Abstract
Background/Aim: Leptomeningeal carcinomatosis (LMC) with hydrocephalus is particularly difficult to treat, and its prognosis is extremely poor. The therapeutic outcomes of 14 patients with LMC-associated hydrocephalus who were treated with cerebrospinal fluid shunting are reported. Patients and Methods: The study subjects were 14 LMC patients with solid primary cancer who had developed hydrocephalus. Results: Postoperatively, both symptoms and Karnofsky performance status improved in 100% of patients. Postoperative therapy consisted of whole-brain radiotherapy in 4 cases and molecular targeted therapy in 4, with 6 patients not receiving any postoperative treatment. Median overall survival was 3.7 months, with no significant difference between those who underwent postoperative therapy and those who did not. However, two of those who received molecular targeted therapy survived for more than one year. Conclusion: Cerebrospinal fluid shunting for LMC-associated hydrocephalus is an effective therapeutic procedure from the palliative viewpoint. Patients for whom molecular targeted therapy is indicated may have better long-term survival.
As a central nervous system (CNS) complication of advanced cancer, brain metastasis decreases performance status by causing intracranial hypertension and neurological deficits, and it greatly affects survival. However, recent advances in cancer treatment have added molecular targeted therapy and other new drug therapies to the conventional options of surgical resection, whole-brain radiotherapy, and stereotactic radiosurgery as options for the treatment of brain metastases (1-3). As a result, we have entered an era in which multifaceted treatment strategies for brain metastases are feasible, holding out hope for even better therapeutic outcomes for advanced cancer patients with brain metastases. Compared with intracerebral metastases, however, leptomeningeal carcinomatosis (LMC), in which metastasis and dissemination are present in the subarachnoid space, is an intractable central nervous system complication with an extremely poor prognosis that occurs in approximately 5% of patients with solid tumors (4, 5). No standard treatment has yet been established, but cerebrospinal fluid shunting has recently been reported to be effective as part of palliative therapy for LMC-associated hydrocephalus and intracranial hypertension (6-9). The therapeutic outcomes of 14 patients with LMC-associated hydrocephalus who were treated with cerebrospinal fluid shunting are reported along with a discussion of the relevant literature.
Patients and Methods
The study subjects were 14 LMC patients who underwent cerebrospinal fluid shunting in the Department of Neurosurgery of Kindai University Hospital between 2010 and 2019. LMC was diagnosed definitively either by meningeal enhancement on magnetic resonance imaging or by positive cerebrospinal fluid cytology. The indication for cerebrospinal fluid shunting was LMC with communicating hydrocephalus that exhibited symptomatic improvement when 10–20 ml of cerebrospinal fluid was removed by lumbar puncture. Cerebrospinal fluid shunting was conducted by ventriculo-peritoneal (VP) or lumbo-peritoneal (LP) shunting. Survival was evaluated by Kaplan–Meier estimates. Prognostic factors were analyzed using the log-rank test for univariate analysis. Values of p<0.05 were considered significant. The software used for the statistical analysis was Statcel (Microsoft, Redmont, WA, USA).
Results
Tables I and II show the patients’ characteristics and therapeutic outcomes. The patients were 3 men and 11 women, with median age of 64.5 years. The primary lesion was non-small-cell lung cancer in 8 cases and breast cancer in 6. VP shunting was performed in 5 patients, and LP shunting was performed in 9, with a variable pressure valve installed in all cases. In terms of complications, intestinal damage occurred in 1 patient who had undergone VP shunting, and this reoperation of shunting was carried out later after the intestinal damage had recovered. Postoperatively, both symptoms and Karnofsky performance status (KPS) improved in all patients. Postoperative therapy included whole-brain radiotherapy in 4 cases and molecular targeted therapy in 4, with 6 patients not receiving any additional treatment. Median overall survival was 3.7 months, with 36% surviving for 6 months and 14% for 1 year (Figure 1). Median overall survival was 3.7 months whether or not postoperative therapy was administered, and there was no significant difference between these two groups. However, 2 patients survived for more than 1 year, with survival periods of 14.2 months and 17 months. Both these patients had received additional postoperative molecular targeted therapy and showed epidermal growth factor receptor mutations.
Clinical characteristics of patients with CSF shunting for LMC.
Clinical results of patients with CSF shunting for LMC.
Kaplan–Meier curve of overall survival of 14 patients after diagnosis of leptomeningeal carcinomatosis. Median overall survival time was 3.7 months.
Discussion
The median survival for untreated LMC of a solid primary tumor is reported to be 6–8 weeks, and can be extended to 2–8 months by radiotherapy or drug therapy (4, 5). Poor prognostic factors for LMC patients include low performance status (KPS <60), major neurological deficits, extensive systemic disease with few therapeutic options, bulky CNS disease, encephalopathy, and CSF flow interruption (9, 10). The last of these poor prognostic factors was evident in the patients with LMC-associated hydrocephalus who were the subjects of this study. Jung et al. conducted an analysis of 71 patients with LMC and reported that median survival was 2.3 months for patients without hydrocephalus, but only 1.7 months for patients with hydrocephalus who did not undergo cerebrospinal fluid shunting, confirming that the presence of hydrocephalus is a factor associated with a poor prognosis (9). For patients with hydrocephalus who did undergo cerebrospinal fluid shunting, however, median survival was 5.7 months, demonstrating that cerebrospinal fluid shunting can extend the survival of hydrocephalus patients (9). In the present study, cerebrospinal fluid shunting was performed in 14 LMC patients who had developed hydrocephalus. Their median survival was 3.7 months, but both symptoms and KPS improved in 100% of patients, making this a highly effective therapeutic procedure from the palliative viewpoint. One reason for this high level of efficacy may have been that cerebrospinal fluid tap tests were used to determine the indication for surgery. Postoperative treatment had no effect on the duration of survival. However, both of the patients who survived long-term (14.2 months and 17 months) had indications for molecular targeted therapy.
The advent of molecular targeted therapy in recent years has dramatically improved survival for patients with advanced cancers, and even some cases of LMC, against which drug therapies are generally ineffective, have reportedly responded well (11-13). Patients with indications for molecular targeted drugs may thus survive for longer periods, and the use of cerebrospinal fluid shunting as the initial procedure for such LMC patients with hydrocephalus, with the aim of improving KPS, may become an important treatment strategy.
Acknowledgements
The Authors received no financial support for the research, authorship, and/or publication of this article.
Footnotes
Authors’ Contributions
Design of the study: HY, TO. Data collection: HY, TO, TN. Data analysis: HY, TO, MF, JT. HY and TO wrote the first draft, and all Authors contributed to improving the paper. All Authors approved the final version.
Conflicts of Interest
All Authors have no conflicts of interest to disclose in relation to this study.
- Received May 22, 2021.
- Revision received June 5, 2021.
- Accepted June 8, 2021.
- Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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