The Impact of Post-Craniotomy Subdural Effusion in Pediatric Brain Tumors

doi:10.21203/rs.3.rs-4812313/v1

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The Impact of Post-Craniotomy Subdural Effusion in Pediatric Brain Tumors

https://doi.org/10.21203/rs.3.rs-4812313/v1

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Purpose

Over recent decades, survival rates in pediatric brain tumors (PBT) have been significantly improved due to technological advancements in surgical approaches and intensified chemotherapy. Although disease relapse rates have been reduced, these treatments still come with unavoidable complications. Subdural effusion (SDE) is a significant complication that can occur after craniotomy, with its incidence depending on the surgical approach and potentially affecting the prognosis of the disease. The objective of this study is to examine the impact of post-craniotomy SDE on survival outcomes in patients with PBT.

Methods

Our study utilized a retrospective chart review to examine children diagnosed with PBT at Chang Gung Memorial Hospital between January 2013 and December 2023. Survival benefits were assessed using Kaplan-Meier analysis, while differences in continuous variables were examined using Student's t-tests. The statistical analyses were conducted using GraphPad Prism version 9.0 software.

Results

The study included 178 children diagnosed with PBT, and their progress was tracked for a median duration of 3.8 years (IQR 1.6–7.0). The diagnoses consisted of a variety of brain tumors. The incidence of post-craniotomy SDE was 21.3%. The majority of cases (66%) were managed through observation, while surgical intervention was necessary for 34% of cases. The study found that the presence of SDE was associated with slightly lower survival rates (18.4% vs. 15.0%) and slightly higher disease relapse rates (44.7% vs. 35.7%), although these differences did not reach statistical significance.

Conclusion

SDE is still a frequent complication that occurs after craniotomy in PBT patients. The presence of SDE can have a negative impact on both survival rates and the likelihood of disease relapse in PBT.

Pediatric brain tumor

post-craniotomy complications

subdural effusion

overall survival

relapse free survival

The overall survival (OS) of pediatric brain tumors (PBT) has improved from less than 40% to 60–80% in the past decades [1, 2]. This notable survival outcome is largely attributed to technical improvements in surgery, personalized irradiation programs, and the introduction of multi-agent chemotherapy. The increased intensity of multidisciplinary treatments addresses the historically bleak prognosis of PBT but inevitably leads to the development of upfront treatment-related morbidity and complications [3–5]. Clinical physicians have dedicated themselves to striking a balance between treatment efficacy and the associated toxicity.

Subdural effusion (SDE) is a common complication following brain surgery, with its incidence varying across different craniotomy approaches [6–9]. In most cases, the presence of SDE does not necessitate emergent management unless it reaches a considerable size or leads to progressive elevation of intracranial pressure. While not typically life-threatening, SDE appears to be associated with cortical/ependymal defects. Compromised dural integrity may facilitate disease dissemination, potentially impacting survival outcomes negatively [10, 11]. Research efforts have often focused on refining surgical techniques and developing novel therapies, yet little is known about the impact of complications such as SDE on survival outcomes. This study aims to investigate the prognostic impact of SDE in patients with PBT.

Case Enrollment

This retrospective cohort study enrolled pediatric patients diagnosed with brain tumors at Chang Gung Memorial Hospital between January 2013 and December 2023. Patients with less than one year of follow-up were excluded. This study was approved by the Chang Gung Memorial Hospital Institutional review board (Project number 202401075B0).

Diagnosis Confirmation

Diagnosis of PBT was confirmed through histopathological and radiological assessments. Tumors were categorized into glioma, germ cell tumors (GCTs), medulloblastoma (MB), embryonal tumors, atypical teratoid/rhabdoid tumors, craniopharyngioma, and others. Resected tumor slides were independently reviewed by an expert pathologist, with consultation from another pathologist in cases of inconclusive results.

Evaluation of Treatment Response

Radiological evaluations were conducted every 3–6 months to assess treatment response, guided by clinical expertise.

Statistical Analysis

Kaplan-Meier analysis was used to plot survival and relapse curves. Student’s t-tests were employed to analyze differences in continuous variables such as age at diagnosis, follow-up duration, survival period, and relapse-free interval. Chi-square tests were used to assess differences in categorical variables including PBT subtype, gender, surgical approach, presence of SDE, relapse, and mortality. All statistical analyses were performed using GraphPad Prism version 9.0 software.

A total of 178 children diagnosed with PBT were included in the study cohort. The median follow-up duration was 3.8 years (IQR 1.6–7.0). Baseline characteristics are summarized in Table 1. Major PBT subtypes included glioma (40.4%), GCTs (25.3%), and MB (14.6%). The survival analysis of PBT subtypes was shown in Fig. 1. The PBT with low-grade glioma (LGG) subtype exhibited the best prognosis, with a 5-year OS rate of 97.8%. The high-grade glioma (HGG) subtype harbored the poorest prognosis, with a 5-year OS rate of 36.7%. Post-craniotomy SDE occurred in 21.3% of cases. Management was predominantly observational (66%), with surgical intervention required in 34% due to larger SDE size or symptomatic illness. Frontal and occipital approaches were associated with an increased risk of SDE.

Table 1

Baseline characteristics of the PBT cohort.
Characteristics	Median (IQR)
Age at diagnosis (years)	9.7 (5.6–13.7)
Follow-up duration (years)	3.8 (1.6–7.0)
Male-to-Female ratio	1.7
PBT subtype
Germinoma	31 (17.4%)
NGGCT	14 (7.9%)
ATRT	2 (1.1%)
Embryonic tumor	7 (3.9%)
DIPG	10 (5.6%)
Craniopharyngioma	14 (7.9%)
LGG	47 (26.4%)
HGG	15 (8.4%)
MB	26 (14.6%)
Others	12 (6.8%)
Surgical approach
Trans-frontal	84 (47.2%)
Trans-temporal	6 (3.4%)
Trans-occipital	79 (44.3%)
Trans-sphenoid	6 (3.4%)
Trans-parietal	3 (1.7%)
Presence of SDE	38 (21.3%)
Relapse event	67 (37.6%)
Mortality event	28 (15.7%)
Abbreviations: ATRT, atypical teratoid/thabdoid tumor; DIPG, diffuse intrinsic pontine glioma; HGG, high-grade glioma; LGG, low-grade glioma; MB, medulloblastoma; NGGCT, non-germinomatous germ cell tumor; PBT, pediatric brain tumor; SDE, subdural effusion.

The cohort was stratified into SDE-present and SDE-absent subgroups for prognosis analysis (Table 2). Both groups were similar in tumor subtype composition, gender, follow-up duration, and age at diagnosis. Mortality rates were 18.4% and 15% in the SDE-present and SDE-absent groups, respectively (P = 0.6075). Relapse rates were 44.7% and 35.7% in the SDE-present and SDE-absent groups, respectively (P = 0.3086). Kaplan-Meier survival analysis was depicted in Fig. 2, showing 5-year OS and relapse-free survival (RFS) rates of 75.7% vs. 82.9% (P = 0.58) and 51.0% vs. 58.7% (P = 0.37), respectively. Although not statistically significant, the presence of SDE trended towards poorer survival and higher relapse rates.

Table 2

Comparisons between SDE-present and SDE-absent subgroups.
	SDE-present (n = 38)	SDE-absent (n = 140)	P Value
Age at diagnosis (yeas)	6.7 (3.7–14.4)	10 (6.3–13.5)	0.1774
Follow-up duration (years)	2.9 (1.6–5.7)	4.1 (1.6–7.2)	0.2472
Male-to-Female ratio	2.2	1.5	0.2590
Major PBT subtype			0.1025
Germinoma	4 (10.5%)	28 (20%)
NGGCT	2 (5.3%)	11 (7.9%)
LGG	7 (18.4%)	40 (28.6%)
HGG	3 (7.9%)	12 (8.6%)
MB	10 (26.3%)	16 (11.4%)
Mortality rate	18.4%	15.0%	0.6075
Relapse rate	44.7%	35.7%	0.3086
5-year OS rate	75.7%	82.9%	0.58
5-year RFS rate	51.0%	58.7%	0.37
Abbreviations: HGG, high-grade glioma; LGG, low-grade glioma; MB, medulloblastoma; NGGCT, non-germinomatous germ cell tumor; OS, overall survival; PBT, pediatric brain tumor; RFS, relapse-free survival; SDE, subdural effusion.

OS in PBT has increased from < 40% to 60–80% due to advancements in multi-agent chemotherapy, surgical techniques, and supportive care [1, 2]. The application of intensified chemotherapy leads to a better prognosis even in advanced-stage PBT. Furthermore, the utility of autologous stem cell rescue has allowed clinical physicians to initiate more intense high-dose chemotherapy, with the hope that OS and RFS would improve significantly. In this cohort, OS and RFS were 84.3% and 62.4%, respectively, comparable to data from developed countries.

Although the OS and RFS outcomes in this cohort were comparable to those reported in developed countries, a notably poorer RFS was identified in the glioma subgroup, including LGG and HGG. Traditionally, surgical resection is the treatment of choice for patients with LGG or HGG, with chemotherapy or radiotherapy reserved for unresectable tumors or cases of incomplete resection [12]. Despite these treatments, the relapse rate remains high. Recent advances in molecular studies have identified the MAPK pathway as playing a pivotal role in the oncogenesis of malignant gliomas. Several targeted therapies targeting this pathway have been utilized to mitigate the risk of relapse in malignant gliomas, with promising results overall [13]. In our cohort, relapsed LGG and HGG patients would be treated with targeted therapy as salvage treatment if available, which leads to a better OS compared to conventional chemotherapy.

Historically, research has focused on multidisciplinary treatments such as chemotherapy, targeted therapy, and immunotherapy, with less emphasis on surgical outcomes and complications [3, 4]. SDE, a common post-craniotomy complication observed in 21.3% of cases in this cohort study, correlated with trends towards poorer OS and RFS, although statistical significance was not reached. Some studies advocate that the presence of SDE appears to be an indicator of dural damage, which may lead to the risk of disease dissemination [6, 14]. Maintaining dural integrity during surgery, particularly in frontal and occipital approaches, may mitigate SDE risk and improve patient outcomes.

Limitations of this study include its retrospective design and reliance on data from a single institution, which may introduce bias. Larger, prospective studies are necessary to validate these findings and further explore the impact of SDE and surgical approaches on outcomes in pediatric brain tumor patients.

SDE is still a frequent complication that occurs after craniotomy in PBT patients. The risk of SDE is higher with frontal and occipital craniotomy approaches. The presence of SDE can have a negative impact on both survival rates and the likelihood of disease relapse in PBT.

Conflicts of Interest

The authors declared no conflicsts of interest.

Funding

This research received no external funding.

Author Contribution

Conceptualization Chieh-Tsai Wu; methodology and formal analysis Tzu-Chin Lin; writing—original draft preparation Yi-Lun Wang and Ju-En Nien; writing—review and editing Ju-En Nien, Shih-Hsiang Chen, Tang-Her Jaing, and Tsung-Yen Chang; visualization Yi-Lun Wang; project administration Tang-Her Jaing and Chieh-Tsai Wu; All authors have read and agreed to the published version of the manuscript.

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No competing interests reported.

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Version 1

posted

You are reading this latest preprint version

The Impact of Post-Craniotomy Subdural Effusion in Pediatric Brain Tumors

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Materials & Methods

Case Enrollment

Diagnosis Confirmation

Evaluation of Treatment Response

Statistical Analysis

Results

Discussion

Conclusion

Declarations

Conflicts of Interest

Funding

Author Contribution

References

Additional Declarations

Status:

Version 1