Management of Optic Nerve Glioma and Primary Orbital

Lymphoma

By

Dr Parneet Singh

Max Hospital,Saket

OPTIC NERVE TUMOURS

• Rare neoplasm involving optic nerve

• Tumor of children(<15yrs), females, NF and genetic factors

• Slow growing

• Histologically low grade gliomas- Gr I, II

• Both Pilocytic and ODG seen

• 75 % cases occur in 1st decade of life

• Can involve optic nerve, chiasma, adjacent tract

CLINICAL FEATURES

• Depends on the site & nature of disease process

• M/C -Ocular / orbital swelling, proptosis

• Assymetry on movement of eyeball

• Changes in vision, diplopia

• Eyelid drooping/ fullness

• Associated pain , photophobia

• Vision defects,

• Nystagmus

• Endocrine effects

• Raised ICP

EXAMINATION

CLINICAL EXAMINATION

• GPE: LNs, thyrotoxicosis

• External ocular examination: conjunctiva, sclera, cornea, pupils and lacrimal

system

• Eyelids: Lid lag, lid edema (thyroid ophthalmopathy)

• Proptosis measurement (>21mm or 2mm asymmetry)

• Ocular motility

• Optic nerve: Visual Acuity, perimetry

• IOP

• Slit lamp microscope,

• Opththalmoscopy

• Xray orbit, whole skull: Waters (occipitomental),

Caldwell (occipitofrontal)

Rhese view - optic foramen

• Bony destruction, metastatic deposit, sutural separation,

calcification

• CT/MRI can yield diagnostic accuracies 95%.

Confirmation of diagnosis

• FNAC

• Incision biopsy

• Excision biopsy

USG

Nature of lesion-cystic, solid, angiomatous, infiltrative

CT Scan

• Coronal & axial – help to determine relationship of an orbital tumour to optic nerve, extraocular ms, globe, sinuses , brain

• Bony landmarks-Imp for surgical / RT planning

Optic Glioma on CT

• Fusiform thickening

• Thickening of same density as the nerve.

• Kinking of the nerve.

• Smooth edges.

• Optic canal enlarged.

• No bone erosion/hyperostosis.

• Calcifications rare.

Coronal noncontrast T1-weighted MRI reveals a large intraorbital mass centered on the optic

nerve.

Enlargement, often iso to hypointense compared to the contralateralside

Coronal postgadolinium T1-weighted MRI with fat saturation reveals diffuse, intense enhancement of the

intraorbital mass

Homogenous Enhancement

Axial postgadolinium T1-weighted MRI with fat saturation reveals diffuse, intense enhancement of the intraorbital mass. The lesion is confined to the orbit.

Axial postgadolinium T1-weighted shows enhancement of the intracranial optic nerve slightly expanded.

Axial noncontrast T1-weighted MRI reveals bilateral, fusiform enlargement of the optic nerves

with bilateral optic nerve gliomas.

T2 Images-Hyperintense centrally

Treatment Strategies

• Surveillance

• Radiation therapy

• Chemotherapy

• Surgery

• Combination of Therapies

ROLE OF SURGERY

• Role Limited

• For Diagnosis: - Biopsy(not necessary)

• In cases of progressive loss of vision

• No useful vision in eye

• Debulking: Large unresectable tumor

• To relieve hydrocephalus

• Transcranial orbital resection

• Although completeness of Sx (rare) correlates with survival, leads to significant vision loss

Chemotherapy

• Used to delay radiation upto 5 years of age or till progression

• To achieve delay in radiation as long term sequel is neuro-cognitive dysfunction

• Vincristine ,carboplatin

• Cisplatin or CCNU based

• French society of pediatric oncology 5 year progression free survival of 34% and 5 year radiation free survival of 61% and 5 year overall survival 89%

• Cog trial A9952 compared VCR and carbo vs procarbazine,ccnu and VCR in <10 year children with OPG

• COG trial ,ACNS0223 is evaluating vcr,carbo and TMZ in chiuldern <10years with optic pathway glioma.results are pending

ROLE OF RADIOTHERAPY

ADVANTAGES & OBJECTIVES:

1. Vision preservation

2. To cure the disease

3. Cosmesis

Local radiotherapy-

• In optic gliomas of post location (post optic tract)

• Intracranial chiasmatic location

• Recc after sx

• Optic nerve gliomas long term local control is 100% with RT

• Chiasmal gliomas have a poorer prognosis than optic nerve tumours

Recurrence rate – 56 % vs 22 %

• Overall survival for chiasmatic tumors in 90-100%

• For posterior gliomas progression free survival at 5 years is 20-60%

• Radiation therapy beneficial to chiasmal gliomas – improving vision &decreasing recurrence rates by 41 %

Conventional Radiation portals

• Ant + lat 45 wedges-2 field technique

• 3 field in case of intracranial location -1vertex + 2 lateral

• B/l lateral fields

• Superior and inferior oblique

• Newer Techniques-Conformal Radiation, IMRT and FSRT and Proton therapy

Ant & Lateral Wedge pair technique

• Anterior field:-

• Superior : supraorbital ridge

• Inferior: infraorbital ridge

• Medial: C/L medial canthus

• Lateral: Lateral canthus

• Lateral field:-

• Anterior: lateral canthus

• Posterior: front of tragus

• Superior & inferior same

Superior and inferior oblique fields

• More role in anteriorly lying tumors

• Proptosis

Advantages:

• Avoids C/L orbit with uniform irradiation of the entire orbital contents.

Lateral fields

• Parallel opposed with anterior half beam block

• B/l eye disease

• ON glioma involving optic chiasma

RESULTS

Long term survival 80-100%, Relapse free survival(6yrs) 75-80%.

3 Field Technique

• Three field technique

– 2 lateral opposed and 1 vertex field -

– 15-30 °wedge

– Typically 5x5 cm field used,

• centered on sella

• Position - supine

• Head and neck flexed

• Head typically held at 45°

– Tilting –head base plate immobilization system

• All patients were treated in a supine position with flexion of the head so that base of the skull was in right angle to the couch and parallel to the central plane

• Dose: Adults: 50 Gy@ 2Gy/#

Children: 45Gy@ 1.6-1.8Gy/#

Orbital lymphoma

• Lymphoid tumors -common despite the orbit not containing lymph nodes or a well defined lymphatic vasculature.

• Incidence 13% of all orbital tumors.

• Primary or associated with systemic disease.

• Represents 8 % of all extranodal NHL & 1 % of all NHL

• Approx 35% of patients with lymphoid tumors of orbital tumors will eventually develop systemic lymphoma

• Presenting age- 15- 70 yrs

• Majority are low grade- 84 %

• Most lesions are in the superior orbit.

• 20 % bilateral

• Majority of primary ocular lymphomas are large cell type and a CNS LYMPHOMA should be excluded

• 85-90% diffuse low grade, B cell

• 15% follicular or nodular characterstics

• Progressive painless proptosis over several wks to months.

• The classic lesion is a smooth, pink-orange mass ("salmon patch") under an intact conjunctiva.

• Biopsy

• Worked up for systemic disease

• Including a complete physical exam, a complete blood count, bone marrow biopsy and CT scans of the thorax, abdomen and pelvis.

• CSF examination

• CT scan -homogeneous mass with well defined borders that does not destroy surrounding structures or bone.

• MRI – to assess extent of disease

• PET CT

Staging

T1 axial

Hypointense on T1

T1 Coronal Fat Sat

T1 Axial

T1 c

Homogenous Enhancement

T2 Coronal

Hyperintense on T2

Radiotherapy

• Stage I, II- RT main t/t

• - Whole orbit is to be treated

• Energy- 1.25 Mv / 6 Mv

• Supine

• Immobilise

• Ant & lat field using 45 wedges

• Looks into beam,

• dose- 25- 30 Gy@ 1.8- 2 Gy/#

• Bilateral disease- parallel opposed fields

• If there is a forward displacement of eveball

• Involvement of post or anteromedial part of orbit

• Sup & inf oblique fields

• Stage III. IV- Combined CCT(3-4 Cycles) + RT

In ocular lymphomas with involvement of brain & CSF systemic chemotherapy with CHOP regime

Intrathecal methotrexate biweekly

Combined with WBRT and ORT

Results: All patients had a complete response to RT. Intraorbital recurrence developed in previously uninvolved areas not included in the initial target volume in 4 patients (33%) treated with partial orbit RT. All were salvaged by repeat RT or surgery. No patient treated with whole orbit RT developed intraorbital recurrence. The acute and long-term toxicity was similar in both groups. All but 1 patient retained good vision.

Conclusion: Patients with orbital lymphoma should be treated to the entire orbit.

Complication Post Radiotherapy

Radiation induced Second malignant neoplasm within RT • Osteosarcoma / fibrosarcoma / other spindle cell sarcoma / malignant

melanoma/ thyroid carcinoma

Facial / orbital deformities

Short strature

Endocrinological disorders

Moyamoya syndrome-veno-occlusion in circle of willis

Opthalmic :

• Dry eye• Corneal damage • Cataract• Retinal damage

MANAGING RADIATION REACTIONS

• Dryness of eye: Artificial tear drops

Antibiotic eye drops

Steroid eye drops (increased cataract)

• Epiphora: Rectify any ill fitting eye shield

• Lid deformities: managed surgically

• Cataract: IOL implantation

PRECAUTIONS AND PREREQUISITES OF

RADIATION THERAPY

RADIATION TOLERANCE OF NORMAL TISSUES

LENS

• TD5/5=10Gy, TD50/5= 18Gy

• Most radiosensitive structure in orbit.

• RT causes cell death in the germinative zone, which is the ring of mitotically

active cells at the periphery of the lens.

• Degenerated fibers and debris migrate to post pole of lens, resulting in

opacities (latency 2-3yrs).

Merrium and Focht observed lens opacities after as low as 3.6Gy and an

invariable cataract after 10.5Gy.

HOWEVER, the cataract if developed can be treated by IOL implantation.

CORNEA• TD 5/5= 50Gy, TD 50/5= 60Gy

• Second most radiovunerable structure in the eye.

• Doses >30Gy @ 2Gy/# leads to acute keratitis

>50Gy leads to scarring, perforation

Initially pin head erosions

Punctate erosions leading to irritation and increased lacrimation

Edema and keratitis with decreased corneal sensation

ultimatly scarring and phthisis bulbi.

• Corneal blindness is an unacceptable side effect of RT .

RETINA

• TD 5/5=45Gy, TD 50/5=65Gy

• Injury mechanism: endothelial cell death in small vessels leading to ischemic changes.

• Ophthalmoscopic findings: microaneurysms, new vessel formation, hemorrhages, cotton wool exudates.

• Latent period 18-30 months for symptoms.

OPTIC NERVE

• TD 5/5=50Gy, TD50/5= 55Gy

• RT tolerance similar to brainstem, very low risk <50Gy

• Optic neuropathy can lead to blindness.

LACRIMAL GLANDS

• Dose <40Gy unlikely to cause severe dry eye syndrome.

• Dose >40Gy, leads to tear film # causing corneal damage.

• Shielding in the lateral aspect of superior orbit reduces occurrence of dry eye syndrome.

BONY ANOMALIES

• RT usually avoided in children <3yr

• Mid facial anomalies: Hypotelorism, Enophthalmos, Depressed temporal bone, Depressed nasion.

Conclusions

• Orbital tumours though rare very imp in field of oncology

• Neoplasms can arise from any structure

• Important prerequisite is not only diagnosis but also histopathological type & extent of lesion

• Radiation is indicated in almost 70 % cases

• A major principle in management– to deliver therapeutic dose without causing damage to critical neighboring structure

• Cure is the aim but vision preservation and cosmesis are important factors to be considered while selecting treatment modality.

• Prevention of long term Radiation toxicity and management of acute reactions are important issues