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Show EDITORIAL Radiation Toxicity To the Visual System James T. Parsons, MD This issue of the Journal of Neuro- Ophthalmology includes several articles regarding radiation- induced injury to the visual system, including one by Monheit et al ( 1) describing visual field loss due to occipital lobe necrosis. Although the latter type of injury has apparently not been previously reported, its occurrence is hardly surprising. One would predict a very high risk of necrosis of any central nervous system site after exposure to approximately 60 Gy of fractionated irradiation, followed by re- irradiation with a single high dose ( 32 Gy) fraction. Although nine years had passed since the first course of radiation therapy ( RT) in Monheit et al's patient, some degree of latent neural and vascular damage from the first course of RT no doubt persisted. Intensive hypo fractionated ( single fraction or a few high- dose fractions) treatment of any human tissue is accompanied by an increased risk of necrosis compared with fractionated treatment, and residual toxic damage further compounds the risk. Unfortunately, the site of this patient's necrosis involved a highly eloquent part of the brain. This case is not, however, indicative of any particular sensitivity of the occipital lobes to radiation toxicity. On the other hand, the report by van den Bergh et al ( 2) is an important confirmation of the low risk of optic neuropathy following RT for nonfunctioning pituitary adenomas. Using doses of 45- 50.4 Gy, van den Bergh et al reported no injuries. Given the lack of a significant dose response above 45 Gy in 25 fractions, most centers now do not exceed that regimen. Probably because of pre- existing opticochiasmatic compression, the optic nerves in patients with nonfunctioning pituitary adenomas are somewhat more susceptible to injury after RT than the optic nerves in patients without pre- existing compression. As noted in the authors' Table 2 ( 2), even 45 Gy in 25 fractions has been responsible for injury in a few reported patients. In the University of Florida pituitary adenoma series ( 3), two patients whose optic nerves received 50 Gy in 30 fractions at 1.67 Gy per fraction also developed neuropathy. Injury after treatment with either of these dose fractionation schemes in non-pituitary patients would be extraordinarily unusual, and I am unaware of any such reports. Until the 1960s and early 1970s, it was thought that the retina and optic nerve were relatively resistant to the effects of RT. The sparse literature that existed at that time considerably overestimated the tolerance of these structures, suggesting that 68 Gy in 30 fractions at 2.27 Gy per fraction was within retinal tolerance ( 4). The last 25 years have brought considerable understanding of the types of injury that RT can induce ( 5). If the orbital contents are irradiated, there is a risk of injury to the lacrimal tissue. In the University of Florida series ( 5,6), patients who suffered significant injury to lacrimal tissue were usually symptomatic within one month of completion of RT, and were noted to have severe corneal opacification and vascularization by nine to ten months. Corneal reactions included edema, ulceration, bacterial infection, vascularization, opacification, perforation of the globe, symblepharon, and phthisis bulbi. Enucleation or evisceration because of continued pain or perforation of the globe was required in half of the patients. Radiation dose response is not an all or none phenomenon. The shape of the dose response curve is Cancer Care Specialists, Inc., Bethesda Memorial Hospital, Department of Radiation Oncology, Boynton Beach, Florida. Address correspondence to James T. Parsons, MD, Cancer Care Specialists, Inc., Bethesda Memorial Hospital, Department of Radiation Oncology, 2815 S. Seacrest Blvd., Boynton Beach, FL 33435; E- mail: James. Parsons@ Bethesdahealthcare. com J Neuro- Ophthalmol, Vol. 24, No. 3, 2004 193 JNeuro- Ophthalmol, Vol. 24, No. 3, 2004 Editorial sigmoid, such that the risk of injury to the lacrimal tissue goes up steeply when total dose exceeds 35 Gy fractionated at 1.8- 2.0 Gy per fraction. If it is possible to shield enough lacrimal tissue to prevent dry eye syndrome, then at higher doses one risks radiation retinopathy, which usually develops two to three years after RT and has many characteristics of diabetic retinopathy ( 5,7,8). Approximately half of the patients with severe radiation retinopathy develop rubeosis iridis or neovascular glaucoma. The risk of radiation retinopathy increases steeply above 45 Gy to external beam portals that include the majority of the retina. Pan- retinal laser photocoagulation may offer some benefit in preventing progression to neovascular glaucoma ( 7). There is increased risk of retinopathy in those treated with fraction sizes > 1.9 Gy, in those who have received chemotherapy, in older patients, and in those with diabetes mellitus. If the patient does not experience retinal injury, blindness may still result from optic nerve or chiasm injury ( 5,8, 9). These structures have approximately the same radiation sensitivity as the spinal cord; the risk of injury increases steeply above 55 Gy. Among nerves that received > 60 Gy, dose per fraction has been more important than total dose ( 8). In an earlier study ( 8), the 15- year actuarial risk of optic neuropathy after > 60 Gy was 11% with < 1.9 Gy per fraction as compared with 47% with > 1.9 Gy per fraction. There was also a greater risk with increasing age. There is no effective treatment of optic neuropathy; although hyperbaric oxygen and corticosteroids are worth trying, most patients do not respond favorably. Vision loss after RT is most often unilateral, but bilateral blindness may also occur. The most common scenario leading to bilateral blindness includes ipsilateral radiation retinopathy ( which is often " expected" when there is extensive orbital involvement by paranasal sinus cancer), and contralateral optic neuropathy. Bilateral optic neuropathy or chiasm injury may also occur. Better target delineation as well as three- dimensional conformal and intensity-modulated techniques and stereotactically aided treatment setups are all useful in limiting the dose to these vital structures ( see the article by Pan and Hayman [ 10] in this issue). These techniques allow optimal patient positioning and field reproducibility, unconventional angles of beam entry, geometric shaping of the radiation beam so that it corresponds to the " beam's- eye" view of the target, and geometric shaping of the isodose distribution by altering beam intensity ( fluence). These features allow deliberate inhomogeneity across target and avoidance areas. The radiation oncologist must pay careful attention to time- dose parameters ( fractionation) and carefully calculate total dose and fraction size to each vital structure and attempt to limit the volume of tissue receiving that dose. Despite the greatest attention to detail, the most sophisticated protocols, and the best equipment, optic neuropathy and retinopathy will still occasionally be seen when attempting to control advanced cancers with high- dose RT. This is because many large tumors occur in close proximity to or engulf healthy tissues in such a manner that no amount of careful planning can avoid their receiving a toxic dose. REFERENCES 1. Monheit BE, Fiveash JB, Girkin CA. Radionecrosis of the inferior occipital lobes with altitudinal visual field loss after gamma knife radiosurgery. JNeuroophthalmol 2004; 24: 195- 199. 2. van den Bergh ACM, Schoorl MA, Dullaart RPF, et al. Lack of radiation optic neuropathy in 72 patients treated for pituitary adenoma. J Neuroophthalmol 2004; 24: 200- 205. 3. McCullough WM, Marcus RB Jr., Rhoton AL Jr., et al. Long- term follow- up of Radiotherapy for Pituitary Adenoma: The Absence of Late Recurrence after greater or equal to 4500 cGy. IntJRad Oncol BiolPhys 1991; 21: 607- 14. 4. Shukovsky LJ, Fletcher GH. Retinal and optic nerve complications in a high dose irradiation technique of ethmoid sinus and nasal cavity. Radiology 1972; 104: 629- 34. 5. Parsons JT, Fitzgerald CR, Hood CI, et al. The effects of irradiation on the eye and optic nerve. Int JRadiat Oncol Biol Phys 1983; 9: 609- 22. 6. Parsons JT, Bova FJ, Fitzgerald CR, et al. Severe dry- eye syndrome following external beam irradiation. Int J Radiat Oncol Biol Phys 1994; 30: 775- 80. 7. Parsons JT, Bova FJ, Fitzgerald CR, et al. Radiation retinopathy after external beam irradiation: analysis of time- dose factors. Int J Radiat Oncol Biol Phys 1994; 30: 765- 73. 8. Parsons JT, Kies MS. Cancer of the Nasal Vestibule, Nasal Cavity, and Paranasal Sinus. In: Harrison LB, Sessions RB, Ki Hong W. Head and Neck Cancer, A Multidisciplinary Approach. Philadelphia: Lippincott Williams & Wilkins, 2004: 480- 528. 9. Parsons JT, Bova FJ, Fitzgerald CR, et al. Radiation optic neuropathy after megavoltage external- beam irradiation: analysis of time-dose factors. Int J Radiat Oncol Biol Phys 1994; 30: 755- 63. 10. Pan CC, Hayman JA. Recent advances in radiation oncology. J Neuroophthalmol 2004; 24: 251- 257. 194 © 2004 Lippincott Williams & Wilkins |
