# Radiation Oncology/Toxicity/Vision

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials

## Ocular Neuropathy
### Single Fraction

* Optic nerve & chiasm MTD: conservatively 10 Gy, point dose 12 Gy. No DVH data available
* Majority <2 years, but can develop 3+ years later
* Mayo, 2003 PMID 12654424 -- "A study on the radiation tolerance of the optic nerves and chiasm after stereotactic radiosurgery." (Stafford SL, Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1177-81.)
** Retrospective. 218 gamma knife plans (122 sellar/parasellar, 89 pituitary, 7 cranipharyngiomas). Prior RT in 11% patients. Median F/U 40 months
** RT: median max 10 Gy (0.4-16.0)
** Radiation optic neuropathy: 4 patients (2%) at median 48 months. All had prior surgery, 3/4 prior EBRT (risk 0.5% vs. 13%).
** Conclusion: Risk of RON 1% if "short" segment dose <=12 Gy. "Long" segment to 9 Gy may carry a significant risk. Short vs. long not enough data to define
* Maryland, 2000 PMID 11180138 -- "Preservation of visual fields after peri-sellar gamma-knife radiosurgery." (Ove R, Int J Cancer. 2000 Dec 20;90(6):343-50.)
** Retrospective. 20 patients, 90% pituitary adenomas. Median F/U 24 months
** RT: mean max dose 9 Gy (2.5-14.1), volume average of optic chiasm 5.2 Gy.
** Complications: none
** Conclusion: 8 Gy conservative, 10 Gy justifiable
* Graz, 1998 (Austria) PMID 9420071 -- "Dose-response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery." (Leber KA, J Neurosurg. 1998 Jan;88(1):43-50.)
** Retrospective. 50 patients with gamma knife treatment of middle cranial fossa. Mean F/U 40 months
** Optic neuropathy: 0% if <10 Gy, 27% if 10-15 Gy, 78% if >15 Gy
** Other CN neuropathy: none, doses 5-30 Gy
** Conclusion: 10 Gy MTD
** Critique: same imprecise technique as used in Pittsburgh/MGH study below
* Pittsburgh/MGH, 1993 PMID 8407394 -- "Tolerance of cranial nerves of the cavernous sinus to radiosurgery." (Tishler RB, Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):215-21.)
** Retrospective. 62 patients with lesions around cavernous sinus. Treated with GKS (33 patients) or 6MV linac (29 patients). Median F/U 19 months
** Optic complications: 4 patients, dose response seen (4/17 dose >8 Gy; 0/35 dose <8 Gy)
** Conclusion: Dose to optic apparatus should be <8 Gy
** Critique PMID 12654424: 1) planning done on CT, where it is hard to visualize optics, 2) max dose determined by manually overlaying computer isodose printouts over CT images, and with steep dose falloff, 8 and 10 Gy isodoses are only several mm apart => possible measurement error

### Fractionated EBRT

* Optic nerves & chiasm MTD: 60 Gy (RTOG protocols currently recommend 55 Gy; pediatric CCG protocols recommend 50.4 Gy)
* Retina MTD: 50 Gy
* Lacrimal glands MTD: 40 Gy
* Chiba; 2006 (1994-2000) PMID 16182466 -- "Outcomes of visual acuity in carbon ion radiotherapy: analysis of dose-volume histograms and prognostic factors." (Hasegawa A, Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):396-401. Epub 2005 Sep 22.)
** Retrospective. 163 patients, tumors of H&N or skull base treated with carbon ion. Analyzed 54 optic nerves in 30 patients. Median prescribed dose 56 GyE at 3-4 GyE/fraction
** Outcome: If <57 GyE, no visual loss. If >57 GyE, 58% decrease in visual acuity. D20 significantly associated with visual loss
** Conclusion: D20 >60 GyE associated with decreased visual acuity at 3-4 Gy/fx
* Michigan, 1997 (1985-1992) PMID 9226313 -- "Dose-volume complication analysis for visual pathway structures of patients with advanced paranasal sinus tumors." (Martel MK, Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):273-84.)
** Retrospective. 20 patients with advanced PNS tumors. 3D planning analyzed
** Complications: 2 severe (1 ipsilateral light perception only onset 1 year, 1 bilateral temporal vision loss onset 4 years); 1 moderate (nasal visual field defect at 1.5 years), 3 mild complications (all resolved)
** Optic chiasm: 1 complication (mean 55.2 Gy, max 59.5 Gy), no complication 19 chiasms (mean avg 45.2 Gy, mean max 59 Gy, max avg 53.7 Gy, max max 70 Gy). Complication NTCP was 15% using Emami data. Overall good fit to model using n=0.25, m=0.14 TD50=65 Gy)
** Optic nerve: 4 moderate/severe complications (mean avg 59.4 Gy, mean max 75.5 Gy, max avg 70 Gy, max max 75.5 Gy), no complications 34 nerves (mean avg 46.3 Gy, mean max 73 Gy, max avg 56.8 Gy, max max 80.5 Gy). All moderate/severe complications when max dose > 60Gy. Severe complications NTCP 81%, 80% and 23%; moderate complications NTCP 15%; mild complications NTCP 5% and 1% using Emami data. Additional 13 nerves had NTCP 19%-83% without complication. Overall good fit to model using n=0.25, m=0.14 TD50=72 Gy (increased from original 65 Gy)
** Retina: 1 mild complication (mean 63.3 Gy, max 76.1 Gy), no complication 39 retinas (mean avg 29.8 Gy, mean max 64 Gy, max avg 51.4 Gy, max max 77 Gy). NTCP 56%, model using n=0.2, m=0.19, TD50=65 Gy)
** Recommend calculating total NTCP for patient blindness (ipsilateral + contralateral and retina + optic nerves + optic chiasm)
* Florida
** 2005 (1964-2000) PMID 15990010 -- "Does altered fractionation influence the risk of radiation-induced optic neuropathy?" (Bhandare N, Int J Radiat Oncol Biol Phys. 2005 Jul 15;62(4):1070-7.)
*** Retrospective. 273 patients with H&N cancer, fields included optic nerves/chiasm. Min F/U 1 year
*** Outcome: Radiation neuropathy 9%. 5-year freedom from RION: <=63 Gy/QD 95%, <=63 Gy/BID 98%, >63 Gy/QD 78%, >63 Gy/BID 91%. On MVI, total dose significant. Patient age, fractionation, and overall treatment time predictors trend to significance. No effect of adjuvant chemotherapy
*** Conclusion: Probability of RION influenced by total dose
** 1996 PMID 8823799 -- "Response of the normal eye to high dose radiotherapy." (Parsons JT, Oncology (Williston Park). 1996 Jun;10(6):837-47; discussion 847-8, 851-2.)
*** Review of 157 patients. Minimum F/U 3 years
*** MTD: lacrimal glands 40 Gy, retina 50 Gy, optic nerve/chiasm 60 Gy
** 1994 (1964-1989) PMID 7960976 -- "Radiation optic neuropathy after megavoltage external-beam irradiation: analysis of time-dose factors." (Parsons JT, Int J Radiat Oncol Biol Phys. 1994 Nov 15;30(4):755-63.)
*** Retrospective. 215 optic nerves in 131 patients treated for H&N tumors. Endpoint: visual acuity <20/100. Minimum F/U 3 years
*** Complications: Anterior optic neuropathy 5 nerves (median 30 months), Retrobulbar optic neuropathy 12 nerves (median 28 months)
*** Dose-response: no injury if dose <59 Gy. If dose >=60 Gy, 15-year risk of optic neuropathy 11% if fraction size <1.9 Gy, 47% if fraction size >=1.9 Gy

## Ocular neuromyotonia

* Rare disorder
* Clinical characteristics:
** Intermittent diplopia lasting seconds to minutes
** Paroxysm may last up to several minutes, and occur multiple times per day
** Amount and pattern of eye deviation (leading to diplopia) may vary without any pattern
* Physical examination
** CN exam typically normal
** Can be provoked by having patient hold excentric gaze, and then by changing gaze direction (see Abnormal gaze movie at BMJ.com)
* Pathogenesis:
** Presumed radiation-induced cranial neuropathy due to segmental demyelination, manifesting as spontaneous discharge from axons with unstable cell membranes
** This leads to involuntary tonic contraction of one or more ocular muscles innervated by CN III, CN IV and CN IV
** Subsequently, patients develop a paroxysmal binocular misalignment
* May be radiation-induced
** Intracranial masses (typically near skull base); medulloblastoma; pituitary tumors
** Nasopharyngeal CA
** Whole brain RT
* Treatment:
** Prism glasses
** Neurontin or Tegretol
* Rostock, 1999 (Germany) PMID 10401502 -- "Neuromyotonia of the abducens nerve after hypophysectomy and radiation." (Becskulin A, Strabismus. 1999 Mar;7(1):37-40.)
** Case report and literature review