Predictive factors for clinical outcome of palliative ventriculoperitoneal shunt in the treatment of leptomeningeal metastasis
Highlight box
Key findings
• Lumbar puncture pressure is the only independent predictor of clinical outcomes in leptomeningeal metastasis (LM) patients undergoing ventriculoperitoneal shunt (VPS).
What is known and what is new?
• VPS improves outcomes in LM patients with hydrocephalus.
• Lumbar puncture pressure, not hydrocephalus, is the key factor in predicting VPS outcomes.
What is the implication, and what should change now?
• Clinicians should prioritize lumbar puncture pressure assessment when considering VPS, and further studies are needed to refine treatment strategies.
Introduction
Background
Leptomeningeal metastasis (LM) occurs in 10–15% of patients with advanced cancer, particularly those with solid tumors (1). As imaging and systemic therapies continue to improve survival rates, the prevalence of LM is expected to rise, presenting ongoing challenges in patient management. The infiltration of malignant cells into the meninges can cause significant neurological impairment and is frequently associated with hydrocephalus, which arises either from obstruction of cerebrospinal fluid (CSF) pathways or impaired CSF absorption (2,3).
Rationale and knowledge gap
Hydrocephalus in LM patients presents with severe neurological symptoms, including headaches, cognitive dysfunction, and gait abnormalities, significantly limiting the feasibility of aggressive cancer treatments (4). Ventriculoperitoneal shunting (VPS) is commonly used to alleviate intracranial pressure (ICP) and restore CSF flow. However, the prognostic implications of VPS in LM patients are not well defined. While clinical factors such as the extent of metastasis, lumbar puncture pressure, and timing of VPS placement may affect outcomes, their specific influence on prognosis remains unclear (5,6).
Objective
This study aims to analyze the clinical predictors, including lumbar puncture pressure and VPS timing, to better understand their impact on prognosis in patients with hydrocephalus due to LM. The findings provide insights to guide future therapeutic strategies and improve patient care. We present this article in accordance with the STROBE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-766/rc).
Methods
Patients
In this retrospective study, we evaluated 37 consecutive patients diagnosed with LM who underwent VPS placement at the Department of Neurosurgery, Huashan Hospital, Fudan University, between June 2018 and June 2024. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of Huashan Hospital, Fudan University (No. 2024-685). Informed consent was obtained from all participants prior to their involvement in the study. The study included patients with LM, both with hydrocephalus and without hydrocephalus, but with poor quality of life (QOL). Patients with primary brain tumors were excluded. Detailed medical records were reviewed to extract data on clinical presentation, type of primary malignancy, time from diagnosis of primary tumor to diagnosis of LM, treatment before VPS, hydrocephalus status, location and extent of LM, preoperative single lumbar puncture pressure (measured in mmH2O), equipment company, and change in Karnofsky performance status (KPS), defined as the difference in scores between preoperative and 1-week postoperative assessments. A good outcome was qualitatively summarized as “≥30%” improvement in KPS, while a poor outcome was qualitatively summarized as “<30%” improvement in KPS. The cutoff values were determined based on previous studies on KPS scores in advanced cancer patients.
The diagnosis of LM was based on the demonstration of malignant tumor cells in CSF and/or focal or diffuse enhancement of the meninges, ependyma, tentorium, basal ganglia, and sulci on magnetic resonance imaging (MRI) (7,8). Hydrocephalus was classified as obstructive, resulting from a mass effect impeding CSF flow, or communicating, defined by the presence of leptomeningeal enhancement on MRI or positive CSF cytology (8).
The indication for VPS was primarily based on uncontrollable intracranial hypertension despite aggressive management or progressive neurological deficits associated with LM. VPS procedures employed a programmable valve system (Johnson & Johnson/Braun/Medtronic® Programmable Valve System).
Statistical analysis
Statistical analysis was conducted to evaluate the impact of various risk factors on post-VPS outcomes. These factors included age, sex, type of primary malignancy, time from diagnosis of primary tumor to diagnosis of LM, treatment before VPS, hydrocephalus status, location and extent of LM, preoperative lumbar puncture pressure, and equipment company. Univariate analyses were conducted to assess potential associations between these variables and outcomes. To further refine our understanding of independent predictors influencing survival, multivariate analyses were performed using the Cox proportional hazards model. All statistical tests were deemed significant at a P value threshold of <0.05.
Results
The comparative analysis of patient outcomes based on various clinical parameters provides valuable insights into the factors influencing the efficacy of VPS treatment (Table 1). The mean age of patients in the good-outcome group was 53.53 years, slightly younger than the 55.77 years observed in the poor-outcome group, suggesting that age may influence treatment outcomes. Notably, hydrocephalus was present in 73.3% of patients in the good-outcome group, while only 27.3% of those in the poor-outcome group had hydrocephalus, suggesting that hydrocephalus management may confer a protective effect. Additionally, lumbar puncture pressure was significantly higher in the good-outcome group (313.2 mmH2O) compared to the poor-outcome group (201.1 mmH2O), indicating that the alleviation of elevated ICP may correlate with better CSF dynamics and improved outcomes. The postoperative KPS scores also showed a significant improvement in functional status for the good-outcome group, compared to the poor-outcome group. These findings highlight the importance of timely interventions, such as VPS, in optimizing patient outcomes in oncology settings.
Table 1
| Factor | Good-outcome group | Poor-outcome group |
|---|---|---|
| Age (years) | 53.53±10.85 | 55.77±11.73 |
| Sex (male/female) | 8/7 (53.3/46.7) | 12/10 (60/40) |
| Primary malignancy | ||
| Lung cancer | 13 (43.3) | 17 (56.7) |
| Breast cancer | 1 (20.0) | 4 (80.0) |
| Colorectal cancer | 0 (0.0) | 1 (100.0) |
| Gastric cancer | 1 (100.0) | 0 (0.0) |
| LMS time (months) | 21.4±19.2 | 25.6±28.1 |
| Treatment before VPS | ||
| None | 3 (60.0) | 2 (40.0) |
| Systemic chemotherapy | 2 (25.0) | 6 (75.0) |
| Systemic chemotherapy, radiosurgery | 4 (80.0) | 1 (20.0) |
| Systemic chemotherapy, targeted therapy | 5 (41.7) | 7 (58.3) |
| Radiosurgery | 0 (0.0) | 1 (100.0) |
| Systemic chemotherapy, radiosurgery, targeted therapy | 1 (16.7) | 5 (83.3) |
| Hydrocephalus (yes/no) | 11/4 (73.3/26.7) | 6/16 (27.3/72.7) |
| Location | ||
| Leptomeninges | 12 (54.5) | 10 (45.5) |
| Dura | 2 (50.0) | 2 (50.0) |
| Leptomeninges and dura | 1 (9.1) | 10 (90.9) |
| Extent (diffuse/local) | 9/6 (60/40) | 10/12 (45.5/54.5) |
| Equipment company | ||
| Johnson & Johnson | 8 (34.8) | 15 (65.2) |
| Medtronic | 4 (66.7) | 2 (33.3) |
| Braun | 2 (40.0) | 4 (60.0) |
| Lumbar puncture pressure (mmH2O) | 313.2±34.8 | 201.1±61.7 |
| KPS (preoperative/postoperative) | 31.88±4.03/85.63±5.12 | |
Data are presented as n (%) or mean ± SD. KPS, Karnofsky performance status; LMS, Leptomeningeal metastasis; SD, standard deviation; VPS, Ventriculoperitoneal shunt.
Univariate analysis identified several factors associated with a favorable outcome. The presence of hydrocephalus was significantly associated with a good outcome, with an odds ratio (OR) of 7.333 (P=0.008), underscoring the critical role of hydrocephalus management in clinical decision-making. Moreover, the location of metastasis was a significant determinant, with an OR of 2.980 (P=0.02), suggesting that therapeutic strategies should be tailored according to the metastatic site (Figures 1-3). In contrast, factors such as age (P=0.55), sex (P=0.94), and the extent of malignancy (P=0.39) did not yield statistically significant results. Interestingly, lumbar puncture pressure was also found to be a significant predictor, with an OR of 1.043 (P=0.003), highlighting its potential role in treatment efficacy and patient management (Table 2). Collectively, these findings underscore the importance of specific clinical parameters in predicting patient outcomes and advocate for more personalized treatment approaches in oncological care.
Table 2
| Factor | OR | 95% CI | P |
|---|---|---|---|
| Age | 1.018 | 0.960–1.084 | 0.55 |
| Sex | 0.952 | 0.253–3.611 | 0.94 |
| Primary malignancy | 1.676 | 0.710–5.529 | 0.29 |
| LMS time | 1.007 | 1.007–0.980 | 0.61 |
| Treatment before VPS | 1.320 | 0.817–2.208 | 0.27 |
| Hydrocephalus | 7.333 | 1.788–35.981 | 0.008 |
| Location | 2.980 | 1.268–9.106 | 0.02 |
| Extent | 1.800 | 0.481–7.096 | 0.39 |
| Equipment company | 0.599 | 0.214–1.491 | 0.28 |
| Lumbar puncture pressure | 1.043 | 1.021–1.083 | 0.003 |
CI, confidence interval; LMS, leptomeningeal metastasis; OR, odds ratio; VPS, ventriculoperitoneal shunt.
Multivariate analysis further assessed key variables that may influence clinical outcomes. Among the variables examined, lumbar puncture pressure emerged as a significant predictor of treatment success, with an OR of 1.040 (P=0.006) (Table 3). This suggests that higher lumbar puncture pressures may be associated with improved outcomes after VPS, emphasizing its relevance in clinical decision-making. Although other variables did not show significant correlations with patient outcomes, primary malignancy exhibited an OR of 1.749 (P>0.99), indicating a potential association worthy of further investigation despite the wide confidence interval. The location of metastasis displayed an OR of 3.176, although it did not reach statistical significance (P=0.10), suggesting that tumor location may still contribute to outcome variability. Hydrocephalus had an OR of 5.138, but the lack of statistical significance (P=0.18) necessitates cautious interpretation. Overall, while several factors showed promise, only lumbar puncture pressure achieved statistical significance, reinforcing the need for further comprehensive research to better understand the complex interactions between these variables in treatment planning.
Table 3
| Factor | OR | 95% CI | P |
|---|---|---|---|
| Age | 1.035 | 0.963–1.123 | 0.36 |
| Sex | 0.795 | 0.119–4.822 | 0.80 |
| Primary malignancy | 1.749 | 0.542–10.292 | >0.99 |
| LMS time | 0.999 | 0.959–1.042 | 0.97 |
| Treatment before VPS | 0.905 | 0.421–1.881 | 0.79 |
| Hydrocephalus | 5.138 | 0.534–86.601 | 0.18 |
| Location | 3.176 | 0.872–15.426 | 0.10 |
| Extent | 0.831 | 0.135–4.446 | 0.83 |
| Equipment company | 0.541 | 0.140–1.752 | 0.32 |
| Lumbar puncture pressure | 1.040 | 1.019–1.083 | 0.006 |
CI, confidence interval; LMS, leptomeningeal metastasis; OR, odds ratio; VPS, ventriculoperitoneal shunt.
Discussion
The management of patients with tumor-related LM poses significant challenges in neuro-oncology, particularly when accompanied by symptomatic hydrocephalus. This condition often leads to elevated ICP, which can exacerbate neurological deficits and severely impair QOL (9). A growing body of evidence supports the notion that effective management of hydrocephalus through shunting can lead to enhanced clinical outcomes for individuals suffering from meningeal metastasis (10). However, predicting the clinical outcomes of this approach remains challenging.
Univariate analysis findings of our study showed that the potential of hydrocephalus and lumbar puncture pressure (P<0.05) as significant prognostic factors following shunt placement. Neuroimaging modalities, particularly MRI and computed tomography (CT) scans, have demonstrated their utility in assessing the degree of ventricular enlargement and the underlying CSF flow dynamics disrupted by tumor obstruction. Previous research has indicated that more severe preoperative hydrocephalus may correlate with worse postoperative outcomes, reinforcing the necessity of thorough radiological evaluations prior to surgical intervention (11,12). Multivariate analysis showed that hydrocephalus was not an independent prognostic factor in LM patients with VPS when other factors were taken into account. With respect to imaging findings, the role of ICP as a crucial prognostic factor is established in our multivariate analysis results. Elevated ICP not only aggravates existing neurological symptoms but also poses risks of cerebral ischemia and long-term neurological compromise, leading to suboptimal survival rates (13,14). As highlighted in the literature, maintaining optimal ICP levels post-surgery is essential for improving cerebral perfusion and overall outcomes in patients with brain metastases (15). Thus, monitoring of ICP should be an integral part of determining whether VPS is beneficial for patients with LM, allowing for timely interventions to improve patient status so that the patient can tolerate subsequent treatment.
Despite the encouraging results that we observed, there are inherent limitations within our study that warrant consideration. The retrospective nature of our analysis introduces potential biases and limits the generalizability of our findings. Additionally, the relatively small sample size highlights the need for multicenter collaborations that can produce larger datasets, thereby facilitating more robust statistical analyses. The challenges associated with patient follow-up, including issues with compliance and the feasibility of long-term tracking, limited the availability of comprehensive KPS data, which should also be considered as a constraint. Such efforts could elucidate the nuances of treatment response in varied patient populations and contribute to the refinement of management strategies.
In conclusion, VPS represents a valuable surgical option for improving patient status resulting from tumor-related meningeal metastases. Patients with a high level of lumbar puncture pressure were more likely to benefit from VPS. Comprehensive prospective studies are imperative to establish clearer prognostic indicators, ultimately guiding therapeutic decision-making and optimizing patient outcomes in this challenging clinical scenario.
Conclusions
In conclusion, our study identifies lumbar puncture pressure as the only independent predictive factor for the clinical outcomes of VPS in patients with LM. While hydrocephalus and elevated ICP play important roles in the management of these patients, lumbar puncture pressure remains the most reliable indicator of postoperative success. These findings emphasize the critical importance of assessing lumbar puncture pressure as part of the preoperative evaluation to guide clinical decision-making and improve patient outcomes following VPS. Further research is needed to refine these insights and enhance the treatment strategies for patients with LM.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-766/rc
Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-766/dss
Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-766/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-766/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of Huashan Hospital, Fudan University (No. 2024-685) and informed consent was obtained from all patients for this retrospective analysis.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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