1. Treatment strategy of intracranial hemangiopericytoma
: Clinical efficacy of Surgical grading system
Department of Neurosurgery
The Catholic University of Korea
Jae Hyun Park, Young Il Kim, Sin Soo Jeun

2. Intracranial Hemangiopericytoma (HPC)
Introduction
Intracranial Hemangiopericytoma (HPC)
Rare mesenchymal tumor (1st decribed in 1942)
2.5% of all meningeal tumors
<1% of all primary CNS tumors
Extent of surgical resection & Postoperative radiotherapy
▶ Overall survival ▲ & Recurrence free survival ▲
Complete resection ? Grossly total resection ?
In most reported cases, HPC is attached to the venous sinuses or major vessels
▶Actually impossible to completely remove the tumor
Hemangiopericytoma is a rare mesenchymal tumor which was first described in It accounts for 2.5% of all meningeal tumors and less than 1% of all primary CNS tumors.
Recent studies insist that the extent of surgical resection and postoperative radiotherapy correlate with improved overall survival and recurrence-free survival. But the definitions of complete resection or grossly total resection in previous studies are equivocal. In most reported cases, since HPC is attached to the venous sinuses or major vessels, so it is actually impossible to literally completely remove the tumor. Assuming that these ambiguous classifications on the extent of resection might have had a measurement bias, we reviewed our cases of HPCs focusing on the clinical efficacy of surgical resection graded by Simpson grading system (which is largely used in meningioma removal). The disease features, treatment strategies, and clinical courses of relevant cases from our experience were also analyzed.

3. Retrospective analysis
Material & Method
Retrospective analysis
Duration : Jan,1995 ~ Dec, 2014 (20-year period)
Total case : 17 cases
Clinical presentation
Radiological appearance
Results of treatment
Follow-up outcomes
We retrospectively reviewed the patients with HPC treated in our institute from January 1995 to December 2014 (the 20-year period). The total number of patients was 17. The medical records of the 17 patients were reviewed and analyzed. Clinical presentations, radiologic finding, pathology, the extent of resection, radiation, follow-up outcomes.
Operative records, including notes and video, were reviewed to determine gross tumor extension to adjacent vessels and completeness of resection.

4. Simpson grading system Complete resection or Grossly total resection
Material & Method
Simpson grading system
Grade
Degree of removal I
Macroscopically complete removal with excision of dural attachment and abnormal bone (including sinus resection when involved) II
Macroscopically complete with endothermy coagulation of dural attachment
III
Macroscopically complete without resection or coagulation of dural attachment or of its extradural extensions IV
Partial removal leaving tumor in situ V
Simple decompression (±Biopsy)
Complete resection or Grossly total resection
Assuming that these ambiguous classifications on the extent of resection might have had a measurement bias, we reviewed our cases of HPCs focusing on the clinical efficacy of surgical resection graded by Simpson grading system (which is largely used in meningioma removal). The disease features, treatment strategies, and clinical courses of relevant cases from our experience were also an
The extent of resection was divided into three categories (gross total resection, partial resection, biopsy); it was also divided into five categories by Simpson grading system.
alyzed.

5. Patient Characteristics
Results
Patient Characteristics
Case No.
Sex
Age
Tumor location
Adjacent vessels
Tumor size
(mm)
Extent of
resection
Simpson
grade
Mitosis (/10HPF)
Ki-67 (%)
Pathology
(WHO grade)
Radiotherapy
(cGy)
KPS score
(PreOp/Final)
Overall
survival
(month)
Recurrence
Metastasis 1 M 29
Sphenoid wing
YES 50 PR 4
N/A II
6000
20/0 13 3
None 2 41
Parasagittal 40
GTR 17
5580
20/20
197
104 20 30
III 51 22 12 9 54 11 85 10
2700 (CK)
20/30 5 58
Convexity NO 60
3.6
60/60
138 52
Tentorial
Biopsy
90/90
171
90/100 36 27 25
1500 (CK) 63 33 24 26 73 15
5400
80/80 21 6 59
5949
80/90 53 7 72 56
40/40 61
40/0 8
5940
Falx
80/30 19 35 55 38 32 F 42 45
5500
90/80
CPA
5000
118 14 37
70/80 16 48 23 28
80/100

6. Patient Characteristics
Results
Patient Characteristics
Age : 26 ~ 73 (mean : 48)
M : F = 14 : 3
Initial symptom : Headache (m/c : 67%)
Tumor location
: Parasagittal (8, 47.1%), Tentorial (3, 17.6%), Falx (2, 11.8%),
Convexity (2, 11.8%), Sphenoid wing (1, 5.9%), CPA (1, 5.9%)
Operation : 26 (including reOp for recurrences)
No operative mortality
The mean age at the time of the initial diagnosis was 48 years, with the range from 26 to 73 years. The patient group included 14 (82.4%) males and 3 (17.6%) females. The most common presenting symptom was headache, followed by vomiting, visual field defects, and seizures. The preferential area of tumor origin was parasagittal (8 patients, 47.1%), which is adjoined to superior sagittal sinus. Distributions of the remaining tumor locations were as follows: tentorial (3 patients, 17.6%), falx (2 patients, 11.8%), convexity (2 patients, 11.8%), cerebellopontine angle (1 patient, 5.9%), and sphenoid wing (1 patient, 5.9%). A total number of 26 operations were performed for the resection of either primary or recurrent intracranial HPCs.

7. Adjoin adjacent vessels
Results
Adjoin adjacent vessels
No adjacent vessels
To evaluate the correlation between location and the extent of resection, these locations were grouped into 2 categories (Table 2): those that adjoin adjacent vessels such as superior sagittal sinus, transverse sinus (Figure 1), or sigmoid sinus, and those that have no adjacent major vessels (Figure 2). The results of Fisher’s exact test suggest, that the extent of resection was statistically significantly associated neither with the location of tumor, nor with the existence of adjacent vessels (p=0.35 and 0.60, respectively).
Extent of resection & Location of tumor (p=0.35)
Extent of resection & Existence of adjacent vessels (p=0.60)

8. Histopathological results
All specimens obtained in each surgery
including recurrence were reviewed
WHO grade II : 11 (42.3%)
WHO grade III : 15 (57.7%)
Progression (WHO GII ▶ GIII) : 2 patients (11.8%)
Ki-67 proliferative index : 1~40% (Mean : 14%)
▶ WHO GII : 4.8% / WHO GIII 21.2%
The clinical outcomes were evaluated according to the Karnofsky performance scale (KPS). The mean KPS at final outcome was 65 (initial mean KPS was 65.8). The mean follow-up period was 55 months, with the range from 10 to 197 months.

9. Treatment modalities Both at convexity
Results
Treatment modalities
Surgery & Adjuvant radiotherapy
No perioperative mortalities / No unexpected events during surgery
GTR ▶11 (64.7%)
: Simpson G1 - 2 (11.8%) / G2 – 7 (41.2%) / G3 – 2 (11.8%)
PR (Simpson G4) ▶ 4 (23.5%)
Biopsy (Simpson G5) ▶ 2 (11.8%)
PostOp RTx : 16 (94.1%) (Dose : 5000~6000cGy, mean 5757cGy)
CK radiosurgery : 2 patients for recurred HPC (1500cGy, 2700cGy)
Both at convexity
Treatment modalities consisted of surgery and adjuvant radiotherapy. All patients were initially treated with surgery and there were no perioperative mortalities and no unexpected events during the operations. At the initial operation, a grossly total resection (GTR) was accomplished in 11 patients (64.7%), a partial resection (PR) in 4 patients (23.5%), and an endoscopic biopsy in 2 patients (11.8%). In Simpson grading system (Table 1), GTR was divided into 3 grades, grades 1 to 3. PR was the same as Simpson grade 4 and biopsy was same as Simpson grade 5. Dividing GTR group into Simpson grading system, grade 1 was done in 2 patients (11.8%), grade 2 in 7 patients (41.2%), and grade 3 in 2 patients (11.8%). In most cases, because of the location of tumor adjoined to the venous sinus, surgical resection was possible only by Simpson grade 2 or 3. Venous sinus was preserved in all patients. The location of tumor in 2 patients who underwent surgical resection by Simpson grade 1 was both at convexity.
Postoperative radiotherapy (RT) was delivered in 16 patients (94.1%), regardless of the extent of resection. One patient (Case Number 9 in Table 2) rejected active treatment after initial surgery. The mean total dose of radiotherapy was 5757cGy, with the range from 5000 to 6000cGy. 2 patients (11.8%) underwent stereotactic radiosurgery using cyberknife for the treatment of recurred HPC (total dose of 1500cGy and 2700cGy each).

10. Karnofsky performance scale (KPS)
Results
Clinical outcomes
Karnofsky performance scale (KPS)
Final mean KPS : 65 / Initial mean KPS : 65.8
Follow up : 10~197 months (mean : 55)
Distant metastases : None
The clinical outcomes were evaluated according to the Karnofsky performance scale (KPS). The mean KPS at final outcome was 65 (initial mean KPS was 65.8). The mean follow-up period was 55 months, with the range from 10 to 197 months. 2 of the 17 patients died during the follow-up period. Clinical follow-up and additional image studies, such as PET-CT scans, did not suggest distant metastases.

11. Results Local recurrence : 5 (29.4%) Median RFS : 51 months
Overall survival (Month)
Survival Probability
Local recurrence : 5 (29.4%)
Median RFS : 51 months
Recurrence-free survival (Month)
Survival Probability
The mean overall survival (OS) was 13 months with median OS not reached. 5 patients (29.4%) developed local recurrence and the median recurrence-free survival (RFS) was 51 month.
Median OS : not reached
Mean OS : 13 months

12. Extent of resection Results GTR PR Biopsy
Recurrence-free survival (Month)
Survival Probability
Biopsy PR
GTR
The mean time for local recurrence of patient who underwent GTR was 68.3 months, PR was 37.1 months, and biopsy was 3.5 months, which was statistically significant (p=0.003 by log-rank test)
P=0.003

13. Simpson grade Results Grade 1 Grade 3 Grade 2 Grade 4 Grade 5
Recurrence-free survival (Month)
Survival Probability
Grade 5
Grade 2
Grade 1
Grade 3
Grade 4
Additionally, Simpson grading system for surgical resection of intracranial HPC was significantly associated with higher RFS (p=0.011 by log-rank test)
P=0.011

14. Radiotherapy Results Adjuvant radiotherapy Survival Probability None
Recurrence-free survival (Month)
Survival Probability
None
Adjuvant radiotherapy
Regarding adjuvant RT, the mean time for local recurrence was 80.5 months in patients who received RT against 19.5 months in those who did not
Although the mean time values for local recurrence were 66.2 months and 38.1 months in the patients with WHO grade II HPC and WHO grade III HPC, respectively, the pathological diagnosis for WHO grades II and III was not statistically significantly associated with the time for local recurrence (p=0.49 by log-rank test).
P=0.0003

15. WHO grade II WHO grade III
Results
Pathology
WHO grade II
: 66.2month
WHO grade III
: 38.1month
Mean time value for local recurrence
Although the mean time values for local recurrence were 66.2 months and 38.1 months in the patients with WHO grade II HPC and WHO grade III HPC, respectively, the pathological diagnosis for WHO grades II and III was not statistically significantly associated with the time for local recurrence (p=0.49 by log-rank test). However, possibly due to the small number of the investigated cases, this difference did not reach statistical significance.
P=0.49

16. Adjuvant radiation ? Extent of resection ? Simpson grading system ?
Discussion
Extent of resection ? Simpson grading system ?
Statistically significant correlation between each grade & RFS
▶ Seems to be safer to remove the tumor as much as possible
Adjuvant radiation ?
Completely removed tumor ? Grade II HPC ?
As suggested by Bassiouni et al., the classification introduced by Simpson in 1957 to describe the resection rate in meningiomas can also be usefully applied in intracranial HPCs, since, in most cases, these tumors are dura-based. We divided GTR into 3 Simpson grades, grades 1 to 3. The results of the statistical analysis of the correlation between the extent of resection and recurrence suggest statistical significance like other several studies. Conventional classification of dividing into GTR, PR and biopsy showed that each class of resection is significantly associated with RFS; Simpson grading system showed statistically significant correlations between each grade and RFS as well. To prevent local recurrence, it seems to be safer to remove the tumor as much as possible, even when the remaining tumor is adjoined to the adjacent structures, such as the dural sinus.
In many series, intracranial HPCs have been shown to recur even after complete GTR. Thus, several authors have recommended adjuvant RT for a better outcome. Similarly to other series, our experience shows that the patients who received adjuvant RT tend to have longer RFS . We performed adjuvant RT regardless of the extent of resection and pathologic grade in most of the patients. 16 out of 17 patients (94.1%) received adjuvant RT to the mean dose of 5757cGy; no significant radiation-related complications were observed.
Regardless of the extent of resection and pathologic grade

17. Complete tumor resection
Conclusion
Complete tumor resection
Adjuvant RTx
Long term follow up
Attempt to reach Simpson grade 1 removal
Surgical resection of intracranial HPC, in an attempt to reach Simpson grade 1 removal of the tumor, is necessary in the initial surgery. This attempt to reach Simpson grade 1 removal should be performed within the safe limit. Additionally, adjuvant RT should be done to prevent recurrence, even in the patients who have tumor completely resected and who have been diagnosed as WHO grade II HPC.