Irinotecan and temozolomide in recurrent Ewing sarcoma: an analysis in 51 adult and pediatric patients.

BACKGROUND: Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited. METHODS: Patients receiving TEM 100 mg/m2/day oral, and IRI 40 mg/m2/day intravenous, days 1-5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed. RESULTS: The median age of the 51 patients was 21 years (range 3-65 years): 34 patients (66%) were adults (≥18 years of age), 24 (48%) had ECOG 1 and 35 (69%) were presented with multiple site recurrence. TEMIRI was used at first relapse/progression in 13 (25%) patients, while the remainder received TEMIRI for second or greater relapse/progression. Fourteen (27%) patients had received prior myeloablative therapy with busulfan and melphalan. We observed five (10%) CR, 12 (24%) PR and 19 (37%) SD, with a DCR of 71%. 6-mos PFS was 49% (95% CI 35-63) and it was significantly influenced by ECOG (6-mos PFS 64% [95% CI 45-83] for ECOG 0, 34% [95% CI 14-54] for ECOG ≥1; p = .006) and LDH (6-mos PFS 62% [95% CI 44-79] for normal LDH, 22% [95% CI 3-42] for high LDH; p = .02), with no difference according to line of treatment, age and metastatic pattern. One-year OS was 55% (95% CI 39-70), with RECIST response (p = .001) and ECOG (p = .0002) independently associated with outcome. Grade 3 and 4 toxicity included neutropenia in 12% of patients, thrombocytopenia in 4%, diarrhea in 4%. CONCLUSIONS: This series confirms the activity of TEMIRI in both adults and pediatric patients. This schedule offers a 71% DCR, independently of the line of chemotherapy. Predictive factors of response are ECOG and LDH.

Two-stage phase II study of imatinib mesylate in subjects with refractory or relapsing neuroblastoma.

BACKGROUND: Cure rate for subjects with refractory or relapsing metastatic neuroblastoma is <5%. In the search for a novel therapy, continuous daily oral administration of imatinib mesylate was evaluated. PATIENTS AND METHODS: Twenty-four subjects were enrolled in a two-stage study. Imatinib was administered for the first 4 weeks (cycle) at 170 mg/sqm b.i.d. If no major toxicity occurred, the dose was escalated to 300 mg/sqm b.i.d. for a maximum of 12 cycles. Clinical response and toxicity were evaluated according to international criteria. Pharmacokinetics (PK) profiles and tyrosine hydroxylase (TH) mRNA expression were also determined in a subset of subjects. RESULTS: Five (21%) complete responses, with one subject still alive at 68 months, and 2 (8%) partial responses lasting up to 29 months were obtained. No grade 4 toxicity was observed. At steady-state, PK exposure (69.7 µg h/ml) was similar to that of adults receiving 1000 mg/die. Responses appear to correlate with the absence or presence of metastasis in the bone marrow (BM) alone, with low TH expression levels at study entry and low imatinib exposure. CONCLUSIONS: Imatinib mesylate was well-tolerated and effective in the subset of subjects with low BM infiltration as only site of metastasis. Study identifier EudraCT: 2005-005778-63.

Primary metastatic Ewing's family tumors: results of the Italian Sarcoma Group and Scandinavian Sarcoma Group ISG/SSG IV Study including myeloablative chemotherapy and total-lung irradiation.

BACKGROUND: The Italian Sarcoma Group and the Scandinavian Sarcoma Group designed a joint study to improve the prognosis for patients with Ewing's family tumors and synchronous metastatic disease limited to the lungs, or the pleura, or a single bone. PATIENTS AND METHODS: The study was opened in 1999 and closed to the enrollment in 2008. The program consisted of intensive five-drug combination chemotherapy, surgery and/or radiotherapy as local treatment, and consolidation treatment with high-dose busulfan/melphalan plus autologous stem cell rescue and total-lung irradiation. RESULTS: During the study period, 102 consecutive patients were enrolled. The median follow-up was 62 months (range 24-124). The 5-year event-free survival probability was 0.43 [standard deviation (SD) = 0.05] and the 5-year overall survival probability was 0.52 (SD = 0.052). Unfavorable prognostic factors emerging on multivariate analysis were a poor histological/radiological response at the site of the primary tumor [relative risk (RR) = 3.4], and incomplete radiological remission of lung metastases after primary chemotherapy (RR = 2.6). One toxic death and one secondary leukemia were recorded. CONCLUSIONS: This intensive approach is feasible and long-term survival is achievable in ∼50% of patients. New treatment approaches are warranted for patients responding poorly to primary chemotherapy.

Nonmetastatic Ewing family tumors: high-dose chemotherapy with stem cell rescue in poor responder patients. Results of the Italian Sarcoma Group/Scandinavian Sarcoma Group III protocol.

BACKGROUND: High-dose chemotherapy (HDT) was added to conventional chemotherapy in Ewing sarcoma family tumor (EFT) patients, poor responders (PRs) to induction chemotherapy in order to improve their survival. PATIENTS AND METHODS: Patients aged ≤40 years with nonmetastatic Ewing sarcoma (ES) received vincristine (V), doxorubicin (A), cyclofosfamide (C), actinomycin (Ac), ifosfamide (I) and etoposide (E) (VACAc-IE regimen) as induction chemotherapy. As maintenance treatment, good responders (GR) received nine cycles of VACAc-IE regimen. PRs received three cycles of VAC-IE, mobilizing cycle with CE and HDT with Busulfan and Melphalan with stem cell support. RESULTS: Three hundred patients [median age 15 years (3-40 years)] entered the study. One patient refused local treatment, 242 (81%) underwent surgery [with radiotherapy (RT) in 80] and 57 (19%) RT alone. No toxic deaths were recorded. Overall GR were 146 (49%). Twenty-eight PR did not receive HDT. At a median follow-up of 64 months (21-116 months), 5-year overall and event-free survival (EFS) were 75% and 69%, respectively. Five-year EFS was 75% for GR, 72% for PR treated with HDT and 33% for PR who did not receive HDT. CONCLUSIONS: High-dose therapy added to the VACA-IE regimen in PR patients is feasible and effective. Selected groups of patients with ES can benefit from HDT.

Central nervous system relapse in high-risk stage 4 neuroblastoma: The HR-NBL1/SIOPEN trial experience.

BACKGROUND: There is rising concern on the impact of new strategies, such as high-dose chemotherapy (HDC) and immunotherapy, on the pattern of relapse in high-risk neuroblastoma (HR-NBL). Our aim is to evaluate the incidence and identify risk factors for first recurrence in the central nervous system (CNS) in HR-NBL. PATIENTS AND METHODS: Data from patients with stage 4V HR-NBL included from February 2002 to June 2015 in the prospective HR-NBL trial of the European International Society of Pediatric Oncology Neuroblastoma Group were analysed. Characteristics at diagnosis, treatment and the pattern of first relapse were studied. CNS imaging at relapse was centrally reviewed. RESULTS: The 1977 included patients had a median age of 3 years (1 day-20 years); 1163 were boys. Among the 1161 first relapses, 53 were in the CNS, with an overall incidence of 2.7%, representing 6.2% of all metastatic relapses. One- and three-year post-relapse overall survival was 25 ± 6% and 8 ± 4%, respectively. Higher risk of CNS recurrence was associated with female sex (hazard ratio [HR] = 2.0 [95% confidence interval {CI}: 1.1-3.5]; P = 0.016), MYCN-amplification (HR = 2.4 [95% CI: 1.2-4.4]; P = 0.008), liver (HR = 2.5 [95% CI: 1.2-5.1]; P = 0.01) or >1 metastatic compartment involvement (HR = 7.1 [95% CI: 1.0-48.4]; P = 0.047) at diagnosis. Neither HDC nor immunotherapy was associated with higher risk of CNS recurrence. Stable incidence of CNS relapse was reported over time. CONCLUSIONS: The risk of CNS recurrence is linked to both patient and disease characteristics, with neither impact of HDC nor immunotherapy. These findings support the current treatment strategy and do not justify a CNS prophylactic treatment.

Skip pattern approach toward the early access of innovative anticancer drugs.

BACKGROUND: With the rapid development of innovative anticancer treatments, the optimization of tools able to accelerate the access of new drugs to the market by the regulatory authority is a major issue. The aim of the project was to propose a reliable methodological pathway for the assessment of clinical value of new therapeutic innovative options, to objectively identify drugs which deserve early access (EA) priority for solid and possibly in other cancer scenarios, such as the hematological ones. MATERIALS AND METHODS: After a comprehensive review of the European Public Assessment Report of 21 drugs, to which innovation had previously been attributed by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA), an expert panel formulated an algorithm for the balanced use of three parameters: Unmet Medical Need (UMN) according to AIFA criteria, Added Benefit (AB) according to the European Society for Medical Oncology's Magnitude of Clinical Benefit Scale (ESMO-MCBS) criteria and Quality of Evidence (QE) assessed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) method. By sequentially combining the above indicators, a final priority status (i.e. EA or not) was obtained using the skip pattern approach (SPA). RESULTS: By applying the SPA to the non-curative setting in solid cancers, the EA status was obtained by 5 out of 14 investigated drugs (36%); by enhancing the role of some categories of the UMN, additional 4 drugs, for a total of 9 (64%), reached the EA status: 2 and 3 drugs were excluded for not achieving an adequate score according to AB and QE criteria, respectively. For hematology cancer, only the UMN criteria were found to be adequate. CONCLUSIONS: The use of this model may represent a reliable tool for assessment available to the various stakeholders involved in the EA process and may help regulatory agencies in a more comprehensive and objective definition of new treatments' value in these contexts. Its generalizability in other national contexts needs further evaluation.

Efficacy of topotecan plus vincristine and doxorubicin in children with recurrent/refractory rhabdomyosarcoma.

BACKGROUND: This study investigates the efficacy and the feasibility of a chemotherapy regimen with topotecan plus vincristine and doxorubicin (TVD) given on an individually tailored basis to patients with refractory/recurrent rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Nine patients received TVD therapy at relapse, and six were assessable for response. RESULTS: All the six patients experienced objective response after two cycles of chemotherapy: one minor response, four partial response, and one complete response. CONCLUSIONS: The value of our study is severely limited by the small number of cases, the single-institutional setting and the individually tailored treatment, but we nonetheless confirmed the feasibility and tolerability of topotecan-based chemotherapy in RMS.

Poor prognosis osteosarcoma: new therapeutic approach.

Over the past 30 years, a significant improvement in the prognosis of localized osteosarcoma of the extremities has been observed. Despite these results, approximately 30-40% of patients will relapse, mostly within the first 3 years from diagnosis. The prognosis of patients with recurrent disease or metastases at diagnosis is poor. To improve the survival in this patient population, several attempts have been made. An increased dose intensity of chemotherapy induces short lasting remission but does not increase the survival. In the era of targeted therapy, few drugs have been tested with dismal results. The use of biological agents endowed with immunomodulant activity (that is IL-2) or reduced-intensity allogeneic hemopoietic SCT has produced intriguing results that need further confirmation. In this context, an ongoing study explores the antitumor activity of specific T-cytotoxic lymphocytes.

Response to melphalan in up-front investigational window therapy for patients with metastatic Ewing's family tumours.

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.

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.

Expression and parental imprinting of the H19 gene in human rhabdomyosarcoma.

The expression of Insulin-like Growth Factor 2 (IGF-2) and H19, two genes located on human chromosome 11p15 and provided with cell growth modulating activity, is regulated by parental imprinting, in that the activity of their alleles is dependent on the parental origin. Parental bias in the genetic alterations of chromosome 11p15 observed in several pediatric cancers suggests the involvement of imprinted genes in tumor development. We have previously reported that the number of functional IGF-2 alleles is frequently increased in rhabdomyosarcoma (RMS), as a consequence of either relaxation of imprinting (LOI) or gene duplication. Here we show that the expression of the H19 gene is significantly suppressed with respect to normal muscle tissue in 13 out of 15 rhabdomyosarcomas with embryonal histology (ERMS) and in three out of 11 rhabdomyosarcomas classified as alveolar subtype (ARMS). Since a growth-inhibitory activity has been found associated with the H19 gene, the extinction of its expression can contribute to RMS development. Parental imprinting of the H19 gene was found conserved in all informative RMSs, including those whose ICF-2 imprinting was relaxed, indicating that LOI is a gene-specific event. Seven ERMSs and one ARMS displaying low H19 RNA levels showed an underrepresentation of the expressed allele in their genotype. This result is consistent with the paternal imprinting of the H19 gene and with the preferential loss of the maternal 11p15 alleles in these neoplasms. Low H19 expression was also found in four out of eight RMSs retaining the heterozygosity at 11p15, but showing IGF-2 LOI. These findings suggest that the genetic and epigenetic alterations affecting chromosome 11p15 in a high number of RMSs cause deregulation of more than one imprinted gene, possibly affecting tumor growth, including the extinction of H19 expression and an increase in the number of active IGF-2 alleles.

Therapy-related myelodysplastic syndromes: FAB classification, bone marrow histology, and immunohistology in the prognostic assessment.

In this study we describe the morphologic and immunohistochemical evaluation of bone marrow biopsies from 14 patients with therapy-related myelodysplastic syndromes (t-MDS). We employed CD34, anti-HLA-Dr, anti-elastase, CD68, anti-glycophorin, CD61 monoclonal antibodies immunostaining, and enzyme histochemistry for chloroacetate esterase. Moreover, we used PC10, a MAb raised against the proliferating cell nuclear antigen, to study the proliferative capacity of these marrows. Our data suggest that diagnosis of refractory anemia with excess of blasts (versus chronic myelomonocytic leukemia), the abnormal localization of immature precursors, marrow fibrosis, and augmented CD34 expression in the bone marrow biopsy are ominous prognostic factors at a statistically significant level (p < 0.0005). A combined morpho-immunohistochemical analysis of bone marrow biopsy correctly classifies t-MDS cases according to the biologic and clinical aggressiveness.

Survival from acute non-lymphocytic leukaemia (ANLL) and chronic myeloid leukaemia (CML) in European children since 1978: a population-based study.

We used data supplied by population-based cancer registries, collected and quality controlled using a common protocol, to analyse survival from acute non-lymphocytic leukaemia (ANLL) and chronic myeloid leukaemia (CML) among children in 17 European countries. Variations in survival in relation to age, country, histologic subtype and period of diagnosis (1978--1992) were examined. These are rare malignancies and survival can be studied reliably only by examination of data from a very large population (in this case EUROCARE). 5 years after diagnosis, overall survival was 44% (95% CI 33--55) for CML and 37% (95% CI 32--43) for ANLL. For both types of leukaemia, survival was slightly better for girls and worse in children under 5 years of age. Consistent with clinical literature, the ANLL subtypes with poorer prognosis were monocytic, megakaryocytic and erythroleukaemia. For ANLL, 5-year survival was better in Finland, the UK, The Netherlands and Germany (> or =40%); for CML, 5-year survival was highest in Italy, although the 95% CI were wide. The risk of death from ANLL and CML fell by 7% per year and 5% per year, respectively, after adjustment for age, gender and country. Since these rare childhood malignancies were virtually untreatable until 1970, these are very welcome trends.

Differentiation in paediatric peripheral primitive neuroectodermal tumours of bone. A critical contribution to its assessment.

Differentiation was studied in 73 paediatric peripheral primitive neurorectodermal tumours (pPNETs) of bone observed during 1974 through 1992. The presence of rosettes, pseudorosettes, and/or a rosette-like arrangement of tumour cells (the morphological neural marker, MNM) occurred in 29% of these cases. NSE and N-CAM were expressed by nearly all tumours; synaptophysin was present in 30% of cases, not significantly associated with the MNM status. Neuroendocrine (NE) markers were present in 25% (chromogranin B, secretogranin II) to 40% (chromogranin A, 7B2 protein) of cases. Focal expression of cytokeratins, S100 protein and/or desmin was also noted in a minority of cases. In univariate statistical analysis, only the presence of MNM conferred a significantly higher (about twofold) risk of death than its absence. This study demonstrates the occurrence of at least one immunocytochemical N and/or NE differentiation marker in all pPNETs of bone and a focal expression of cytokeratins, S100 protein and/or desmin in a minority of cases. Synaptophysin and MNM were present each in less than 1/3 of the cases, and no association was noted between them. Statistical analyses highlighted the prognostic role of MNM per se and discourage the sole use of immunocytochemistry in the assessment of neuroectodermal differentiation for prognostic purposes in paediatric pPNETs of bone.

Abnormal Neutrophil Chemotaxis after Successful Bone Marrow Transplantation.

Twenty patients with self-sustaining hematopoiesis were evaluated for neutrophil functions and bone marrow histology 7 to 34 months after bone marrow transplantation (BMT) (7 allogeneic, 13 autologous) performed for acute leukemia in complete remission (11 patients), Hodgkin's lymphoma (2 patients), chronic myeloid leukemia (6 patients) or severe aplastic anemia (1 patient). The chemotactic response toward zymosan-treated serum was severely depressed (<35% of normal) in peripheral neutrophils of 11 patients (2 allogeneic and 9 autologous BMT) and moderately defective (35-70% of normal) in 5 others (2 allogeneic and 3 autologous BMT). On the other hand, phagocytic activity, activation of the metabolic burst and surface expression of CD11/CD18 molecules were within normal limits or moderately increased. The chemotactic defect was independent of age, sex, conditioning regimen and the time period after marrow infusion. The incidence of defective chemotaxis was much greater in patients receiving an autologous BMT (92% of the patients) than in those who had an allogeneic BMT (57% of the patients). Simultaneous bone marrow biopsy studies showed significant stromal alterations in most of our patients; since the bone marrow microenvironment plays an essential role in the process of blood cell formation and release, these observations suggest that defective neutrophil chemotaxis may well serve as a marker of abnormal post-transplant hematopoiesis.

Accuracy and clinical correlates of two different methods for chromogranin A assay in neuroendocrine tumors.

Measurement of chromogranin A (CgA) plays a major role in the management of neuroendocrine tumors (NET); however, reliable assaying of CgA is made difficult by the rapid hydrolysis following its release into the bloodstream. This study was aimed at the assessment of two assays for CgA in NET patients. CgA was measured in 93 patients by means of an enzyme-linked immunosorbent assay (ELISA) and an immunoradiometric assay (IRMA). The specificity and sensitivity of CgA were evaluated in relation to tumor histology. The clinical accuracy of the two assays was evaluated by receiver-operating characteristic (ROC) curve analysis. Regression analysis demonstrated different immunoreactivity for CgA of the antibodies used in the two kits (r = 0.61). The two assays had different accuracy also in classifying patients according to their clinical condition (91% vs 64% specificity and 79% vs 79% sensitivity for the ELISA and IRMA assay, respectively) and tumor histology (81% vs 85% sensitivity for the ELISA and IRMA assays, respectively, in carcinoids; 92% vs 67% sensitivity for the ELISA and IRMA assays, respectively, in pancreatic islet cell tumors). The different clinical accuracy of the two assays was confirmed by the ROC analysis (AUC = 0.90 vs AUC = 0.87 for the ELISA and IRMA assays, respectively). In conclusion, because of the poor standardization of the commercially available measurement tools the clinical accuracy of CgA measurement depends on the assay used. This makes it difficult to compare CgA values measured with different kits and affects the clinical accuracy of the different assays for CgA.

Retrospective analysis of ploidy in primary osseous and extraosseous Ewing family tumors in children.

AIMS: To retrospectively study the DNA content in a series of childhood Ewing Family Tumors (EFT), and to investigate its prognostic value. METHODS: The study was performed on a series of 27 EFTs (osseous Ewing's sarcoma, 18 cases; extraosseous Ewing's sarcoma, 2; peripheral neuroepithelioma, 4; Askin Rosai tumors, 3). Ploidy was investigated using both flow cytometry (FCM) and image cytometry (ICM) on tumor cell suspensions from formalin-fixed paraffin-embedded specimens or fresh frozen tissue obtained from the primary tumor at diagnosis. RESULTS: Ploidy was evaluable by FCM in all cases, and by ICM in 23/27. When fresh frozen tissue and paraffin-embedded samples from the same tumor were available for analysis, they yielded equal results. The rate of agreement between FCM and ICM was 82%. The majority of cases were diploid, and in the present series aneuploidy seemed to be associated with a poor outcome. CONCLUSIONS: These results suggest that aneuploidy could be an indicator of a bad prognosis in EFT; however, the small number of cases precludes any conclusion of statistical value. Larger retrospective studies on ploidy using archival material could be performed and their reliability is supported by the concordance of results from fresh and formalin-fixed tissue.

Antineuronal antibody in a patient with neuroblastoma and opsoclonus-myoclonus-ataxia: a case report.

We describe a case of a patient with neuroblastoma and opsoclonus- myoclonus ataxia displaying serum and CSF anti-Hu antibodies that were able to recognize antigens of the patient's own tumor.

Prognostic value of clinicopathologic characteristics including neuroectodermal differentiation in osseous Ewing's sarcoma family of tumors in children.

AIMS AND BACKGROUND: The aim of the present study was to determine the relationship between clinico-pathologic parameters, including neuroectodermal differentiation, and their impact on survival in a series of pediatric patients with osseous tumors of the Ewing's sarcoma family admitted to the Pediatric Department of the Istituto Nazionale Tumori of Milan. METHODS: Seventy-three patients were enrolled. The variables analyzed were sex, age, site of primary tumor, serum lactate dehydrogenase (LDH) level at diagnosis, involvement of periosseous soft tissues by primary tumor, presence of metastatic disease, status of disease after the treatment plan, as well as the presence of mitoses, morphologic and immunocytochemical neural markers, and neuroendocrine markers in the primary tumor. RESULTS: Neural and neuroendocrine markers were not significantly associated with any of the other parameters. In the univariate analysis, significant risk factors related to unfavorable outcome were elevated LDH, metastatic disease, lack of complete remission after treatment, presence of mitoses and of morphological neural markers; immunocytochemical neural and neuroendocrine markers lacked prognostic value. In the multivariate analysis, only LDH levels and the status of disease following the treatment were retained. CONCLUSIONS: LDH level at diagnosis might be a useful marker to identify different risk levels; neuroectodermal differentiation might have no clear-cut impact on the clinical management of osseous Ewing's sarcoma family of tumors.

Antineuronal antibodies in patients with neuroblastoma: relationships with clinical features.

We evaluated the frequency of serum antineuronal antibodies in a cohort of 39 neuroblastoma patients and related their presence to clinical features. Twelve patients displayed antineuronal antibodies at immunocytochemistry. Only one of these 12 patients suffered from a clinically overt paraneoplastic syndrome. No significant differences emerged between autoantibody-positive and autoantibody-negative patients in terms of progression-free and overall survival, although when only patients evolving to disease progression were considered, the time interval between diagnosis and progression was slightly longer in autoantibody-positive patients.