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/m2/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.

Phase I Trial, Pharmacokinetics, and Pharmacodynamics of Vandetanib and Dasatinib in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma

“…Osteonecrosis was seen by knee MRI in two patients 4 and 8 months after the start of therapy; both had received dexamethasone. Further details about cartilaginous and bony effects of this therapy were previously reported (30). …”

Growth plate abnormalities in pediatric cancer patients undergoing phase 1 anti‐angiogenic therapy: A report from the children's oncology group phase I consortium

“…Recent experimental work has shown discordance between radiologic and histologic Pediatr Blood Cancer DOI 10.1002/pbc dimensions of the zone of provisional calcification along the developing physis [35]. Others have suggested that MRI may provide a more sensitive and quantitative means of detecting skeletal toxicity in patients undergoing anti-angiogenic therapy, including growth plate abnormalities and osteonecrosis [36,37]. The MRI findings presented here showed physeal cartilage expansion and growth plate widening and were comparable to the histologic abnormalities that have been described in preclinical models of anti-angiogenic agent toxicity following exposure of animals to VEGF-targeted anti-angiogenics (Fig.…”