Multimodal therapy in children and adolescents with newly diagnosed atypical teratoid rhabdoid tumor: individual pooled data analysis and review of the literature.

Atypical teratoid rhabdoid tumour (ATRT) is a malignant tumour of the central nervous system with a dismal prognosis. There is no consensus on optimal treatment and different multimodal strategies are currently being used in an attempt to improve outcomes. To evaluate the impact of high-dose chemotherapy followed by autologous stem-cell rescue (HD48 SCR), radiotherapy (RT) at first line, intrathecal chemotherapy (IT) and extent of surgical resection upon recurrence-free survival (RFS) and overall survival (OS). An online database search identified prospective and retrospective studies focused on the treatment of children and adolescents with newly diagnosed ATRT. Clinical, therapeutic and outcome data were extracted and an individual pooled data analysis was conducted. Out of 389 publications, 12 manuscripts were included in our review. Data from 332 patients were analysed. Median age at diagnosis was 37 months (range 1-231). HD-SCR, RT and IT had been administered to 28.6% (58/203), 49.6% (118/238) and 21% (65/310) of the patients, respectively. Gross total resection (GTR) had been achieved in 46.5% (152/327) of the cases. In the multivariate analysis, hazard ratios (95% Confidence Interval) for HD-SCR were: RFS-HR = 0.570 (0.357-0.910) p = 0.019, and OS-HR = 0.388 (0.214-0.704) p = 0.002; and for RT: RFS-HR = 0.551 (0.351-0.866) p = 0.01, and OS-HR = 0.393 (0.216-0.712) p = 0.002. IT and GTR were not significantly associated with improved RFS or OS in the multivariate analysis. In our pooled data review, HD-SCR and RT at first line were associated with improved outcomes in children and adolescents with newly diagnosed ATRT.

Bloodstream infection in paediatric cancer centres--leukaemia and relapsed malignancies are independent risk factors.

UNLABELLED: In a prospective multicentre study of bloodstream infection (BSI) from November 01, 2007 to July 31, 2010, seven paediatric cancer centres (PCC) from Germany and one from Switzerland included 770 paediatric cancer patients (58% males; median age 8.3 years, interquartile range (IQR) 3.8-14.8 years) comprising 153,193 individual days of surveillance (in- and outpatient days during intensive treatment). Broviac catheters were used in 63% of all patients and Ports in 20%. One hundred forty-two patients (18%; 95% CI 16 to 21%) experienced at least one BSI (179 BSIs in total; bacteraemia 70%, bacterial sepsis 27%, candidaemia 2%). In 57%, the BSI occurred in inpatients, in 79% after conventional chemotherapy. Only 56 % of the patients showed neutropenia at BSI onset. Eventually, patients with acute lymphoblastic leukaemia (ALL) or acute myeloblastic leukaemia (AML), relapsed malignancy and patients with a Broviac faced an increased risk of BSI in the multivariate analysis. Relapsed malignancy (16%) was an independent risk factor for all BSI and for Gram-positive BSI. CONCLUSION: This study confirms relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. On a unit level, data on BSIs in this high-risk population derived from prospective surveillance are not only mandatory to decide on empiric antimicrobial treatment but also beneficial in planning and evaluating preventive bundles. WHAT IS KNOWN: • Paediatric cancer patients face an increased risk of nosocomial bloodstream infections (BSIs). • In most cases, these BSIs are associated with the use of a long-term central venous catheter (Broviac, Port), severe and prolonged immunosuppression (e.g. neutropenia) and other chemotherapy-induced alterations of host defence mechanisms (e.g. mucositis). What is New: • This study is the first multicentre study confirming relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. • It describes the epidemiology of nosocomial BSI in paediatric cancer patients mainly outside the stem cell transplantation setting during conventional intensive therapy and argues for prospective surveillance programmes to target and evaluate preventive bundle interventions.