 years n/N (%) p Variables at diagnosis Age at diagnosis 14/20 (70) 0.4 >5 years 3/6 (50) Gender Male 12/20 (60) 0.3 Female 5/6 (83) Histology on initial biopsy Embryonal 9/16 (56) 0.1 Botryoid 8/9 (89) Tumor location Prostate 4/7 (57) 0.6 Bladder 11/15 (73) Bladder-prostate 2/4 (50) Tumor size 5/7 (71) 0.7 >5 cm 12/19 (63) T-stage T1 7/10 (70) 0.7 T2 10/16 (62.5) Treatment variables Treatment protocol RMS 88 5/7 (71.5) 0.5 RMS 96 4/8 (50) RMS 2005 6/8 (75) Tumor response at 9 weeks Complete response (CR) 0/1 (0) 0.4 Partial response (PR) > 2/3 9/13 (69) Minor response (MR) > 1/3 but 4/7 (57) No response or stable disease (SD) 4/4 (100) Preoperative radiotherapy No 8/12 (67) 1 Yes 9/14 (64) Pathology variables Tumor location on surgical specimen Prostate 5/8 (62.5) 0.1 Bladder 11/14 (78.5) Bladder-prostate 1/4 (25) Surgical margins Negative 7/12 (58) 0.1 Positive 7/8 (87.5) Diameter of tumor at the surgical specimen 10/12 (83) 0.06 >5 cm 3/8 (37) Histological differentiation Differentiated 11/13 (84.5) 0.002 Undifferentiated 1/7 (14) Myxoid 3/4 (75)

BACKGROUND: Nasopharyngeal carcinoma (NPC) is very rare in childhood. It differs from its adult counterpart in the prevalence of the nonkeratinizing, undifferentiated subtype and by an advanced clinical stage at onset and better chances of survival. The risk of long-term treatment-related toxicity also may be a more important issue in younger individuals. METHODS: A prospective chemoradiotherapy protocol for pediatric NPC was started in Italy in 2000 within the framework of the Rare Tumors in Pediatric Age (TREP) project. Three courses of cisplatin/5-fluorouracil induction chemotherapy were followed by radiotherapy (doses up to 65 grays) with concomitant cisplatin. RESULTS: Forty-six patients (ages 9-17 years) were considered eligible for the study over a 10-year period. The ratio of observed to expected cases based on epidemiological data was approximately 1 for both children and adolescents. All but 1 patient had lymph node involvement, and 5 patients had distant metastases. The rate of response to primary chemotherapy was 90%. The 5-year overall and progression-free survival rates were 80.9% and 79.3%, respectively (median follow-up, 62 months). The only statistically significant prognostic variable was the presence or absence of distant metastases. A 65% incidence of late sequelae was reported. CONCLUSIONS: This study demonstrates the feasibility and efficacy of a prospective protocol even for such rare tumors as pediatric NPC. The use of lower radiotherapy doses than those used in adults did not affect locoregional failure rates. Long-term follow-up will be needed to obtain more information on both survival and treatment sequelae. The next objective will be to establish broader, international prospective cooperation schemes. Cancer 2011. © 2011 American Cancer Society.

Medulloblastoma (MB) is the most common malignant brain tumor of childhood. We have investigated for novel chromosomal imbalances and prognostic markers of pediatric MB. Forty MBs out of 64, were analyzed using high resolution prometaphase comparative genomic hybridization. Chromosome 10q26.1-q26.3 loss combined with 17q24.3-q25.3 gain and/or 7q34-q36.3 gain in tumors predicted poor patient's survival. A minimal deleted region of 14.12cM at 10q26.1-q26.3 was refined by LOH analysis. We propose a new prognostic marker for pediatric MB patient risk stratification based on the presence of 10q26.1-q26.3 loss plus 17q24.3-q25.3 gain and/or 7q34-q36.3 gain associations.

Beckwith-Wiedemann syndrome is an overgrowth disorder characterized by neonatal macrosomia, abdominal wall defects, macroglossia, renal anomalies, organomegaly, hypoglycemia, and cancer predisposition. Hepatoblastoma is the second most frequent tumor and periodic serum alpha-fetoprotein (αFP) dosage is the cornerstone of the tumor surveillance for its early detection. In this report, we describe the outstanding case of a Beckwith-Wiedemann syndrome (BWS) newborn with severe phenotype and paternal chromosome 11 uniparental disomy (UPD11) associated with a high tumor risk. Based on the clinical picture and previous reports, a close monitoring of αFP was commenced. The marker was normal immediately after birth, but rapidly raised in 20 days, leading to the diagnosis of an extremely aggressive hepatoblastoma. The latter was successfully treated with pre-surgical reductive chemotherapy, gross total mass resection, and subsequent chemotherapy. Based on this observation, the tumor surveillance routinely suggested every 3 months should be more intense and with closer time intervals in newborns with severe BWS phenotype. We suggest monitoring neonatal αFP every 20 days in such cases.

Aim The RMS4.99 study was designed to explore the role of multiple sequential high-dose chemotherapy cycles administered early in the treatment of children with metastatic rhabdomyosarcoma. Patients and methods Seventy patients were enrolled and received three cycles of initial standard chemotherapy, followed by a course of cyclophosphamide and etoposide to obtain peripheral blood stem cells (PBSC), then three consecutive high-dose combinations followed by PBSC rescue. This was followed by surgery and/or radiotherapy, after which a final maintenance treatment with six courses of vincristine, actinomycin D and cyclophosphamide was administered. Results Sixty-two patients underwent the high-dose chemotherapy phase. The 3-year overall survival (OS) and progression free survival (PFS) rates for the 70 patients were 42.3% (95% confidence interval [CI] 39.5–53.6) and 35.3% (95% CI, 24.3–46.5), respectively. By multivariate analysis survival correlated strongly with age > 10 years. In a subset of patients with only one or no unfavourable prognostic factors (age > 10 years, unfavourable site of primary tumour, bone or bone marrow involvement and number of metastatic sites >2) the PFS was significantly higher, i.e. 60.5% at 3 years. Conclusion Our study confirms that patients with favourable prognostic characteristics have a better survival. The use of sequential cycles of high-dose chemotherapy did not appear of benefit for patients with metastatic rhabdomyosarcoma.

Brainstem tumors (BSTs) are usually gliomas and are divided into diffuse BSTs (DBSTs) and focal BSTs (FBSTs). The aim of this study is to investigate the different outcomes of these two entities.Thirty-one patients with BSTs were admitted to our institution from 1995 to 2003. Patients with DBSTs were treated with locoregional radiotherapy (1.8 Gy/day for 54 Gy) and weekly vincristine for radiosensitization (1.5 mg/sm for six total doses). Patients with FBSTs underwent surgical resection. Chemotherapy and/or radiotherapy were considered in progression.Fourteen patients were diagnosed as having DBSTs. The responses to treatment were ten cases of partial response, three of stable disease, and one of progressive disease. General and/or neurological symptoms improved in more than 80% of patients. The median time from diagnosis to progression and to death were, nonetheless, 8 (range of 3-13) and 13 (range of 4-25) months, respectively, with a 2-year overall survival rate of 12.3% [standard error (SE) 11.2]. Seventeen patients were diagnosed as having FBSTs. Gross total removal was achieved in 4/17 cases, subtotal removal in 7/17, and partial removal in 6/17. There was one surgery-related death. Eight out of 17 patients had adjuvant chemo- and/or radiotherapy after progression: 6/8 are without neurological symptoms and 2/8 have died due to tumor progression. The 4-year overall and disease-free survival rates are 87.4 (SE 8.4) and 58.8% (SE 11.9), respectively, the extent of resection being the most important prognostic factor (p=0.012). DBSTs continue to carry a dismal prognosis, thus demanding new treatment modalities; FBSTs can be treated surgically and patients benefit from a better prognosis.

In this study the authors retrospectively evaluated the feasibility and effectiveness of prolonged oral etoposide therapy in children with recurrent ependymoma. Twelve ependymoma patients with documented recurrent or persistent disease were treated between May 1998 and October 2003. All patients were treated monthly with oral VP-16 administered at a dose of 50 mg/m2/d for 21 days, with a 7-day interval between cycles, for a planned minimum number of six cycles. Response (complete plus partial) after two cycles occurred in 5 of the 12 patients (41.6%). Response plus stable disease occurred in 10 of the 12 (83.3%), with a median duration of response or stable disease of 7 months (range 4-30). The median survival was 7 months; the 2-year progression-free survival was 16.7%. These results emphasize that oral etoposide is an attractive option for childhood recurrent ependymomas in terms of administration, tolerability, and neuroradiologic response.

Medulloblastoma (MB) is one of the most aggressive pediatric brain tumor. We report genome-wide pooled-analysis of classic MB variant of patients over 3 years of age at diagnosis. We combined array comparative genomic hybridization (aCGH) results from experimental analysis (31 cases) with two public databases (55 cases) in a final evaluation of 86 MBs. The most common chromosome structural aberrations were gains of 17q (45.3%), 1q (22.1%), and losses of 8p (15.1%), 10q (19.8%), 17p (37.2%), and 16q (16.3%). Isochromome (17q) was observed in 29.1% MBs. A significant association between poor patients survival and losses of 9q (p