Ventricular size determination and management of ventriculomegaly and hydrocephalus in patients with diffuse intrinsic pontine glioma: an institutional experience

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  • 1 Division of Haematology Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Ontario, Canada;
  • | 2 Division of Oncology, Department of Pediatrics, Hospital Virgen Del Rocio, Seville, Spain;
  • | 3 Division of Neurosurgery, Department of Surgery, The Hospital for Sick Children, University of Toronto; and
  • | 4 Department of Radiation Oncology, The Hospital for Sick Children, University of Toronto, Ontario, Canada
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OBJECTIVE

There is no consensus on the optimal clinical management of ventriculomegaly and hydrocephalus in patients with diffuse intrinsic pontine glioma (DIPG). To date, the impact on survival in patients with ventriculomegaly and CSF diversion for hydrocephalus in this population remains to be elucidated. Herein, the authors describe their institutional experience.

METHODS

Patients diagnosed with DIPG and treated with up-front radiation therapy (RT) at The Hospital for Sick Children between 2000 and 2019 were identified. Images at diagnosis and progression were used to determine the frontal/occipital horn ratio (FOR) as a method to measure ventricular size. Patients with ventriculomegaly (FOR ≥ 0.36) were stratified according to the presence of symptoms and categorized as follows: 1) asymptomatic ventriculomegaly and 2) symptomatic hydrocephalus. For patients with ventriculomegaly who did not require CSF diversion, post-RT imaging was also evaluated to assess changes in the FOR after RT. Proportional hazards analyses were used to identify clinical and treatment factors correlated with survival. The Kaplan-Meier method was used to perform survival estimates, and the log-rank method was used to identify survival differences between groups.

RESULTS

Eighty-two patients met the inclusion criteria. At diagnosis, 28% (n = 23) of patients presented with ventriculomegaly, including 8 patients who had symptomatic hydrocephalus and underwent CSF diversion. A ventriculoperitoneal shunt was placed in the majority of patients (6/8). Fifteen asymptomatic patients were managed without CSF diversion. Six patients had resolution of ventriculomegaly after RT. Of 66 patients with imaging at the time of progression, 36 (55%) had ventriculomegaly, and 9 of them required CSF diversion. The presence of ventriculomegaly at diagnosis did not correlate with survival on univariate analysis. However, patients with symptomatic hydrocephalus at the time of progression who underwent CSF diversion had a survival advantage (p = 0.0340) when compared to patients with ventriculomegaly managed with conservative approaches.

CONCLUSIONS

Although ventriculomegaly can be present in up to 55% of patients with DIPG, the majority of patients present with asymptomatic ventriculomegaly and do not require surgical interventions. In some cases ventriculomegaly improved after medical management with steroids and RT. CSF diversion for hydrocephalus at the time of diagnosis does not impact survival. In contrast, our results suggest a survival advantage in patients who undergo CSF diversion for hydrocephalus at the time of progression, albeit that advantage is likely to be confounded by biological and individual patient factors. Further research in this area is needed to understand the best timing and type of interventions in this population.

ABBREVIATIONS

DIPG = diffuse intrinsic pontine glioma; ETV = endoscopic third ventriculostomy; FOR = frontal/occipital horn ratio; HR = hazard ratio; OS = overall survival; PFS = progression-free survival; QOL = quality of life; RT = radiation therapy; VP = ventriculoperitoneal.

OBJECTIVE

There is no consensus on the optimal clinical management of ventriculomegaly and hydrocephalus in patients with diffuse intrinsic pontine glioma (DIPG). To date, the impact on survival in patients with ventriculomegaly and CSF diversion for hydrocephalus in this population remains to be elucidated. Herein, the authors describe their institutional experience.

METHODS

Patients diagnosed with DIPG and treated with up-front radiation therapy (RT) at The Hospital for Sick Children between 2000 and 2019 were identified. Images at diagnosis and progression were used to determine the frontal/occipital horn ratio (FOR) as a method to measure ventricular size. Patients with ventriculomegaly (FOR ≥ 0.36) were stratified according to the presence of symptoms and categorized as follows: 1) asymptomatic ventriculomegaly and 2) symptomatic hydrocephalus. For patients with ventriculomegaly who did not require CSF diversion, post-RT imaging was also evaluated to assess changes in the FOR after RT. Proportional hazards analyses were used to identify clinical and treatment factors correlated with survival. The Kaplan-Meier method was used to perform survival estimates, and the log-rank method was used to identify survival differences between groups.

RESULTS

Eighty-two patients met the inclusion criteria. At diagnosis, 28% (n = 23) of patients presented with ventriculomegaly, including 8 patients who had symptomatic hydrocephalus and underwent CSF diversion. A ventriculoperitoneal shunt was placed in the majority of patients (6/8). Fifteen asymptomatic patients were managed without CSF diversion. Six patients had resolution of ventriculomegaly after RT. Of 66 patients with imaging at the time of progression, 36 (55%) had ventriculomegaly, and 9 of them required CSF diversion. The presence of ventriculomegaly at diagnosis did not correlate with survival on univariate analysis. However, patients with symptomatic hydrocephalus at the time of progression who underwent CSF diversion had a survival advantage (p = 0.0340) when compared to patients with ventriculomegaly managed with conservative approaches.

CONCLUSIONS

Although ventriculomegaly can be present in up to 55% of patients with DIPG, the majority of patients present with asymptomatic ventriculomegaly and do not require surgical interventions. In some cases ventriculomegaly improved after medical management with steroids and RT. CSF diversion for hydrocephalus at the time of diagnosis does not impact survival. In contrast, our results suggest a survival advantage in patients who undergo CSF diversion for hydrocephalus at the time of progression, albeit that advantage is likely to be confounded by biological and individual patient factors. Further research in this area is needed to understand the best timing and type of interventions in this population.

Diffuse intrinsic pontine gliomas (DIPGs) are high-grade gliomas that arise from the pons and are lethal within a few months after diagnosis.1,2 DIPGs account for the most common cause of death in children with brain tumors.3,4

The incidence of ventriculomegaly in patients with pontine tumors has not been previously evaluated. Furthermore, the term “hydrocephalus” has been used in the literature without objective and reproducible parameters for evaluation. Symptomatic increased intracranial pressure is not considered a typical presenting symptom of DIPG, although due to their location, obstruction of the sylvian aqueduct or the fourth ventricle is often seen and, as a result, obstructive triventricular ventriculomegaly can be observed during the course of the disease in some patients.

A few series have described the development and management of hydrocephalus in patients with DIPG. Amano et al.5 and Roujeau et al.6 reported their experience in the incidence and treatment of hydrocephalus in patients with DIPG. Nevertheless, there were no specific criteria for diagnosis or description of the severity of hydrocephalus in either report. Most recently, in a retrospective cohort of 94 patients, Giussani et al.7 used radiological signs to diagnose hydrocephalus, which they defined as the enlargement of temporal horns, bowing of the third ventricle, bundling of cerebral sulci, increased ventricular volume, presence of transependymal edema, and aggravation of the clinical status.

The frontal/occipital horn ratio (FOR) method was described by O’Hayon et al.8 and was developed to take into account the disproportionate occipital horn expansion seen in pediatric patients who develop hydrocephalus. Kulkarni et al.9 later demonstrated that the FOR was a reliable and reproducible method to determine the presence and severity of hydrocephalus in the pediatric population.

The purpose of this study was to describe the incidence and the management of ventriculomegaly by using a standardized ventricle size assessment method in a cohort of pediatric patients diagnosed with diffuse pontine tumors at our institution, and to determine the impact of ventriculomegaly and its management on overall survival (OS).

Methods

After approval from our institutional research ethics board, we performed a retrospective study of consecutive patients with a clinical and radiological diagnosis of DIPG for the period from 2000 to 2019 at The Hospital for Sick Children. Patients were identified using the Division of Neurosurgery and the Pediatric Brain Tumor Program databases. Demographics, length of symptoms, and treatment and outcome data were retrospectively collected. Only patients treated with up-front radiation therapy (RT) were included in the analysis.

Ventricular Size Determination

MRI and/or CT scans obtained at diagnosis and at disease progression were assessed. Axial images were used for ventricular measurements. The FOR method9 was used to determine the presence or absence of ventriculomegaly. Briefly, this method measures the widest distances across the frontal horns and the occipital horns. The average of these measurements is then divided by the largest biparietal diameter. The FOR was calculated as a ratio for each image. A normal upper value of 0.35 was previously established for the FOR.

Definitions

For this study, any patients with an FOR ≥ 0.36 were diagnosed as having ventriculomegaly. The degree of ventriculomegaly was categorized as follows: mild, FOR of 0.36–0.41; moderate, 0.42–0.54; and severe, ≥ 0.55 (Fig. 1), as previously described by Kulkarni et al.9

FIG. 1.
FIG. 1.

Determination of the FOR measurements in 3 different patients. A: Axial T2 FLAIR sequence MRI obtained in a patient with mild hydrocephalus. B: Axial T2 FLAIR sequence MRI obtained in a patient with moderate hydrocephalus. C: Axial CT scan obtained in a patient with severe hydrocephalus. Figure is available in color online only.

Patients with ventriculomegaly were categorized based on the presence or absence of symptoms. Symptomatic hydrocephalus was defined as patients with ventriculomegaly and symptoms of increased intracranial pressure requiring CSF diversion.

OS was defined as the time from diagnosis to death or date of last contact and censored at the date of latest follow-up for patients who were event free and alive, respectively. Progression-free survival (PFS) was defined as the time from diagnosis to first radiological disease progression. Postprogression survival was defined as the time between radiological disease progression and death or the date of last contact.

Correlative Analyses

To investigate the relationship between the duration of symptoms prior to diagnosis and the presence of ventriculomegaly at diagnosis, we performed a logistic regression in which ventriculomegaly was used as a binary variable. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported.

The Kaplan-Meier method was used for survival estimates, and the log-rank method was used to investigate survival differences between groups. A univariate proportional hazards analysis was performed to analyze the impact of ventriculomegaly and CSF diversion on OS and postprogression survival. A p value ≤ 0.05 was considered statistically significant. All statistical analyses were performed using STATA version 14.4 (StataCorp).

Results

Eighty-nine consecutive patients diagnosed with DIPG between 2000 and 2019 were treated at our institution. The median age at diagnosis was 6.83 years (range 2.07–16.9 years). A slight female predominance was observed: 47 (57%) patients (Table 1).

TABLE 1.

Characteristics of 82 patients with DIPG

CharacteristicAll PatientsPatients w/ Ventriculomegaly
At DxAt Progression*
No. of patients8223 (28%)36 (55%)
Age in yrs at Dx, median (range)6.83 (2.07–16.89)6.64 (2.1–16.05)7.02 (3.09–15.5)
Sex
 Female47 (57%)14 (61%)18 (50%)
 Male35 (43%)9 (39%)18 (50%)
FOR, median (range)0.33 (0.23–0.46)0.38 (0.36–0.46)0.40 (0.36–0.60)
 Mild19 (83%)22 (61%)
 Moderate4 (17%)13 (36%)
 Severe01 (3%)
CSF diversion1989
 VP shunt176 (75%)9 (100%)
 ETV22 (25%)0

Dx = diagnosis.

Includes 12 patients with hydrocephalus at diagnosis and at progression.

Represents the FOR measured at the time of progression.

Includes 2 patients with postsurgical complications requiring CSF diversion.

To ensure the homogeneity of the population analyzed, 7 patients who were not treated with RT up front were excluded from the analysis. Their median age was 2.18 years (range 0–12.77 years). Five patients were younger than 3 years of age, including a neonate. RT was not considered or accepted by the family as a therapeutic option. Two additional older patients elected not to receive any therapeutic interventions and were excluded from the survival analyses.

Ventricular Size Determination and Management of Symptomatic Hydrocephalus at Diagnosis

Diagnostic brain MRI (n = 80) or CT (n = 2) was used to measure the ventricle size with the FOR method.9 The median FOR was 0.33 (range 0.23–0.46). At diagnosis, 28% (n = 23) of patients presented with ventriculomegaly (FOR ≥ 0.36), and the median FOR for patients with ventriculomegaly was 0.38 (range 0.36–0.46). The majority (19/23; 83%) of patients had mild ventriculomegaly. Severe ventriculomegaly was not seen in any case at that time point.

The median duration of symptoms prior to diagnosis was 3 weeks (range 0.2–36 weeks), with the majority of patients presenting with symptoms lasting < 3 weeks (n = 43 [52%]), followed by 4–6 weeks (n = 18 [22%]), 7–12 weeks (n = 14 [17%]), 13–23 weeks (n = 5 [6%]), and > 24 weeks (n = 2 [2%]). In a logistic regression analysis, patients with a duration of symptoms between 7 and 12 weeks had a higher likelihood of presenting with ventriculomegaly (OR 12.85, p = 0.001) when compared to patients who presented with a shorter or longer history of symptoms (Table 2).

TABLE 2.

Logistic regression correlation between duration of symptoms and ventriculomegaly at diagnosis

Duration of Symptoms Prior to DxORp Value95% CI
<3 wksBaseline
4–6 wks1.470.5830.37–5.81
7–12 wks12.850.0013.12–52.88
≥13 wks2.050.4390.33–12.80

Boldface type indicates statistical significance.

Eight patients with symptomatic hydrocephalus underwent CSF diversion at the time of diagnosis and prior to RT (Fig. 2). Headache and persistent vomiting were present in 5/8 patients, and altered level of consciousness was seen in 3/8 patients. Four of them had mild ventriculomegaly and a ventriculoperitoneal (VP) shunt was used in 6 patients, whereas endoscopic third ventriculostomy (ETV) was used in only 2.

FIG. 2.
FIG. 2.

Chart showing ventriculomegaly at diagnosis and progression, demonstrating the flow of patients in the study. Asterisk denotes 2 patients with persistent hydrocephalus at progression in whom CSF diversion was in place (1 VP shunt, 1 ETV). Hydro = symptomatic hydrocephalus; unknown = patients without follow-up imaging; ventriculomegaly = asymptomatic ventriculomegaly. Plot generated using https://rawgraphs.io. Figure is available in color online only.

Fifteen patients with asymptomatic ventriculomegaly at diagnosis were managed conservatively without CSF diversion. The median FOR at diagnosis for these patients was 0.37 (range 0.36–0.43). MRI postradiation (approximately 6 weeks after RT) was available for 11 patients, and the median FOR postradiation was 0.35 (range 0.32–0.38). Importantly, 6 patients had resolution of ventriculomegaly after RT. Of these 15 patients, imaging was available for 12 at the time of progression, and none of these patients were receiving steroids. Ventriculomegaly was documented in 10/12 patients with a median FOR of 0.39 (range 0.36–0.49). Supplemental Table 1 provides the FOR of these 12 patients throughout the disease course.

A total of 7 patients underwent diagnostic biopsy. Five patients did not have ventriculomegaly at diagnosis, with a median FOR of 0.33 (range 0.28–0.34). One of these patients developed a postoperative intraventricular hemorrhage and required an EVD insertion that was later removed, and a second patient developed postoperative hydrocephalus requiring a VP shunt insertion. One patient presented with symptomatic hydrocephalus (FOR of 0.44 and significant deterioration of the level of consciousness) and underwent VP shunt insertion at the time of biopsy. Finally, 1 patient with mild asymptomatic ventriculomegaly (FOR 0.36) underwent biopsy, but CSF diversion was not required.

Ventricular Size Determination and Management of Symptomatic Hydrocephalus at Progression

Imaging at the time of progression was available for 66 patients: MRI in 54 (82%) and CT in 12 (18%). The median FOR at the time of progression was 0.36 (range 0.20–0.60). Thirty-six patients were found to have ventriculomegaly with a median FOR of 0.40 (range 0.36–0.60).

Of the 36 patients with ventriculomegaly at progression, the large majority presented with mild (n = 22 [61%]) and moderate (n = 13 [36%]) ventriculomegaly. Sixty-nine percent (n = 25) of the 36 patients were managed conservatively. One patient with an ETV in place and 1 patient with a VP shunt in place had ventriculomegaly despite previous CSF diversion, with FORs of 0.47 and 0.43, respectively. Symptomatic hydrocephalus was the indication for shunt insertion in 9 patients: 8/9 presented with severe headaches, nausea, and vomiting, and 4/9 had an associated decreased level of consciousness, including 1 patient who presented in a stupor and with new onset of seizures.

Three patients experienced complications associated with the VP shunt. One patient developed an inguinal hernia containing the VP shunt tubing and required surgical repair. A second patient experienced a shunt infection requiring externalization of the drain and had an associated intraventricular hemorrhage. Finally, 1 patient developed nodular lesions along the path of the VP shunt tubing, which were later confirmed to be dissemination of H3K27 M glioma.10

Outcomes

Survival outcomes were available for 81 patients, and 1 patient was lost to follow-up. The median time to progression was 8 months, and the median time to death was 12 months. The PFS and OS at 12 months were 19% (95% CI 0.11–0.28) and 50% (95% CI 0.39–0.61), respectively. The PFS and OS at 24 months were 5% (95% CI 0.01–0.12) and 9% (95% CI 0.03–0.16), respectively.

In a univariate Cox proportional hazards analysis (Table 3), the sole presence of ventriculomegaly at diagnosis (hazard ratio [HR] 0.65; p = 0.118) or at progression (HR 1; p = 0.987) did not impact the OS or postprogression survival, respectively, of patients with DIPG. Furthermore, among patients with ventriculomegaly at diagnosis, there was no difference in survival between patients with symptomatic hydrocephalus at diagnosis and patients with asymptomatic ventriculomegaly (HR 0.60; p = 0.316).

TABLE 3.

Univariate Cox proportional hazards analyses

VariableNo.HRp Value95% CI
At Dx: OS
 Age (continuous)811.000.9050.94–1.06
 Ventriculomegaly (no vs yes)810.650.1180.38–1.11
 Asymp ventriculomegaly vs symp hydrocephalus220.600.3160.22–1.62
 No ventriculomegaly57Baseline
 Asymp ventriculomegaly150.820.5370.45–1.51
 Symp hydrocephalus70.470.0890.20–1.12
At progression: postprogression survival
 Ventriculomegaly (no vs yes)661.000.9870.60–1.64
 Asymp ventriculomegaly vs symp hydrocephalus330.420.0370.18–0.95
 No ventriculomegaly26Baseline
 Asymp ventriculomegaly241.320.3350.74–2.32
 Symp hydrocephalus90.510.0990.23–1.13

Asymp = asymptomatic; symp = symptomatic.

In contrast, a postprogression survival advantage was observed in patients with symptomatic hydrocephalus at the time of progression who underwent CSF diversion (p = 0.037) when compared to the group of patients with asymptomatic ventriculomegaly managed conservatively. The median time to death postprogression for this latter group was 2.2 months (range 0.1–19 months) compared to 8.2 months (range 2.2–14.5 months) in the group of patients with ventriculomegaly managed with CSF diversion (log-rank test, p = 0.0321; see Fig. 3). Patients who underwent CSF diversion at disease progression (n = 9) had a median time to progression (i.e., PFS) of 12 months (range 4–35 months) versus a median PFS of 6 months (range 1–17 months) in the group of patients (n = 25) who had asymptomatic ventriculomegaly (p = 0.1094).

FIG. 3.
FIG. 3.

Postprogression survival of patients with asymptomatic ventriculomegaly (Asymp Ventri) and symptomatic hydrocephalus (Symp Hydro). The chart shows postprogression survival time in months for patients with ventriculomegaly at disease progression. Blue line: asymptomatic ventriculomegaly; red line: symptomatic hydrocephalus. Figure is available in color online only.

Discussion

DIPG carries a dismal prognosis with a 2-year OS under 10%. Currently, the standard therapeutic interventions are considered palliative and are aimed to provide symptom control and improve the quality of life (QOL) while having a moderate impact on life prolongation. Surgical or invasive therapeutic techniques in this population represent an ethical challenge. Ideally, interventions should be performed in the context of prospective clinical trials and require careful evaluation and clear discussions between healthcare providers, patients, and families.

Ventriculomegaly and Hydrocephalus in DIPG

Due to the lack of uniform diagnostic criteria, the incidence of ventriculomegaly and hydrocephalus in patients with DIPG has not been clearly described. Our study applied the FOR method to determine ventricular size and symptomatic hydrocephalus at diagnosis and at progression in a large cohort of pediatric patients diagnosed with diffuse pontine tumors. Our results demonstrate that 55% of the patients will present with increased ventricular size at some point during their disease course. Previous reports from Roujeau et al.6 and Giussani et al.7 reported slightly lower proportions, with 22% and 35% of patients developing hydrocephalus in their cohorts, respectively. In contrast, Amano et al.5 reported hydrocephalus in 89.9% of the patients. These differences are probably related to different criteria used to define and quantify hydrocephalus, and none of the reports available in the literature have used objective criteria for definition.

Our study determined that some patients (28%) present with ventriculomegaly at diagnosis—nevertheless, most patients presented with mild ventriculomegaly and required no intervention. Amano et al.5 reported similar proportions in their cohort, with 25% of patients presenting with hydrocephalus at the time of diagnosis. In contrast, in Roujeau et al.6 the investigators reported only 1 patient presenting with symptomatic hydrocephalus at diagnosis, and in Giussani et al.’s7 cohort, patients developed hydrocephalus soon after diagnosis, but no one had hydrocephalus on initial presentation. This is probably explained by the fact that 83% of the patients with ventriculomegaly at diagnosis in our cohort had mild ventriculomegaly and could have been easily underestimated by typical radiological criteria. Most importantly, the large majority of our patients had asymptomatic ventriculomegaly.

Management of Hydrocephalus

Our study demonstrated that only a small proportion of patients present with symptomatic hydrocephalus at diagnosis requiring CSF diversion. Furthermore, approximately 50% of patients with asymptomatic ventriculomegaly at diagnosis had resolution of the hydrocephalus after RT and steroids, as seen in the follow-up imaging. Our results did not demonstrate a survival advantage for patients undergoing CSF diversion at diagnosis, in contrast with a previous report by Massimino et al.,11 who identified a 1-year OS of 60% in patients undergoing CSF diversion versus 22% in those managed conservatively. Importantly, the sample size in that study was small (N = 25) and did not account for the multiple therapeutic interventions that patients received.

Interestingly, the management of hydrocephalus at the time of progression has different implications in this population. Our results suggest that CSF diversion for symptomatic hydrocephalus at the time of progression is associated with prolonged survival of these patients. Notwithstanding, patients who underwent CSF diversion at the time of progression had a longer median time to progression (12 months) when compared to the group of patients managed conservatively (6 months). Albeit not statistically significant (p = 0.1094), it suggests that patients with a longer “honeymoon” period are more likely to undergo CSF diversion in association with other therapeutic interventions. In fact, of these 9 patients, 4 underwent reirradiation and 1 patient was enrolled in a clinical trial. These considerations suggest that the survival advantage observed in patients undergoing CSF diversion at the time of disease progression may be confounded by many unobserved variables, including unknown biological factors, because most of these patients did not have a histopathological diagnosis. Similarly, patient-related factors such as the willingness to pursue other therapeutic options could be an important confounder of the survival advantage observed.

Last, QOL is an important consideration in patients with this fatal disease. Due to the retrospective nature of this study, we were unable to perform an objective assessment of QOL in our cohort. Nevertheless, 3 patients experienced complications related to the VP shunt and required further surgical interventions. Although complications are rare, they need to be considered when evaluating the need for CSF diversion, especially in patients with a limited life expectancy. Although QOL was not assessed in this study, one could hypothesize that surgical interventions and lengthy hospital admissions would negatively impact the QOL of these patients.

These considerations reinforce the role of a conservative approach in noncritically ill patients with DIPG who present with ventriculomegaly at diagnosis. It is recommended to reserve surgical interventions for patients with persistent or worsening symptomatic hydrocephalus despite early initiation of radiation and/or steroids.

Our study is limited by its retrospective nature and the small sample of patients in the intervention group. Our analyses were not powered to account for therapeutic interventions, and therefore the survival advantage seen in these patients needs to be carefully evaluated. Additionally, due to the small number of patients managed with ETV, we are unable evaluate the most appropriate procedure for CSF diversion in our cohort.

Conclusions

Up to 55% of patients with DIPG develop ventriculomegaly, although the majority of patients with ventriculomegaly at diagnosis do not require surgical interventions for CSF diversion. In addition, CSF diversion for the management of hydrocephalus at the time of diagnosis does not impact survival, and in some cases resolves spontaneously after the initiation of RT and steroids.

Acknowledgments

This work was supported by the We Love You Connie Foundation and Meagan's Hug Foundation.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Fonseca, Solano, Ramaswamy, Tabori, Huang, Drake, Laperriere, Bartels, Kulkarni, Bouffet. Acquisition of data: Fonseca, Solano, Bouffet. Analysis and interpretation of data: Fonseca, Ramaswamy, Tsang, Laperriere, Bartels, Kulkarni, Bouffet. Drafting the article: Fonseca, Solano, Bartels, Bouffet. Critically revising the article: Fonseca, Solano, Ramaswamy, Tabori, Huang, Drake, Tsang, Laperriere, Kulkarni, Bouffet. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Fonseca. Statistical analysis: Fonseca, Ramaswamy, Tsang, Bartels, Kulkarni, Bouffet. Study supervision: Bartels, Kulkarni, Bouffet.

Supplemental Information

Online-Only Content

Supplemental material is available with the online version of the article.

Previous Presentations

Previously presented in abstract form at the 19th International Symposium of Pediatric Neuro-Oncology (ISPNO 2020) in Karuizawa, Nagano, Japan, December 2020.

References

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Supplementary Materials

Illustration from Kim et al. (pp 1164–1172). Copyright Eui Hyun Kim. Published with permission.

  • View in gallery

    Determination of the FOR measurements in 3 different patients. A: Axial T2 FLAIR sequence MRI obtained in a patient with mild hydrocephalus. B: Axial T2 FLAIR sequence MRI obtained in a patient with moderate hydrocephalus. C: Axial CT scan obtained in a patient with severe hydrocephalus. Figure is available in color online only.

  • View in gallery

    Chart showing ventriculomegaly at diagnosis and progression, demonstrating the flow of patients in the study. Asterisk denotes 2 patients with persistent hydrocephalus at progression in whom CSF diversion was in place (1 VP shunt, 1 ETV). Hydro = symptomatic hydrocephalus; unknown = patients without follow-up imaging; ventriculomegaly = asymptomatic ventriculomegaly. Plot generated using https://rawgraphs.io. Figure is available in color online only.

  • View in gallery

    Postprogression survival of patients with asymptomatic ventriculomegaly (Asymp Ventri) and symptomatic hydrocephalus (Symp Hydro). The chart shows postprogression survival time in months for patients with ventriculomegaly at disease progression. Blue line: asymptomatic ventriculomegaly; red line: symptomatic hydrocephalus. Figure is available in color online only.

  • 1

    Freeman CR, Perilongo G.Chemotherapy for brain stem gliomas. Childs Nerv Syst. 1999;15(10):545553.

  • 2

    Hargrave D, Bartels U, Bouffet E.Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol. 2006;7(3):241248.

  • 3

    Renzi S, Michaeli O, Ramaswamy V, et al. Causes of death in pediatric neuro-oncology: the sickkids experience from 2000 to 2017. J Neurooncol. 2020;149(1):181189.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Ostrom QT, Cioffi G, Gittleman H, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the united states in 2012-2016. Neuro Oncol. 2019;21(suppl5):v1v100.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Amano T, Inamura T, Nakamizo A, et al. Case management of hydrocephalus associated with the progression of childhood brain stem gliomas. Childs Nerv Syst. 2002;18(11):599604.

    • Crossref
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