Martina Di Martino

Prognostic factors in pleuro‐pulmonary blastoma

To evaluate the prognostic factors in a series of children affected by pleuropulmonary blastoma (PPB).

Local Lymph Node Involvement in Pediatric Renal Cell Carcinoma: A Report From the Italian TREP Project

One of the most important adverse prognostic factors for adult renal cell carcinoma (RCC) is the retroperitoneal lymph node involvement. The aim of this article is to study the prognostic significance of local lymph node involvement in pediatric RCC and the role of retroperitoneal lymph node dissection (RLND) at diagnosis.

Synchronous Bilateral Wilms Tumor A Report from the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)

The optimal management of bilateral Wilms tumor (BWT) is challenging, and their survival is lower than for unilateral tumors. This report discusses a large series of BWTs treated in Italy in the last 2 decades.

Influence of methylenetetrahydrofolate reductase gene polymorphisms on the outcome of pediatric patients with non-Hodgkin lymphoma treated with high-dose methotrexate

Abstract High-dose methotrexate (MTX) is a key component of most treatment protocols for childhood and adolescent non-Hodgkin lymphoma (NHL). Recent studies have suggested that the toxicity of antifolate drugs, such as MTX, is affected by inherited single nucleotide polymorphisms (SNPs) in folate metabolizing genes. The aim of our study was to investigate the potential influence of the C677T and A1298C genetic variants of the methylenetetrahydrofolate reductase (MTHFR) gene on the clinical toxicity and efficacy of MTX in pediatric patients with NHL (n = 95) treated with therapeutic protocols Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) LNH-97 and EURO LB-02. We demonstrated that patients with the 677T genotype had an approximately six-fold greater risk of developing hematological toxicity compared with wild-type carriers, especially in the 1 g/m2 treatment group (p = 0.01). Moreover, we identified a correlation between the risk of relapse and the T genotype: T carriers had reduced disease-free survival compared with wild-type patients (67% vs. 100%). Our data suggest a pharmacogenetic influence on the adverse effects of high-dose MTX in the 1 g/m2 treatment group.

Kaposiform hemangioendothelioma of the kidney: an unusual presentation of a rare vascular neoplasm.

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive, vascular spindle-cell proliferation, with resemblance to Kaposi sarcoma. Usually, this tumor occurs in the skin and the retroperitoneum. We described a girl with a kidney localization and extension into the inferior vena cava and even into the right atrium. The case presented here is unique in 2 ways. First, kidney involvement of KHE has never been described in the literature until now. Second, and most remarkably, extensive tumor thrombosis suggests surgical excision even with cardiopulmonary bypass. The KHE of the kidney is a rare tumor but should be taken into account in the differential diagnosis with other pediatric renal neoplasms.

Salvage rates and prognostic factors after relapse in children and adolescents with malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumor (MPNST) is one of the most common nonrhabdomyosarcoma soft tissue sarcomas encountered in pediatric age, and it is generally characterized by poor outcome, particularly for relapsing patients.

Biliary tract rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Associazione Italiana Ematologia Oncologia Pediatrica

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.

Targeted molecular therapy (modified RIST regimen) in relapsed high risk stage IV neuroblastoma: two cases report

The prognosis for children with recurrent or refractory neuroblastoma remains a significant clinical challenge, and currently there are no known curative salvage regimens. In this paper we investigated the effect of imatinib with rapamycin and the chemotherapeutic agents temozolomide and irinotecan. We treated two children with recurrent neuroblastoma with this so called RIST protocol. Both patients, off therapy for 15 and 31 months, respectively are well, and developing normally, without any complications. These findings suggest that a combination regimen of RIST may provide a therapeutic benefit with a favorable toxicity profile to a unfortunate subset of patients with neuroblastoma.

Genetic and epigenetic analyses guided by high resolution whole-genome SNP array reveals a possible role of CHEK2 in Wilms tumour susceptibility

Wilms tumour (WT), the most frequent malignant childhood renal tumour, shows a high degree of genetic and epigenetic heterogeneity. Loss of imprinting on chromosome 11p15 is found in a large fraction of cases and mutations in a few genes, including WT1, CTNNB1, WTX, TP53 and, more recently, SIX1, SIX2 and micro RNA processing genes (miRNAPGs), have been observed. However, these alterations are not sufficient to describe the entire spectrum of genetic defects underlying WT development. We inspected data obtained from a previously performed genome-wide single nucleotide polymorphism (SNP) array analysis on 96 WT samples. By selecting focal regions commonly involved in chromosomal anomalies, we identified genes with a possible role in WT development, based on the prior knowledge of their biological relevance, including MYCN, DIS3L2, MIR562, HACE1, GLI3, CDKN2A and CDKN2B, PALB2, and CHEK2. The MYCN hotspot mutation c.131C>T was detected in seven cases (7.3%). Full sequencing of the remaining genes disclosed 16 rare missense variants and a splicing mutation. Most of these were present at the germline level. Promoter analysis of HACE1, CDKN2A and CDKN2B disclosed partial methylation affecting HACE1 in a consistent fraction of cases (85%). Interestingly, of the four missense variants identified in CHEK2, three were predicted to be deleterious by in silico analyses, while an additional variant was observed to alter mRNA splicing, generating a functionally defective protein. Our study adds additional information on putative WT genes, and adds evidences involving CHEK2 in WT susceptibility.

Commentary: Time trends of cancer incidence in Campania: 25 years of observation

Introduction: Childhood cancer is relatively uncommon and the European age-standardized rate was 164 new case per million per year among 0 to 15 years old children (95% CI 158-170). We analyzed data collected in the Mod. 1.01 of the AIEOP (Association Italian Pediatric Hematology-Oncology) over 25 years (1990-2014) about patients with malignant disease diagnosed in 90 towns of the “Ground of fires” (56 in Napoli and 34 in Caserta province). Methods: Thanks to the wide monitored population we defined 5 time trends: 1990-94; 1995-99; 2000-04; 2005-09; and 2010-14. We calculated the ratio between observed cases (O) and expected (E) numbers of cases among the children from “Terra dei fuochi”. Results: 2037 cancer patients (0-15 years) were registered in the AIEOP database: 1144 males (56.1%) and 893 females (43.8%). Conclusions: It is note-worthy to underline that our cases needed to be integrated with the Hospital Informative System and Register of births, marriage and deaths to have a better collection of observed cases. This is a limit of our study. The data analysis do not show significant differences in number of observed cases and type of diseases respect to our previous epidemiological study on cancer cases registered in Campania.