Defining Radiographic Progression, Preserving Vision, and Strategic Use of Treatment Lines

In this segment, Dr. Chintagumpala, Dr. Margol, and Dr. Chi discuss how to define true radiographic progression in pediatric pediatric low-grade glioma (PLGG) and confront the challenge of preserving vision across multiple lines of therapy.

Chiasmatic-hypothalamic tumors are typically large (3 cm or more), making percentage-based thresholds more applicable than in small tumors. A 25% growth cutoff is a reasonable trigger for initiating therapy in a steadily growing, large tumor in an older, non-NF1 patient, particularly when there is a documented pattern of regrowth after stopping therapy, although waiting too long risks irreversible vision loss given the lag between radiographic progression and visual decline. RAPNO (Response Assessment in Pediatric Neuro-Oncology) criteria work well for clinical trial assessment, where objective drug efficacy must be measured, but a tension exists: Trial criteria may force discontinuation of a therapy still providing clinical benefit despite meeting a technical progression threshold. RAPNO provides measurement recommendations and response assessment, not guidance on when to initiate the next therapy.

Strategically, clinicians should avoid "burning through" treatment options too quickly, especially in young children with large tumors who may need three, four, or five therapies over their childhood. Vision preservation remains the most difficult challenge in treating optic pathway gliomas: despite multiple promising therapies, many children still experience severe vision loss, and vision assessment itself is difficult in young children, compounding the challenge.

In the next episode, "Choosing First-Line Therapy in PLGG: Chemotherapy, Targeted Agents, and Tumor Biology," the panel discusses first-line treatment selection for BRAF-fusion and BRAF V600E-mutant PLGG, the role of chemotherapy versus targeted agents, and the unanswered question of tumor senescence.