QUANTEC: ORGAN-SPECIFIC PAPER Central Nervous System: Optic Nerve/Chiasm RADIATION DOSE–VOLUME EFFECTS OF OPTIC NERVES AND CHIASM CHARLES MAYO,PH.D.,* MARY K. MARTEL,PH.D., y LAWRENCE B. MARKS, M.D., z JOHN FLICKINGER, M.D., x JIHO NAM, M.D., z AND JOHN KIRKPATRICK, M.D., PH.D. { *Department of Radiation Oncology, University of Massachusetts School of Medicine, Worcester, MA; y Department of Radiation Oncology, M. D. Anderson Cancer Center, Houston, TX; z Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC; x Department of Radiation Oncology, University of Pittsburgh Presbyterian Hospital, Pittsburgh, PA; { Department of Radiation Oncology, Duke University Medical Center, Durham, NC Publications relating radiation toxicity of the optic nerves and chiasm to quantitative dose and dose–volume measures were reviewed. Few studies have adequate data for dose–volume outcome modeling. The risk of toxicity increased markedly at doses >60 Gy at z1.8 Gy/fraction and at >12 Gy for single-fraction radiosurgery. The evidence is strong that radiation tolerance is increased with a reduction in the dose per fraction. Models of threshold tolerance were examined. Ó 2010 Elsevier Inc. Optic, Nerve, Chiasm, Tolerance, Radiotherapy. 1. CLINICAL SIGNIFICANCE The therapeutic dose levels for tumors in the central nervous system and head-and-neck area are often constrained by the radiation tolerance of the optic apparatus. Visual impairment from radiation-induced optic neuropathy (RION) is uncom- mon but disabling (1, 2). It usually presents with painless rapid visual loss. Vasculature injury has been suggested as a significant contributor to RION (3, 4). Treatment of radio- therapy (RT)-associated visual loss is limited. 2. ENDPOINTS Visual impairment is typically defined according to the visual acuity (3, 5–8) and is typically defined as 20/100 vision or less, meaning that the patient can see at 20 feet no more than a normal person can see at 100 feet. Furthermore, impairment is often described by the size/extent of the ‘‘visual fields’’ (how much of the potentially visible region can be visualized). For instance, patients often lose vision of one-half or a quadrant of the visual field owing to injury of a part of the optic nerves/chiasm. The interval between RT and the development of visual symptoms is generally #3 years (mode, 1–1.5; median, 2.5) (2, 9). Optic nerve injury typically results in monocular visual loss, except if it occurs very close to the optic chiasm, where fibers looping up from the contralateral medial eye/retina can be affected. Injury to the entire chiasm can cause bilateral vision loss. Temporary injury limited to the inferior central optic chiasm from pituitary adenoma results in bilateral upper outer quadrant visual field impairment. The loss of a proximal optic tract causes loss of the same half of the visual field in each eye. Because the optic tracts spread out on their way toward the occipital cortex, injuries along the way typically result in small visual field cuts. Uncertainties exist in scoring the toxicity. Acuity problems can result from cataracts, dry eye or radiation retinopathy (usually distinguishable by examination). Vascular insuffi- ciency to the retina, optic nerves, tracts, or occipital lobes can also cause visual impairments, particularly visual field deficits. Because patients often undergo RT to many of these areas concurrently, it can be challenging to know how to accurately ascribe the clinical events. Lesions anterior to the chiasm will affect the ipsilateral eye, lesions of the chiasm will affect the bilateral temporal visual fields, and lesions posterior to the chiasm will affect visual fields in both eyes. 3. CHALLENGES DEFINING VOLUMES The optic nerves progress from the posterior aspect of the center of the globe roughly through the center of the orbit, bracketed by the rectus muscles. They angle up through the optic canals just medial to the anterior clinoid process of the lesser wings of the sphenoid bone. The axonal bundles of the left and right optic nerves, divide at the optic chiasm. Reprint requests to: Charles Mayo, Ph.D., Department of Radia- tion Oncology, HB-200, University of Massachusetts Memorial Medical Center, 55 Lake Ave. N, Worcester, MA 01655. Tel: (774) 442-5551; Fax: (774) 422-5006; E-mail: charles.mayo@ umassmemorial.org Conflict of interest: none. Received Nov 14, 2008, and in revised form July 10, 2009. Accepted for publication July 15, 2009. S28 Int. J. Radiation Oncology Biol. Phys., Vol. 76, No. 3, Supplement, pp. S28–S35, 2010 Copyright Ó 2010 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/10/$–see front matter doi:10.1016/j.ijrobp.2009.07.1753