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Neoplastic meningitis
Objective:
To evaluate the value of shunting surgery in the treatment for patients with meningeal carcinomatosis.
Methods: The therapeutic process of shunting surgery was analyzed in 5 meningeal carcinomatosis patients.
Results: The intracranial pressure could effectively be controlled, and the associated symptoms could be relieved. No complications associated with shunting surgery were found during the hospitalization and follow-up. One patient, who did not receive the surgery, died in 2 months later.
Conclusion: Shunting surgery can effectively relieve the intracranial pressure caused by meningeal carcinomatosis, decrease the mortality and morbidity caused by intractable intracranial hypertension in these patients, and improve their live quality.
Neoplastic meningitis (NM) is a debilitating and increasingly frequent neurological complication of cancer characterized by infiltration of tumor cells into the leptomeninges and the subarachnoid space. Although NM is rarely curable, combined intrathecal chemotherapy and focal radiation can improve disease-related symptoms and survival. Hydrocephalus occurs in a significant proportion of patients, is associated with poor prognosis and reduced quality of life, and usually precludes the use of intrathecal therapy.
Since January of 2005, the authors have used a combined treatment approach for patients with both NM and hydrocephalus that employs a subcutaneously placed reservoir connected in series to an on/off valve and a ventriculoperitoneal shunt for both diversion of CSF and injection of intrathecal chemotherapy. They conducted a retrospective, case-controlled study from 2 independent institutions to review their experience.
Twenty-four patients with NM and hydrocephalus underwent placement of a CSF reservoir-on/off valve-ventriculoperitoneal shunt (RO-VPS) construct. There was no perioperative mortality, and there were only 2 minor complications. One shunt failure and no shunt-associated infections were observed over a median of 28 weeks of follow-up. Symptomatic improvement and improved performance status were seen in 20 patients (83.3%) and were sustained over 6 months. Eighteen patients received intraventricular chemotherapy without unexpected toxicity, and cytological responses were found in 11 patients (61.1%). Median progression-free and overall survival was 14 and 31 weeks, respectively. Compared with a contemporaneous comparison group of 24 demographically matched patients with NM who underwent CSF reservoir placement only, those who received RO-VPS constructs (p = 0.02) and had primary diagnosis of breast cancer (p = 0.04) had significant advantage in overall survival.
A combined RO-VPS system is safe and practical to install, results in symptomatic improvement in most patients, and allows uncomplicated and effective administration of intrathecal chemotherapy in patients with NM. Cerebrospinal fluid diversion surgery should be considered in NM patients in conjunction with intrathecal and systemic treatments.
The authors assessed cerebrospinal fluid (CSF) flow in patients with carcinomatous meningitis using technetium-99m-DTPA (Tc-99) ventriculography to determine the frequency of flow abnormalities, their reversibility with treatment, and the implications for successful therapy and survival.
Technetium-99m-DTPA flow studies were performed in 31 patients after placement of Ommaya reservoirs (Baxter, McGaw Park, IL). Two millicuries of Tc-99 were injected into the reservoir. Planar images of the head and entire spine were obtained after 10 and 30 minutes and after 1, 4, 6, and 24 hours. Follow-up studies were performed for 12 patients whose initial studies were abnormal or who developed complications of therapy.
In 19 of the 31 patients (61%), ventricular-outlet, spinal, or convexity blocks were identified. In 11 of these 19 patients, focal radiotherapy to the site of the block restored normal flow. Survival among patients with initially normal, abnormal but correctable, and abnormal but uncorrectable CSF flow differed significantly (6.9, 13.0, and 0.7 months respectively; P < 0.001). Some patients who were treated intrathecally despite abnormal CSF flow experienced drug-related toxicity.
Cerebrospinal fluid-flow blocks are common in patients with carcinomatous meningitis and may occur at the skull base, in the spinal canal, and over the convexities. These flow abnormalities often can be corrected with appropriately directed radiotherapy. If untreated, CSF tumor progression (protected site effect), neurotoxicity (high concentration effect), and systemic toxicity (reservoir effect) can occur, resulting in shortened survival and treatment-related morbidity. Therefore, intrathecal chemotherapy should be preceded by a radionuclide flow study and should be delayed if abnormal flow is documented until appropriate radiotherapy reestablishes normal flow.
Leptomeningeal metastatic disease occurs in a minority of patients with systemic neoplastic disease. Before the initiation of intrathecal chemotherapy, hydrocephalus must be addressed with a cerebrospinal fluid (CSF)-diverting shunt. CSF diversion can theoretically prematurely divert chemotherapeutic drugs that are administered intrathecally, thereby potentially reducing the efficacy of such treatments.
We report on a patient with leptomeningeal disease and hydrocephalus secondary to metastatic bladder carcinoma requiring insertion of a programmable ventriculoperitoneal shunt and intrathecal chemotherapy. A novel method was utilized to administer intrathecal chemotherapy, in which the valve pressure setting was transiently increased during a 4-hour treatment session for intrathecal chemotherapy. No clinical complications occurred. Nuclear imaging was obtained sequentially after the injection of indium tracer into the ventricular system with the programmable valve at its baseline setting as well as at a maximal pressure setting. In the maximal valve setting condition, reduced outflow of nuclear tracer was observed at 1.5 and 4 h after injection, and normalized by 24 hours after injection.
Programmable shunt valves can be utilized in a safe, controlled fashion to treat hydrocephalus associated with leptomeningeal disease, as well as regulate the outflow of CSF and minimize diversion of intrathecal chemotherapeutic agents.
Neoplastic meningitis (NM) occurs in 5% to 8% of cancer patients, commonly as an end-stage process in previously metastatic disease. As newer therapeutics extend patient survival by maintaining long-term control of systemic malignancies, the incidence of NM is likely to rise. This can be expected both because of a change in the natural history of the underlying disease and the generally poor penetrance of many newer anticancer drugs into the central nervous system, thereby creating a sanctuary site for malignant cells. Currently available treatments have provided limited benefit in overall survival in NM, although long-term survival does occur. Because of the morbidity occasionally associated with treatment, prognostic indicators are being analyzed to identify patients who may benefit from systemic and/or intrathecal therapy before making the decision to initiate treatment. Additionally, because of the relative insensitivity of traditional cerebrospinal fluid analysis, new markers of NM are being investigated. This endeavor is being aided by ongoing research into the underlying biology of the metastatic process.
Leptomeningeal metastasis occurs in approximately 5% of all patients with cancer. This review summarizes recent literature regarding methods of diagnosis and treatment of leptomeningeal metastasis.
Staging of leptomeningeal metastasis should include contrast-enhanced brain and spine MRI, and though controversial, radionuclide cerebrospinal fluid (CSF) flow study. Treatment of leptomeningeal metastasis often requires involved-field radiotherapy to bulky or symptomatic disease sites as well as intra-CSF and systemic chemotherapy. The use of high-dose systemic therapy may benefit patients with leptomeningeal metastasis and obviate the need for intra-CSF chemotherapy. Intra-CSF drug therapy primarily utilizes one of three chemotherapeutic agents [i.e. methotrexate, cytosine arabinoside (both free and liposomal) and thio-tetraethylenepentamine] administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Novel intra-CSF agents increasingly utilized in the treatment of leptomeningeal metastasis are targeted mAbs such as rituximab and trastuzumab.
Although treatment of leptomeningeal metastasis is palliative with median patient survival of 2-3 months, treatment may afford stabilization and protection from further neurologic deterioration in patients with leptomeningeal metastasis.
Neoplastic meningitis (NM) is a common problem in neuro-oncology, occurring in approximately 5% of all patients with cancer.
Notwithstanding frequent focal signs and symptoms, NM is a disease affecting the entire neuraxis, and therefore staging and treatment need encompass all cerebrospinal fluid (CSF) compartments.
Central nervous system staging of NM includes contrast-enhanced cranial computerized tomography or magnetic resonance imaging (MR-Gd), contrast-enhanced spine magnetic resonance imaging or computerized tomographic myelography and radionuclide CSF flow study. Treatment of NM incorporates involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (i.e., methotrexate, cytosine, arabinoside, and thio-TEPA) administered by a variety of schedules either by intralumbar or intraventricular drug delivery.
Although treatment of NM is palliative with an expected median patient survival of 2 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM.
The authors reviewed 37 patients with leptomeningeal metastasis (LM) who required a ventriculoperitoneal shunt (VP shunt) for management of intracranial hypertension. Improvement was seen in 27 (77%) patients; subdural hematoma developed in one and shunt malfunction in three. Median overall survival was 2 months (range 2 days to 3.6 years) after VP shunt placement, but there was no procedure-related mortality. The prognosis of LM remained poor, but VP shunt can be an effective palliative tool when required.
Neoplastic meningitis (NM) is the result of the diffuse or multifocal localization of cancer cells in the cerebral spinal fluid (CSF). NM is more often a late complication of solid tumor or lymphoproliferative malignancies. At present, the goal of therapeutic strategies is palliative and the evaluation of high or low risk is important in identifying which patients could benefit from aggressive treatments such as radiation therapy and chemotherapy. Given that NM is a cancer complication that can spread throughout the entire subarachnoid space, chemotherapy, whether intrathecal or systemic, is currently considered the best treatment option, but optimal treatment is still controversial. This review summarizes intrathecal and systemic chemotherapeutic options in the treatment of NM and the related toxicities.