Radiation Oncology/CNS/CSF involvement

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This page is for treatment of CSF-positive disease.

Introduction

Neoplastic meningitis affects 4-15% of pts with solid tumors (carcinomatous meningitis), 5-15% of pts with leukemia or lymphoma, and 1-2% of pts with primary brain tumors. Adenocarcinoma is the most common histology. Breast, lung, and melanoma are the most likely to metastasize to the meninges. Small cell lung cancer also has a high chance of leptomeningeal involvement, but its overall incidence is lower.

Tumor most commonly involves the base of the brain (basilar cisterns) and the dorsal surface of the spinal cord, usually the cauda equina.

Signs and symptoms

CN VI involvement is the most common cranial nerve affected, followed by III and IV. Trigeminal (sensory or motor), cochlear, and optic neuropathy are also common. Spinal symptoms include weakness, dermatomal pain or sensory loss. Nuchal rigidity is rare.

Diagnosis

CSF examination is the most useful. Positive findings are: increased opening pressure (>200 mm H₂O), increased leukocytes (>4 per mm^3), elevated protein (>50 mg/dL), or decreased glucose (<60 mg/dL). Diagnosis is confirmed by the presence of malignant cells in the CSF. Yield of finding malignant cells is increased by a 2nd lumbar puncture with a yield of >80% (up to 45% are negative on initial exam).

MRI with contrast of the brain and spine. Radionuclide studies to evaluate CSF flow.

Prognosis

Prognosis for all pts is extremely poor, with a median survival on the order of 4 months.

Treatment

Treatment may be intrathecal chemotherapy (through lumbar puncture or intraventricular, such as by Ommaya reservoir), radiotherapy, or systemic chemotherapy. Radiotherapy is indicated for bulky disease (chemotherapy only penetrates to 3mm depth of tumor nodules) and CSF flow abnormalities. Radiotherapy also indicated for palliation of symptoms, such as cauda equina syndrome or cranial nerve abnormalities.

Intra-CSF chemotherapy: methotrexate, cytarabine, and thiotepa. Sustained-release liposomal form of cytarabine (DepoCyt) results in cytotoxic levels in CSF for > 10 days. Usually given 2-3x/week for induction, then weekly x 4 weeks (consolidation), then once a month (maintenance).

Systemic chemotherapy can penetrate into the CSF in areas of leptomeningeal metastasis where the blood-brain barrier is disrupted and will therefore reach a therapeutic level throughout the CSF, not just locally. Also, high-dose systemic MTX or ara-C can penetrate adequately into the CSF.

Radiation therapy:
30 Gy in 10 fractions recommended to symptomatic and bulky disease.

Guidelines:
Since prognosis is poor and systemic progression of disease is common, aggressive CNS treatment should not be offered for many patients. However, breast cancer patients often have extended survival and should be offered aggressive treatment.

Radiation technique

Helmet field: Technique: place isocenter 2 cm posterior to lens marker. This allows for quasi half-beam technique to reduce divergence to the lens. Inferior field edge at bottom of C2. 5 mm margin at cribriform plate and temporal lobe.

PMID 11286856, 2001 — "Does the standardized helmet technique lead to adequate coverage of the cribriform plate? An analysis of current practice with respect to the ICRU 50 report." Weiss E et al. Int J Radiat Oncol Biol Phys. 2001 Apr 1;49(5):1475-80.

Reviews

PMID 16215819, 2005 — "Leptomeningeal metastases from solid malignancy: a review." Tallibert S et al. J Neurooncol. 2005 Oct;75(1):85-99.
PMID 15908671, 2005 — "Neoplastic meningitis." Chamberlain MC. J Clin Oncol. 2005 May 20;23(15):3605-13.
PMID 9696379, 1998 — "Current diagnosis and treatment of leptomeningeal metastasis." DeAngelis LM. J Neurooncol. 1998 Jun-Jul;38(2-3):245-52.