Malignancies of the Central Nervous System

Leptomeningeal Carcinomatosis

By Stephanie Liu

Background of CNS Tumours

• CNS malignancies are uncommon: approximately 2% of all

cancer deaths

• 1.4: 1 male to female ratio

• Affect adults and children alike

• Benign and malignant

• Aetiological factors:

– Ionising radiation

– Immunosuppression

• 80% primary 20% secondary metastasis (Bomford, 2003)

What is the Leptomeninges?

• Composed of:

– pia mater

– arachnoid mater

• Forms subarachnoid space

boundaries

• Separated by CSF (Leal,

2011)

http://www.emedicinehealth.com/head_injury/article_em.htm (29th Sept 2012)

What is Leptomeningeal Carcinomatosis?

• Infiltration of leptomeninges by malignant cells (Buckner,

2007)

• Occurs in 5% of patients with cancer (Buckner, 2007)

• Most common primaries:

– Breast: 12%-34%

– Lung: 10%-26% (Chamberlain, 1998)

• Initial haematogenous spread (mainly) (Buckner, 2007)

• Neuroaxis dissemination via CSF (Leal, 2011)

Clinical Presentation

Cerebral signs Cranial nerve signs Spinal cord and root signs

Headaches Diplopia Reflex asymmetry

Nausea and vomiting

Hearing impairment Weakness

Encephalopathy Facial numbness Sensory loss

Seizures Decreased visual acuity

Parasthesias

Communicating hydrocephalus

Leal, 2011

Diagnosis and Staging

• Lumbar punctures

• Contrast enhanced craniospinal imaging (MRI preferred)

(Leal, 2011; Chamberlain, 1998)

http://www.mayoclinic.com/health/medical/IM01849 Sept 29th 2012

Treatment Rationale

• Treatment intent: Palliative

• Limited roles for surgery and chemotherapy

• Mainly managed through radiotherapy

• Decisions dependent upon:

– Tumour type and burden

– Patient’s symptoms

– Patient’s performance status (Chamberlain, 1998)

• Two fold:

– Symptom alleviation

– Improve survival

• Treatment sites:

– Symptomatic and bulky

disease

– Areas of CSF flow

obstruction

• Treatment technique:

– Localised radiotherapy

– Craniospinal radiotherapy

• Dose and fractionation:

– Small fractions size (1.2-1.8

Gy)

– Total dose dependent upon

tumour burden

Management with Radiation Therapy

Leal, 2011

Craniospinal Irradiation

• Treats entire craniospinal axis

• Technique:

– 2 opposed lateral brain fields

– 1 or 2 posterior spine fields

• Patient position:

– Prone (department

dependent)

• Median survival:

– 8 weeks

Craniospinal set-up (Mehta, 2005)

Craniospinal IrradiationBeam Junctioning

Post Field Dosimetry

Mehta, 2005

Barrett, 2009

Localised Irradiation • Palliative treatment of areas with high tumour burden

• Treatment sites:

– Whole brain: Lateral opposed pair

– Segmental spinal irradiation: posterior field

• Patient position:

– Whole brain: supine; thermoplastic cast

– Segmental spinal irradiation:

– prone/supine (as per department)

• Dose and fractionation:

– 20-40Gy; 2-4Gy/Fx; daily

• Median additional survival:

– 5.7 months (Hermann, 2001)

Whole brain (Barrett, 2009)

Radiation Related Toxicity

Acute Toxicity

• Within first few weeks

• Hair loss, skin reaction, sore

throat, dysphagia, nausea and

vomiting, fatigue

• Bone marrow suppression

• CNS toxicity

– Acute radiation

encephalopathy

– Early cerebral necrosis

Late Toxicity

• After four weeks

• Bone marrow suppression

• CNS toxicity

– Delayed cerebral necrosis

– Delayed cranial nerve damage

– Delayed radiation myelopathy

– Delayed motor-neuron

syndrome

Mehta, 2005

Conclusion • Leptomeningeal carcinomatosis is rare but devastating

• Poor overall prognosis

• Management is controversial

– Requires further research

• Without therapy median survival is 4-6 weeks

• Radiotherapy provides palliation

– Craniospinal radiotherapy

– Localised radiotherapy

• Associated with debilitating toxicities

References • Barrett A, Dobbs J, Morris S, Roques T (2009) Practical Radiotherapy Planning 4th Edition Chapter 8: Head and Neck: General Considerations. Hodder Publications,

London

• Barrett A, Dobbs J, Morris S, Roques T (2009) Practical Radiotherapy Planning 4th Edition Chapter 18: Central Nervous System. Hodder Publications, London

• Blaney SM, Poplack DG (2000) Med Oncol 17: 151-162

• Bomford, CK; Kunkler, IH (2003), Walter and Miller’s Textbook of Radiotherapy: Radiation Physics, Therapy and Oncology, Chapter 30. Churchill Livingstone,

Edinburgh, 6th Edition 345-377

• Buckner JC, Brown PD, O’Neill BP, Meyer FB, Wetmore CJ Uhm JH (2007) Mayo Clin Proc 82(10):1271-1286

• Chamberlain MC, Sandy AD, Press GA (1990) Neurology 40: 435-438

• Chamberlain, MC (1998) Journal of Neuro-Oncology 37: 271-284

• Christ G, Denninger D, Dohm OS, Weigel B, Hones A, Paulsen F (2008) Strahlentherapie und Onkologie 184: 530-535

• Grossman SA, Krabak MJ (1999) Cancer Treat Rev 25: 103-119

• Hermann B, Hultenschmidt B, Sautter-Bihl ML (2001) Strahlenther Onkol 177:195-199

• Jayson GC, Howell A (1996) Ann Oncol 7:773-786

• Kaplan J, DeSouza T, Farkash A, Shafran B, Pack D, Rehman F, Fuks J, Portenoy R (1990) J Neuro-Oncol 92: 25-229

• Kokkoris C (1983) Cancer 51:154-160

• Leal T, Chang JE, Mehta M, Robins HI (2011) Current Cancer Therapy Reviews 7: 319-327

• Mehta M, Bradley K (2005) Cancer treatment and research 125: 147-158

• Omar AI, Mason WP (2009) Leptomeningeal metastases. Neurologic complications of cancer. 2nd edition Oxford University Press, Inc, New York: 240-281

• Sause WT, Crowley J, Eyre HJ (1988) J Neuro-Oncol 6:107-112

• Wasserstrom W, Glass J, Posner J (1982) Cancer 49: 759-772

• Wrensch M, Minn Y, Chew T, Bondy M, Berger MS (2002) Neuro Oncol 4(4):278-299