Cummings Ch 179 Stereotactic Radiation Treatment of Benign Tumors of the Cranial Base Sophie Shay, MD February 5, 2014 Department of Head and Neck Surgery

Key Points Stereotactic radiation therapy demonstrates good short-term control for many benign cranial base tumors Short-term quality of life outcomes favor stereotactic radiation therapy over conventional surgical management Radiation-induced cranial nerve injury has been reduced as lower doses of radiation have come into use Long-term control and radiation-induced malignancy risk will be known in the next decade with further study

Overview/Principles Goal = growth arrest of benign tumors Introduced in 1967 by Lars Leksell – early complications including brainstem radiation damage, hydrocephalus, cranial neuropathies Definition: application of any kind of ionizing radiation in a precise dosing mechanism to a target while limiting radiation exposure and damage to the adjacent surrounding tissues

From Pasha’s small paragraph on this topic… Good treatment option for elderly patients Avoid radiation in children, tumors with undocumented growth, or tumor prone (ie – NF-2) patients Consider for tumors < 2.5 cm Risk of CNVII and CNVIII injury may be less than surgical excision for small tumors

Basics of delivery Gamma Knife Linear Accelerators (LINACs) Single dose vs fractionated Ionizing radiation  excites electrions  free radical change  DNA damage  Apoptosis

Outcomes and Complications Tumor CONTROL: No growth of tumor vs. tumors that required no further treatment 1-2% of vestibular schwannomas resolve completely, tumor control is achieved in 74-100% Hearing loss Over 6-24 months, with an average decline of 15-20 dB Hearing loss also related to initial tumor size Facial nerve injury – rare and usually transient Trigeminal nerve toxicity – mild hypesthesia to trigeminal neuralgia Hydrocephalus

Types of Tumors Treated Vestibular Schwannomas/Acoustic Neuroma NF-2 related Vestibular Schwannomas Also effective at tumor control University of Pittsburgh – tumor volume is a predictor of tumor control 0.01-0.3% malignant transformation Cystic Schwannomas More controversial, can enlarge s/p radiation surgery Jugular Foramen Schwannomas (CN IX, X, XI, XII) Paraganglioma (CN VII, VIII)

COCLIA Questions

QUESTION 1: Describe the risks and benefits of using either stereotactic radiosurgery or skull base resection of vestibular schwannomas

SRS vs Surgery for Vestibular Schwannomas Benefits Decreased immediate morbidity to CNVII, CNVIII Faster recovery, lower cost Risks Malignant transformation Requires long term surveillance Risk of treatment failure (particularly for large tumors) Higher incidence of CNV injury This is difficult because different measurement outcomes are used…

SRS vs Surgery for Vestibular Schwannomas Surgical approaches to CPA Translabyrinthine (+) direct route, excellent exposure, less risk of CNVII injury (-) sacrifices hearing, higher risk of CSF leak Retrosigmoid/Suboccipital (large tumors) (+) wide exposure, hearing preservation (-) Limited exposure to IAC, higher risk of CNVII injury Middle Cranial Fossa (Small IAC lesions) (+) Hearing preservation (-) Retraction of temporal lobe, higher risk of CNVII injury Retrolabyrinthine (not for VS) (+) preserves hearing, shorter operative time (-) limited exposure (cannot access IAC or porus acousticus)

QUESTION 2: What are the long-term control rates for vestibular schwannoma using stereotactic radiosurgery?

VS Control Rates 1-2% of vestibular schwannomas resolve completely 74-100% tumor control over varied durations of follow up 5-year progression-free tumor control = 95% for single dose SRS and 94% for fractionated regimens Data is limited Literature is limited to retrospective studies Tumor Control is not well defined (ranging from no radiographic enlargement over a set parameter to failures requiring surgical treatment)

SRS: definitions and applications Application of any kind of ionizing radiation in a precise dosing mechanism to a target while limiting radiation exposure and damage to the adjacent surrounding tissues Applications: Vestibular schwannomas/Acoustic neuromas, Paragangliomas, Jugular Foramen Schwannomas

QUESTION 4: What are some absolute and relative contraindications to radiation therapy?

Contraindications to radiation Absolute contraindication Gorlin’s Syndrome (proliferation of BCC) Relative contraindication Previous head and neck radiation Inability to make appointments Connective tissue disorders (i.e. – SLE, scleroderma) with significant vasculitis

QUESTION 5: What are the complications of primary radiation therapy QUESTION 5: What are the complications of primary radiation therapy? What are the acute and late effects of radiation therapy?

Complications of radiation Acute: during the course of radiation Mucositis, odynophagia, dysphagia, hoarseness, xerostomia, dermatitis, weight loss, alopecia Late: occurring after the completion of treatment Xerostomia, osteoradionecrosis, fibrosis in normal tissues, thyroid dysfunction, vascular complications (i.e.- carotid artery rupture, pseudoaneurysm), fistula formation, neurologic complications (Myelopathy – paresis, numbness, sphincter dysfunction), radiation-induced cancer, otologic sequelae, cataracts, nonfunction larynx, stricture/stenosis

QUESTION 6: What are the effects of radiation on a cellular/molecular level?

Radiobiology Rad=Radiation Absorbed Dose 1 Gy = 100 Rads, 1cGy=1 Rad Cells are considered “killed” when they lose clonogenic survival Direct damage to DNA, cell membranes Indirect damage (secondary damage) – DNA injury from production of free radicals, cell death Larger tumors have a more hypoxic center = less sensitive to radiation (fewer free radicals) Cell death occurs with proliferation – rapidly growing tumors are more susceptible to RT

QUESTION 7: Discuss the 4 "Rs" of radiation therapy: Reassortment/Redistribution, Repair, Regeneration, and Reoxygenation.

4 “R’s” Of Radiation Biology = Fractionation Reassortment/Redistribution Fractionation allows for cells to proceed in their cycle to more radiosensitive stages of their cell cycle (mitosis, late G1, early S-phases) Reoxygenation Fractionation allows for reoxygenation of previously more hypoxic cells (making them more susceptible to RT)  more free radical generation Repopulation/Regeneration Prolonged waiting between fractions results in regrowth of tumor cells from sublethal damage Repair Normal tissue tends to have better repair than tumor cells, and therefore recovers more quickly

QUESTION 8: Name all those holes in the base of the skull and tell us what goes through each.

QUESTION 9: Review the boundaries of anterior, middle and posterior cranial fossa.

Anterior cranial fossa Anterior anterior border = posterior wall of the frontal sinus Posterior border = the anterior clinoid processes and the planum sphenoidale, which forms the roof of the sphenoid sinus. Lateral border = the frontal bone forms the lateral boundaries. The frontal bone houses the supraorbital foramina, which, along with the frontal sinuses, form 2 important surgical landmarks during approaches involving the anterior skull base.

Middle cranial fossa Anterior border = the greater wing of the sphenoid Posterior border = clivus Lateral border = the greater wing of the sphenoid forms the lateral limit as it extends laterally and upward from the sphenoid body to meet the squamous portion of the temporal bone and the anteroinferior portion of the parietal bone. Floor = The greater wing of the sphenoid forms the anterior floor of the fossa. The anterior aspect of the petrous temporal bone forms the posterior floor of the middle cranial fossa.

Posterior cranial fossa Anterior border = the apex of the petrous temporal. The petrous portion of the temporal bone and the greater wings of the sphenoid bone are particularly important for identifying structures. Posterior border = the occipital bone, with contributions from the sphenoid and temporal bones. Lateral border = the posterior surface of the petrous temporal bone and the lateral aspect of the occipital bone The overlying tentorium cerebelli separates the cerebellum from the cerebral hemispheres above

QUESTION 10: Discuss the classification of glomus tumors (Fisch vs QUESTION 10: Discuss the classification of glomus tumors (Fisch vs. Glasscock)

Pasha Table 8-4 Glasscock-Jackson Classification Glomus Tympanicum small mass limited to the promontory Tumor filling the middle ear space Tumor extending into the mastoid Tumor extending into the mastoid, EAC, and anterior to the carotid artery

Glomus Jugulare Small tumor involving jugular bulb, middle ear, and mastoid Tumor extending under IAC with or without intracranial extension Tumor extending into petrous apex with or without intracranial extension Tumor extending into the clivus, infratemporal fossa, may have intracranial extension

Fisch Classification Tumor involves middle ear only (glomus tympanicum) Tumor involves middle ear and mastoid Tumor extend in the infralabyrinthine region toward petrous apex Tumors with < 2 cm intracranial extension (D1) or >2cm (D2)