PEER-REVIEW REPORTS GEORGE KWOK CHU WONG ET AL.
study on cognitive dysfunction after spontaneous subarachnoid haemorrhage: patient profiles and relationship to cholinergic dysfunction. Acta Neurochir (Wien) 151:1601-1607, 2009.
TUMOR
35. Woodworth GF, Biard CJ, Garces-Ambrossi G, Tornascia J, Tamargo RJ: Inaccuracy of the administrative database: comparative analysis of two databases for the diagnosis and treatment of intracranial aneurysms. Neurosurgery 65:251-256, 2009. 36. Yasuno K, Bilguvar K, Bijlenga P, Low SK, Krischek B, Auburger G, Simon M, Krex D, Arlier Z, Nayak N, Ruigrok YM, Niemela M, Tajima A, von und zu Fraunberg M, Doczi T, Wirjatijasa F, Hata A, Blasco J, Oszvald A, Kasuya H, Zilani G, Schoch B, Singh P, Stuer C, Risselada R, Beck J, Sola T, Ricciardi F, Aromaa A, Illig T, Schreiber S, van Duijn CM, van
INCIDENCE AND MORTALITY OF SPONTANEOUS SAH IN HONG KONG
den Berg LH, Perret C, Proust C, Roder C, Ozturk AK, Gaal E, Berg D, Geisen C, Friedrich CM, Summers P, Frangi AF, State MW, Wichmann HE, Breteler MM, Wijmenga C, Mane S, Peltonen L, Elio V, Stirkenboom MC, Lawford P, Bryne J, Macho J, Sandalcioglu EI, Mayer B, Raabe A, Steinmetz H, Rufenacht D, Jaaskelainen JE, Hernesniemi J, Rinkel GJ, Zembutsu H, Inoue I, Palotie A, Cambien F, Nakamura Y, Lifton RP, Gunel M: Genome-wide association study of intracranial aneurysm identifies three new loci. Nat Genet 42:420-425, 2010. 37. Yasuno K, Bakircioglu M, Low SK, Bilguvar K, Gaal E, Ruigrok YM, Niemela M, Hata A, Bijlenga P, Kasuya H, Jaaskelainen JE, Krex D, Auburger G, Simon M, Krischek B, Zembutsu H, Inoue I, Palotie A, Cambien F, Nakamura Y, Lifton RP, Gunel M: Common variant near the
endothelin receptor type A (EDNRA) gene is associated with intracranial risk. Proc Natl Acad Sci USA 108:19707-19712, 2011.
Conflict of interest statement: This study was supported by the Neurosurgery Research and Training Fund, the Chinese University of Hong Kong. Received 26 October 2012; accepted 27 July 2013; published online 22 September 2013 Citation: World Neurosurg. (2014) 81, 3/4:552-556. http://dx.doi.org/10.1016/j.wneu.2013.07.128 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.
Intracranial Hemangiopericytoma—Our Experience in 30 Years: A Series of 43 Cases and Review of the Literature Angelina Graziella Melone1, Alessandro D’Elia1, Francesca Santoro2, Maurizio Salvati3, Roberto Delfini1, Giampaolo Cantore3, Antonio Santoro1
Key words Hemangiopericytoma - Intracranial - Recurrence - Survival - Treatment -
Abbreviations and Acronyms EBRT: External beam radiotherapy GTR: Gross total resection HPC: Hemangiopericytoma OS: Overall survival STR: Subtotal resection WHO: World Health Organization From the Departments of 1Neurosurgery and 2 Neuroradiology, Sapienza University of Rome; and the 3Department of Neurosurgery INM—IRCCS Neuromed, Pozzilli (Isernia), Sapienza University of Rome, Rome, Italy To whom correspondence should be addressed: Angelina Graziella Melone, M.D. [E-mail:
[email protected]] Citation: World Neurosurg. (2014) 81, 3/4:556-562. http://dx.doi.org/10.1016/j.wneu.2013.11.009 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.
INTRODUCTION
- OBJECTIVE:
Meningeal hemangiopericytoma (HPC) is a rare, aggressive central nervous system tumor that tends to invade locally and to metastasize, and has a high rate of recurrence.
- METHODS:
This study presents a retrospective review of patients managed for intracranial HPC at Rome University Hospital.
- RESULTS:
A total of 43 patients with intracranial HPC were treated from 1980 to 2010. Treatment and follow-up information was available for analysis on 36 patients. The median survival for all patients was 83.5 months after date of diagnosis, with 1-year, 5-year, and 10-year survival rates of 100%, 94.4%, and 72.2%, respectively. Eighteen patients (41.86%) had HPC recurrence. The median time until recurrence was 72.24 months, with 1-year, 5-year, and 10-year progression-free survival rates of 98%, 51%, and 29%, respectively. Five patients (11.62%) developed extracranial metastasis. Patients undergoing any form of adjuvant radiation treatment, including external beam radiotherapy, Gamma Knife radiosurgery, and/or proton beam therapy, had no longer median overall survival (OS) (178 vs. 154 months, respectively; P [ .2); but did have a significantly improved recurrence-free interval (108 vs. 64 months; P [ .04) compared with patients who did not undergo radiation treatment. Tumor characteristics associated with earlier recurrence included size ‡7 cm (log-rank, P < .05) and sinus invasion (log-rank, P < .05).
- CONCLUSIONS:
Strategies combining adjuvant radiation with tumor resection seemed to hinder tumor progression, but had no effect on OS or the development of metastases. Greater extent of resection was associated with increased OS (log-rank, P < .05). Anaplastic HPC was associated with reduced OS and with reduced recurrence interval (log-rank, P < .05).
Intracranial hemangiopericytoma (HPC) is a rare, vascularized mesenchymal tumor. It develops from malignant transformation
556
www.SCIENCEDIRECT.com
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2013.11.009
PEER-REVIEW REPORTS
of pericytes, cells that form the walls of capillaries and postcapillary venules. HPC exhibits a characteristically monotonous appearance under low-power microscopy, as well as well-developed branching staghorn vasculature with walls of varying thickness (16). HPC is almost always attached to the dura, and has a strong tendency to recur locally and to metastasize outside the central nervous system (5, 7, 27, 35, 36, 38). Recurrence usually precedes metastasis (14, 26). Although found in similar arachnoid locations as generally benign meningiomas, HPC has a more aggressive biology facilitating local recurrence and distant metastasis (9). HPC is considered a World Health Organization grade II neoplasm, with anaplastic variants classified as grade III (25). HPC remains a rare entity thought to represent 0.4% of all primary central nervous system tumors, making meningioma approximately 50 to 60 times more common (25, 28). Extracranial location is more frequent in HPCs than in meningiomas (4). These extremely vascular tumors are challenging to treat, especially in pediatric cases because of the smaller overall blood volume in children. The surgeon must be careful when interrupting the blood supply to the tumor, and preoperative endovascular embolization is recommended. Infantile HPC is characterized by a more benign course, with responsiveness to chemotherapy and even a tendency to spontaneous regression. In contrast, the behavior of HPC in children older than 1 year does not seem to differ from that of HPC in adults (24). Because HPC closely mimics meningioma in clinical and radiographic presentation, histological confirmation is the only definitive means of distinguishing these lesions (32). In terms of histological grading, Zhou et al. (37) found that intracranial anaplastic HPC tended to have more marked lobulated and cross-leaf growth and was more likely to bleed. Features useful in distinguishing anaplastic HPC from its lower-grade counterparts include necrosis and cystic components, and anaplastic HPC is more likely to show heterogeneous signal on neuroimaging and less likely to exhibit the dural tail sign. Destruction of adjacent skull and
TREATMENT AND PROGNOSIS OF INTRACRANIAL HEMANGIOPERICYTOMA
peritumoral edema also are more commonly seen in anaplastic HPC, as are recurrence and extracranial metastasis. PATIENTS AND METHODS The series presented herein was generated by reviewing the histopathological records at Sapienza University of Rome Hospital, Department of Neurosurgery, to identify all patients diagnosed with HPC since 1980 (comprising some cases retrospectively reviewed after 1993). Some patients underwent initial treatment for the primary disease at another institution and were later seen at our institution for follow-up or management of recurrent disease. In these cases, primary treatment was determined via review of medical and radiological records. All patients had pathologically confirmed HPC reviewed by the neuropathology department at our institution. Pathology reports were reviewed to confirm diagnosis; in addition, all specimens were graded according to the Mena classification (26) into low or high grade. According to these criteria, high-grade meningeal HPC was characterized by the presence of necrosis and/or more than 5 mitoses for 10 microscopic fields (magnification 400), and at least 2 of the following microscopic features: hemorrhage, moderate to high nuclear atypia, and moderate to high cellularity. Data on demographics, tumor characteristics, treatment modalities, survival, and length of follow-up also were recorded. All cases of HPC recurrence and metastasis were documented radiographically, and mortality data were confirmed by chart review. Patient data were analyzed by sex, age, length of survival, and mortality. Tumor data were analyzed by size, location, recurrence, and metastasis. Tumor size was determined by measuring the maximum radiographic diameter. Recurrence was defined as reappearance of tumor within the cranial cavity, or an increase in size of residual tumor. Metastasis was defined as the presence of HPC tissue in any extracranial location. Treatment data were analyzed by modality, extent of resection, use of adjuvant radiotherapy, use of Gamma Knife radiosurgery, and amount of radiation received; none of our patients were treated with chemotherapy. All treatment analyses performed were based on
WORLD NEUROSURGERY 81 [3/4]: 556-562, MARCH/APRIL 2014
the primary intervention that a patient received, whether that occurred at an outside institution or at our institution. Follow-up time for overall survival (OS) was defined as the time between primary surgery and death or the last known date of posttreatment follow-up. Follow-up time for recurrence-free survival was defined as the time between primary surgery with pathological diagnosis of HPC and the most recent imaging study demonstrating radiographic absence or progression of tumor. Follow-up time for metastasis was defined as the time until radiographic evidence of HPC progression extracranially, or the last known date of follow-up. Univariate survival analysis was performed using the Kaplan-Meier method to evaluate the prognostic significance of patient and tumor characteristics, and the efficacy of various treatment modalities. Significance was determined using the log-rank test, with the P value considered significant at the 5% (P ¼ .05) level. A multivariate Cox regression analysis was then performed to determine the independent impact of factors found to be significant or trending toward significance in univariate analysis. All descriptive and statistical analysis was performed using SPSS version 12.0. RESULTS Forty-three cases of HPC with proven histological diagnosis were identified between 1980 and 2010. All patients were initially treated with microsurgical resection. Subtotal resection (STR) was performed when gross total resection (GTR) was not possible. Twenty-six patients were female (60.5%) and 17 (39.5%) were male, with a median age at first operation of 46.9 years (range 19 to 79 years). Tumors most frequently occurred superficially and closely related to the meninges, in the falx/parasagittal area (55%). Eight (18.6%) tumors were associated with venous sinus compression or invasion. Symptoms were related to tumor location. The most common symptoms were headache (40%) and upper and/or lower limb weakness (12%). Seven patients who lived overseas were lost to follow-up after the initial surgery and were excluded from further analysis. The median follow-up period was 118 months (range 24 to 384 months). Seven patients were diagnosed and underwent
www.WORLDNEUROSURGERY.org
557
TUMOR
ANGELINA GRAZIELLA MELONE ET AL.
PEER-REVIEW REPORTS ANGELINA GRAZIELLA MELONE ET AL.
TUMOR
initial treatment at other hospitals. These patients were included in the study because subsequent treatment was carried out at our institution. The median survival for all patients was 83.5 months after date of diagnosis, with 1-year, 5-year, and 10-year OS rates of 100%, 94.4%, and 72.2%, respectively (Figure 1). Thirty-three tumors (76.7%) were classified as World Health Organization (WHO) grade II and 10 (23.3%) as WHO grade III. Eighteen (41.86%) of the 43 had at least 1 recurrence. Nine of 18 recurrences were WHO grade III. Extracranial metastasis was seen in 5 cases, all of which were WHO grade III HPC and were situated in the lung (1), liver (3), and peritoneum (1). For surgical removal of the lesions, we used the operating microscope, microsurgical instrumentation, a neuronavigation system, brain mapping techniques, and neurophysiological intraoperative monitoring (from 2000). GTR Is Associated with Longer OS and Longer Recurrence-Free Interval At first operation, GTR was achieved in 30 (69.76%) cases and STR in 13 (30.23%) cases. Six patients with GTR received preoperative embolization, and 6 patients who underwent STR also received preoperative embolization. After GTR, 11 patients (36.67%) received adjuvant external beam radiotherapy (EBRT). Most patients receiving STR were further treated with adjuvant radiation, including 10 of the 13 (76.9%) who received EBRT, 5 (50%) of whom received Gamma Knife radiosurgery and 5 (50%) of whom received proton beam therapy (Table 1). Eighteen patients (41.86%) had HPC recurrence. The
TREATMENT AND PROGNOSIS OF INTRACRANIAL HEMANGIOPERICYTOMA
Table 1. Treatment Strategy: Subgroups Treatment Strategy
Patients (n)
Recurrence (n)
Metastasis (n)
Mortality (n)
GTR alone
19
5
1
1
GTR þ EBRT
11
4
1
2
3
3
1
4
10
6
2
7
STR alone STR þ EBRT
EBRT, external beam radiotherapy; GTR, gross total resection; STR, subtotal resection.
median time until recurrence was 72.24 months after the first surgery (mean 64 months), with 1-year, 5-year, and 10-year progression-free-survival rates of 98%, 51%, and 29%, respectively. The recurrence rate at 1, 5, and 10 years was 2.7%, 50%, and 72%, respectively (Figure 2). All patients with local recurrence underwent repeat surgery. Ten patients received GTR, 2 of whom received 60 Gy of adjuvant EBRT to the resection bed. Eight patients received STR, 2 of whom received postoperative EBRT to residual tumor, Gamma Knife surgery with a 16-Gy marginal dose, as recommended by Kim et al. (22), who found that doses higher than previously used (around 15 Gy) are desirable for better local tumor control of HPCs and are not associated with severe adverse radiation effects. The median OS after the second operation was 48 months (range 8 to 60 months). Six patients had a second recurrence after the initial retreatment; they all underwent repeat surgery and 5 went on to have a third recurrence, at which point no more operations or radiotherapy were performed. The
Figure 1. Overall survival rate.
558
www.SCIENCEDIRECT.com
average survival period for these patients was 28.3 months (range 4 to 57 months, median 32 months). In the period after the first, second, and third operations, median Karnofsky Performance Status passed from 85 to 80 and subsequently to 60. The 5 (11.62%) patients in whom extracranial metastases developed, with metastases involving the liver (3 patients), lung (1 patient), and peritoneum (1 patient), all died of systemic disease. Overall, patients in the complete excision group had both a longer OS (235 vs. 175 months; P ¼ .047) and a longer recurrence-free interval (117 vs. 54 months; P ¼ .0025) (Table 2). Anaplastic HPC Is Associated with Reduced OS and Reduced RecurrenceFree Interval Thirty-three (76.7%) patients were classified as having low-grade tumors. Overall mean survival was 256 and 142 months in the low- and high-grade tumor groups respectively, a difference of 114 months (P ¼ .03). Eighteen tumors recurred, 9 of which were high-grade, and the remainder were low-grade. All patients experiencing recurrence underwent revision surgery. Of 9 low-grade lesions, 4 (44.4%) demonstrated high-grade transformation and had a second recurrence. High-grade tumors recurred an average of 36 months earlier than low-grade tumors (59 vs. 95 months, respectively; P ¼ .1) (Table 3). Adjuvant Radiation Therapy Does Not Confer a Longer OS but Does Prolong the Recurrence-Free Interval Patients undergoing any form of adjuvant radiation treatment, including EBRT, Gamma Knife radiosurgery, and/or proton beam therapy, did not have longer median
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2013.11.009
PEER-REVIEW REPORTS ANGELINA GRAZIELLA MELONE ET AL.
TREATMENT AND PROGNOSIS OF INTRACRANIAL HEMANGIOPERICYTOMA
Histological Grade
Figure 2. Recurrence rate.
OS (178 vs. 154 months, respectively; P ¼ .2), but did have a significantly improved recurrence-free interval (108 vs. 64 months, respectively; P ¼ .04) compared with patients who did not undergo radiosurgery. The 1-, 5-, and 10-year recurrence rates for irradiated tumors were 24%, 35%, and 65%, respectively; for nonirradiated tumors, the rates were 36%, 48%, and 88%, respectively (Figure 3). No adverse effects, such as radiation necrosis or marked peritumoral edema, were observed in any patients.
Adjuvant Radiation Treatment, not Extent of Resection, Increases the RecurrenceFree Interval When considering extent of resection, STR with adjuvant radiation trended toward independently predicting increased time to recurrence when compared with GTR alone (log-rank, P ¼ .132) (Figure 4). We found no significant difference in time until recurrence among patients receiving GTR with adjuvant radiation vs. patients receiving GTR alone (log-rank, P ¼ .286), in patients receiving STR with adjuvant radiation vs. patients receiving STR alone (log-rank, P ¼ .299), or in patients receiving GTR with EBRT vs. patients receiving STR with EBRT (log-rank, P ¼ .713).
Extent of Resection, not Adjuvant Radiation Treatment, Is Associated with Increased OS There was a statistical trend toward worse OS among patients receiving any form of adjuvant radiation treatment with surgical resection vs. those receiving surgery alone (log-rank, P ¼ .08). When analyzing extent of resection, patients receiving GTR demonstrated extended OS compared with those receiving STR with any form of adjuvant radiation (log-rank, P < .05) (Figure 5); unlike the study by Ghia et al., which reported that patients undergoing STR with postoperative EBRT compared favorably with those undergoing GTR alone with respect to OS (17). The median survival advantage was 20.4 years for patients receiving GTR compared with 9.3 years for patients receiving STR with adjuvant radiation. We found no significant difference in OS among patients receiving GTR with adjuvant radiation vs. patients receiving GTR alone (log-rank, P ¼ .315) or in patients receiving STR with adjuvant radiation vs. patients receiving STR alone (log-rank, P ¼ .631). There was no evidence that extent of resection or adjuvant radiation could prevent or extend the development of metastatic HPC (logrank, P ¼ not significant).
Table 2. Degree of Resection, Overall Survival, Recurrence-Free Survival Grade of Excision
Overall Survival
Recurrence-Free Interval
Gross total resection (69.76)
235 months
117 months
Subtotal resection (30.23%)
175 months
54 months
WORLD NEUROSURGERY 81 [3/4]: 556-562, MARCH/APRIL 2014
Overall Survival
Recurrence-Free Interval
Low grade
256 months
95 months
High grade
114 months
59 months
Tumor Size and Anatomic Location Predict Recurrence The maximum tumor diameter ranged from 2.5 cm to 12 cm. On univariate analysis, we found that tumors 7 cm recurred significantly earlier than those 7 cm recurred at a median time of 3 years, vs. 13.1 years for tumors
