BACKGROUND

What is the typical age distribution of patients diagnosed with optic pathway gliomas (OPGs)?

OPGs have a bimodal distribution with peaks at 5 yrs and 52 yrs of age. 75% of all OPGs occur in children <10 yo.

OPG represents what % of all CNS tumors in children?

OPG represents 5% of all CNS tumors in children.

What histologic grade is typical of OPG?

OPGs are typically low grade. Pilocytic astrocytoma (grade I) is the predominant histology. However, grade II has been reported.

Is there a sex predilection in OPG?

Yes. In children, girls are more commonly affected than boys. In adults, males are more commonly affected than females.

What genetic syndrome is associated with OPG?

OPG is strongly associated with NF-1. Most patients with OPGs have NF-1 (typically diagnosed before age 6 yrs due to screening), while ∼15%–20% of NF-1 pts have OPG. (NF-2 is associated with acoustic neuromas.)

What are the subtypes of OPGs?

OPGs are organized by location:

1. Ant/prechiasmal

2. Chiasmatic

3. Hypothalamic

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?

A common presenting Sx is painless proptosis. Other Sx include ↓ visual acuity, visual field defects, changes in appetite or sleep/precocious puberty (hypothalamic), and new-onset HA and n/v (obstructive hydrocephalus).

WORKUP/STAGING

What is the workup for pts with suspected OPG?

Suspected OPG workup: H&P (including a neuro-ophthalmic exam with a quantitative visual acuity assessment), MRI brain and orbits, genetic evaluation, and baseline endocrinology

What is the DDx of an optic nerve mass?

Optic neuritis, retinoblastoma, optic nerve meningioma, and lymphoma, hamartomas

How do OPGs appear on MRI?

On MRI, OPGs appear as well-circumscribed, homogeneously enhancing lesions (isointense on T₁ and iso- to hyperintense on T₂). Contrast enhancement and presence of cysts are more common in sporadic OPGs than in NF-1 associated.

Is Bx necessary for Dx?

No. Imaging and the clinical exam are sufficient for OPG Dx.

TREATMENT/PROGNOSIS

What is the preferred initial Tx for pts with OPGs?

OPG Tx (controversial): Initial management most commonly is observation. Tx is typically reserved for pts with documented progression or declining visual acuity.

What is the Tx paradigm once pt progresses?

1. Chemo: first step due to risks of local therapy, especially if pt <10 yo

2. RT: good tumor control but typically delayed as long as possible due to long-term toxicity

3. Debulking surgery: reserved for refractory or symptomatic

What chemo agents are generally used for OPG?

Carboplatin + vincristine or etoposide

What data support prolonged chemo as a way of avoiding/delaying RT without compromising OS or visual function?

Laithier V et al. prospectively evaluated prolonged chemo (alternating procarbazine/carboplatin, etoposide/cisplatin, and vincristine/cyclophosphamide q3wks). 2^nd-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 data support initial RT instead of initial chemo?

Awdeh RM et al. from St. Jude’s prospectively followed 20 pts (IJROBP 2012). Visual acuity was better in patients treated with upfront RT compared to those treated with chemotherapy and RT as salvage therapy.

What is the ongoing Children’s Cancer Group (CCG) protocol (A9952) comparing?

CCG A9952 compares 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 using what RT dose, fractionation, and technique?

OPGs are typically treated to 45–54 Gy in 1.8Gy/fx. Proton therapy may have dosimetric advantages, especially in children. Fractionated stereotactically guided RT has good outcomes (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)