# Radiation Oncology/Craniopharyngioma

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Craniopharyngioma

## Overview

* Represents 6-9% of pediatric brain tumors (#3 after gliomas and medulloblastoma)
* Histoligically benign tumors
* Clinically present with headaches (~50%), visual disturbances (40-70%), and pituitary dysfunction (up to 90%)
** Children: hypothyroid and GH deficiency
** Adults: sexual dysfunction (men erectile dysfunction, women amenorrhea)
* Due to its locally advancing nature, often gives rise to endocrine deficits chiefly of pituitary origin
* Bimodal distribution in incidence: pediatric (infants/children) and adult (55-65 years)

## Anatomy

* Derived from Rathke's pouch remnant (embryonic precursor of the anterior pituitary)
* Most commonly suprasellar location (pituitary stalk) with possible extension into posterior and middle cranial fossae
* 70% retrochiasmatic, often extending to 3rd ventricle and along hypothalamus
* Commonly has both solid and cystic components
* Size varies from small well-circumscribed lesions to very large multiple cysts

## Histology

* Benign tumor of squamous cell origin
* Histologic subtypes include:
** Adamantinoma: epithelial mass forming a reticulum - most common in children
** Mucoid epithelial cyst
** Squamous papillary
* Presumably arise from embryonic remnant and grow slowly since birth; however, de novo case in a 55 year-old has been documented

## Diagnosis

* Classic CT findings are calcified suprasellar mass with cysts
** Mass is usually a mixed cystic and solid lesion
** 75% have at least 1 cyst
** 80% have calcifications
* Endocrine work up should be performed prior to initiation of therapy

## Treatment

* Total resection may be attempted, but radical surgery can have as high a mortality rate as 10%, and a high severe morbidity rate.
* Maximal safe resection followed by irradiation is the currently accepted modality of management. Subtotal resection + RT has nearly equivalent local control and overall survival as gross total resection.
* Tumor responds slowly to radiation, and in some patients, radiation induced edema can worsen the symptoms.
* Role of chemotherapy in this condition is not documented to date, but intracystic bleomycin has been shown to cause tumor response.

### Combined Modality Therapy

* Pittsburgh, 2002 (1971-92) - PMID 12243827 -- "External beam irradiation of craniopharyngiomas: long-term analysis of tumor control and morbidity." Varlotto JM et al. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):492-9.
** 24 pts w/ craniopharyngioma tx'd w/ EBRT as part of treatment course (19 pts w/ subtotal resection, 2 w/ bx alone).
** 10 yr actuarial local control was 89%; 20 yr actual local control 54%
** Multivariate analysis showed dose (>55 Gy) to be significant prognostic factor for control, and tx complication probability was related to hypopituitarism at presentation.
* St. Jude's, 2002 (1984-97) - PMID 12062594 -- "Craniopharyngioma: the St. Jude Children's Research Hospital experience 1984-2001." Merchant TE et al. Int J Radiat Oncol Biol Phys. 2002 Jul 1;53(3):533-42.
** 30 pts w/ craniopharyngioma (15 tx'd w/ radical surgery, 15 tx'd w/ limited surgery + upfront RT)
** Surgery group lost avg of 9.8 IQ points, limited surgery + RT group lost avg of 1.25 points.
** Surgery group had more frequent neurologic, ophthalmologic, and endocrine complications.
* Joint Center/Children's Hospital, 1994 (1970-1990)
** PMID 7841082 -- "Surgery, radiation, and combination therapy in the treatment of childhood craniopharyngioma--a 20-year experience." Scott RM et al. Pediatr Neurosurg. 1994;21 Suppl 1:75-81.
** 61 pts w/ craniopharyngioma (9 w/ RT alone, 15 w/ surgery alone, 37 w/ surgery + RT)
** 10 yr actuarial survival 91%
** PMID 8407391 -- "20-year experience in childhood craniopharyngioma." Hetelekidis S et al. Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):189-95.
** 10 yr PFS in surgery group 31%, in RT alone group 100%, in surgery + RT group 86%.
** Size of tumor (>5cm) correlated w/ risk of recurrence.
* Royal Marsden, 1961 - PMID 13753942 -- "Craniopharyngiomas. Treatment by combined surgery and radiation therapy." Kramer S et al. J Neurosurg. 1961 Mar;18:217-26.
** 6 pts w/ craniopharyngioma tx'd w/ limited surgery + RT. All 6 achieved 15 yr PFS.

## Radiation Techniques

* Radiation therapy is targeted to the tumor volume,encompassing all its components.
* A classical coronal arc configuration of treament portal is recommended, or conventional 2- 3 field technique can be used.
* Current techniques include 3D conformal RT, IMRT or proton beam.
** CTV expansion on GTV should be at least 1cm (for cyst expansion, not because of microscopic invasion)
** In spite of CTV expansion a significant percentage found to move out to RT field during RT course (35%). Current areas of study include determination of necessity of imaging during RT course.
* Dose prescription is 50-60 Gy, and if beyond 60 Gy, optic neuropathy and brain necrosis can be expected.
* Cystic lesions can be treated with stereotactically applied intracystic colloidal Yttrium-90.
** Dose prescription is 200-300 Gy to the inner surface of the cyst wall.
** Major toxicity of intracystic beta emitters is visual toxicity.

## Proton Therapy

* Harvard; 2009 (2001-2007) PMID 18676089 -- "Surveillance of craniopharyngioma cyst growth in children treated with proton radiotherapy." (Winkfield KM, Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):716-21.)
** Retrospective. 17 children with surveillance imaging during RT.
** Outcome: 24% cysts growth beyond original treatment fields. 1 patient field reduction, 1 patient cyst drainage to avoid enlargement of treatment fields
** Conclusion: Routine imaging during treatment is recommended; at least q2 weeks
* Loma Linda; 2006 PMID 16630407 -- "Fractionated proton radiation treatment for pediatric craniopharyngioma: preliminary report." (Luu QT, Cancer J. 2006 Mar-Apr;12(2):155-9.)
** Retrospective. 16 patients. Dose 50.4 - 59.4 CGE.
** Outcome: LC in 14/15 (93%). OS 12/15 (80%)
** Toxicity: panhypopituitarism, CVA, and out-of-field meningioma in patient with prior RT
** Conclusion: Fractionated proton therapy effective for craniopharyngeioma