Abstract
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) carries a high mortality rate and lacks effective treatment options with a median overall survival (OS) of 8-12 months. Convection-enhanced delivery (CED) has demonstrated safety in phase I trials, but efficacy is indeterminate. Evaluating anatomic patterns of relapse may aid in determining therapeutic efficacy of local CED drug delivery strategies. METHODS: Sixty-three children with DIPG were retrospectively reviewed for first radiographic progression. All patients were treated using conventional external beam radiation (EBRT) and 31 were treated with CED of radiolabeled 124-iodine-omburtamab (NCT01502917). Anatomic patterns of initial progression were coded by independent neuroradiologists. OS and cumulative incidence of progression at each anatomic site were assessed in a competing risk analysis with death as a competing variable and were stratified based on CED treatment. RESULTS: Median OS was 14.67 months for the cohort. Patients receiving CED demonstrated higher rates of progression in general, when considering progression at all anatomical sites (HR 1.79, P = .047); no significant difference was found in OS when stratified by CED treatment (P = .22). However, CED treatment was associated with significantly lower cumulative incidence of local pontine and medullary progression (HR: 0.42, P = .03; HR 0.14, P = .01, respectively) relative to non-CED-treated patients. CONCLUSIONS: Anatomically defined patterns of relapse provide evidence for locoregional control in children with DIPG treated with radioimmunotherapy administered by CED. Future CED or local surgical therapy trials can benefit from including detailed patterns of relapse as a prospective outcome.