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Radiation-Induced Cavernous Hemangioma (RICH) is a possible consequence of brain irradiation that rarely causes symptoms but can result in severe hemorrhage and neurological symptoms. To date, only small numbers of RICH cases have been reported in the literature. We report on a case of a 16-year old male who underwent surgery for RICH due to intralesional hemorrhage. Follow-up imaging showed increasing hemorrhage of one of the lesions over time since irradiation. Additionally, the patient experienced headache and seizure-like events. Therefore, microsurgical resection was performed to prevent further hemorrhage and the risk of a symptomatic bleeding event. Imaging carried out after surgery showed no sign of any new hemorrhage but still multiple other RICH lesions.Patients with RICH are often asymptomatic, but still it can lead to severe hemorrhage. Thus, follow-up imaging after brain irradiation is crucial to detect early signs of RICH and assess its evolution. To prevent symptomatic hemorrhage, surgery for RICH should be carefully considered on a case-by-case basis if the patient becomes symptomatic or if imaging shows increasing hemorrhage.

Abstract: We conducted a clinical trial and report the long-term outcome of 773 children with acute lymphoblastic leukemia upon risk-adapted therapy accrued in trial CoALL 07-03 (from the Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia). In a 2-step stratification, patients were allocated to receive either low- or high-risk treatment, based on initial white blood cell count, age, and immunophenotype. A second stratification was performed according to the results of in vitro pharmacosensitivity toward prednisolone, vincristine, and asparaginase (PVA score) and in vivo response after induction therapy (minimal residual disease [MRD]). Therapy was reduced for both risk groups in patients with a low PVA score or negative MRD result, and intensified in patients with a high PVA score. Overall outcome improved significantly compared with the predecessor CoALL 06-97 trial, with identical therapy backbone despite treatment reduction in 15.8% of patients (10-year probability of event-free survival, 83.5% vs 73.9%; overall survival, 90.7% vs 83.8%). Outcome for patients in the reduced treatment arms was superior to that of patients in the standard arms, associated with a profound reduction in frequency and severity of infectious complications. Importantly, we observed a lack of correlation between in vitro and in vivo drug response, as well as a lower predictive value of in vitro drug testing, reflecting an intrinsic limitation of this methodology that prevents its use for treatment stratification in future trials. In conclusion, it might be possible to reduce chemotherapy in children with acute lymphoblastic leukemia selected by stringent in vivo measurement of MRD without jeopardizing overall outcome.