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.

Italian guidelines for the management of infectious complications in pediatric oncology: empirical antimicrobial therapy of febrile neutropenia.

The Italian Association for Paediatric Haematology and Oncology prepared a guideline document aimed at unifying and rationalising as much as possible the management of febrile neutropenia in children with cancer, because of the potential impact of these procedures on hospital costs and on the development of antibiotic resistance. Before starting anti-infective therapy, at least 2 blood cultures, a throat swab, urine-culture, and cultures from any suspected infected site, should be performed. Routine chest X-rays at onset of febrile neutropenia are probably not necessary, in absence of respiratory signs. At the present time, the safer option probably remains the combination of a beta-lactam and an aminoglycoside, and treating febrile neutropenia outside of hospital should be considered an investigational approach. The choice of the most appropriated regimen for each institution should be based also on the local bacteriological statistics and patterns of bacterial resistance. Antibiotic toxicity and cost should be other important factors. Every subsequent addition or substitution of antibiotics should be based on objective signs of clinical deterioration. The only accepted empirical modification is empirical antifungal therapy, while the empirical addition of a glycopeptide antibiotic cannot be recommended.

[Malignant tumors in children living in the province of Trieste, 1972-1993: descriptive epidemiology and the quality of diagnostic-therapeutic services]. / I tumori maligni nei bambini residenti nella provincia di Trieste, 1972-1993: epidemiologia descrittiva e qualità dei servizi diagnostico-terapeutici.

The study objectives were: 1) to analyse the incidence and death rates from cancer among children aged 0-14 years resident in the north-eastern Italian province of Trieste between 1972-1993, using data from the population-based Trieste Cancer Registry; 2) to evaluate the local diagnostic facilities by analysing the accuracy of histological diagnoses, the causes of delay in the diagnosis, and the interval between onset of symptoms and diagnosis of cancer; 3) to calculate the proportion of patients treated following the most effective therapy protocols known at the time of the tumour detection, and to compute the actuarial five-year survival rates since diagnosis. We recorded 123 new cases of cancer (93% microscopically verified) corresponding to a rate, age-standardized to the world population, of 161.9 (standard error [SE] = 15.1) per million child-years. The most common diagnostic group was that of primary brain tumours: 40 cases, rate = 51.0 (SE = 8.4). In 102 cases the diagnosis was made at hospitals in the province of Trieste, with a median time of seven days (25th-75th percentile = 1-16) between admission and diagnosis. In 37 cases the length of the interval between the advancing of the diagnostic hypothesis of cancer and the microscopic diagnosis ranged from eight to 57 days: 20% of the interval was spent in the identification of the lesion, 50% elapsed between the identification and the biopsy, and 30% was spent in performing the microscopic diagnosis. Out of 123 cases, 30 were partly treated or completely treated at centres not located in our province, i.e., at seven different Italian hospitals (14 cases), nine European hospitals (15 cases), and at one North-American centre (one case). The 40 children with brain tumours were spread among 12 institutions. The five-year survival rate increased from 52.4% (SE = 6.3) for the 63 children with cancers diagnosed in 1972-1981 to 62.5% (SE = 7.0) for the 48 with malignancies detected in 1982-1990.

Avascular necrosis of bone in children undergoing allogeneic bone marrow transplantation.

Avascular necrosis of bone (AVNB) is reported in two children after allogeneic bone marrow transplantation. Preparation therapy for transplantation included cyclophosphamide and total body irradiation. Corticosteroids, cyclosporine A, and methotrexate were used for graft-versus-host-disease prophylaxis. The possible role of combination therapy in development of AVNB is discussed, but a direct relationship with single agents was not found. However, an early diagnosis is important to institute conservative treatment and prevent irreversible damage to affected joints. Magnetic resonance imaging was found to be more sensitive than plain radiography in early detection of AVNB.

[Computerized tomography of the skull in children with lymphoblastic leukemia treated with prophylactic cranial radiation]. / Tomografia computerizzata del cranio in bambini con leucemia acuta linfoblastica sottoposti ad irradiazione cranica profilattica.

Thirty asymptomatic patients with acute lymphoblastic leukemia who had received prophylactic cranial irradiation (16 pts had 2400 cGy, 14 pts 1800 cGy) and intrathecal methotrexate were studied by computed tomography of the brain 60 to 148 months after initiation of prophylaxis. Three of 30 (10%) patients presented abnormal findings: widening of frontal subarachnoid space (1 patient), little area of decreased attenuation coefficient (1 patient), and intracerebral calcifications (1 patient Tomography abnormalities could be detected either in patients treated with 2400 cGy and in those treated with 1800 cGy. None of our patients showed central nervous system dysfunctions on physical examination. The results of our study suggest that tomography findings have a poor clinical significance.

Leukemia in a child with Wilms' tumor.

A case is described which illustrates an acute non-lymphocytic leukemia following multimodal control and apparent cure of Wilms' tumor. Literature cases are reviewed, and therapeutic inadequacies according to present protocols and their importance for the subsequent development of secondary leukemia are discussed.

[Bilateral adrenal neuroblastoma of multicentric origin]. / Neuroblastoma surrenale bilaterale di origine polifocale.

Bilateral neuroblastoma is extremely rare. In the literature few cases are reported which are mostly considered to represent metastases rather than multicentric tumoral occurrence. A case of bilateral adrenal neuroblastoma is reported; given its various aspects, and especially the prognosis features, this tumor is, in our opinion, of a multicentric origin.