What is leptomeningeal carcinomatosis (LC), a condition where cancer cells spread to the leptomeninges?

From the Guidelines

Leptomeningeal carcinomatosis is a severe condition that requires prompt and aggressive treatment, and the most effective approach involves a combination of intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, with a focus on improving quality of life and reducing symptoms. The diagnosis of leptomeningeal carcinomatosis typically involves MRI with contrast, lumbar puncture to analyze cerebrospinal fluid for cancer cells, and neurological examination 1. Treatment options include intrathecal chemotherapy with medications like methotrexate, cytarabine, or thiotepa; systemic chemotherapy that can cross the blood-brain barrier; radiation therapy to symptomatic areas; and supportive care to manage symptoms 1.

Key Considerations

• The prognosis for leptomeningeal carcinomatosis is generally poor, with a median survival of 2-6 months without treatment 1.
• Early diagnosis and aggressive treatment are crucial for improving outcomes and quality of life 1.
• Management should be multidisciplinary, involving oncologists, neurologists, and palliative care specialists to address both the cancer spread and symptom management 1.
• Patients often experience headaches, nausea, vomiting, mental status changes, and various neurological deficits that require careful symptom management alongside cancer-directed therapies 1.

Treatment Approaches

• Intrathecal chemotherapy is a key component of treatment, with medications like methotrexate, cytarabine, or thiotepa commonly used 1.
• Systemic chemotherapy that can cross the blood-brain barrier is also important, with options like osimertinib and trastuzumab deruxtecan showing promise 1.
• Radiation therapy, including proton-beam craniospinal irradiation, can be effective in controlling symptoms and improving quality of life 1.
• Supportive care, including pain management, nausea control, and other symptom management strategies, is essential for improving patient outcomes 1.

Future Directions

• Further research is needed to improve our understanding of leptomeningeal carcinomatosis and to develop more effective treatment strategies 1.
• The use of novel therapies, such as immune checkpoint inhibitors and antibody-drug conjugates, may offer new hope for patients with leptomeningeal carcinomatosis 1.
• A better understanding of the biology of leptomeningeal carcinomatosis and the development of more effective treatment strategies will be crucial for improving patient outcomes and quality of life 1.

From the Research

Definition and Diagnosis of Leptomeningeal Carcinomatosis

• Leptomeningeal carcinomatosis (LC) is a rare but serious complication of cancer in which cancer cells spread to the leptomeninges, the membranes that surround the brain and spinal cord 2.
• The diagnosis of LC can be challenging due to non-specific symptoms and the difficulty of accessing the leptomeninges for a biopsy 3.
• The diagnosis is most commonly made by lumbar puncture, although the CSF cytology is persistently negative in about 10% of patients with leptomeningeal carcinomatosis 2.
• Radiologic studies may reveal subarachnoid masses, diffuse contrast enhancement of the meninges, or hydrocephalus without a mass lesion 2.

Treatment and Management of Leptomeningeal Carcinomatosis

• The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy 4.
• The choice of treatment modalities depends on the type of LC, additional systemic involvement, and additional involvement of the CNS parenchyma 4.
• Intrathecal chemotherapy is most important in cases of LC of the non-adherent type, with three substances for routine use: methotrexate, cytarabine, and thiotepa 4.
• A triple drug combination of methotrexate, cytosine arabinoside, and hydrocortisone given intrathecally for patients with LC showed good control of symptoms and reasonable survival 5.
• Combination intrathecal chemotherapy with liposomal cytarabine and methotrexate is a safe and tolerable option in solid tumor LC 6.

Prognosis and Survival

• Without treatment, the median survival of patients with LC is 4-6 weeks, and death occurs from progressive neurologic dysfunction 2.
• Early diagnosis and therapy are critical to preserving neurologic function, and radiation therapy to symptomatic sites and disease visible on neuroimaging studies and intrathecal chemotherapy increases the median survival to 3-6 months 2.
• The major favorable prognostic factors include excellent performance status, absence of serious fixed neurologic deficits, normal CSF flow scans, and absent or responsive systemic tumor 2.
• Median overall survival at 6 and 12 months was 38% and 14%, respectively, in a study of patients with LC treated with triple intrathecal chemotherapy 5.