What is the management and treatment approach for a patient with a brain tumor who requires an Ommaya (implantable reservoir) port for frequent intrathecal administration of medications, such as chemotherapy agents like methotrexate or cytarabine?

Ommaya Reservoir Management for Intrathecal Chemotherapy

Primary Recommendation

Ommaya reservoirs are the preferred method for delivering intrathecal chemotherapy in patients with leptomeningeal metastases requiring repeated drug administration, offering superior survival outcomes, drug distribution, and patient comfort compared to lumbar administration. 1, 2

Indications for Ommaya Reservoir Placement

Place an Ommaya reservoir when patients require repeated intrathecal chemotherapy delivery without elevated intracranial pressure or hydrocephalus. 2

• Ommaya reservoirs are indicated for patients with leptomeningeal metastases requiring frequent intrathecal chemotherapy administration or repeated CSF sampling for cytologic monitoring 2
• Early device placement should be considered in patients requiring frequent CSF sampling or in clinical research settings for improved pharmacokinetic monitoring 1
• The device is appropriate for patients with normal or mildly elevated intracranial pressure and no evidence of CSF flow obstruction 2

Survival and Clinical Advantages

Intraventricular drug delivery via Ommaya reservoir is associated with improved survival compared to lumbar drug delivery. 1, 2

• Drug exposure in ventricular CSF after intraventricular administration is ten times higher than after an equivalent intralumbar dose 1, 2, 3
• Ommaya reservoirs permit more uniform drug distribution throughout the neuraxis 1
• Even without CSF flow obstruction, lumbar administration does not guarantee therapeutic drug levels at higher CSF levels 1

Patient Comfort Benefits

• Ommaya reservoirs eliminate the need for repeated lumbar punctures, which are cumbersome and resource-intensive 1, 3
• The device reduces anxiety, avoids post-dural puncture headaches, low back pain, and radiculopathy 2
• Ommaya reservoirs obviate the need for anticoagulation holds, making them preferred for patients requiring long-term anticoagulation therapy 2

Surgical Technique and Safety

Modern Ommaya reservoir placement has a low complication rate of 1.8-9.8%, with infection rates of only 0.74 per 10,000 reservoir-days. 2

Infection Prevention Protocol

• Administer preprocedural cefazolin 2
• Use perioperative chlorhexidine shampoo with hair clipping 2
• Place the reservoir under a skin flap at a safe distance from the incision site 2
• Staphylococcus species and Cutibacterium acnes are the most common infectious organisms 2

Navigation-Guided Placement

• Navigation-guided Ommaya reservoir placement is associated with very low complication rates (1.2%) and appears safe and effective 4
• The technique allows real-time verification of catheter position during the procedure 4

Common Complications

• Perioperative hemorrhage, Ommaya malfunction, wound dehiscence, and catheter tract leukoencephalopathy are the most common complications 2
• Revision is required in less than 5% of patients 2
• The device remains functional as long as needed 2

Intrathecal Chemotherapy Administration

Intrathecal chemotherapy is most effective in patients with thin linear leptomeningeal deposits and unobstructed CSF flow. 1

Drug Selection and Dosing

• Methotrexate (MTX) is the most frequently used agent for solid tumors at doses of 10-15 mg 3, 5
• For meningeal leukemia, age-based dosing is recommended: <1 year = 6 mg; 1 year = 8 mg; 2 years = 10 mg; ≥3 years = 12 mg 5
• Other available agents include cytarabine, sustained-release cytarabine (DepoCyt), and thiotepa 1, 3

Treatment Schedule

• Typical schedule for intrathecal MTX: twice weekly for 8 treatments, followed by weekly for 4 treatments, then monthly maintenance 3
• For meningeal leukemia treatment, administer at intervals of 2-5 days until CSF cell count normalizes, then one additional dose 5
• Administration at intervals less than 1 week may result in increased subacute toxicity 5

Critical Administration Technique

Isovolumetric administration is critically important—the intra-CSF fluid volume must not be greater after chemotherapy than before administration. 1, 3

• Remove CSF for laboratory studies, fluid for flushing the chemotherapy syringe, and additional fluid to account for the volume of administered chemotherapy before instillation 1
• Patients with neoplastic meningitis are precariously positioned on the ventricular compliance curve, and even small amounts of additional fluid can precipitate headache, nausea, vomiting, obtundation, or herniation 1, 3
• Dilute preservative-free methotrexate to a concentration of 1 mg/mL in sterile, preservative-free medium such as 0.9% Sodium Chloride Injection 5

Response Monitoring

Cytologic evaluation of CSF is a critical component of response assessment during intrathecal therapy. 1, 3

• Sample CSF at each site (lumbar and ventricular) from which malignant cells were identified before treatment 1, 3
• Two successive negative cytologic evaluations from each site are required before declaring treatment response 1, 3
• Overall survival remains the most objective outcome measurement in leptomeningeal metastases clinical trials 1

Important Caveats

CSF Flow Abnormalities

• Abnormalities in CSF flow are present in up to one-third of patients and interfere with homogeneous drug distribution 1, 3
• Radiotherapy to sites of abnormal CSF flow can reverse the flow abnormality and allow safe administration of intrathecal chemotherapy 1, 3

Limitations of Intrathecal Therapy

• Intrathecal chemotherapy cannot reliably eradicate bulky disease seen on MRI due to limited drug diffusion into subarachnoid tumor deposits, along nerve root sleeves, and into Virchow-Robin spaces 1, 3
• Focal radiotherapy may be necessary for symptomatic or bulky areas of leptomeningeal disease 3

Systemic Considerations

• Methotrexate given intrathecally appears significantly in the systemic circulation and may cause systemic toxicity 5
• Systemic antileukemic therapy should be appropriately adjusted, reduced, or discontinued 5
• Systemic therapies with CNS bioactivity and blood-CSF barrier permeability should be prioritized in all patients with leptomeningeal metastases 1

Prognosis

• Untargeted intrathecal therapies (methotrexate, cytarabine, thiotepa, topotecan) confer a median survival of 2-4 months in historical clinical trials 1
• More recently investigated intrathecal therapies (trastuzumab, nivolumab, pemetrexed) have median survival of 4-9 months in modern phase I/II trials 1