Boris Hristov and Ori Shokek
What is the origin of craniopharyngioma?
Epithelial tumor arising from an incompletely involuted hypophyseal-pharyngeal duct (Rathke pouch) from an anatomic region called the tuber cinerium
In what region of the brain does it usually arise?
Suprasellar region (most common), sella proper (less common)
Are craniopharyngiomas malignant?
No. They are histologically benign but are problematic due to local progression around critical structures.
Approximately how many cases of craniopharyngioma occur annually in the U.S.?
~300–350 cases/yr of craniopharyngioma in the U.S.
At what ages does craniopharyngioma occur?
Median age 5–10 yrs; higher risk age <20 yrs and >40 yrs (bimodal); one third of cases occur in pts age 0–14 yrs.
What are the 2 histologic subtypes of craniopharyngioma?
Adamantinomatous and squamous
Which subtype is characterized by a solid and cystic pattern?
Adamantinomatous craniopharyngioma has a solid and cystic pattern.
Historically, how has the cyst fluid consistency been described?
“Machine oil” like (very proteinaceous fluid)
What structures do cysts usually abut superiorly?
Tumors/cysts usually abut the 3rd ventricle and the hypothalamus superiorly.
Name the most common presenting signs/Sx of craniopharyngioma.
HA, N/V (i.e., ↑ICP), visual change, diabetes insipidus
What is the most common hormone deficiency at presentation?
At presentation, GH is the most common hormone deficiency.
Which type of craniopharyngioma has a better prognosis: calcified or noncalcified?
Noncalcified craniopharyngioma has a better prognosis.
Do craniopharyngioma tumors respond rapidly or slowly to RT?
Craniopharyngioma tumors respond very slowly to RT.
What is the workup for a craniopharyngioma?
Craniopharyngioma workup: H&P, basic labs, pituitary panel, and MRI brain
What ancillary studies need to be done before Tx?
Endocrine, audiology, vision, and neuropsychiatric studies
What is the classic appearance of craniopharyngiomas on CT/MRI?
Craniopharyngiomas are partially calcified and cystic on CT/MRI.
Is histology absolutely necessary for the Dx of craniopharyngioma?
No. A Dx can be made based on radiographic appearance and cyst fluid analysis.
What is the staging of craniopharyngioma?
There is no formal staging.
What is the Tx paradigm for craniopharyngioma?
Craniopharyngioma Tx paradigm: max safe resection, EBRT/intracystic chemo adjuvantly or at recurrence
What surgical approach is typically employed for craniopharyngioma resection?
Lat pterional approach (temporal craniotomy)
Is observation ever appropriate after incomplete resection for craniopharyngioma?
Yes. Observation is especially appropriate in young pts. Adj and salvage therapy may have similar LC in closely followed pts.
What are the RT doses used for craniopharyngioma?
54 Gy with EBRT, 12–14 Gy with SRS
What volumes are typically irradiated for craniopharyngioma?
GTV is decompressed/postop volume = tumor + cyst wall (cysts decompressed before Tx); PTV is GTV + 1–1.5 cm; no CTV.
What % of attempted craniopharyngioma GTRs result in STR?
Depends on location, but overall, 20%–30% (Tomita T et al., Childs Nerv Syst 2005)
Estimate the 10-yr LC with surgery alone vs. surgery + postop RT for craniopharyngioma.
Surgery (GTR + STR) alone ~42%; surgery + RT ~84% (Stripp DC et al., IJROBP 2004)
Estimate the 10-yr LC with adj RT vs. salvage RT.
Both ~83%–84% (Stripp DC et al., IJROBP 2004). RT can be deferred for children <5–7 yo after surgery.
In what 3 ways can craniopharyngioma cysts be managed?
Aspiration, radioactive isotope injection, and bleomycin injection
What isotopes have been used for intracystic RT? To what dose?
β-emitting isotopes (yttrium-90, P-32, Rh-186); 200–250 Gy to the cyst wall
Why is P-32 conjugated to a sugar moiety, and why is it toxic to the brain tissue if it leaks outside the cyst?
It is conjugated to a large sugar molecule so it stays within the cyst. It is toxic because the preservative in the P-32 suspension (Na benzoate) is neurotoxic.
What is the energy and half-life of P-32, and to what depth is it effective?
0.7 MeV, 2 wks. The effective depth is 3–4 mm.
What are the indications for intralesional cyst management (vs. cyst aspiration)?
Intralesional Tx is an option if the cyst is >50% of total tumor bulk and the number of cysts is ≤3.
What intracystic chemo has been used?
Bleomycin typically has been used for intralesional cyst management.
If a pt has worsening visual Sx while getting adj RT, is this likely due to an acute side effect from RT?
No. Acute Sx during RT are likely due to a rapidly enlarging cystic component; therefore, urgent surgical intervention for decompression is indicated (some even advocate serial MRIs during RT).
What is the typical response rate to intralesional brachytherapy?
80%, with stable or visual Sx improvement in 51%. MS is 9 yrs. (Julow J et al., Acta Neurochir 1985)
What is the typical response rate to intralesional bleomycin?
Limited data, ~65% overall response rate (29% CR). Median PFS is 1.8 yrs. (Hukin J et al., Cancer 2007)
Which institution showed feasibility of fractionated proton RT for craniopharyngioma?
Loma Linda (Luu QT et al., Cancer 2006)
What factors have been shown to correlate with inferior LC in craniopharyngioma?
Size >5 cm (Joint Center data: Hetelekidis S et al., IJROBP 1993) and RT dose <55 Gy (Pittsburgh data: Varlotto JM et al., IJROBP 2002)
What is the significance of cyst regrowth after RT?
Cyst regrowth may occur after definitive Tx (does not mean failure, as RT can take a long time to exert its ablative effects). Repeat aspirations are in order if the pt is symptomatic.
What recent study proposed a risk-stratification scheme to guide the aggressiveness/extent of surgery? What did it show?
A French study by Puget et al. showed significant reductions in endocrine and hypothalamic dysfunction if pts stratified prospectively before surgery based on the degree of hypothalamic involvement: grades 0–1, attempt GTR; grade 2, STR (+RT if >5 yo, observe if <5 yo). (J Neurosurg 2007)
What is the 5-yr OS of pts with craniopharyngioma?
5-yr OS for pts with craniopharyngioma is 80%.
What is the long-term survival for pts with craniopharyngioma?
The 20-yr OS is 60%. Though benign, it does shorten life!
What is the long-term outcome of recurrent craniopharyngioma?
The 20-yr OS is ~25% for recurrent lesions.
What are the most common/serious side effects of surgery?
Vision loss (< 2%), hypopituitarism, and hypothalamic injury (hypothalamic eating disorders, defective short-term memory, sleep disturbances)
What are some concerning side effects of RT for craniopharyngioma?
Cognitive dysfunction/↓IQ (10%), endocrine dysfunction, 2nd malignancy, cystic enlargement, and vasculopathy
What is the mortality rate from radical surgery for craniopharyngioma?
As high as 10%. Because of this and because STR + RT = GTR in terms of outcomes, radical surgery is not a must. Also, St. Jude data (2002) showed that the surgery group lost an avg of 9.8 IQ points; the more limited surgery + RT group lost an avg of 1.25 points.
How long does it usually take for tumors to regrow? What follow-up is needed?
2 yrs on avg. However, there is a big range, and regrowth can take up to 9 yrs. Thus, the pt requires long-term follow-up with serial MRIs and neuro-ophthalmology/edocrinology exams.
The hypothalamus should be kept at or below what total RT dose?
If possible, the hypothalamus should not exceed 45 Gy.