John P. Christodouleas and Timothy A. Chan
Are optic pathway gliomas (OPGs) more commonly seen in children or adults?
75% of all OPGs occur in children <10 yo.
What is the median age at Dx?
OPGs have a bimodal distribution with peaks at 5 yrs and 52 yrs of age.
OPG represents what % of all CNS tumors in children?
OPG represents 5% of all CNS tumors in children.
Are OPGs typically low grade or high grade?
OPGs are typically low grade (grade 1).
Is there a gender predilection in OPG?
Yes. In children, females are more commonly affected than males. In adults, males are more commonly affected than females.
What genetic syndrome is associated with OPG?
OPG is strongly associated with NF-1. 10%−38% of OPG pts have NF-1, and 15%−40% of NF-1 pts have OPG. (NF-2 is associated with acoustic neuromas.)
What are the subtypes of OPGs?
OPGs are organized by location:
Which OPG subtype is more common in children vs. adults?
Ant OPG is more common in younger children (and in pts with NF-1). Chiasmatic and hypothalamic gliomas are more common in adults.
Which subtype has the worst prognosis?
Hypothalamic OPG has the worst prognosis (OS 50%–80%/LC 40%–60% vs. other types (OS 90%–100%/LC 60%–90%).
How do pts with OPGs typically present?
The most common presenting Sx is painless proptosis. Other Sx include ↓ visual acuity, temporal field defects (chiasmatic), changes in appetite or sleep (hypothalamic Sx), and new-onset HA and n/v (obstructive hydrocephalus).
What is the workup for pts with suspected OPG?
Suspected OPG workup: H&P, basic labs, MRI brain, visual acuity and field examination (preferably by a neuro-ophthalmologist), and a baseline endocrinology evaluation
What is the DDx of an optic nerve mass?
Optic neuritis, retinoblastoma, optic nerve meningioma, and lymphoma
How do OPGs appear on MRI?
On MRI, OPGs appear as well-circumscribed, homogeneously enhancing lesions.
Is Bx necessary for Dx?
No. Imaging and the clinical exam are sufficient for OPG Dx.
What is the preferred Tx paradigm for pts with OPGs?
Preferred OPG Tx paradigm: consider observation or chemo 1st (especially in young children) +/− RT. Surgery typically is reserved for refractory and symptomatic Dz or as a means of delaying RT in young children.
What chemo agents are generally used for OPG?
Cisplatin/carboplatin + etoposide or vincristine
What data support prolonged chemo as a way of avoiding/delaying RT without compromising OS or visual function?
Laithier et al. prospectively evaluated prolonged chemo (alternating procarbazine/carboplatin, etoposide/cisplatin, and vincristine/cyclophosphamide q3wks). 2nd-line chemo was given at relapse before RT. The objective response rate was 42%, 5-yr OS was 89%, and 5-yr freedom from RT was 61%. (JCO 2003)
What is the ongoing Children's Cancer Group (CCG) protocol (A9952) comparing?
CCG A9952 is comparing chemo regimens (carboplatin/vincristine vs. thioguanine/procarbazine/lomustine/vincristine)
When is RT indicated in OPG?
RT is typically used after chemo options are exhausted, when there are progressive Sx, or when there is intracranial extension.
OPGs are typically treated to what RT dose and fractionation?
OPGs are typically treated to 45–54 Gy in 1.8–2 Gy/fx.
What is the preferred RT technique used to treat OPGs?
Proton therapy has dosimetric advantages, though there is limited clinical data. FSR has shown promising results (5-yr PFS 72%) (Combs SE et al., IJROBP 2005).
What is the estimated 5-yr OS in OPG?
The estimated 5-yr OS is 89%. (Laithier V et al., JCO 2003)
What is the main risk of surgery for OPGs?
Visual morbidity is the main surgical risk.
What are common late complications of RT in the Tx of OPGs?
Common late complications of RT include endocrine dysfunction and vision loss.
What is the main disadvantage of RT in NF-1 pts?
High incidence of 2nd CNS tumors (RR 5.3: Sharif S et al., JCO 2006)
What is the RT TD 5/5 dose threshold for developing hypopituitarism?
The hypopituitarism TD 5/5 is 40–45 Gy (GH levels ↓ 1st, then LH/FSH, then TSH/ACTH.)