Magnetic resonance imaging is the preferred method to assess treatment-related skeletal changes in children with brain tumors

Abstract

Purpose: To evaluate the growing skeleton for potential altered skeletalgenesis associated with antiangiogenesis therapy.

Patients and methods: Knee radiographs and magnetic resonance imaging (MRI) were prospectively obtained on patients enrolled on two consecutive clinical trials using vandetanib, a potent oral (VEGF receptor 2) VEGFR-2 inhibitor alone or combined with dasatinib, a multiple tyrosine kinase inhibitor, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

Results: Fifty-nine patients (32 females) underwent 119 MRIs; 51 patients underwent 89 radiographs of the knees. The median age at enrollment was 6.2 years (range, 2.4-17.6 years). The dose of vandetanib ranged from 50 to 145 mg/m(2) /day. The median treatment duration was 205 days. Only two patients have not experienced disease progression after 18 and 60 months from diagnosis. MRI identified clinically significant premature physeal fusion in both knees of one patient, focal physeal thickening in one, osteonecrosis in eight patients (present at enrollment in one), and bony spicules crossing the physis in two patients (bilateral in one). MRI follow-up period averaged 5.3 months (range, 0-25.5 months; median, 3.5 months). Radiographs delineated normally fused physes in two patients but no cases of premature physeal fusion, osteonecrosis or bony spicules.

Conclusions: As MRI provided greater information than radiographs, and thus would be a more sensitive test to assess skeletalgenesis in pediatric patients.

Keywords: VEGF; antiangiogenesis agents; chemotherapy; magnetic resonance imaging; pediatric brain tumors; skeletalgenesis.

Fig. 1

Patient cohort for radiographic and magnetic resonance (XR/MRI) imaging of the knees.

Fig. 2

Six-year-old female who developed extensive ostenecrosis and focal physeal fusion while on therapy. This patient had received 10 mg/m² dexamethasone and 50 mg/m²/day vandetanib. A: Normal baseline appearance of the knee on sagittal T1- and (B) coronal STIR. Three-month follow-up shows extensive diffuse intramedullary lacey pattern on the sagittal (C) and coronal (D) images outlined with edema and involving the epiphysis, metaphysis, and diaphysis. Focal physeal thickening is indicated by the arrow (E) and (F) 7-month follow-up showing increase in size of the focal femoral physeal thickening (arrows), persistence of diffuse epiphyseal, metaphyseal, diaphyseal, and patellar changes of presumed osteonecrosis. Note that the involved areas of intramedullary changes appear to be better demarcated and the interstices somewhat thicker. G–I: Nine-month follow-up MR demonstrating focal central physeal bridging tibia and femur (arrows) in the site of previous cartilaginous in growth on the femur. Note thickening of interstices of intramedullary changes and some degree of regression of the extent of involvement of osteonecrosis.