Treatment > Methotrexate • Radiation Related Pathology

Meeting Abstract

Cranial radiation therapy following four courses of high-dose methotrexate: Late follow-up of MRI features of leukoencephalopathy

S. J. Kellie, J. Chaku, L. Lockwood, P. O'Regan, K. D. Waters, C. K. F. Wong

ANZCCSG; The Children's Hosp - Westmead, Sydney, Australia; University of Sydney, Sydney, Australia; Royal Children's Hospital, Brisbane, Australia; Royal Children's Hospital, Melbourne, Australia

We previously conducted a Phase II study of four courses of preradiation combination chemotherapy including high-dose methotrexate (HDMTX) 8 gm/m² in children with newly diagnosed CNS embryonal tumors. (Med Pediatr Oncol 39:168, 2002)
The current investigation is a late follow-up of survivors of the previous study to assess the incidence and severity of MRI features of leukoencephalopathy when patients receive HDMTX before cranial radiation therapy.
This is significant because of emerging interest in adding HDMTX to the treatment of infants with CNS tumors who may subsequently receive cranial radiation therapy and because of the well described observation of severe leukoencephalopathy when methotrexate administration follows cranial irradiation.
Twelve patients aged from 3.5 - 14.2 yrs, (median 6.9 yrs), at the time of initial diagnosis underwent MRI brain scans 4.0 - 10.5 yrs, (median 6.5 yrs) after chemotherapy and radiation therapy.
MRI studies comprised a minimum of T1, T1 & gadolinium and T2 sequences and were centrally reviewed by three investigators using the 'Leukoencephalopathy-associated radiological findings' criteria of the NCI Common Toxicity Criteria, v2.0.
Grade 1 changes (mild increase in subarachnoid space, and/or mild ventriculomegaly, and/or small/focal T2 hyperintensities) were evident in 8/12 patients; Grade 2 (moderate increase in subarachnoid space an/or moderate ventriculomegaly, and/or focal T2 hyperintensities extending to the centrum ovale) in 2/12, and Grade 3 changes were present in 2/12 patients based solely on the presence of lacunes, representing small areas of focal white matter necrosis, with Grade 2 changes otherwise.
We found that repeated courses of HDMTX followed by cranial radiation therapy was not associated with evidence of severe diffuse white matter changes at late MRI follow-up.

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