Gian Luca De Salvo

Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: Results of a pooled analysis from United States and European groups

BACKGROUNDnNon-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with initially unresected tumours represent a particular subset of patients with a poor outcome. Various international research groups pooled their data in a joint study in order to investigate prognostic variables and treatment modalities.nnnMETHODSnThe study population consisted of 304 patients <21 years old treated between 1980 and 2005 using a multimodality therapeutic strategy.nnnRESULTSnSynovial sarcoma and malignant peripheral nerve sheath tumour (MPNST) were the most frequent histotypes. Most patients received initial chemotherapy: major responses were recorded in 41% and minor in 16% of cases. Overall survival (OS) was 60.0% and 51.5% at 5 and 10 years, respectively, and it was significantly associated with patients age, histological subtype, tumour site and size, quality of delayed surgical resection, radiotherapy administration and response to induction chemotherapy. MPNST associated to neurofibromatosis type 1 was the tumour type with the worst rate of response to chemotherapy and the worst outcome.nnnCONCLUSIONSnIn unresected NRSTS patients, radiotherapy and delayed surgery are of crucial importance. Patients who respond to chemotherapy have better chance of survival. However, given the relatively poor prognosis, research on intensive multimodal treatment approaches and novel strategies is warranted.

Evaluating Access to Pediatric Cancer Care Centers of Children and Adolescents With Rare Tumors in Italy: The TREP Project

A national project focusing on rare malignant pediatric tumors (the TREP project) was launched in Italy in 2000. The present study compared the number of these tumors expected to be diagnosed in Italy with the number of cases actually enrolled in the TREP database in 2000–2006.

Inflammatory myofibroblastic tumors in childhood: a report from the Italian Cooperative Group studies.

Inflammatory myofibroblastic tumors (IMTs) are myofibroblastic lesions with unpredictable biologic behavior that occur at a young age. For this report, the authors investigated clinicopathologic features in a series of pediatric IMTs. The objective of the study was to identify morphologic or immunohistochemical prognostic markers and the possible pathogenic role of human herpes virus 8 (HHV‐8).

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.

Salvage rates and prognostic factors after relapse in children and adolescents with initially localised synovial sarcoma

BACKGROUNDnPrevious studies have reported a poor outcome for synovial sarcoma patients whose tumours relapse.nnnMETHODSnThis study analysed 44 relapsing cases in a series of 118 consecutive patients <21 yr of age with non-metastatic synovial sarcoma prospectively enrolled in Italian paediatric protocols between 1979 and 2006. In an effort to identify a possible risk-adapted stratification enabling a better planning of second-line treatment, the relapsing patients outcome was analysed vis-à-vis their clinical picture at onset, first-line treatments, clinical findings at the time of first relapse and second-line treatment modalities.nnnRESULTSnThe first event was a local recurrence in only 15 cases, and metastatic in 29 (associated with local relapse too in 7 cases). The time to relapse ranged from 4 to 108 months (median 20 months). Overall survival was 29.7% and 21.0% five and ten years after relapsing, respectively. The variables influencing survival were the timing and type of relapse (combined) and the chances of a secondary remission, which correlated strongly with the feasibility of complete surgery.nnnCONCLUSIONSnOur study confirmed a largely unsatisfactory prognosis after recurrences in children and adolescents with synovial sarcoma: the chances of survival can be estimated on the basis of several variables for the purposes of planning risk-adapted salvage protocols. An aggressive surgical approach should be recommended. New effective systemic agents are warranted, and experimental therapies can be offered to patients with little chance of salvage.

Cutaneous Melanoma in Children and Adolescents: The Italian Rare Tumors in Pediatric Age Project Experience

OBJECTIVEnTo describe a series of cutaneous melanoma in children collected by the Italian Rare Tumors in Pediatric Age project.nnnSTUDY DESIGNnFrom 2000 to 2012, 54 patients younger than 18 years of age were prospectively registered and treated at 12 Italian pediatric centers on the basis of the same diagnostic/therapeutic recommendations and with the same forms to record clinical data.nnnRESULTSnConsidering the estimated annual incidence in Italy, the registered cases accounted for 30% of those expected in children and 10% of adolescents. Clinically, 47% of the tumors were amelanotic and 81% were raised, 39% of cases had tumor thickness >2 mm, and 36% had lymph node involvement. For the whole series, 5-year event-free survival and overall survival rates were 75.2% and 84.6%, respectively. Patient survival correlated with tumor stage and ulceration. No relapses were recorded for T1-2 (thickness <2 mm), N0, and stage 0-I-II cases.nnnCONCLUSIONnWe suggest that the variables influencing survival in children with melanoma are the same as for adults, the clinical approach used in adults is feasible in children, and pediatric cases are more likely to have advanced disease at diagnosis but similar survival. New effective drugs are needed for advanced disease, and biological studies and international cooperative schemes are warranted.

Features predicting unresectability in hepatoblastoma

Approximately 20% of patients who have hepatoblastoma (HB) still have unresectable disease after preoperative chemotherapy (POC). In these circumstances, orthotopic liver transplantation (OLT) should be performed 1 month after POC. The authors sought to identify presenting features that would predict unresectability in patients with HB and to provide suggestions for early referral and listing for OLT.

Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience

BACKGROUNDnInfantile fibrosarcoma (IFS) is a very rare disease occurring in young infants characterised by a high local aggressiveness but overall with a favourable survival. To try to reduce the total burden of therapy, the European pediatric Soft tissue sarcoma Study Group has developed conservative therapeutic recommendations according to initial resectability.nnnMATERIAL AND METHODSnBetween 2005 and 2012, children with localised IFS were prospectively registered. Initial surgery was suggested only if possible without mutilation. Patients with initial complete (IRS-group I/R0) or microscopic incomplete (group II/R1) resection had no further therapy. Patients with initial inoperable tumour (group III/R2) received first-line vincristine-actinomycin-D chemotherapy (VA). Delayed conservative surgery was planned after tumour reduction. Aggressive local therapy (mutilating surgery or external radiotherapy) was discouraged.nnnRESULTSnA total of 50 infants (median age 1.4 months), were included in the study. ETV6-NTRK3 transcript was present in 87.2% of patients where investigation was performed. According to initial surgery, 11 patients were classified as group I, 8 as group II and 31 as group III. VA chemotherapy was first delivered to 25 children with IRS-III/R2 and one with IRS-II/R1 disease. Response rate to VA was 68.0%. Mutilating surgery was only performed in three cases. After a median follow-up of 4.7 years (range 1.9-9.0), 3-year event-free survival and overall survival were respectively 84.0% (95% confidence interval [CI] 70.5-91.7) and 94.0% (95% CI 82.5-98.0).nnnCONCLUSIONSnConservative therapy is possible in IFS as only three children required mutilating surgery, and alkylating or anthracycline based chemotherapy was avoided in 71.0% of patients needing chemotherapy. VA regimen should be first line therapy in order to reduce long term effects.

Synovial sarcoma in children and adolescents: A critical reappraisal of staging investigations in relation to the rate of metastatic involvement at diagnosis

BACKGROUNDnEuropean protocols for paediatric synovial sarcoma (SS) require that all children routinely undergo chest computed tomography (CT) scanning and bone scanning as initial staging procedures. This study aims to determine the rate of initial metastases in paediatric SS based on specific clinical characteristics, thereby investigating whether these diagnostic procedures are really necessary in all patients.nnnMETHODSnData on 258 previously-untreated SS patients <21 years old were pooled from the databases of different European paediatric groups (study period 1988-2005) for this analysis, and the associations between patients characteristics and any presence of metastasis were estimated.nnnRESULTSnFifteen cases (5.8%) had distant metastases at diagnosis (86% pulmonary). The presence of metastases was unassociated with patients gender or age, tumour grade or site, but it was influenced by T-status, and especially primary tumour size: the risk of metastases was 32 times higher in cases of tumour >5 cm than for tumours ≤ 5 cm.nnnCONCLUSIONSnOur findings suggest that tumour diameter can be used as a variable for identifying patients at greater risk of metastases and warranting more accurate radiological investigations. Chest CT scanning may improve the accuracy of pulmonary staging over X-ray, but requires different ionising radiation exposures that might have carcinogenic potential: it can be omitted for patients with tumours ≤ 5 cm. Given the very low risk of bone metastases, bone scans may be recommended only in cases with evidence of lung metastases.

Adrenocortical tumors in Italian children: analysis of clinical characteristics and P53 status. Data from the national registries.

AIMnAdrenocortical tumors are very rare in children. The distinction between adenoma and carcinoma is complex because of their clinical/histological characteristics. The analysis of the cases registered in two consecutive Italian Studies is described, in order to provide additional insight into their nature and possibly identify benign and malignant lesions.nnnMATERIALS AND METHODSnThe analysis includes patients registered from?? 1.1982 to 6.2011 into two consecutive Italian protocols.nnnRESULTSnFifty-eight children (age 2-210months) were evaluated. Endocrine manifestations were the most frequent symptoms. Stage distribution at diagnosis was: ST I 35, ST II 17, ST III 1, ST IV 5. Treatment consisted in mitotane for ST II, mitotane+chemotherapy for ST III/IV. Forty-four patients are alive without evidence of disease, 1 is alive with disease, 12 died of disease and 1 because of cardiomyopathy. The Wienecke score system was applied in 24 patients with good significance. A p53 mutation was found in 7 cases, and it was diagnostic for Li-Fraumeni syndrome in 2 benign tumors.nnnCONCLUSIONSnThe results highlight the importance of a complete excision to obtain the cure of patients. The efficacy of chemotherapy is controversial, however it was able to control the disease in 4 patients in ST II. The value of the Wienecke score system in predicting patients outcome was confirmed. p53 mutation was more frequent in malignant tumors and represented the sentinel of the Li-Fraumeni syndrome.