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Article

Improved Survival and Symptom Relief Following Palliative Cerebrospinal Fluid Diversion for Leptomeningeal Disease from Brain Cancers: A Case Series and Systematic Review

by
Adela Wu
1,*,
James Zhou
2 and
Stephen Skirboll
1,3
1
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94304, USA
2
Kaiser Permanente Los Angeles Medical Center, Elk Grove, CA 95757, USA
3
Section of Neurosurgery, VA Palo Alto Health Care System, Palo Alto, CA 93404, USA
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(2), 292; https://doi.org/10.3390/cancers17020292
Submission received: 22 December 2024 / Revised: 12 January 2025 / Accepted: 15 January 2025 / Published: 17 January 2025
(This article belongs to the Special Issue Impact of Surgery on Brain Cancer and Other Central Nervous System Tumors)
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Simple Summary

Leptomeningeal disease from cancer indicates widespread or advanced cancer and can lead to obstructive hydrocephalus, for which palliative cerebrospinal fluid diversion may be indicated to relieve symptoms, such as headaches and nausea. The authors of this study performed a review of published clinical outcomes for patients diagnosed with hydrocephalus from leptomeningeal disease. In addition, an analysis of a single-institution case series of adult patients was conducted to evaluate surgical outcomes, including complication and symptom relief rates. Symptom relief and improved survival can be achieved with permanent cerebrospinal fluid diversion for palliative purposes with low complication rates. Hence, this patient population may benefit from surgery to alleviate symptoms from hydrocephalus despite the poor prognoses development of leptomeningeal disease portends. Still, prospective studies are needed in the future to evaluate specific needs and impacts on quality of life for these patients.

Abstract

Background: Leptomeningeal disease (LMD) from cancer indicates advanced cancer and can lead to obstructive hydrocephalus, for which palliative cerebrospinal fluid (CSF) diversion may be indicated to alleviate symptoms. We investigated surgical outcomes for hydrocephalus for adult patients with LMD and conducted a systematic review on pediatric and adult cases. Methods: We analyzed outcomes from a 10-year period of patients with neoplastic LMD, obstructive hydrocephalus, and documented date of death. We also searched databases from inception until 20 August 2022, using search terms including ‘cancer’, ‘hydrocephalus’, and ‘shunt’. Preferred reporting items for systematic reviews and meta-analyses guidelines were followed. Results: Among 50 patients, 30 (60%) underwent CSF diversion after LMD diagnosis with comparable median age in both the surgery (58.4 ± 14.4 years) and non-surgery (57.8 ± 14.5 years) groups. Twenty-three patients (76.7%) achieved symptom relief. The surgery group lived longer after LMD diagnosis than the non-surgery group (6.6 ± 6.0 vs. 1.3 ± 4.3 months, p < 0.001) and had a higher likelihood of survival (hazard ratio 2.49, 95% confidence interval 1.37–4.52, p = 0.002). Median survival after surgery was 2.8 ± 3.8 months. From 23 articles, 995 patients (34.3%) presented with LMD. Complication rates were 0–37.7% with no extraneural metastases. Symptom relief rates were 50–100%. Three studies reported median survival after surgery (2–3.3 months). Conclusions: A rare entity with dismal prognosis, LMD can present as symptomatic hydrocephalus in patients with cancer. Symptom relief and improved survival can be achieved with palliative CSF diversion with low complication rates. Prospective studies are needed to assess the outcomes and needs of these patients.

1. Introduction

Leptomeningeal disease (LMD) is a devastating indication of widespread or advanced cancer that involves the meninges or has disseminated through the cerebrospinal fluid (CSF) system. LMD can be diagnosed at initial presentation for 2–12% of metastatic solid cancer cases, and rare etiologies, such as primary leptomeningeal melanoma, derived from melanocytes of the leptomeninges, have also been reported [1,2]. Presenting characteristics include cranial nerve palsies, weakness, sensation loss, as well as headache, nausea, vomiting, and obtundation from symptomatic hydrocephalus. Patients with neoplastic LMD have a poor prognosis, with a median survival of 1–4 months if untreated [1,3]. However, treating hydrocephalus with palliative CSF diversion, such as endoscopic third ventriculostomy (ETV) or placement of ventriculoperitoneal (VP) or lumboperitoneal shunts, can be effective for symptom relief. Despite potential complications of infection, revision, and peritoneal seeding of disease, patients diagnosed with LMD could benefit from undergoing palliative surgery.
We analyzed a cohort of adult patients with cancer from our institution who developed LMD and symptomatic obstructive hydrocephalus. We evaluated various outcomes, including rates of symptom relief and of complications as well as survival data following palliative CSF diversion surgery. The systematic review summarizes published series of adult and pediatric patients diagnosed with symptomatic hydrocephalus from neoplastic LMD and assesses the rates of surgery for CSF diversion. We evaluated various outcomes, including the rates of symptom relief and of complications as well as survival data following palliative shunt or ETV surgery.

2. Materials and Methods

2.1. Case Series

2.1.1. Data Source and Patient Selection

All adult (age > 18) patients who were diagnosed with cancer, LMD, and obstructive hydrocephalus along with a date of death documented in the Stanford Health Care electronic medical record system between 1 January 2012 and 31 December 2022 were included for further analysis. Collected metrics included patient characteristics (age, sex, and racial/ethnic background), primary cancer type, date of primary cancer diagnosis, date of LMD diagnosis, date of CSF diversion surgery if applicable, date of death, and surgical outcomes (alleviated symptoms, surgical complications, and time between surgery and death). This study was approved by the Stanford University Institutional Review Board, and patient consent was waived based on the study design.

2.1.2. Statistical Analysis

Categorical variables characterizing individual patients were analyzed using either the χ2 test or Fisher’s exact test. Fisher’s exact test was used when expected values fell below a numerical cut-off of 5. Continuous data were analyzed using the Wilcoxon rank-sum test. Survival analysis was calculated with the Kaplan–Meier analysis using the Cox proportional hazards model to evaluate differences between groups. All statistical testing was performed in R version 4.3.1.

2.2. Systematic Review

The literature search was developed by defining the population, intervention, comparison, outcomes, timing, and study design (PICOTS) questions and inclusion and exclusion criteria (Figure 1). The criteria, outcome measures, and search strategy were defined prior to analysis. The register number is CRD42022349960 ID.

2.2.1. Search Strategy

The protocol was designed in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines [4]. The review included quantitative studies of pediatric and adult patients with primary or systemic cancers and tumors involving LMD and symptomatic hydrocephalus treated with CSF diversion, with at least five subjects, and which were written in English. The exclusion criteria included gray literature, non-systematic reviews, commentaries, and case reports [5]. In collaboration with a university librarian, we deployed a comprehensive search strategy within the PubMed, Embase, and Web of Science databases from inception until 20 August 2022. Synonymous words for key search terms were included to maintain the high inclusivity of the initial search.

2.2.2. Study Selection

Duplicates were removed and study eligibility was determined using the PICOTS question and inclusion and exclusion criteria (Figure 1). The titles and abstracts, followed by article full texts, were independently screened by three study authors (A.W., J.Z., S.S.), with group discussion used to adjudicate discrepancies.

2.2.3. Data Extraction and Analysis

We extracted key features from the eligible studies, including design, patient population characteristics, diagnosis of LMD, and surgical outcomes involving palliation and survival.

2.2.4. Quality Assessment

Two authors (A.W. and J.Z.) independently used the Newcastle–Ottawa Scale to assess the quality of the studies [6]. The studies were graded as very low, low, medium, or high quality based on selection criteria, risk of bias, and overall study design [7]. No studies were excluded from analysis due to quality.

3. Results

3.1. Case Series

3.1.1. Patient Characteristics

Fifty patients were identified, of whom thirty underwent surgery for CSF diversion due to symptomatic hydrocephalus. For the surgical group, the median age was 58.41 ± 14.38 years, while the median age of the non-surgical patient cohort was 57.83 ± 14.50 years (Table 1). There was no significant difference in patient age between the two groups (p = 0.426). The proportion of male patients in the non-surgical group (55.0%) was significantly greater than the surgical group percentage (23.3%) (p = 0.022). There were no significant differences in the breakdown of racial/ethnic backgrounds between the two cohorts. Within the surgical group, nine patients (30%) received Ommaya reservoirs; all others had VP shunts with programmable valves and antibiotic-impregnated catheters. The most common primary diagnosis was lung cancer in both the non-surgical (40.0%) and surgical (66.7%) groups. Nineteen patients from the surgical group underwent CT chest–abdomen–pelvis imaging for evaluation of their primary disease around the time of CSF diversion surgery, with no evidence of peritoneal disease seen on imaging.
Within the group of patients who did not undergo CSF diversion surgery, most were ultimately deemed not to be appropriate surgical candidates based on procedural risks outweighing potential benefits. Other reasons included unfavorably high protein count in CSF and patients’ refusal to undergo surgery.

3.1.2. Outcomes of Palliative Cerebrospinal Fluid Diversion

The most common specified symptoms of obstructive hydrocephalus were headaches and nausea/vomiting for both patient groups. Other presenting symptoms were cranial neuropathies, gait imbalance, altered mental status, and bladder or bowel incontinence. Within the surgical cohort, headaches (36.7%) and nausea/vomiting (33.3%) were most commonly alleviated with CSF diversion. Overall, 22 patients (73%) reported some level of symptom relief or had improved neurologic status postoperatively. One complication occurred during the immediate postoperative period, which was a patient who unfortunately developed hemiparesis from the surgery.
There was a significant increase in the median time between LMD diagnosis and death for the surgical cohort (6.62 ± 6.00 versus 1.28 ± 4.29 months, p < 0.001) (Table 1). The median time between surgery and death was 2.75 ± 3.75 months. In the Kaplan–Meier survival curve analysis, there was a significant difference between the two groups, and there was a significantly lower likelihood of death with CSF diversion surgery (hazard ratio [HR] 0.402, 95% confidence interval [CI] 0.221–0.730, p = 0.002) (Figure 2).

3.2. Systematic Review

The search yielded 2440 studies for screening, of which 647 were duplicated studies and immediately excluded (Figure 3). Based on title and abstract review, we then excluded 1641 studies. A further 132 records were excluded based on full-text review. After inclusion of three additional studies based on a manual check of references, a final total of 23 studies was reviewed, with total 2895 patients, of which 995 had LMD on presentation.

3.2.1. Study Characteristics

Studies were published between 1993 and 2022. These studies spanned eight countries (n = 8 United States [8,9,10,11,12,13,14,15]; n = 4 Korea [16,17,18,19]; n = 4 Japan [20,21,22,23]; n = 3 Canada [24,25,26]; n = 1 United Kingdom [27]; n = 1 Switzerland [28]; n = 1 France [29]; n = 1 Taiwan [30]). Twenty-two studies were retrospective cohort studies, and one was a case–control study in design. The most commonly reported data related to LMD included presenting symptoms and rates of LMD diagnosed on presentation. The most commonly reported surgical outcomes were rates of permanent CSF diversion, median overall survival, complication rates, and rates of hydrocephalus-related symptom relief.

3.2.2. Patient Characteristics

Across all the studies, the patients’ diagnoses were primary brain tumors (n = 14) [8,10,13,14,15,17,18,20,24,25,26,27,28,29], such as medulloblastoma and glioma, as well as solid and hematologic malignancies, including lymphoma, lung, and breast cancers (n = 11) [9,11,12,15,17,19,21,22,23,30]. Both pediatric and adult patients were represented, with the median age at diagnosis ranging from 2.5 to 64.5 years old. The overall average percentage of male patients from the 18 studies that reported the statistic was 47.8%.

3.2.3. Symptomatic Hydrocephalus

Nine studies reported diagnosing LMD and tumor dissemination through CSF cytology evaluation and/or evidence of leptomeningeal spread on neuraxis imaging [8,9,11,14,16,18,20,24,27]. Overall, LMD was diagnosed based on positive CSF cytology (9–82.6%) or MRI enhancement (56–100%). Studies that evaluated LMD with both cytology and MRI had higher percentages of LMD diagnosis based on imaging; for example, 100% of LMD was diagnosed in brain and spine MRI compared to 37.5% of cases resulting with positive CSF findings in Kwon et al.’s case series [18]. Among the studies that described the proportion of LMD diagnosed on presentation, 4.6–100% of patients had evidence of LMD on disease presentation [8,9,10,11,12,13,14,15,16,17,18,19,21,22,23,25,26,27,28,29,30].
The presenting symptoms of hydrocephalus commonly included headache, nausea/vomiting, seizures, cranial nerve palsies, obtundation, hemiparesis, and ataxia. Not all patients diagnosed with LMD develop symptomatic hydrocephalus. Ten studies reported a range of 13.8–80% of patients diagnosed with both neoplastic LMD and symptoms of increased intracranial pressure [8,9,11,13,14,16,19,26,28,29].

3.2.4. Outcomes of Palliative Cerebrospinal Fluid Diversion

Fourteen studies reported proportions of patients with a disseminated tumor and hydrocephalus who underwent surgery for permanent CSF diversion (range: 9.9–100%) [8,9,11,12,16,17,18,21,22,23,25,26,27,30]. In total, 561 patients across all studies underwent CSF diversion for hydrocephalus from tumor dissemination. Specific data from studies that reported on types of surgical procedures included 5 endoscopic third ventriculostomies (ETV), 389 ventriculoperitoneal (VP) shunts, and 61 lumboperitoneal shunts. Of note, Lin et al. described the management of symptomatic hydrocephalus with a VP shunt equipped with an on–off valve on the reservoir [11]. Other methods of CSF diversion were placement of Ommaya reservoirs or Torkildsen shunts.
Among the patients who underwent surgery for palliative CSF diversion, in five studies that reported data on improvement in features of symptomatic hydrocephalus, 106 people (68%; range: 50–100%) experienced rapid symptom relief [11,12,17,22,23]. Murakami et al. investigated the impact of surgery on specific symptoms of increased intracranial pressure, including 88% of patients who reported relief from headaches and 67% of patients who had improved cognitive function and nausea relief [22]. One study documented Karnofsky Performance Scores (KPS) pre- and postoperatively; the median KPS improved from 30 prior to palliative CSF diversion to 70 postoperatively [23].
Postoperative complication rates were 0–37.7%, as reported by seven studies, with no cases of extraneural metastases via shunt. Other complications included shunt malfunction. Median overall survival for patients diagnosed with LMD ranged from 2.1 to 17.1 months in 14 studies. While Jung et al. reported a median survival after shunt surgery of 5.7 months, Omuro et al. described an additional median survival after shunt surgery of 2 months beyond a median survival after LMD diagnosis of 4 months [12,16]. The cohort in Bander et al.’s study had a median survival after shunt surgery of 2.43 months [9].

3.2.5. Study Quality

Using the Newcastle–Ottawa Scale, 1 study was found to be of moderate quality and 22 were of low quality (Table 2). None were found to be of high quality.

4. Discussion

In our case series of 50 patients presenting with obstructive hydrocephalus from LMD secondary to cancer, we found that patients who underwent palliative surgery for CSF diversion had high rates of symptom relief, minimal surgical complications, and significantly longer survival than their counterparts. We also performed a systematic review of 23 studies, investigating rates and outcomes of palliative CSF diversion for symptomatic hydrocephalus resulting from neoplastic LMD. There were no randomized controlled trials that met our eligibility criteria, so future prospective studies regarding the impact of palliative CSF diversion for meningeal carcinomatosis are warranted.
LMD can develop from numerous tumor etiologies and portends poor survival. While the majority of neoplastic LMD spreads from metastatic breast or lung cancer, there is a range of studies about patients diagnosed with both metastatic primary or secondary brain cancers and rare syndromes, such as primary leptomeningeal melanoma [31]. With advances in diagnostic evaluations as well as oncologic management, the overall incidence of LMD is increasing, highlighting the importance of addressing LMD’s clinical sequelae for patients despite its devastating prognosis [32]. The clinical manifestations of LMD vary among patients, as cerebral involvement can result in headaches, nausea/vomiting, seizures, cranial nerve palsies, and obtundation, among other neurologic deficits [33,34]. These symptoms are characteristic of hydrocephalus, a common LMD-related cause of mortality and morbidity, which can develop as a result of tumor cells interfering with the outflow of CSF through arachnoid granulations in addition to consequences of reactive inflammation from tumor infiltration [33].
The placement of shunts or other interventions for CSF diversion are considered palliative for patients suffering from LMD and symptomatic hydrocephalus, as these procedures do not reverse disease course. There are certain complications commonly associated with shunt placement regardless of the primary disease process, including wound healing issues and shunt infection or malfunction, in addition to the rare risk of malignant ascites or the peritoneal seeding of disease through shunt catheters for patients diagnosed with metastatic tumors [35,36,37,38]. Among the case series described in this review, Kim, Murakami, and Omuro et al. were the only studies that specifically recorded the rates of peritoneal seeding and found no patients with this complication [12,17,22]. However, surgery for CSF diversion can effectively alleviate numerous debilitating symptoms of increased intracranial pressure. The few studies in our review that reported data on survival following shunt surgery cite up to an average of 5.7 months, which is nevertheless a substantial amount of time for meaningful symptom relief [9,12,16]. There are not enough studies with standardized methodology to compare the utility of ETV versus ventriculo- or lumboperitoneal shunts, however. As for the nonsurgical management of symptomatic hydrocephalus arising from the leptomeningeal spread of cancer, few options beyond anti-emetics and pain medications directed at symptoms are available, such as repeated lumbar punctures [39]. Otherwise, treatment for leptomeningeal disease that involves radiation, chemotherapy, and palliative steroids may impact CSF flow and alleviate some symptoms of hydrocephalus temporarily [16].
Beyond patient-reported relief from a finite sample of preoperative symptoms, the impact of palliative CSF diversion could potentially be better understood with additional measures of quality of life and functional status postoperatively. No recent studies specifically reported standardized metrics related to quality of life prior to or following CSF diversion. Some studies included KPS as an indication of functional status, with improvements in condition after palliative surgery seen in Yoshioka et al.’s cohort [9,23,30]. While the collection of data on patients’ functional status (i.e., Karnofsky Performance Status, ECOG Performance Status) was not standardized among our cohort either, understanding a global picture of impairment versus functional independence would be valuable additional information for not only cancer prognosis but potentially surgical candidacy and recovery as well [40].
The limitations of this study include the heterogeneity of the study design and the cohort size and type, such as the various tumor etiologies of neoplastic LMD, thereby restricting the generalizability of reported outcomes. The patients included in the case series were also assessed in a non-standardized manner due to different providers’ clinical practices. Therefore, certain data were not available for further analysis, including the Karnofsky Performance Scale and other factors pertaining to patients’ functional status. This systematic review also describes retrospective studies, which involve biases and confounding factors. Furthermore, this review is also limited by the nature and heterogeneous scope of outcomes, as studies do not uniformly report data, such as on rates of symptom relief or complications, for example.

5. Conclusions

A rare entity with a dismal prognosis, LMD and disseminated tumors can present as symptomatic hydrocephalus in patients with cancer. Symptom relief, including improved headaches and cognition, can be achieved with palliative surgery for permanent CSF diversion with relatively low complication rates and no incidence of extraneural metastases through shunt catheters. Further prospective studies are needed to further assess additional outcomes and needs as well as aspects of quality of life for this patient population.

Author Contributions

Conceptualization, A.W. and S.S.; methodology, A.W.; data curation, A.W. and J.Z.; writing—original draft preparation, A.W.; writing—review and editing, J.Z. and S.S.; supervision, S.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was reviewed by the Stanford University Institutional Review Board, and patient consent was waived based on the study design.

Informed Consent Statement

Patient consent was waived due to the retrospective nature of this study, which used existing data or records (e.g., medical charts and surveys) collected before the research was initiated, making it impractical or impossible to obtain informed consent from the individuals involved in the original data collection.

Data Availability Statement

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.

Acknowledgments

We thank John Borghi for his help in creating the search strategies for this systematic review.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
CSFCerebrospinal fluid
ETVEndoscopic third ventriculostomy
KPSKarnofsky Performance Scores
LMDLeptomeningeal disease

References

  1. Lamba, N.; Wen, P.Y.; A Aizer, A. Epidemiology of brain metastases and leptomeningeal disease. Neuro-Oncology 2021, 23, 1447–1456. [Google Scholar] [CrossRef] [PubMed]
  2. Xie, Z.-Y.; Hsieh, K.L.-C.; Tsang, Y.-M.; Cheung, W.-K.; Hsieh, C.-H. Primary leptomeningeal melanoma. J. Clin. Neurosci. 2014, 21, 1051–1052. [Google Scholar] [CrossRef] [PubMed]
  3. Shapiro, W.R.; Johanson, C.E.; Boogerd, W. Treatment Modalities for leptomeningeal metastases. Semin. Oncol. 2009, 36, S46–S54. [Google Scholar] [CrossRef]
  4. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. BMJ 2009, 339, 332–336. [Google Scholar] [CrossRef]
  5. Adams, R.J.; Smart, P.; Huff, A.S. Shades of Grey: Guidelines for Working with the Grey Literature in Systematic Reviews for Management and Organizational Studies. Int. J. Manag. Rev. 2016, 19, 432–454. [Google Scholar] [CrossRef]
  6. Wells, G.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. 2013. Available online: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed on 20 October 2024).
  7. Lilley, E.J.; Khan, K.T.; Johnston, F.M.; Berlin, A.; Bader, A.M.; Mosenthal, A.C.; Cooper, Z. Palliative care interventions for surgical patients a systematic review. JAMA Surg. 2016, 151, 172–183. [Google Scholar] [CrossRef]
  8. Andersen, B.M.; Miranda, C.; Hatzoglou, V.; DeAngelis, L.M.; Miller, A.M. Leptomeningeal metastases in glioma: The Memorial Sloan Kettering Cancer Center experience. Neurology 2019, 92, e2483–e2491. [Google Scholar] [CrossRef]
  9. Bander, E.D.; Yuan, M.; Reiner, A.S.; Garton, A.L.A.; Panageas, K.S.; Brennan, C.W.; Tabar, V.; Moss, N.S. Cerebrospinal fluid diversion for leptomeningeal metastasis: Palliative, procedural and oncologic outcomes. J. Neuro-Oncol. 2021, 154, 301–313. [Google Scholar] [CrossRef]
  10. Castro, B.A.; Imber, B.S.; Chen, R.; McDermott, M.W.; Aghi, M.K. Ventriculoperitoneal Shunting for Glioblastoma: Risk Factors, Indications, and Efficacy. Neurosurgery 2017, 80, 421–430. [Google Scholar] [CrossRef]
  11. Lin, N.; Dunn, I.F.; Glantz, M.; Allison, D.L.; Jensen, R.; Johnson, M.D.; Friedlander, R.M.; Kesari, S. Benefit of ventriculoperitoneal cerebrospinal fluid shunting and intrathecal chemotherapy in neoplastic meningitis: A retrospective, case-controlled study. J. Neurosurg. 2011, 115, 730–736. [Google Scholar] [CrossRef]
  12. Omuro, A.M.; Lallana, E.C.; Bilsky, M.H.; DeAngelis, L.M. Ventriculoperitoneal shunt in patients with leptomeningeal metastasis. Neurology 2005, 64, 1625–1627. [Google Scholar] [CrossRef] [PubMed]
  13. Rennert, R.C.; Brandel, M.G.; Srinivas, S.; Prajapati, D.; Al Jammal, O.M.; Brown, N.J.; Diaz-Aguilar, L.D.; Elster, J.; Gonda, D.D.; Crawford, J.R.; et al. Palliative endoscopic third ventriculostomy for pediatric primary brain tumors: A single-institution case series. J. Neurosurg. Pediatr. 2021, 28, 387–394. [Google Scholar] [CrossRef] [PubMed]
  14. Rinaldo, L.; Brown, D.; Lanzino, G.; Parney, I.F. Outcomes following cerebrospinal fluid shunting in high-grade glioma patients. J. Neurosurg. 2018, 129, 984–996. [Google Scholar] [CrossRef] [PubMed]
  15. Sandberg, D.I.; Bilsky, M.H.; Souweidane, M.M.; Bzdil, J.; Gutin, P.H. Ommaya reservoirs for the treatment of leptomeningeal metastases. Neurosurgery 2000, 47, 49–55. [Google Scholar] [CrossRef]
  16. Jung, T.-Y.; Chung, W.-K.; Oh, I.-J. The prognostic significance of surgically treated hydrocephalus in leptomeningeal metastases. Clin. Neurol. Neurosurg. 2014, 119, 80–83. [Google Scholar] [CrossRef]
  17. Kim, H.S.; Park, J.B.; Gwak, H.-S.; Kwon, J.-W.; Shin, S.-H.; Yoo, H. Clinical outcome of cerebrospinal fluid shunts in patients with leptomeningeal carcinomatosis. World J. Surg. Oncol. 2019, 17, 59. [Google Scholar] [CrossRef]
  18. Kwon, J.-E.; Hwang, K.; Go, K.-O.; Wee, C.W.; Kim, I.A.; Kim, Y.J.; Choe, G.; Choi, B.S.; Han, J.H.; Kim, C.-Y. Clinical Characteristics of High-Grade Glioma with Primary Leptomeningeal Seeding at Initial Diagnosis in a Single Center Study. Brain Tumor Res. Treat. 2020, 8, 77–82. [Google Scholar] [CrossRef]
  19. Lee, S.H.; Kong, D.S.; Seol, H.J.; Nam, D.-H.; Lee, J.-I. Ventriculoperitoneal shunt for hydrocephalus caused by central nervous system metastasis. J. Neuro-Oncol. 2011, 104, 545–551. [Google Scholar] [CrossRef]
  20. Matsumoto, J.; Kochi, M.; Morioka, M.; Nakamura, H.; Makino, K.; Hamada, J.-I.; Kuratsu, J.-I.; Ushio, Y. A long-term ventricular drainage for patients with germ cell tumors or medulloblastoma. Surg. Neurol. 2006, 65, 74–80. [Google Scholar] [CrossRef]
  21. Mitsuya, K.; Nakasu, Y.; Hayashi, N.; Deguchi, S.; Takahashi, T.; Murakami, H.; Naito, T.; Kenmotsu, H.; Ono, A.; Wakuda, K.; et al. Palliative cerebrospinal fluid shunting for leptomeningeal metastasis-related hydrocephalus in patients with lung adenocarcinoma: A single-center retrospective study. PLoS ONE 2019, 14, e0210074. [Google Scholar] [CrossRef]
  22. Murakami, Y.; Ichikawa, M.; Bakhit, M.; Jinguji, S.; Sato, T.; Fujii, M.; Sakuma, J.; Saito, K. Palliative shunt surgery for patients with leptomeningeal metastasis. Clin. Neurol. Neurosurg. 2018, 168, 175–178. [Google Scholar] [CrossRef] [PubMed]
  23. Yoshioka, H.; Okuda, T.; Nakao, T.; Fujita, M.; Takahashi, J.C. Effectiveness of Palliative Cerebrospinal Fluid Shunting for Patients with Leptomeningeal Carcinomatosis-related Hydrocephalus. Anticancer Res. 2021, 41, 4169–4172. [Google Scholar] [CrossRef]
  24. Allcutt, D.; Michowiz, S.; Weitzman, S.; Becker, L.; Blaser, S.; Hoffman, H.J.; Humphreys, R.P.; Drake, J.M.; Rutka, J.T. Primary leptomeningeal melanoma: An unusually aggressive tumor in childhood. Neurosurgery 1993, 32, 721–729. [Google Scholar] [CrossRef] [PubMed]
  25. Riva-Cambrin, J.; Detsky, A.S.; Lamberti-Pasculli, M.; Sargent, M.A.; Armstrong, D.; Moineddin, R.; Cochrane, D.D.; Drake, J.M. Predicting postresection hydrocephalus in pediatric patients with posterior fossa tumors. J. Neurosurg. Pediatr. 2009, 3, 378–385. [Google Scholar] [CrossRef] [PubMed]
  26. Schneider, C.; Ramaswamy, V.; Kulkarni, A.V.; Rutka, J.T.; Remke, M.; Tabori, U.; Hawkins, C.; Bouffet, E.; Taylor, M.D. Clinical implications of medulloblastoma subgroups: Incidence of CSF diversion surgery. J. Neurosurg. Pediatr. 2015, 15, 236–242. [Google Scholar] [CrossRef] [PubMed]
  27. Kirkman, M.A.; Hayward, R.; Phipps, K.; Aquilina, K. Outcomes in children with central nervous system tumors disseminated at presentation: A large single-center experience. Child’s Nerv. Syst. 2018, 34, 2259–2267. [Google Scholar] [CrossRef] [PubMed]
  28. Fischer, C.M.; Neidert, M.C.; Péus, D.; Ulrich, N.H.; Regli, L.; Krayenbühl, N.; Woernle, C.M. Hydrocephalus after resection and adjuvant radiochemotherapy in patients with glioblastoma. Clin. Neurol. Neurosurg. 2014, 120, 27–31. [Google Scholar] [CrossRef]
  29. Le Fournier, L.; Delion, M.; Esvan, M.; De Carli, E.; Chappé, C.; Mercier, P.; Menei, P.; Riffaud, L. Management of hydrocephalus in pediatric metastatic tumors of the posterior fossa at presentation. Child’s Nerv. Syst. 2017, 12, 220–1480. [Google Scholar] [CrossRef]
  30. Su, Y.-H.; Chiang, C.-L.; Yang, H.-C.; Hu, Y.-S.; Chen, Y.-W.; Luo, Y.-H.; Chen, C.-J.; Wu, H.-M.; Lin, C.-J.; Lee, C.-C. Cerebrospinal fluid diversion and outcomes for lung cancer patients with leptomeningeal carcinomatosis. Acta Neurochir. 2022, 164, 459–467. [Google Scholar] [CrossRef]
  31. Nayar, G.; Ejikeme, T.; Chongsathidkiet, P.; Elsamadicy, A.A.; Blackwell, K.L.; Clarke, J.M.; Lad, S.P.; Fecci, P.E. Leptomeningeal disease: Current diagnostic and therapeutic strategies. Oncotarget 2017, 8, 73312–73328. [Google Scholar] [CrossRef]
  32. Kumar, A.; Sardhara, J.C.; Singh, G.; Kanjilal, S.; Maurya, V.P.; Behari, S. Malignant Meningitis Associated with Hydrocephalus. Neurol. India 2021, 69, S443–S455. [Google Scholar] [CrossRef] [PubMed]
  33. Le Rhun, E.; Taillibert, S.; Chamberlain, M. Carcinomatous meningitis: Leptomeningeal metastases in solid tumors. Surg. Neurol. Int. 2013, 4, S265–S288. [Google Scholar] [CrossRef] [PubMed]
  34. Groves, M. Advances in Treating Leptomeningeal Metastases. In Educational Book; American Society of Clinical Oncology: Alexandria, VA, USA, 2008. [Google Scholar]
  35. Newton, H.B.; Henson, J.; Walker, R.W. Extraneural metastases in ependymoma. J. Neuro-Oncol. 1992, 14, 135–142. [Google Scholar] [CrossRef] [PubMed]
  36. Ingold, B.; Moschopulos, M.; Hutter, G.; Seeger, H.; Röthlisberger, B.; Landolt, H.; Yonekawa, Y.; Jochum, W.; Heppner, F.L. Abdominal seeding of an atypical teratoid/rhabdoid tumor of the pineal gland along a ventriculoperitoneal shunt catheter. Acta Neuropathol. 2006, 111, 56–59. [Google Scholar] [CrossRef] [PubMed]
  37. Schneider, M.; Wispel, C.; Potthoff, A.-L.; Heimann, M.; Borger, V.; Schaub, C.; Herrlinger, U.; Vatter, H.; Schuss, P.; Schäfer, N. Patients with Leptomeningeal Carcinomatosis and Hydrocephalus-Feasibility of Combined Ventriculoperitoneal Shunt and Reservoir Insertion for Intrathecal Chemotherapy. Curr. Oncol. 2024, 31, 2410–2419. [Google Scholar] [CrossRef]
  38. Lee, M.H.; Lee, J.I. Malignant ascites after subduroperitoneal shunt in a patient with leptomeningeal metastasis. J. Korean Neurosurg. Soc. 2011, 50, 385. [Google Scholar] [CrossRef]
  39. Lamba, N.; Fick, T.; Tewarie, R.N.; Broekman, M.L. Management of hydrocephalus in patients with leptomeningeal metastases: An ethical approach to decision-making. J. Neuro-Oncol. 2018, 140, 5–13. [Google Scholar] [CrossRef]
  40. Nadeswaran, P.; Ding, L.; Singh, N.; Plotkin, A.; A Magee, G.; Han, S.M.; Garg, P.K. Functional performance status and risk of cardiovascular events and mortality following endovascular repair of thoracic and abdominal aortic pathology. Vascular 2022, 30, 206–216. [Google Scholar] [CrossRef]
Cancers 17 00292 g001
Figure 1. PICOTS question and inclusion and exclusion criteria.
Figure 1. PICOTS question and inclusion and exclusion criteria.
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Figure 2. Kaplan–Meier survival curve for non-surgical and surgical patient groups with leptomeningeal disease.
Figure 2. Kaplan–Meier survival curve for non-surgical and surgical patient groups with leptomeningeal disease.
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Figure 3. Flow diagram of the systematic review process.
Figure 3. Flow diagram of the systematic review process.
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Table 1. Patient characteristics in case series of patients who did and did not undergo surgery for cerebrospinal fluid diversion.
Table 1. Patient characteristics in case series of patients who did and did not undergo surgery for cerebrospinal fluid diversion.
No Surgical Diversion
(n = 20, 40.0%)		Surgical Diversion
(n = 30, 60.0%) 		p-Value
Age at diagnosis (median ± SD)57.83 ± 14.5058.41 ± 14.380.426
Male11 (55.0%)7 (23.3%)0.022
Race
White9 (45.0%)14 (46.7%)0.908
Asian6 (30.0%)11 (36.7%)0.626
Other5 (25.0%)5 (16.7%)0.494
Hispanic3 (15.0%)1 (3.3%)
Primary cancer diagnosis
Lung8 (40.0%)20 (66.7%)0.063
Brain3 (15.0%)3 (10.0%)0.672
Breast4 (20.0%)5 (16.7%)1
GI3 (15.0%)1 (3.3%)0.289
Other2 (10.0%)1 (3.3%)0.556
Initial LMD symptoms
Headache6 (30.0%)14 (46.7%)0.239
Nausea/vomiting7 (35.0%)12 (40.0%)0.721
Cranial neuropathies2 (10.0%)2 (6.7%)1
Altered mental status6 (30.0%)10 (33.3%)0.805
Gait4 (20.0%)5 (16.7%)1
Incontinence1 (5.0%)2 (6.7%)1
Miscellaneous9 (45.0%)9 (30.0%)0.279
Symptoms alleviated
HeadacheN/A11 (36.7%)N/A
Nausea/vomitingN/A10 (33.3%)N/A
Cranial neuropathiesN/A1 (3.3%)N/A
Altered mental statusN/A3 (10.0%)N/A
GaitN/A2 (6.7%)N/A
IncontinenceN/A0 (0.0%)N/A
MiscellaneousN/A7 (23.3%)N/A
Time between LMD and death (months ± SD)1.28 ± 4.296.62 ± 6.00<0.001
Time between surgery and death (months ± SD)N/A2.75 ± 3.75N/A
Table 2. Summary of twenty-three eligible studies with >5 patients. CN: cranial nerve. CNS: central nervous system. CSF: cerebrospinal fluid. DIPG: diffuse infiltrative pontine glioma. ETV: endoscopic third ventriculostomy. GBM: glioblastoma. LMD: leptomeningeal disease. LP: lumboperitoneal. VP: ventriculoperitoneal.
Table 2. Summary of twenty-three eligible studies with >5 patients. CN: cranial nerve. CNS: central nervous system. CSF: cerebrospinal fluid. DIPG: diffuse infiltrative pontine glioma. ETV: endoscopic third ventriculostomy. GBM: glioblastoma. LMD: leptomeningeal disease. LP: lumboperitoneal. VP: ventriculoperitoneal.
Study ID (Country of Study)Study Design;
Study Quality [7]		Study Time PeriodInclusion CriteriaSample SizePertinent Study Findings on Hydrocephalus TreatmentSurvival
Allcutt et al., 1993
(Canada) [26]		Retrospective; Low1961–1991All pediatric patients with primary leptomeningeal melanoma at The Hospital for Sick Children with sufficient diagnostic information 8% with permanent CSF diversion: 6 (75%) [4 LP shunts; 1 VP shunt; 1 Torkildsen shunt]Median overall survival: 6 months
Andersen et al., 2019 (United States) [9]Retrospective; Low2001–2016All adult patients with confirmed LMD from Grade 2–4 glioma at Memorial Sloan Kettering Cancer Center188% with permanent CSF diversion: 36 (23%) [36 VP shunts]Median overall survival of LMD at presentation: 8.3 months
Bander et al., 2021 (United States) [10]Retrospective; Low2010–2019All patients diagnosed with LMD and treated hydrocephalus at Memorial Sloan Kettering Cancer Center190% with permanent CSF diversion: 190 (100%) [189 VPS; 1 V-pleural shunt]Median overall survival: 4.14 months; Median survival after shunt: 2.43 months
Castro et al., 2017 (United States) [11]Retrospective; Low2004–2014All patients with surgically resected GBM at University of California at San Francisco 841No specific data availableNo specific data available
Fischer et al., 2014 (Switzerland) [30]Retrospective; Low2007–2011All patients with completely resected and treated GBM151No specific data availableNo specific data available
Jung et al., 2014 (Korea) [18]Retrospective; Low2005–2012Adult patients with LMD from systemic solid tumors treated at Chonnam National University Hwasun Hospital71% with permanent CSF diversion: 7 (9.9%) [7 VP shunt]Median survival after shunt surgery: 5.7 months; Median overall survival: 2.1 months
Kim et al., 2019 (Korea) [19]Retrospective; Low2002–2017Patients with confirmed LMD and treated hydrocephalus at National Cancer Center in Korea 70% with permanent CSF diversion: 100% [51 VP shunt; 19 LP shunt]Median survival after LMD diagnosis: 8.7 months
Kirkman et al., 2018 (United Kingdom) [29]Retrospective; Low2003–2016All pediatric patients with confirmed central nervous system (CNS) tumors with tumor dissemination evident on MRI361% with permanent CSF diversion among patients with LMD: 36 (67.9%)No specific data available
Kwon et al., 2020 (Korea) [20]Retrospective; Low2004–2019Patients with confirmed primary LMD from high-grade glioma (Grade III-IV) 9% with permanent CSF diversion: 66.7% [4 VP shunt; 2 Ommaya]Median survival: 263 days
Lee et al., 2011 (Korea) [21]Retrospective; Low2003–2010Patients with diagnosed CNS metastases who underwent VP shunt50No specific data availableMedian survival after LMD diagnosis: 3.5 months
Le Fournier et al., 2017 (France) [31]Retrospective; Low 2005–2015All pediatric patients with newly diagnosed posterior fossa tumor admitted to Angers University Hospital and Rennes University Hospital29No specific data available No specific data available
Lin et al., 2011 (United States) [13]Case-control; Moderate2005–2009All adult patients with LMD treated at Huntsman Cancer Institute or Brigham and Women’s Hospital/Dana-Farber Cancer Institute 24 (case); 24 (control)% with permanent CSF diversion among cases: 24/24 (100%) [24 RO-VP shunt]Median progression-free survival among cases: 14 weeks
Matsumoto et al., 2006
(Japan) [22]		Retrospective; Low1979–2003Patients with diagnosed germ cell tumor or medulloblastoma and hydrocephalus treated with percutaneous long-tunneled ventricular drainage (PLTVD) at single institution13No specific data available No specific data available
Mitsuya et al., 2019 (Japan) [23]Retrospective; Low2008–2017Patients with LMD from lung adenocarcinoma and hydrocephalus requiring treatment at Shizuoka Cancer Center31% with permanent CSF diversion: 100% [13 VP shunt; 19 LP shunt]Median overall survival after LMD diagnosis: 4.5 months; Median overall survival after shunt surgery: 3.5 months
Murakami et al., 2018
(Japan) [24]		Retrospective; Low 2007–2016Patients with palliative shunt placement for hydrocephalus and LMD not amenable for surgical resection at a single institution11% with permanent CSF diversion: 100% [8 VP shunt; 3 LP shunt]Median survival after LMD diagnosis: 3.9 months; Median survival after shunt surgery: 3.3 months
Omuro et al., 2005 (United States) [14]Retrospective; Low1995–2003All adult patients with diagnosed LMD (primary brain tumors excluded) and VP shunt treated at Memorial Sloan-Kettering Cancer Center37% with permanent CSF diversion: 100% [37 VP shunt]Median survival after LMD diagnosis: 4 months; Median survival after shunt surgery: 2 months
Rennert et al., 2021 (United States) [15]Retrospective; Low2010–2020Pediatric patients with ETV for hydrocephalus from primary brain tumors at Rady Children’s Hospital of San Diego15No specific data available Median survival among patients with LMD: 2.5 months
Rinaldo et al., 2018 (United States) [16]Retrospective; Low2001–2016Patients with Grade III or IV glioma with hydrocephalus treated by shunting at Mayo Clinic Rochester41No specific data available No specific data available
Riva-Cambrin et al., 2009 (Canada) [27]Retrospective; Low 1989–2003Patients ≤ 17 years of age with newly diagnosed posterior fossa tumors at Hospital for Sick Children in training cohort; pediatric patients with posterior fossa tumors at British Columbia Children’s Hospital in validation cohortTraining cohort (343); validation cohort (111)Training cohort: % with permanent CSF diversion: 15/107 (14.3%)No specific data available
Sandberg et al., 2000 (United States) [17]Retrospective; Low1995–1998Patients with LMD and Ommaya reservoirs and surgically treated hydrocephalus at Memorial Sloan-Kettering Cancer Center107No specific data availableMedian survival after LMD diagnosis: 8.5 months
Schneider et al., 2015 (Canada) [28]Retrospective; Low1991–2013Patients with medulloblastoma and hydrocephalus treated at The Hospital for Sick Children130% with permanent CSF diversion among patients with LMD/solid metastases: 12/28 (42.9%)No specific data available
Su et al., 2022 (Taiwan) [32]Retrospective; Low2017–2020Patients with LMD from lung cancer treated at a single institution50% with permanent CSF diversion: 40/50 (80%) [33 VP shunt; 7 LP shunt]Median overall survival: 4.9 months
Yoshioka et al., 2021 (Japan) [25]Retrospective; Low2010–2019Patients with diagnosed LMD and hydrocephalus who underwent treatment at Kindai University Hospital14% with permanent CSF diversion: 100% [5 VP shunt; 9 LP shunt]Median overall survival: 3.7 months
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Wu, A.; Zhou, J.; Skirboll, S. Improved Survival and Symptom Relief Following Palliative Cerebrospinal Fluid Diversion for Leptomeningeal Disease from Brain Cancers: A Case Series and Systematic Review. Cancers 2025, 17, 292. https://doi.org/10.3390/cancers17020292

AMA Style

Wu A, Zhou J, Skirboll S. Improved Survival and Symptom Relief Following Palliative Cerebrospinal Fluid Diversion for Leptomeningeal Disease from Brain Cancers: A Case Series and Systematic Review. Cancers. 2025; 17(2):292. https://doi.org/10.3390/cancers17020292

Chicago/Turabian Style

Wu, Adela, James Zhou, and Stephen Skirboll. 2025. "Improved Survival and Symptom Relief Following Palliative Cerebrospinal Fluid Diversion for Leptomeningeal Disease from Brain Cancers: A Case Series and Systematic Review" Cancers 17, no. 2: 292. https://doi.org/10.3390/cancers17020292

APA Style

Wu, A., Zhou, J., & Skirboll, S. (2025). Improved Survival and Symptom Relief Following Palliative Cerebrospinal Fluid Diversion for Leptomeningeal Disease from Brain Cancers: A Case Series and Systematic Review. Cancers, 17(2), 292. https://doi.org/10.3390/cancers17020292

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