Ewing Sarcoma of the Bone in Children under 6 Years of Age

BACKGROUND: Ewing Sarcoma Family Tumours (ESFT) are rare in early childhood. The aim of this study was to report the clinical characteristics and outcome of children under 6 years of age affected by ESFT of the bone in Italy. METHODS: The records of all the children diagnosed with osseous ESFT in centres members of the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) from 1990 to 2008 were reviewed. The Kaplan-Meier method was used for estimating overall and progression-free survival (OS, PFS) curves; multivariate analyses were performed using Cox proportional hazards regression model. RESULTS: This study includes 62 patients. An axial primary localization was present in 66% of patients, with the primary site in the chest wall in 34%. Fourteen (23%) patients presented metastatic disease. The 5-year OS and PFS were 73% (95% confidence interval, CI, 58-83%) and 72% (95% CI 57-83%) for patients with localized disease and 38% (95% CI 17-60%) and 21% (95% CI 5-45%) for patients with metastatic disease. Metastatic spread, skull/pelvis/spine primary localization, progression during treatment and no surgery predicted worse survival (P<0.01), while patients treated in the last decade had better survival (P = 0.002). In fact, the 5-year OS and PFS for patients diagnosed in the period 2000-2008 were 89% (95% CI 71-96%) and 86% (95% CI 66-94%), respectively. CONCLUSION: The axial localization is the most common site of ESFT in pre-scholar children. Patients treated in the most recent period have an excellent outcome

Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies

As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (\ub12) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in&nbsp;vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T&nbsp;cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies

Unraveling the impact of upfront chemotherapy and proton beam therapy on treatment outcome and follow-up in central nervous system germ cell tumors: a single center experience

BackgroundGerm cell tumors (GCT) account for a minority of central nervous system (CNS) malignancies, highly prevalent in adolescents and young adults. Despite their aggressive biological behavior, prognosis is excellent in most cases with risk stratified treatment, consisting in a combination of chemotherapy and radiotherapy. Whole ventricular irradiation (WVI) and craniospinal irradiation, the treatment of choice for localized and metastatic disease, pose significant risk of collateral effects, therefore proton beam radiation (PBT) has been recently proposed for its steep dose fallout.Materials and methodsWe report our experience in a consecutive series of 17 patients treated for CNS GCT at our Institution from 2015 to 2021.ResultsMost frequent lesion location were sellar/suprasellar (35%) and bifocal germinoma (35%), followed by pineal (18%) and thalamic (12%). Two patients (12%), had evidence of disseminated disease at the time of diagnosis. At the latest follow-up all but one patient showed complete response to treatment. The only relapse was successfully rescued by additional chemotherapy and PBT. PBT was well tolerated in all cases. No visual, neurological or endocrinological worsening was documented during and after treatment. Neuropsychological evaluation demonstrated preservation of cognitive performance after PBT treatment.ConclusionsOur data, albeit preliminary, strongly support the favourable therapeutic profile of PBT for the treatment of CNS germ cell tumors

The Fight Just Born&mdash;Neonatal Cancer: Rare Occurrence with a Favorable Outcome but Challenging Management

The occurrence of cancer in newborns within the first 28 days of life is uncommon, with different clinical presentation from other age groups. Prenatal diagnosis is reported in about half of patients, while a genetic predisposition condition is supposed. The management of a newborn with cancer can be challenging and needs to be tailored according to the histology and the primary tumor site; surgery represents the main strategy, while chemotherapy should be considered with caution because of the higher toxicity and mortality due to different pharmacokinetics in neonates compared to older children. We describe the first Italian series over a 15-year period of patients affected by both benign and malignant neoplastic diseases diagnosed within the first 28 days of life; 74 newborns were diagnosed with neonatal tumors, representing 1.5% of the cancer population in the same period, and a prevalence of germ cell tumors (55%) and neuroblastoma (16%) was observed. Surgery was performed on 80% of patients, while chemotherapy was necessary for about 20% of patients. The 5-year overall survival (OS) exceeded 90%; treatment-related deaths are a major concern, representing 80% of overall deaths. A genetic/syndromic condition was detected in 16% of the population; additionally, a cancer predisposition syndrome (CPS) was identified in about 10% of patients. According to our experience, all newborns affected by cancer should warrant genetic counselling and a screening test for CPS

Focal nodular hyperplasia and hepatic regenerating nodules in pediatric oncology patients: how much invasive approach is necessary?

Introduction. Hepatic regenerating nodules (HRN) and focal nodular hyperplasia (FNH) are benign regenerating lesions of the liver that rarely occur in children. An increased incidence of these lesions is reported in children treated for cancer.Material and methods. Eight children who developed FNH and HRN after treatment for malignancies in the Oncology unit at the “Bambino Gesu” Pediatric Hospital in Rome, were retrospectively analyzed.Results. The lesions, considered in the differential diagnosis with metastatic relapse of the primitive disease, have been monitored with US or other available imaging techniques. Evolution of the lesions was observed in only 1 patient three years after the initial diagnosis of FNH.Conclusion. In conclusion serial monitoring with imaging techniques is sufficient to rule out liver metastasis and to monitor the evolution of the lesions. Surgery is suggested only in the case of complications

The Prognostic Role of the C-Reactive Protein and Serum Lactate Dehydrogenase in a Pediatric Series of Bone Ewing Sarcoma

Background: Ewing sarcoma (ES) is a rare and aggressive pediatric cancer. Numerous studies have attempted to identify new prognostic biomarkers. The predictive value of serum LDH and CRP has not been clearly described, to date. Methods: The objective of our retrospective study was to investigate the prognostic value of LDH and CRP levels and their association with overall survival in a series of ES patients. Results: Between 2004 and 2019, 89 ES patients were included. In a univariable analysis, high levels of LDH and CRP were associated with the worst prognosis. In a multivariable analysis, only higher LDH values remained associated with a lower survival. The high-LDH-level group experienced all 21 deaths registered in our population (24%) and about 90% of disease progressions. The 5-year overall survival was 66.4% in the high-LDH-level group, while no deaths were observed in the low-LDH-level group. The 5-year progression-free survival was 57.9% in the high-LDH-level group versus 80.4% in the low-LDH-level group. Conclusions: In our study, LDH levels at diagnosis were strongly correlated with the prognosis, and they might be considered a prognostic factor in Ewing sarcoma. The LDH value, along with its very low cost and its reproducibility in almost all centers, make it suitable as a potential prognostic biomarker in clinical practice

Inflammatory Myofibroblastic Tumor of the Upper Airways Harboring a New TRAF3-ALK Fusion Transcript

Inflammatory myofibroblastic tumor (IMT) is a rare disease that mainly involves the lung and the abdomen with an intermediate clinical course but a recurrence rate between 15–30%. Radical surgery represents the gold standard of treatment, while chemotherapy and radiotherapy are considered for unresectable lesions. The identification of ALK translocations in IMT opened the option for the use of target therapies. Indeed, the ALK inhibitors have changed the treatment approach for aggressive lesions, improving the prognosis. Intraluminal upper-way IMT is extremely rare and represents a medical challenge. We reported an endotracheal IMT case presenting a previously unknown TRAF3-ALK fusion transcript

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

Background: Previous studies have reported a poor outcome for synovial sarcoma patients whose tumours relapse. Methods: This 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-a-vis their clinical picture at onset, first-line treatments, clinical findings at the time of first relapse and second-line treatment modalities. Results: The 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. Conclusions: Our 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. (C) 2012 Elsevier Ltd. All rights reserved