Challenges with defining response to antitumor agents in pediatric neuro-oncology: a report from the response assessment in pediatric neuro-oncology (RAPNO) working group

Abstract

Criteria for new drug approval include demonstration of efficacy. In neuro-oncology, this is determined radiographically utilizing tumor measurements on MRI scans. Limitations of this method have been identified where drug activity is not reflected in decreased tumor size. The RANO (Response Assessment in Neuro-Oncology) working group was established to address limitations in defining endpoints for clinical trials in adult neuro-oncology and to develop standardized response criteria. RAPNO was subsequently established to address unique issues in pediatric neuro-oncology. The aim of this paper is to delineate response criteria issues in pediatric clinical trials as a basis for subsequent recommendations.

Keywords: RANO; brain; imaging; pediatric; response; tumor.

Fig. 1.

CNS tumor distribution by diagnosis in children ages 0–14 years as reported by the Central Brain Tumor Registry of the United States (with permission) [9].

Fig. 2.

T1-weighted, post-contrast axial (A) and sagittal (B) images from a 7-month-old infant with pilocytic astrocytoma (WHO I) demonstrating irregular, lobulated shape, and metastatic spread.

Fig. 3.

Low-grade dorsal midbrain glioma in a 15-year-old patient treated with proton beam radiotherapy after prior progression on vincristine/carboplatin. A: Pre-radiation. B: Three months post-radiation therapy showing increase in enhancement. C: Twelve months post-radiation therapy showing subsequent regression in the area of enhancement.

Fig. 4.

Tumor burden assessed by post-contrast and FLAIR imaging in two patients with DIPG. A: Sagittal T1-weighted post-contrast and (B) FLAIR sequences for Patient 1 demonstrating heterogeneous enhancement, and (C) axial T1-weighted and (D) FLAIR sequences for Patient 2 demonstrating tumor burden on FLAIR in a non-enhancing lesion.