Cavernous malformations (CM) are cerebral irradiation-related late complications. Little is known about their natural history and the pathogenetic role of concomitant chemotherapy. We present a retrospective, single-institution study of 108 children affected with medulloblastoma, ependymoma, or germinoma treated with radio- and chemotherapy. The frequency, clinical and radiological presentations, and outcomes were analyzed to investigate the relationship among radiation dose, associated chemotherapy, age, latency and localization of radiation-induced CM. 100 out of 108 children were treated with radiotherapy for primary brain tumor; 34 (27 with medulloblastoma and 7 with other histologies) out of 100 patients developed CM. No significant relationship was found between CM and gender (p = 0.70), age (p = 0.90), use of specific chemotherapy (standard versus high-dose, p = 0.38), methotrexate (p = 0.49), and radiation dose (p = 0.45). However, CM developed more frequently and earlier when radiotherapy was associated with methotrexate (70 % of cases). Radiation-induced CM prevailingly occurred in the cerebral hemispheres (p = 0.0001). Only 3 patients (9 %) were symptomatic with headache. Three patients underwent surgery for intra- or extra-lesional hemorrhage. CM was confirmed by histopathology for all 3 patients. The vast majority of radiation-induced CM is asymptomatic, and macro-hemorrhagic events occur rarely. Concomitant therapy with methotrexate seems to favor their development. We recommend observation for asymptomatic lesions, while surgery should be reserved to symptomatic growth or hemorrhage.

Data regarding the epidemiology febrile neutropenia during chemotherapy for pediatric central nervous system neoplasia are scarce. Data retrieved from a prospective study performed from January 2002 to December 2004 at G.Gaslini Children Hospital, Genoa, Italy, where analyzed to evaluate proportions, rate for 1000 neutropenic days and etiology of fever in neutropenic children receiving gentle, standard, or peripheral blood stem cell transplant (PBSCT) therapy for central nervous system tumor. During the study duration, 243 periods of neutropenia (granulocyte count <1000/cmm), accounting for 3544 patient-days at risk, were documented in 62 children. A total of 72 febrile episodes were observed in 66 (27%) neutropenic periods, for a rate of 20.31. A primary febrile episode was observed in 10% of neutropenic periods after gentle chemotherapy, in 30% after standard chemotherapy, and in 48% after PBSCT (P<0.0001). The rate of primary febrile episodes was 6.19 after a gentle chemotherapy, 27.02 after standard treatment, and 31.02 after PBSCT (P<0.0001). In a multivariable regression model, the type of chemotherapy (gentle vs. standard and PBSCT) and the thresholds of granulocyte count at neutropenia onset (999-501/cmm and 500-101/cmm vs. ≤100/cmm) were the only factors significantly associated with the development of febrile neutropenia.

The outcome of hepatitis C in our patients is comparable to the one described in European cohorts of adult cancer survivors and perinatally infected subjects. Nevertheless, progression to high degrees of hepatic damage has to be monitored by a careful follow-up.