The H3 K27-altered, Extent of Resection and Survival in Pediatric High-grade Spinal Cord Gliomas

DOI: https://doi.org/10.21203/rs.3.rs-1841896/v1

Abstract

Purpose

Pediatric high-grade spinal cord gliomas (pHGSG) are classified into two prognostically meaningful subtypes. The purpose of our study is to describe clinical characteristics and management of two pHGSG subtypes, especially focus on the effect of surgical resection in these two subtypes.

Methods

We described the clinical characteristics and management and analyzed the prognostic factors of 19 pHGSGs. Based on H3 K27-altered and isocitrate dehydrogenase (IDH) mutation status, pHGSGs were classified into H3 K27-altered and H3/IDH-wildtype pHGSG for assessing effect of surgical resection.

Results

Nineteen patients (11 males and 8 females) with a mean age of 12.7 ± 4.7 years were included in the analysis. The median survival time of all patients was 14 months. Thirteen pHGSG patients had H3 K27-altered tumors, and 6 had H3/IDH-wildtype tumors. All patients received therapeutic surgical resection, 10 (55.6%) patients underwent gross total resection (GTR) and 8 (33.3%) patients underwent subtotal resection (STR). pHGSG patients with H3 K27-altered underwent GTR (HR 0.311, 95% CI 0.075–1.289, p = 0.091) had tended to increase overall survival. For patients of H3/IDH-wildtype pHGSG, there was no survival advantage associated with GTR (p = 0.157).

Conclusions

The extent of surgical resection has the different effects on survival in H3 K27-altered and H3/IDH-wildtype pHGSGs. The patients with H3 K27-altered pHGSG have tended to benefit from a greater extent of surgical resection. Nevertheless the benefit was not evident in the patients with H3/IDH-wildtype pHGSG.

Introduction

Central nervous system (CNS) tumors are the most common form of solid tumors in childhood.[1, 2] It accounts for approximately 25% of malignancies in children under the age of fifteen at diagnosis and is the leading cause of childhood cancer death.[3] In the past, pediatric high-grade gliomas were thought to be counterparts of adult malignant gliomas.[4, 5] However, followed by our understanding of pediatric high-grade gliomas, it is clear that pediatric high-grade gliomas are biologically distinct from their adult counterparts in driver molecular and signaling pathway.[6, 7] For example, H3 K27M mutation is common in pediatric gliomas but absent from adult gliomas. H3 K27M mutation refers to a somatic missense mutation in which a lysine is replaced by methionine at codon 27 on the tail of the histone H3 variants H3.3 and H3.1 that are encoded by the H3F3A, HIST1H3B/C genes.[810] This mutation leads to epigenetic reprogramming and drives the global loss of methylation of histone H3K27.[1116] The global hypomethylation that occurs has been shown to be more hospitable to tumorigenic change.[11, 17]

In the 2021 version of World Health Organization (WHO) classification of tumors of the CNS, the combination of key molecular and histological features was divided pediatric high-grade gliomas into four types.[18] The most common two types found in the spinal cord are “diffuse midline glioma, H3 K27-altered” and “diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype”. There was significant difference in the survival time between the two groups. Pediatric high-grade spinal cord gliomas (pHGSG) with H3 K27-altered have a shorter overall survival than pHGSG with H3-wildtype. Karremann et al. reported that pHGSG with H3 K27-altered had a median survival of 0.4 years compared to pHGSG without H3 K27-altered and isocitrate dehydrogenase (IDH) mutation (H3/IDH-wildtype) who had a median survival of 6.1 years.[8] Due to lack of available data, it is not enough to fully understanding clinical characteristics and management of H3 K27-altered and H3/IDH-wildtype pHGSG. Surgical resection is one of the mainstream treatment modalities for spinal cord gliomas. however, the extent of resection (EOR) continues to be a subject of ongoing debate. Some studies indicate that gross total resection (GTR) is associated with more favorable survival, but other reports indicate that GTR either has no significant effect on survival. It is unclear whether these conflicting results are due to the different effects of surgical resection in H3 K27-altered and H3/IDH-wildtype gliomas. Because the patients of pHGSG from a single institution is often insufficient, we reviewed the pHGSG patients from two neurospine centers. The purpose of our study is to describe clinical characteristics and management of pHGSG, especially focus on the effect of surgical resection in H3 K27-altered and H3/IDH-wildtype pHGSG.

Methods

Patient Population

Between January 2002 and February 2022, eighteen patients with pHGSG from two neurospine centers (Sanbo Brain Hospital, Beijing and Chinese PLA General Hospital, Beijing) were included in the study. The study was approved by the ethics committees of both participating institutions. All patients underwent surgery and were pathological confirmed as diffuse high-grade spinal cord gliomas according to the 2021 WHO Classification of Tumors of the CNS. The inclusion and exclusion criteria were as follows: 1) age at diagnosis was younger than or equal to eighteen years old; 2) H3 K27 and IDH status and were confirmed by sequencing or immunohistochemical (IHC) analysis; 3) medical records and imaging data (MRI and CT) were available; 4) metastatic tumors were excluded from this study. Medical records were reviewed to extract relevant demographics (age and sex), symptoms (symptoms and duration), neurological function status (preoperative and postoperative modified McCormick score), tumor-related factors (location and length), treatment modalities (extent of resection, radiation therapy and chemotherapy) and pathological features (histological grade and molecular marker). The patients’ medical records were reviewed separately by two neurosurgeons (YQS and ZF). Duration of symptom was calculated as the time from the patient first noticed symptom. Preoperative and postoperative neurological function status were assessed on the day of admission and on the day of hospital discharge. Overall survival was defined as the time from date of diagnosis and to any cause of death. A summary of the basic information of pHGSG was shown in Table 1 and Table 2.

Treatment Modalities

EOR were extracted by reviewing operative reports and postoperative imaging. EOR was determined by surgeon's intraoperative impressions and postoperative gadolinium-enhanced T1-weight MRI images, and defined as GTR (≥90%), subtotal resection (STR, ≥50% and <90%), partial resection (PR, ≥10% and <50%), or open biopsy (OB, <10%). Radiation therapy and chemotherapy were obtained from medical records outside medical records and follow up questionnaires. The chemotherapy regimen and radiation therapy followed a standard Stupp regimen protocol. All patients received postoperative adjuvant radiation therapy and chemotherapy, no one receive radiation therapy or chemotherapy before surgical resection.

Pathological Features

All cases were reviewed by two neuropathologists to update and confirm the diagnosis according to the 2021 WHO Classification of Tumors of the CNS. Histopathological evaluation was performed on formalin-fixed, paraffin-embedded (FFPE) samples with hematoxylin and eosin (H&E) staining. H3 K27M, IDH mutation status was determined by immunohistochemistry (IHC) staining or sequencing.

Statistical Analysis

The significance of continuous variable was evaluated by the student's t-test or Mann-Whitney U test. The significance of categorical variable was determined by chi‐square test or Fisher’s exact test. Survival analysis was presented by Kaplan-Meier curves, using Log-Rank test to determine significance. Due to the limited sample size, we only conducted univariable log-rank test. Two-sided p-value ≤0.05 was considered statistically significant, whereas p-value ranging from 0.05 to 0.10 were considered borderline statistically significant. Statistical analysis was performed using SPSS 26.0.0.0 (IBM Corp.) and GraphPad Prism 8.3.1 (GraphPad Software).

Results

Patient Population and Clinical Characteristics

As was mentioned above, the basic information of 19 pHGSG patients was shown in Table 1 and Table 2. Of the 19 patients, 11 were male and 8 were female, and the mean age at diagnosis was 12.7±4.7 years. The age distribution of the 19 pHGSG patients are shown in Fig. 1A. All patients underwent preoperative MRI scanning to identify lesions location and length. 8 (42.1%) lesions were located in the cervical spine, 1(5.3%) in the cervicothoracic spine, 7 (36.8%) in the thoracic spine, and 3 (15.8%) in the thoracolumbar spine. The mean length of lesions is 4.3±2.4 segments. Common symptoms include motor deficit (11, 57.9%), pain (8, 42.1%) and sensory deficit (6, 31.6%). There are 2 patients (10.5%) presented with Bowel/bladder dysfunction. Median duration of symptoms was 2 months (range: 0.3-18). Of preoperative neurological function, modified McCormick score (MMS) grade I-II was observed in 7 patients (36.8%) and MMS grade III-IV was observed in 12 patients (63.2%). Of postoperative neurological function, MMS grade I-II was observed in 10 patients (52.6%) and MMS grade III-IV was observed in 9 patients (47.4%). According to the 2021 WHO Classification of Tumors of the CNS, 12 patients of pHGSG belonged to H3 K27-altered group and 6 patients belonged to H3/IDH-wildtype group.

Thirteen patients of H3 K27-altered pHGSG with a mean age of 12.1±5.3 years old and comprising 53.8% male patients, and 6 patients of H3/IDH-wildtype pHGSG with a mean age of 14.0±3.0 years old and comprising 66.7% male patients. Of H3 K27-altered pHGSG, lesions located in the cervical spine were 53.8% and in the noncervical spine were 46.2%, with the mean length of 3.9±1.7 segments. Of H3/IDH-wildtype pHGSG, lesions located in the cervical spine were 33.3% and in the noncervical spine were 66.7%, with the mean length of 5.2±3.7 segments. The most common symptoms in both H3 K27-altered and H3/IDH-wildtype pHGSG patients were motor deficit, pain and sensory deficit. Median duration of symptoms were 2 (range: 0.3-14) months and 1.5 (range: 1-18) months in H3 K27-altered and H3/IDH-wildtype pHGSG, respectively. Preoperative MMS grade I-II and III-IV were observed in 4 and 9 patients with H3 K27-altered pHGSG, while postoperative MMS grade I-II and III-IV were observed in 7 and 6 patients. Three patients of H3/IDH-wildtype pHGSG have preoperative MMS grade I-II, whose postoperative MMS were still grade I-II; and 3 patients of H3/IDH-wildtype pHGSG have preoperative MMS grade III-IV, whose postoperative MMS were still grade III-IV. Thirteen H3 K27-altered pHGSG included 4 histological grade 3 gliomas and 9 histological grade 4 gliomas; 6 H3 K27-altered pHGSG included 4 histological grade 3 gliomas and 2 histological grade 4 gliomas

We compared the difference of age, sex, lesions location and length, symptoms, duration of symptom, MMS and histological grade between the two groups of pHGSG. There was no statistically significant difference between the two groups.

Treatment Modalities and Clinical Outcome

All patients received therapeutic surgical resection, 10 (55.6%) patients underwent GTR and 8 (33.3%) patients underwent STR. To assess the impact of surgical resection on neurological function of pHGSG, we firstly compare preoperative and postoperative MMS in all pHGSG patients. There was no significant difference between preoperative and postoperative MMS (p = 0.395) (Fig. 1B). In total, 14 (73.7%) of the patients received adjuvant radiation therapy after surgery, and 13 (68.4%) of the patients received adjuvant chemotherapy; adjuvant therapy status was unknown in 2 patients (10.5%). The median survival time of all patients was 14 months. Up to now, an 18-year-old male with a H3/IDH-wildtype tumor is alive for more than 5 years after GTR and adjuvant chemotherapy and radiation therapy.

The lesions located in the noncervical spine (HR 0.383, 95% CI 0.095-1.545, p = 0.048) were associated with a better prognosis, compared with the lesions located in the cervical spine. Histological grade and H3 K27M status are also the important prognostic factors. Histological grade 4 pHGSGs (HR 6.058, 95% CI 1.215-30.202, p = 0.015) have a worse prognosis compared to pHGSGs in histological grade 3. H3 K27-altered pHGSGs (HR 4.262, 95% CI 0.916-19.836, p = 0.044) exhibit a worse prognosis than H3/IDH-wildtype pHGSGs. For treatment modalities, pHGSG patients who underwent GTR (HR 0.218, 95% CI 0.060-0.790, p = 0.012) had better OS than patients who underwent STR. However, patients of pHGSG receiving adjuvant radiation therapy (p = 0.405) or chemotherapy (p = 0.118) did not show any beneficial effect on OS. Fig. 2 depicts the Kaplan-Meier curves of OS for all pHGSG patients in tumor location, histological grade, H3 K27 status and EOR. Table 3 summarizes the results of univariate analysis of all pHGSG patients.

Surgical Resection and Survival in H3 K27-altered and H3/IDH-wildtype pHGSG

We performed a subgroup analysis to further investigate the impact of the EOR on OS in H3 K27-altered and H3/IDH-wildtype pHGSG. Similarly, we separately compare preoperative and postoperative MMS in H3 K27-altered and H3/IDH-wildtype pHGSG patients. There was no significant difference between preoperative and postoperative MMS neither in H3 K27-altered (p = 0.350) (Fig. 1C) nor in H3/IDH-wildtype pHGSG patients (p = 0.881) (Fig. 1D). Interestingly, pHGSG patients with H3 K27-altered underwent GTR (HR 0.311, 95% CI 0.075-1.289, p = 0.091) had tended to increase OS. For patients of H3/IDH-wildtype pHGSG, there was no survival advantage associated with GTR (p = 0.157). The impact of the EOR on OS in two groups showed different results. Fig. 3 shows the Kaplan-Meier survival curves for H3 K27-altered and H3/IDH-wildtype groups.

Discussion

This study describes the clinical features and management of pHGSG, especially, focus on the relationship between H3 K27-altered status and the effect of surgical resection. The survival benefit associated with surgical resection differs based on H3 K27-altered status in pHGSG. Increased EOR tended to benefits patients with H3 K27-altered pHGSG. Nevertheless, we found no survival benefit from greater EOR in H3/IDH-wildtype pHGSG.

H3 K27-altered is an important prognostic factor in pediatric high-grade midline gliomas. Pediatric high-grade gliomas with H3 K27-altered arise from thalamus, pontine, and spinal cord, have a very poor prognosis.[8, 12, 19] Although they have similar prognosis, these tumors originating from these different anatomic sites still exhibit some clinical heterogeneity. Pediatric high-grade gliomas arise from pontine, has the high incidence of H3 K27-altered and pHGSGs have the low incidence. Karremann et al. reported 26 of 27 (96.3%) pediatric diffuse high-grade pontine gliomas have H3 K27-altered and 6 of 11 (54.5%) pHGSGs have H3 K27-altered.[8] In our study, the H3 K27-altered rate was 68.4% in pHGSGs. In addition, the tumors located in thalamus and pontine have two histone variants, H3.1 and H3.3[17, 20], but H3.1 variant is exceedingly rare in spinal cord gliomas.[17, 21, 22] To our knowledge, there is only one previously reported case of H3.1 variants in spinal cord gliomas.[23] Moreover, H3 K27-altered serves as prognostic factor rather than histological grade for pediatric diffuse high-grade pontine gliomas.[12] In pHGSG, both of H3 K27-altered and histological grade are prognostic factors. However, several reports the incidence of H3 K27-altered increases along with histological grade.[24, 25] The same trend was observed in in our study, although no statistical significance was observed. Due to the size of the cohort, we could not perform multivariate analysis to determine whether there is collinearity between these two prognostic factors. Formal validation in larger patient cohorts will be needed to confirm these initial findings.

The tumor located in the noncervical spine had a significantly better prognosis than those located in the cervical spine, which was in agreement with previous reports.[2629] This finding can be explained by the hypothesis that tumors in the cervical spinal cord, especially in upper spinal cord, can infiltrate or affect the brainstem, leading to central respiratory failure. The upper cervical spinal cord is the continuation of the medulla oblongata and the fibers of the cervical spinal cord are often the continuation of the medulla oblongata fibers.[30] Cervical spinal cord glioma cells could migrate along white matter fiber tracts to infiltrate the brainstem.[31, 32]

Different anatomic sites could lead surgeons to choose different surgical treatment. Pontine is usually regarded as the challenging sites for surgical treatment, biopsy was considered as the appropriate treatment option for infiltrative gliomas. For spinal cord gliomas, most neurosurgeons attempt a safe resection with a minimally invasive procedure. The use of intraoperative electrophysiological monitoring is helpful in intramedullary tumors resection in order to minimize postoperative neurological deficits.[33] Our results suggest that surgical resection of spinal cord gliomas, even infiltrative gliomas, does not worsen neurological outcome. Surgical resection has been shown to improve survival in spinal cord gliomas in several clinical studies; however, the EOR continues to be a subject of ongoing debate. GTR both improves the survival and delays cancer recurrence in low-grade spinal cord glioma patients.[3436] For effect of surgical resection in high-grade spinal cord glioma, some studies indicate that GTR is associated with more favorable survival,[37, 38] but other reports indicate that GTR either has no significant effect on survival.[34, 39, 40] In our study, survival analysis demonstrated that GTR was associated with prolonged OS in pHGSG. We next wondered whether surgical resection might have a different effect on the H3 K27-altered and H3/IDH-wildtype pHGSG. The results show GTR was tended to prolonged OS in H3 K27-altered pHGSG; but this trend was not evident in H3/IDH-wildtype pHGSG. Molecular markers have not been considered in previous studies of surgical resection in pHGSG. This might explain the conflicting results found in different retrospective studies. Our study demonstrates the value of using H3 K27-altered in risk stratification at surgical resection. H3 K27-altered should be considered to integrate into the clinical management of pHGSG.

Limitations of this study include the retrospective design and small sample size. Due to its rarity, the small number of patients is an inherent limitation of this disease process. This prevented us from performing a full analysis within our cohort. Randomized controlled trials may not be feasible when evaluating rare diseases. A high-quality, prospective registry of patients with pHGSG should be considered a valuable alternative to understand the relationship between molecular markers and the effect of treatment modalities. Another limitation of our study concerns detection of H3 K27-altered. IHC analysis is the primary method for determining H3 K27M mutation status. Sequencing is only performed in 5 pHGSGs to distinguish HIST1H3B/C or H3F3A K27M mutation and all are histone H3F3A K27M mutation. H3.3 variant encoded by H3F3A is universally associated with short survival, compared with H3.1 variant encoded by HIST1H3B/C.[17] Multiple studies have shown that H3.1 variant is exceedingly rare in spinal cord gliomas.[17, 23] Therefore, histone H3 variants are very unlikely to be a confounding factor in this study, although sequencing is only performed in some pHGSGs. In addition, Sievers et al. reported that H3K27me3 loss could be mediated either by H3 K27M mutation or EZHIP overexpression.[41] We only use IHC analysis or sequencing to identify H3 K27M mutation status, which may underestimate the incidence of H3K27me3 loss in our cohort. However, current reports of EZHIP overexpression focus on the posterior fossa ependymomas and thalamic gliomas,[41, 42] there have been no reports regarding EZHIP overexpression in spinal cord gliomas. The incidence of EZHIP overexpression in spinal cord glioma remains to be studied.

Conculsion

The extent of surgical resection differentially impacts OS among patients with pHGSG based on molecular subtypes as defined by the WHO. Increased EOR tended to benefits patients with H3 K27-altered pHGSG. Nevertheless, we found no survival benefit from greater EOR in H3/IDH-wildtype pHGSG. A high-quality, prospective registry of patients with pHGSG should be considered a valuable alternative to understand the relationship between molecular markers and the effect of treatment modalities.

Declarations

Ethical Approval and Consent to participate Informed consent was obtained from all individual participants or legal guardians included in the study.

Human and Animal Ethics Ethical approval was waived by the local Ethics Committee of Sanbo Brain Hospital and Chinese PLA General Hospital in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

Consent for publication Not applicable

Availability of supporting data All data generated or analysed during this study are included in this published article

Competing interests All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.

Funding No funding, financial interests or potential conflict of interest is involved in this research.

Authors' contributions FT and YXG designed this study. YQS and ZF are responsible for the execution and study coordination. YQS will be involved in data collection and analysis and manuscript writing. FT and YXG supervised the study design and data analysis, and reviewed the data and the paper.

Acknowledgements Not applicable

Authors' information Qi-Shuai Yu, M.D., Medical School of Nankai University, Tianjin, People’s Republic of China. Department of Neurosurgery, the First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China. [email protected].

Fan Zhang, M.D., Spine Center, Sanbo Brain Hospital, Capital Medical University, Beijing, People’s Republic of China. [email protected]

Tao Fan, M.D., Ph.D.*, Spine Center, Sanbo Brain Hospital, Capital Medical University, Beijing, People’s Republic of China. [email protected].

Xin-Guang Yu, M.D., Ph.D.*, Department of Neurosurgery, the First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China. Medical School of Nankai University, Tianjin, People’s Republic of China. [email protected].

* Co-senior authors

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Tables

Table 1. Characteristics of pediatric patients with high-grade spinal cord glioma

Pt. No.

Age (yrs), Sex

Location

HG

H3 K27 Status

IDH Status

EOR

RT

CT

OS (mos)

1

6, F

M-C6

4

Positive

WT

STR

NA

NA

10

2

8, F

C2-6

4

Positive

WT

GTR

Yes

Yes

15

3

15, M

T6-9

4

Positive

WT

GTR

Yes

No

14*

4

16, M

L1-2

4

Positive

WT

GTR

NA

NA

13

5

15, M

C4-T3

4

Positive

WT

GTR

Yes

Yes

5

6

11, M

T10-12

4

Positive

WT

STR

Yes

Yes

8

7

16, F

C3-5

4

Positive

WT

STR

Yes

Yes

6

8

17, M

M-C4

4

Positive

WT

STR

No

No

2

9

2, F

T12-L2

4

Positive

WT

STR

Yes

Yes

27

10

18, M

T10-11

3

Positive

WT

STR

Yes

Yes

3+

11

10, M

C3-4

3

Positive

WT

STR

No

No

1

12

16, F

C4-7

3

Positive

WT

GTR

Yes

Yes

10+

13

18, F

T11-12

3

Positive

WT

GTR

Yes

Yes

39

14

14, F

T1-8

4

Negative

WT

STR

Yes

Yes

8

15

10, F

T3-L1

4

Negative

WT

STR

No

Yes

12*

16

17, M

C1-5

3

Negative

WT

GTR

Yes

Yes

24+

17

12, M

T3-5

3

Negative

WT

GTR

No

Yes

31+

18

13, M

C6-7

3

Negative

WT

GTR

Yes

No

21

19

18, M

T2-5

3

Negative

WT

GTR

Yes

Yes

68

Pt, Patient; No., Number; HG, Histological grade; EOR, Extent of resection; RT, Radiation therapy; CT, Chemotherapy; OS, Overall survival; yrs, years; mos, months; F, Female; M, Male; WT, Wildtype; STR, Subtotal resection; GTR, Gross total resection; NA, Not applicable.

* lost to follow-up

+ indicates patient alive at last known status. 

Table 2. Symptoms and neurological function of pediatric patients with high-grade spinal cord glioma

Variable

Total (%)

H3 K27-altered (%)

H3/IDH-wildtype (%)

P-value

Duration of symptom (Median, mos)

2 (0.3-18)

2 (0.3-14)

1.5 (1-18)

0.106

Symptom

 

 

 

0.952

Pain

8 (42.1)

5 (38.5)

3 (50.0)

 

Motor deficit

11 (57.9)

6 (46.2)

5 (83.3)

 

Sensory deficit

6 (31.6)

4 (30.8)

2 (33.3)

 

Bowel/bladder

2 (10.5)

1 (7.7)

1 (16.7)

 

pre-MMS

 

 

 

0.419

I-II

7 (36.8)

4 (30.8)

3 (50.0)

 

III-IV

12 (63.2)

9 (69.2)

3 (50.0)

 

pre-MMS

 

 

 

0.876

I-II

10 (52.6)

7 (53.8)

3 (50.0)

 

III-IV

9 (47.4)

6 (46.2)

3 (50.0)

 

mos, months; MMS, modified McCormick score. 

Table 3. Univariate analysis of prognostic factors for pediatric patients with high-grade spinal cord glioma

Variable

HR

Confidence interval

OS (mos)

P-value

Low 95%

High 95%

Sex

 

 

 

 

0.766

Male

-

-

-

13

 

Female

1.188

0.379

3.719

12.5

 

Location

 

 

 

 

0.048*

Cervical

-

-

-

8

 

Noncervical

0.383

0.095

1.545

20

 

Pre-MMS

 

 

 

 

0.118

I-II

-

-

-

24

 

III-IV

2.803

0.727

10.809

10

 

Symptom duration (mos)

 

 

 

 

0.538

>3

-

-

-

15

 

≤3

1.448

0.438

4.792

9.5

 

Length (Segments)

 

 

 

 

0.610

>3

-

-

-

12.5

 

≤3

1.352

0.420

4.355

13

 

Histological Grade

 

 

 

 

0.015*

3

-

-

-

30

 

4

6.058

1.215

30.202

9

 

H3 K27 Status

 

 

 

 

0.044*

Wildtype

-

-

-

44.5

 

Altered

4.262

0.916

19.836

10

 

EOR

 

 

 

 

0.012*

STR

-

-

-

7

 

GTR

0.218

0.060

0.790

21

 

RT

 

 

 

 

0.405

No

-

-

-

1.5

 

Yes

.514

0.103

2.559

18

 

CT

 

 

 

 

0.118

No

-

-

-

2

 

Yes

0.339

0.081

1.429

21

 

HR, Hazard ratio; OS, Overall survival; EOR, Extent of resection; STR, Subtotal resection; GTR, Gross total resection; RT, Radiation therapy; CT, Chemotherapy; mos, months.

* indicates statistical significance.