LGG-01. Children with Supratentorial Midline Pilocytic Astrocytomas Exhibit Multiple Progressions and Acquisition of Neurologic Deficits over Time

Pilocytic astrocytomas are the most common solid tumor of childhood and can arise anywhere in the central nervous system, including the posterior fossa (pf-PA), supratentorial midline (sm-PA; including optic pathway, hypothalamus, thalamus), and brainstem (bs-PA). Location (sm, bs) has been previously proposed as a prognostic factor for PA, but is difficult to separate from resection status on multivariate analysis. To overcome this limitation, we assembled a large cohort of children (n = 251) with biopsy-proved PA treated at St. Louis Children’s Hospital from 2003 – 2021 and analyzed outcomes only in patients with subtotal resection (STR; n = 81). We excluded patients with NF1, as NF1-associated gliomas often display a more indolent clinical course than their counterparts. We identified that children with STR sm-PA had a higher likelihood of multiple progressions compared to children with STR bs-PA and pf-PA. This was associated with worsening neurologic deficits over time, consistent with the sm location as a poor prognostic factor. Furthermore, the only children in our cohort with leptomeningeal dissemination or death harbored sm-PAs. Tumors in this location were also associated with an increased likelihood of non-BRAF-fusion genetic alterations and multiple oncogenic mutations. Overall, these data support location as an independent prognostic factor for PA in cases in which a gross-total resection cannot be achieved. Treating neuro-oncologists may thus wish to consider early intervention rather than watch-and-wait strategies at first progression of STR sm-PA. These patients may also benefit from earlier consideration of molecularly targeted therapy.