J Neurooncol DOI 10.1007/s11060-014-1414-5
CLINICAL STUDY
Stereotactic radiosurgery for cavernous sinus hemangiomas Sang Woo Song • Dong Gyu Kim • Hyun-Tai Chung Sun Ha Paek • Jung Ho Han • Yong Hwy Kim • Jin Wook Kim • Young-Hoon Kim • Hee-Won Jung
•
Received: 31 December 2013 / Accepted: 21 February 2014 Ó Springer Science+Business Media New York 2014
Abstract We performed this retrospective study to analyze the outcome of patients with cavernous sinus hemangioma (CSH) after stereotactic radiosurgery (SRS). We analyzed 19 patients with CSHs who were treated with SRS between 1998 and 2011. The median age of the patients was 50 years (range, 35–73 years), and 16 (84.2 %) of the patients were female. SRS was performed as a primary treatment for 18 patients and to treat a residual lesion after surgical resection in one patient. Nine (47.4 %) patients had cranial neuropathies in 14 cranial nerves before SRS, whereas five (26.3 %) patients were initially asymptomatic. The mean volume of the CSHs was 6.1 ± 7.2 cm3 (range, 0.3–32.3 cm3), and the median marginal dose at the 50 % isodose line was 14.5 Gy (range, 11.5–16.0 Gy). The mean follow-up period was 37 months (range, 12–85 months). At the last follow-up, the lesion volume had decreased in all patients. The average tumor volume had decreased to 26 % (range, 0–70 %) of the S. W. Song D. G. Kim (&) H.-T. Chung S. H. Paek J. H. Han Y. H. Kim J. W. Kim Y.-H. Kim H.-W. Jung Department of Neurosurgery, Seoul National University College of Medicine, 101 Daehang-ro Jongno-gu, Seoul 110-744, Korea e-mail: [email protected] S. W. Song Department of Neurosurgery, Konkuk University Medical Center, Seoul, Korea D. G. Kim H.-T. Chung S. H. Paek Y. H. Kim J. W. Kim H.-W. Jung Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea J. H. Han Y.-H. Kim Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
initial volume at the last follow-up MRI. The first followup MRI, performed 6.1 ± 1.0 months after the SRS, showed that the tumor volume had decreased to 41 % (range, 0–88 %) of the initial volume. All 14 of the cranial neuropathies observed before SRS had improved, with complete remission in 12 (85.7 %) cranial nerves and partial remission in two (14.3 %). There were no radiationinduced neuropathies or complications during the followup period. SRS appears to be an effective and safe treatment modality for the management of CSHs. Keywords Stereotactic radiosurgery Cavernous sinus hemangioma Tumor control Cranial neuropathy Cavernous sinus
Introduction Cavernous sinus hemangiomas (CSHs) are rare vascular tumors that account for 1–3 % of all lesions within the cavernous sinus [1–3]. These tumors are extra-axial, interdural, intra-sinus lesions that produce symptoms that result from progressive tumor growth and mass effect. Before the era of MRI, the radiological diagnosis of CSHs was not easy; thus, CSHs were often identified during surgery for lesions that were preoperatively diagnosed as meningiomas or schwannomas [3]. Before the 1980s, surgical mortality was as high as 38 % because of massive intraoperative bleeding from CSHs [3]. Even with recent advances in neurosurgical techniques, the complete removal of CSHs is often impossible, and cranial neuropathies become worse after surgery in approximately 80 % of patients [4]. Recently, stereotactic radiosurgery (SRS) has become an effective alternative to surgical resection and has been
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shown to be safe in terms of cranial neuropathies. Thus, we performed this study to evaluate the efficacy and safety of SRS in the management of CSHs, with a specific focus on clinical symptoms, including cranial neuropathies.
Methods Patient population In total, 21 consecutive patients with CSHs were treated with SRS in our two institutes (Seoul National University Hospital and Seoul National University Bundang Hospital) between 1998 and 2011. Two patients were excluded because they missed a follow-up MRI, although they showed clinical improvement within 1 month after SRS. Thus, a total of 19 patients were finally enrolled in this study. One patient had undergone surgical resection before SRS, and the remaining 18 patients underwent SRS as a primary treatment under the typical radiological diagnosis, as described elsewhere [1, 5–8]. Briefly, CSHs were diagnosed when brain MRI showed characteristic imaging findings, including the following: bright, high signal intensities on T2-weighted images; strong enhancement after contrast (diethylene triamine pentaacetate) injection; a round shape without a dural tail sign; and encasement of the internal carotid artery (ICA) without narrowing [1, 5– 8]. The study was approved by the Institutional Review Board of Seoul National University Hospital and Seoul National University Bundang Hospital (IRB Number: 9911-061-001). Stereotactic radiosurgery All patients underwent single-session SRS. This SRS was performed using the Leksell Gamma Knife (Elekta Instrument AB, Stockholm, Sweden), Model B, C or Perfexion. The Leksell Model G stereotactic frame (Elekta Instrument AB) was applied to the patient’s head under local anesthesia supplemented with intravenous conscious sedation. T1-weighted, three-dimensional, multiplanar, rapid-acquisition, gradient-echo MRI and a T2-weighted sequence were then obtained before and after gadolinium enhancement. The images were exported to a computer workstation for dose planning using Gamma PlanÒ software (Elekta Instrument AB). The radiosurgery isodose, maximum dose, and marginal dose were initially determined according to the tumor volume calculated during dose planning. Multiple isocenter planning was used to minimize the radiation exposure of the optic pathway and other critical neural structures.
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Follow-up The patients were usually followed up at 1, 3, 6 and 12 months after SRS and underwent annual clinical evaluations thereafter. The patients’ tumor volume was measured on follow-up images taken at 6, 12 months and annually after treatment. T2-weighted MR images were used to calculate the tumor volumes, which was measured by multiplying the sum of the areas contoured on each slice by the slice thickness. The tumor volume change was defined as the ratio of the follow-up tumor volume to the initial tumor volume. Management outcomes were evaluated with respect to the tumor control rate and neurologic deficits. Tumor control was classified as ‘‘remarkable shrinkage’’ (a tumor volume on follow-up images of \50 % of the volume on images taken at the time of radiosurgery), ‘‘minimal shrinkage’’ (a tumor volume 50–75 % of the tumor volume before SRS) or ‘‘stationary’’ (a tumor volume of 75–125 % of the tumor volume before SRS). ‘‘Tumor progression’’ covered all other circumstances. The outcome of a cranial neuropathy was considered ‘‘unfavorable’’ if a new cranial deficit appeared and persisted or if existing deficits were aggravated and persisted beyond the preoperative state until the last clinical followup. ‘‘Improvement’’ of a cranial neuropathy was defined as the disappearance of or improvement in any deficits without any unfavorable features. Other outcomes were regarded as ‘‘stationary’’.
Results Sixteen (84 %) patients were female, and three (16 %) were male. The median age of the patients at the time of SRS was 50 years (range, 35–73 years). Nine (47.4 %) patients presented with cranial neuropathies in 14 cranial nerves, and seven (36.8 %) presented with headache. In contrast, five (26.3 %) patients were initially asymptomatic. The mean clinical follow-up was 37 months (range, 12–85 months). The mean volume of the CSHs was 6.1 ± 7.2 cm3 (range, 0.3–32.3 cm3), and the median marginal dose at the 50 % isodose line was 14.5 Gy (range, 11.5–16.0 Gy). The median number of shots was 14 (range, 4–34 shots). The patients’ clinical characteristics and treatment parameters are summarized in Table 1. Tumor control in CSHs Tumor control was achieved in all patients during the follow-up period. Remarkable shrinkage was achieved in 17 (89.5 %) patients and minimal shrinkage was achieved in two (10.5 %) patients. Overall, the average tumor
J Neurooncol Tables 1 Summary of the characteristics of patients with cavernous sinus hemangiomas Case number
Age
Sex
Presenting symptom
Pre-SRS treatment
Marginal dose (Gy)
Tumor volume
1
59
M
Facial hypesthesia
none
14
7.9
66
33
84
2
63
F
Incidental finding
none
15
8.6
27
13
24
3 4
67 39
F F
Incidental finding Headache
none none
14 15
2.4 4.7
53 28
21 12
33 12
5
50
F
Headache
none
16
5.3
51
32
76
6
64
F
Headache
none
15
4.5
24
24
6
7
39
F
Ophthalmoplegia, ptosis
none
13
16.0
45
15
75
8
57
F
Ophthalmoplegia, ptosis
surgery
15
3.4
44
44
6
9
48
F
Headache
none
14
5.0
55
38
43
10
73
F
Incidental finding
none
14.5
4.8
67
41
39
11
64
F
Diplopia
none
15
3.5
19
21
6
12
47
F
Diplopia
none
14
3.0
24
7
30
13
40
M
Diplopia
none
11.5
32.3
65
52
22
14
61
F
Headache
none
15
3.1
70
70
6
15
45
F
Diplopia
none
14
3.5
49
31
14
16
54
F
Loss of consciousness
none
15
2.1
39
24
24
17
35
M
Diplopia
none
15
0.3
0
0
18
18 19
44 45
F F
Incidental finding Diplopia
none none
15 14
3.7 1.3
30 0
18 0
12 10
3
Initial (cm )
Post-SRS 6 months (%)
At the last follow-up (%)
Image follow up period (months)
Fig. 1 Graph showing postSRS volume changes in all patients. All 19 patients had early tumor shrinkage (within 6 months after SRS). The tumor volume gradually decreased over the follow-up period in all patients, and no transient volume expansion was observed. For nine patients, the follow-up period was more than two years
volume had decreased to 26 % (range, 0–70 %) of the initial volume at the last follow-up MRI. No patients experienced ‘‘tumor progression’’ until the final follow-up, and no tumor showed transient expansion after SRS. The first follow-up MRI, performed 6.1 ± 1.0 months after the SRS, showed that the tumor volume had decreased
to 41 % (range, 0–88 %) of the initial volume. Moreover, the tumor volume gradually decreased over the follow-up period in all patients (Fig. 1). In 15 patients who were followed for more than one year (range, 12–84 months) after SRS, the tumor volume had decreased to 22 % of the initial volume (range, 0–41 %).
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J Neurooncol Table 2 Summary of the outcomes of clinical symptoms, including cranial neuropathies, after stereotactic radiosurgery
CN cranial nerve
CN III
CN V
CN VI
Exophthalmos
Orbital pain
Headache
Number of patients
2
2
2
8
1
1
7
Partial remission
0
0
0
2
0
0
2
Complete remission
2
2
2
6
1
1
5
Average time to complete remission (months)
1
1
3.5
1
1
1
7
Clinical outcome of SRS for CSHs The most common presenting symptom was cranial neuropathy, affecting nine patients, followed by headache in five patients. Additionally, in five patients, CSHs were diagnosed incidentally. All preexisting symptoms were categorized as ‘‘improved’’ in all patients, and no adverse radiation effect was observed during the follow-up period. The clinical outcomes are summarized in Table 2. Among the nine patients with cranial neuropathies in 14 cranial nerves, eight had a 6th cranial nerve palsy, and two patients each had 3rd and 4th cranial nerve palsies. Additionally two patients had facial hypesthesia. All 14 of the cranial neuropathies that were observed before SRS improved, with complete remission in 12 (85.7 %) cranial nerves and partial remission in two (14.3 %) patients with a 6th cranial nerve palsy. In those patients with complete remission of their cranial neuropathies, complete symptom remission almost occurred within 1 month after SRS. However, in one patient, facial hypesthesia was completely resolved, even at seven months after SRS. Headache was observed in seven patients and was completely resolved in five patients (71 %). The mean period to complete remission was 7 months (range, 1–15 months). One patient had experienced exophthalmos and orbital pain, and the symptoms were completely resolved within 1 month after SRS.
Illustrative case of CSH A 39-year-old woman (Case No.7 in Table 1) presented with a three-year history of intermittent diplopia and a onemonth history of ptosis. Neurological examination revealed 3rd, 4th, 5th and 6th cranial nerve palsies, and the patient also complained of periorbital pain and exophthalmos. MRI showed a round mass with ICA encasement and bright, high signal intensities at the left cavernous sinus on T2-weighted images (Fig. 2). The measured tumor volume was 16.0 cm3. With a presumptive diagnosis of CHS, SRS was performed as a primary treatment for the patient’s cavernous sinus lesion, and 13 Gy was used as the
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CN IV
marginal dose. The patient’s symptoms had already disappeared by the one-month clinical follow-up after SRS. Six months after SRS, the tumor volume had decreased to 7.2 cm3 (45 % of the initial tumor volume), and at 75 months post-radiosurgery, the tumor size was 2.4 cm3 (15 % of the initial tumor volume). At the last clinical follow-up, diplopia was still observed in the left lateral gaze.
Discussion In the 1980s and 1990s, to overcome surgical mortality and morbidity, radiotherapy was used on the CSHs as an adjuvant treatment after incomplete surgical resection of the CSHs or as a neoadjuvant tool [9–14]. With the use of more than 3,000 cGy with fractionation, tumors were reduced in size and were controlled for a relatively long period [3, 11–13, 15, 16]. Based on the success of radiation therapy for CSHs, Iwai et al. [17] reported the first case of CSHs treated with SRS in 1999. Since then, SRS has become an alternative to surgery and/or radiotherapy for CSH management [1, 5, 18–24]. Recently, a meta-analysis reported that SRS is an effective and safe treatment option for patients with CSHs [24]. Tumor shrinkage was identified in more than 90 % of patients, and new cranial neuropathy developed in only 1.7 % of patients [24]. In our study, remarkable post-SRS tumor shrinkage was also identified. Shrinkage by more than 50 % of the initial tumor volume was observed in 17 (88 %) patients, and partial tumor shrinkage (from 25 to 49 % of the initial tumor volume) was observed in two (12 %) patients. Additionally, clinical symptoms were completely relieved relatively soon after SRS in the majority of patients. The high rate of remarkable tumor shrinkage in this study appears to be related to the high marginal dose (a median dose of 14.5 Gy) and small tumor volume (a mean tumor volume of 6.1 cm3). Although the mechanism of the tumor response after SRS is not well understood, the postSRS early symptomatic response could be explained by rapid volume reduction and subsequent mass effect relief after SRS. To obtain remarkable early tumor shrinkage of
J Neurooncol
Fig. 2 Case 7. Axial T2-weighted image showing a very large CSH in the left cavernous sinus (a). A follow-up image after six months showed marked tumor reduction (b). The tumor volume gradually
decreased in the 15- and 23-month follow-up images (c, d). At 50 months after SRS, the tumor volume had decreased to 20 % of the initial volume (e)
more than 50 % of the initial tumor volume, a higher dose than a 14 Gy marginal dose was suggested [24]. The high complete remission rate for cranial neuropathies in our study also appears to be associated with the early tumor shrinkage that resulted from using a relatively high radiation dose. However, the critical structures around the cavernous sinus, such as the optic apparatus, usually limit the use of high radiation doses, especially for the treatment of large CSHs. Interestingly, in a patient treated with a low marginal dose, 11.5 Gy, for a CSH with a tumor volume of 32.3 cm3, the tumor volume was reduced by only 35 % of the initial volume, and a lateral gaze palsy persisted in a partial remission state until distant follow-up. In fact, remarkable tumor shrinkage could be obtained using a relatively low marginal dose of 10–12 Gy [18, 20]. However, relatively high doses (more than 14 Gy) appear to be optimal for tumor control and symptom relief, as our study shows, because remarkable early tumor shrinkage appears to be related to the complete remission of cranial neuropathies. Therefore, hypofractionated stereotactic radiotherapy may be more effective for the treatment of large CSHs in terms of remarkable early tumor shrinkage and complete symptom remission [25]. Our study had several limitations such as a lack of pathologic confirmation, a relatively short follow-up period and a small sample size. However, the results of this study seem to be important, considering the CSHs’ prompt response to SRS relatively soon after treatment and given the rarity of CSHs. Additionally, more than half of the patients in our series did not have cranial neuropathies. SRS treatment is controversial for incidentally found CSHs, but the efficacy and safety of SRS for the CSHs found in this study could be a rationale for treating incidentally found CSHs, especially small lesions that could be
treated with a relatively high radiation dose. Further studies should be conducted to define the natural history of CSHs and the long-term side effects of their treatment.
Conclusions SRS appears to be an effective and safe treatment modality for the management of CSHs and could be used as a primary treatment. In particular, a marginal dose greater than 14 Gy may be associated with remarkable tumor shrinkage and the complete remission of cranial neuropathies.
Conflict of interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Funding
No financial support or relationships.
References 1. Chou CW, Wu HM, Huang CI, Chung WY, Guo WY, Shih YH, Lee LS, Pan DH (2010) Gamma knife surgery for cavernous hemangiomas in the cavernous sinus. Neurosurgery 67(3):611–616. doi:10.1227/01.NEU.0000378026.23116.E6 (discussion 616) 2. Gonzalez LF, Lekovic GP, Eschbacher J, Coons S, Porter RW, Spetzler RF (2006) Are cavernous sinus hemangiomas and cavernous malformations different entities? Neurosurg Focus 21(1):e6 3. Linskey ME, Sekhar LN (1992) Cavernous sinus hemangiomas: a series, a review, and an hypothesis. Neurosurgery 30(1):101–108 4. Zhou LF, Mao Y, Chen L (2003) Diagnosis and surgical treatment of cavernous sinus hemangiomas: an experience of 20 cases. Surg Neurol 60(1):31–36 (discussion 36-37) 5. Ivanov P, Chernov M, Hayashi M, Nakaya K, Izawa M, Murata N, Kubo O, Ujiie H, Muragaki Y, Nakamura R, Iseki H, Hori T, Takakura K (2008) Low-dose gamma knife radiosurgery for
123
J Neurooncol
6.
7.
8.
9. 10.
11.
12.
13.
14. 15.
16.
cavernous sinus hemangioma: report of 3 cases and literature review. Minim Invasive Neurosurg 51(3):140–146. doi:10.1055/ s-2008-1065346 Lombardi D, Giovanelli M, de Tribolet N (1994) Sellar and parasellar extra-axial cavernous hemangiomas. Acta Neurochir (Wien) 130(1–4):47–54 Yao Z, Feng X, Chen X, Zee C (2006) Magnetic resonance imaging characteristics with pathological correlation of cavernous malformation in cavernous sinus. J Comput Assist Tomogr 30(6):975–979. doi:10.1097/01.rct.0000221953.06135.3e00004728200611000-00019 Suzuki K, Kamezaki T, Tsuboi K, Kobayashi E (1996) Dural cavernous angioma causing acute subdural hemorrhage–case report. Neurol Med Chir (Tokyo) 36(8):580–582 Mori K, Handa H, Gi H (1980) Cavernomas in the middle fossa. Surg Neurol 14(1):21–31 Meyer FB, Lombardi D, Scheithauer B, Nichols DA (1990) Extra-axial cavernous hemangiomas involving the dural sinuses. J Neurosurg 73(2):187–192. doi:10.3171/jns.1990.73.2.0187 Rigamonti D, Pappas CT, Spetzler RF, Johnson PC (1990) Extracerebral cavernous angiomas of the middle fossa. Neurosurgery 27(2):306–310 Shibata S, Mori K (1987) Effect of radiation therapy on extracerebral cavernous hemangioma in the middle fossa Report of three cases. J Neurosurg 67(6):919–922. doi:10.3171/jns.1987.67. 6.0919 Maruishi M, Shima T, Okada Y, Nishida M, Yamane K, Okita S (1994) Cavernous sinus cavernoma treated with radiation therapy–case report. Neurol Med Chir (Tokyo) 34(11):773–777 Jamjoom AB (1996) Response of cavernous sinus hemangioma to radiotherapy: a case report. Neurosurg Rev 19(4):261–264 Miserocchi G, Vaiani S, Migliore MM, Villani RM (1997) Cavernous hemangioma of the cavernous sinus. Complete disappearance of the neoplasma after subtotal excision and radiation therapy. Case report. J Neurosurg Sci 41(2):203–207 Shibata S, Fukushima M, Mori K, Tsujimura M, Yokoyama H (1987) Effect of radiation therapy on extracerebral cavernous hemangioma in the middle fossa. No Shinkei Geka 15(3):307–310
123
17. Iwai Y, Yamanaka K, Nakajima H, Yasui T (1999) Stereotactic radiosurgery for cavernous sinus cavernous hemangioma–case report. Neurol Med Chir (Tokyo) 39(4):288–290 18. Yamamoto M, Kida Y, Fukuoka S, Iwai Y, Jokura H, Akabane A, Serizawa T (2010) Gamma Knife radiosurgery for hemangiomas of the cavernous sinus: a seven-institute study in Japan. J Neurosurg 112(4):772–779. doi:10.3171/2009.6.JNS08271 19. Thompson TP, Lunsford LD, Flickinger JC (2000) Radiosurgery for hemangiomas of the cavernous sinus and orbit: technical case report. Neurosurgery 47(3):778–783 20. Nakamura N, Shin M, Tago M, Terahara A, Kurita H, Nakagawa K, Ohtomo K (2002) Gamma knife radiosurgery for cavernous hemangiomas in the cavernous sinus. Report of three cases. J Neurosurg 97(5 Suppl):477–480. doi:10.3171/jns.2002.97.sup plement5.0477 21. Peker S, Kilic T, Sengoz M, Pamir MN (2004) Radiosurgical treatment of cavernous sinus cavernous haemangiomas. Acta Neurochir (Wien) 146(4):337–341. doi:10.1007/s00701-0040231-6 (discussion 340) 22. Khan AA, Niranjan A, Kano H, Kondziolka D, Flickinger JC, Lunsford LD (2009) Stereotactic radiosurgery for cavernous sinus or orbital hemangiomas. Neurosurgery 65(5):914–918. doi:10.1227/01.NEU.0000356987.98197.71 (discussion 918) 23. Hori S, Hayashi N, Nomoto K, Sato H, Hayashi T, Nagai S, Nishikata M, Endo S (2010) Cavernous sinus cavernous hemangioma largely extending into the sella turcica and mimicking pituitary adenoma: case report. Neurol Med Chir (Tokyo) 50(4):330–332 24. Wang X, Mei G, Liu X, Dai J, Pan L, Wang E (2012) The role of stereotactic radiosurgery in cavernous sinus hemangiomas: a systematic review and meta-analysis. J Neurooncol 107(2):239–245. doi:10.1007/s11060-011-0753-8 25. Wang X, Liu X, Mei G, Dai J, Pan L, Wang E (2012) Phase II study to assess the efficacy of hypofractionated stereotactic radiotherapy in patients with large cavernous sinus hemangiomas. Int J Radiat Oncol Biol Phys 83(2):e223–e230. doi:10.1016/j. ijrobp.2011.12.051
CLINICAL STUDY
Stereotactic radiosurgery for cavernous sinus hemangiomas Sang Woo Song • Dong Gyu Kim • Hyun-Tai Chung Sun Ha Paek • Jung Ho Han • Yong Hwy Kim • Jin Wook Kim • Young-Hoon Kim • Hee-Won Jung
•
Received: 31 December 2013 / Accepted: 21 February 2014 Ó Springer Science+Business Media New York 2014
Abstract We performed this retrospective study to analyze the outcome of patients with cavernous sinus hemangioma (CSH) after stereotactic radiosurgery (SRS). We analyzed 19 patients with CSHs who were treated with SRS between 1998 and 2011. The median age of the patients was 50 years (range, 35–73 years), and 16 (84.2 %) of the patients were female. SRS was performed as a primary treatment for 18 patients and to treat a residual lesion after surgical resection in one patient. Nine (47.4 %) patients had cranial neuropathies in 14 cranial nerves before SRS, whereas five (26.3 %) patients were initially asymptomatic. The mean volume of the CSHs was 6.1 ± 7.2 cm3 (range, 0.3–32.3 cm3), and the median marginal dose at the 50 % isodose line was 14.5 Gy (range, 11.5–16.0 Gy). The mean follow-up period was 37 months (range, 12–85 months). At the last follow-up, the lesion volume had decreased in all patients. The average tumor volume had decreased to 26 % (range, 0–70 %) of the S. W. Song D. G. Kim (&) H.-T. Chung S. H. Paek J. H. Han Y. H. Kim J. W. Kim Y.-H. Kim H.-W. Jung Department of Neurosurgery, Seoul National University College of Medicine, 101 Daehang-ro Jongno-gu, Seoul 110-744, Korea e-mail: [email protected] S. W. Song Department of Neurosurgery, Konkuk University Medical Center, Seoul, Korea D. G. Kim H.-T. Chung S. H. Paek Y. H. Kim J. W. Kim H.-W. Jung Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea J. H. Han Y.-H. Kim Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
initial volume at the last follow-up MRI. The first followup MRI, performed 6.1 ± 1.0 months after the SRS, showed that the tumor volume had decreased to 41 % (range, 0–88 %) of the initial volume. All 14 of the cranial neuropathies observed before SRS had improved, with complete remission in 12 (85.7 %) cranial nerves and partial remission in two (14.3 %). There were no radiationinduced neuropathies or complications during the followup period. SRS appears to be an effective and safe treatment modality for the management of CSHs. Keywords Stereotactic radiosurgery Cavernous sinus hemangioma Tumor control Cranial neuropathy Cavernous sinus
Introduction Cavernous sinus hemangiomas (CSHs) are rare vascular tumors that account for 1–3 % of all lesions within the cavernous sinus [1–3]. These tumors are extra-axial, interdural, intra-sinus lesions that produce symptoms that result from progressive tumor growth and mass effect. Before the era of MRI, the radiological diagnosis of CSHs was not easy; thus, CSHs were often identified during surgery for lesions that were preoperatively diagnosed as meningiomas or schwannomas [3]. Before the 1980s, surgical mortality was as high as 38 % because of massive intraoperative bleeding from CSHs [3]. Even with recent advances in neurosurgical techniques, the complete removal of CSHs is often impossible, and cranial neuropathies become worse after surgery in approximately 80 % of patients [4]. Recently, stereotactic radiosurgery (SRS) has become an effective alternative to surgical resection and has been
123
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shown to be safe in terms of cranial neuropathies. Thus, we performed this study to evaluate the efficacy and safety of SRS in the management of CSHs, with a specific focus on clinical symptoms, including cranial neuropathies.
Methods Patient population In total, 21 consecutive patients with CSHs were treated with SRS in our two institutes (Seoul National University Hospital and Seoul National University Bundang Hospital) between 1998 and 2011. Two patients were excluded because they missed a follow-up MRI, although they showed clinical improvement within 1 month after SRS. Thus, a total of 19 patients were finally enrolled in this study. One patient had undergone surgical resection before SRS, and the remaining 18 patients underwent SRS as a primary treatment under the typical radiological diagnosis, as described elsewhere [1, 5–8]. Briefly, CSHs were diagnosed when brain MRI showed characteristic imaging findings, including the following: bright, high signal intensities on T2-weighted images; strong enhancement after contrast (diethylene triamine pentaacetate) injection; a round shape without a dural tail sign; and encasement of the internal carotid artery (ICA) without narrowing [1, 5– 8]. The study was approved by the Institutional Review Board of Seoul National University Hospital and Seoul National University Bundang Hospital (IRB Number: 9911-061-001). Stereotactic radiosurgery All patients underwent single-session SRS. This SRS was performed using the Leksell Gamma Knife (Elekta Instrument AB, Stockholm, Sweden), Model B, C or Perfexion. The Leksell Model G stereotactic frame (Elekta Instrument AB) was applied to the patient’s head under local anesthesia supplemented with intravenous conscious sedation. T1-weighted, three-dimensional, multiplanar, rapid-acquisition, gradient-echo MRI and a T2-weighted sequence were then obtained before and after gadolinium enhancement. The images were exported to a computer workstation for dose planning using Gamma PlanÒ software (Elekta Instrument AB). The radiosurgery isodose, maximum dose, and marginal dose were initially determined according to the tumor volume calculated during dose planning. Multiple isocenter planning was used to minimize the radiation exposure of the optic pathway and other critical neural structures.
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Follow-up The patients were usually followed up at 1, 3, 6 and 12 months after SRS and underwent annual clinical evaluations thereafter. The patients’ tumor volume was measured on follow-up images taken at 6, 12 months and annually after treatment. T2-weighted MR images were used to calculate the tumor volumes, which was measured by multiplying the sum of the areas contoured on each slice by the slice thickness. The tumor volume change was defined as the ratio of the follow-up tumor volume to the initial tumor volume. Management outcomes were evaluated with respect to the tumor control rate and neurologic deficits. Tumor control was classified as ‘‘remarkable shrinkage’’ (a tumor volume on follow-up images of \50 % of the volume on images taken at the time of radiosurgery), ‘‘minimal shrinkage’’ (a tumor volume 50–75 % of the tumor volume before SRS) or ‘‘stationary’’ (a tumor volume of 75–125 % of the tumor volume before SRS). ‘‘Tumor progression’’ covered all other circumstances. The outcome of a cranial neuropathy was considered ‘‘unfavorable’’ if a new cranial deficit appeared and persisted or if existing deficits were aggravated and persisted beyond the preoperative state until the last clinical followup. ‘‘Improvement’’ of a cranial neuropathy was defined as the disappearance of or improvement in any deficits without any unfavorable features. Other outcomes were regarded as ‘‘stationary’’.
Results Sixteen (84 %) patients were female, and three (16 %) were male. The median age of the patients at the time of SRS was 50 years (range, 35–73 years). Nine (47.4 %) patients presented with cranial neuropathies in 14 cranial nerves, and seven (36.8 %) presented with headache. In contrast, five (26.3 %) patients were initially asymptomatic. The mean clinical follow-up was 37 months (range, 12–85 months). The mean volume of the CSHs was 6.1 ± 7.2 cm3 (range, 0.3–32.3 cm3), and the median marginal dose at the 50 % isodose line was 14.5 Gy (range, 11.5–16.0 Gy). The median number of shots was 14 (range, 4–34 shots). The patients’ clinical characteristics and treatment parameters are summarized in Table 1. Tumor control in CSHs Tumor control was achieved in all patients during the follow-up period. Remarkable shrinkage was achieved in 17 (89.5 %) patients and minimal shrinkage was achieved in two (10.5 %) patients. Overall, the average tumor
J Neurooncol Tables 1 Summary of the characteristics of patients with cavernous sinus hemangiomas Case number
Age
Sex
Presenting symptom
Pre-SRS treatment
Marginal dose (Gy)
Tumor volume
1
59
M
Facial hypesthesia
none
14
7.9
66
33
84
2
63
F
Incidental finding
none
15
8.6
27
13
24
3 4
67 39
F F
Incidental finding Headache
none none
14 15
2.4 4.7
53 28
21 12
33 12
5
50
F
Headache
none
16
5.3
51
32
76
6
64
F
Headache
none
15
4.5
24
24
6
7
39
F
Ophthalmoplegia, ptosis
none
13
16.0
45
15
75
8
57
F
Ophthalmoplegia, ptosis
surgery
15
3.4
44
44
6
9
48
F
Headache
none
14
5.0
55
38
43
10
73
F
Incidental finding
none
14.5
4.8
67
41
39
11
64
F
Diplopia
none
15
3.5
19
21
6
12
47
F
Diplopia
none
14
3.0
24
7
30
13
40
M
Diplopia
none
11.5
32.3
65
52
22
14
61
F
Headache
none
15
3.1
70
70
6
15
45
F
Diplopia
none
14
3.5
49
31
14
16
54
F
Loss of consciousness
none
15
2.1
39
24
24
17
35
M
Diplopia
none
15
0.3
0
0
18
18 19
44 45
F F
Incidental finding Diplopia
none none
15 14
3.7 1.3
30 0
18 0
12 10
3
Initial (cm )
Post-SRS 6 months (%)
At the last follow-up (%)
Image follow up period (months)
Fig. 1 Graph showing postSRS volume changes in all patients. All 19 patients had early tumor shrinkage (within 6 months after SRS). The tumor volume gradually decreased over the follow-up period in all patients, and no transient volume expansion was observed. For nine patients, the follow-up period was more than two years
volume had decreased to 26 % (range, 0–70 %) of the initial volume at the last follow-up MRI. No patients experienced ‘‘tumor progression’’ until the final follow-up, and no tumor showed transient expansion after SRS. The first follow-up MRI, performed 6.1 ± 1.0 months after the SRS, showed that the tumor volume had decreased
to 41 % (range, 0–88 %) of the initial volume. Moreover, the tumor volume gradually decreased over the follow-up period in all patients (Fig. 1). In 15 patients who were followed for more than one year (range, 12–84 months) after SRS, the tumor volume had decreased to 22 % of the initial volume (range, 0–41 %).
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J Neurooncol Table 2 Summary of the outcomes of clinical symptoms, including cranial neuropathies, after stereotactic radiosurgery
CN cranial nerve
CN III
CN V
CN VI
Exophthalmos
Orbital pain
Headache
Number of patients
2
2
2
8
1
1
7
Partial remission
0
0
0
2
0
0
2
Complete remission
2
2
2
6
1
1
5
Average time to complete remission (months)
1
1
3.5
1
1
1
7
Clinical outcome of SRS for CSHs The most common presenting symptom was cranial neuropathy, affecting nine patients, followed by headache in five patients. Additionally, in five patients, CSHs were diagnosed incidentally. All preexisting symptoms were categorized as ‘‘improved’’ in all patients, and no adverse radiation effect was observed during the follow-up period. The clinical outcomes are summarized in Table 2. Among the nine patients with cranial neuropathies in 14 cranial nerves, eight had a 6th cranial nerve palsy, and two patients each had 3rd and 4th cranial nerve palsies. Additionally two patients had facial hypesthesia. All 14 of the cranial neuropathies that were observed before SRS improved, with complete remission in 12 (85.7 %) cranial nerves and partial remission in two (14.3 %) patients with a 6th cranial nerve palsy. In those patients with complete remission of their cranial neuropathies, complete symptom remission almost occurred within 1 month after SRS. However, in one patient, facial hypesthesia was completely resolved, even at seven months after SRS. Headache was observed in seven patients and was completely resolved in five patients (71 %). The mean period to complete remission was 7 months (range, 1–15 months). One patient had experienced exophthalmos and orbital pain, and the symptoms were completely resolved within 1 month after SRS.
Illustrative case of CSH A 39-year-old woman (Case No.7 in Table 1) presented with a three-year history of intermittent diplopia and a onemonth history of ptosis. Neurological examination revealed 3rd, 4th, 5th and 6th cranial nerve palsies, and the patient also complained of periorbital pain and exophthalmos. MRI showed a round mass with ICA encasement and bright, high signal intensities at the left cavernous sinus on T2-weighted images (Fig. 2). The measured tumor volume was 16.0 cm3. With a presumptive diagnosis of CHS, SRS was performed as a primary treatment for the patient’s cavernous sinus lesion, and 13 Gy was used as the
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CN IV
marginal dose. The patient’s symptoms had already disappeared by the one-month clinical follow-up after SRS. Six months after SRS, the tumor volume had decreased to 7.2 cm3 (45 % of the initial tumor volume), and at 75 months post-radiosurgery, the tumor size was 2.4 cm3 (15 % of the initial tumor volume). At the last clinical follow-up, diplopia was still observed in the left lateral gaze.
Discussion In the 1980s and 1990s, to overcome surgical mortality and morbidity, radiotherapy was used on the CSHs as an adjuvant treatment after incomplete surgical resection of the CSHs or as a neoadjuvant tool [9–14]. With the use of more than 3,000 cGy with fractionation, tumors were reduced in size and were controlled for a relatively long period [3, 11–13, 15, 16]. Based on the success of radiation therapy for CSHs, Iwai et al. [17] reported the first case of CSHs treated with SRS in 1999. Since then, SRS has become an alternative to surgery and/or radiotherapy for CSH management [1, 5, 18–24]. Recently, a meta-analysis reported that SRS is an effective and safe treatment option for patients with CSHs [24]. Tumor shrinkage was identified in more than 90 % of patients, and new cranial neuropathy developed in only 1.7 % of patients [24]. In our study, remarkable post-SRS tumor shrinkage was also identified. Shrinkage by more than 50 % of the initial tumor volume was observed in 17 (88 %) patients, and partial tumor shrinkage (from 25 to 49 % of the initial tumor volume) was observed in two (12 %) patients. Additionally, clinical symptoms were completely relieved relatively soon after SRS in the majority of patients. The high rate of remarkable tumor shrinkage in this study appears to be related to the high marginal dose (a median dose of 14.5 Gy) and small tumor volume (a mean tumor volume of 6.1 cm3). Although the mechanism of the tumor response after SRS is not well understood, the postSRS early symptomatic response could be explained by rapid volume reduction and subsequent mass effect relief after SRS. To obtain remarkable early tumor shrinkage of
J Neurooncol
Fig. 2 Case 7. Axial T2-weighted image showing a very large CSH in the left cavernous sinus (a). A follow-up image after six months showed marked tumor reduction (b). The tumor volume gradually
decreased in the 15- and 23-month follow-up images (c, d). At 50 months after SRS, the tumor volume had decreased to 20 % of the initial volume (e)
more than 50 % of the initial tumor volume, a higher dose than a 14 Gy marginal dose was suggested [24]. The high complete remission rate for cranial neuropathies in our study also appears to be associated with the early tumor shrinkage that resulted from using a relatively high radiation dose. However, the critical structures around the cavernous sinus, such as the optic apparatus, usually limit the use of high radiation doses, especially for the treatment of large CSHs. Interestingly, in a patient treated with a low marginal dose, 11.5 Gy, for a CSH with a tumor volume of 32.3 cm3, the tumor volume was reduced by only 35 % of the initial volume, and a lateral gaze palsy persisted in a partial remission state until distant follow-up. In fact, remarkable tumor shrinkage could be obtained using a relatively low marginal dose of 10–12 Gy [18, 20]. However, relatively high doses (more than 14 Gy) appear to be optimal for tumor control and symptom relief, as our study shows, because remarkable early tumor shrinkage appears to be related to the complete remission of cranial neuropathies. Therefore, hypofractionated stereotactic radiotherapy may be more effective for the treatment of large CSHs in terms of remarkable early tumor shrinkage and complete symptom remission [25]. Our study had several limitations such as a lack of pathologic confirmation, a relatively short follow-up period and a small sample size. However, the results of this study seem to be important, considering the CSHs’ prompt response to SRS relatively soon after treatment and given the rarity of CSHs. Additionally, more than half of the patients in our series did not have cranial neuropathies. SRS treatment is controversial for incidentally found CSHs, but the efficacy and safety of SRS for the CSHs found in this study could be a rationale for treating incidentally found CSHs, especially small lesions that could be
treated with a relatively high radiation dose. Further studies should be conducted to define the natural history of CSHs and the long-term side effects of their treatment.
Conclusions SRS appears to be an effective and safe treatment modality for the management of CSHs and could be used as a primary treatment. In particular, a marginal dose greater than 14 Gy may be associated with remarkable tumor shrinkage and the complete remission of cranial neuropathies.
Conflict of interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Funding
No financial support or relationships.
References 1. Chou CW, Wu HM, Huang CI, Chung WY, Guo WY, Shih YH, Lee LS, Pan DH (2010) Gamma knife surgery for cavernous hemangiomas in the cavernous sinus. Neurosurgery 67(3):611–616. doi:10.1227/01.NEU.0000378026.23116.E6 (discussion 616) 2. Gonzalez LF, Lekovic GP, Eschbacher J, Coons S, Porter RW, Spetzler RF (2006) Are cavernous sinus hemangiomas and cavernous malformations different entities? Neurosurg Focus 21(1):e6 3. Linskey ME, Sekhar LN (1992) Cavernous sinus hemangiomas: a series, a review, and an hypothesis. Neurosurgery 30(1):101–108 4. Zhou LF, Mao Y, Chen L (2003) Diagnosis and surgical treatment of cavernous sinus hemangiomas: an experience of 20 cases. Surg Neurol 60(1):31–36 (discussion 36-37) 5. Ivanov P, Chernov M, Hayashi M, Nakaya K, Izawa M, Murata N, Kubo O, Ujiie H, Muragaki Y, Nakamura R, Iseki H, Hori T, Takakura K (2008) Low-dose gamma knife radiosurgery for
123
J Neurooncol
6.
7.
8.
9. 10.
11.
12.
13.
14. 15.
16.
cavernous sinus hemangioma: report of 3 cases and literature review. Minim Invasive Neurosurg 51(3):140–146. doi:10.1055/ s-2008-1065346 Lombardi D, Giovanelli M, de Tribolet N (1994) Sellar and parasellar extra-axial cavernous hemangiomas. Acta Neurochir (Wien) 130(1–4):47–54 Yao Z, Feng X, Chen X, Zee C (2006) Magnetic resonance imaging characteristics with pathological correlation of cavernous malformation in cavernous sinus. J Comput Assist Tomogr 30(6):975–979. doi:10.1097/01.rct.0000221953.06135.3e00004728200611000-00019 Suzuki K, Kamezaki T, Tsuboi K, Kobayashi E (1996) Dural cavernous angioma causing acute subdural hemorrhage–case report. Neurol Med Chir (Tokyo) 36(8):580–582 Mori K, Handa H, Gi H (1980) Cavernomas in the middle fossa. Surg Neurol 14(1):21–31 Meyer FB, Lombardi D, Scheithauer B, Nichols DA (1990) Extra-axial cavernous hemangiomas involving the dural sinuses. J Neurosurg 73(2):187–192. doi:10.3171/jns.1990.73.2.0187 Rigamonti D, Pappas CT, Spetzler RF, Johnson PC (1990) Extracerebral cavernous angiomas of the middle fossa. Neurosurgery 27(2):306–310 Shibata S, Mori K (1987) Effect of radiation therapy on extracerebral cavernous hemangioma in the middle fossa Report of three cases. J Neurosurg 67(6):919–922. doi:10.3171/jns.1987.67. 6.0919 Maruishi M, Shima T, Okada Y, Nishida M, Yamane K, Okita S (1994) Cavernous sinus cavernoma treated with radiation therapy–case report. Neurol Med Chir (Tokyo) 34(11):773–777 Jamjoom AB (1996) Response of cavernous sinus hemangioma to radiotherapy: a case report. Neurosurg Rev 19(4):261–264 Miserocchi G, Vaiani S, Migliore MM, Villani RM (1997) Cavernous hemangioma of the cavernous sinus. Complete disappearance of the neoplasma after subtotal excision and radiation therapy. Case report. J Neurosurg Sci 41(2):203–207 Shibata S, Fukushima M, Mori K, Tsujimura M, Yokoyama H (1987) Effect of radiation therapy on extracerebral cavernous hemangioma in the middle fossa. No Shinkei Geka 15(3):307–310
123
17. Iwai Y, Yamanaka K, Nakajima H, Yasui T (1999) Stereotactic radiosurgery for cavernous sinus cavernous hemangioma–case report. Neurol Med Chir (Tokyo) 39(4):288–290 18. Yamamoto M, Kida Y, Fukuoka S, Iwai Y, Jokura H, Akabane A, Serizawa T (2010) Gamma Knife radiosurgery for hemangiomas of the cavernous sinus: a seven-institute study in Japan. J Neurosurg 112(4):772–779. doi:10.3171/2009.6.JNS08271 19. Thompson TP, Lunsford LD, Flickinger JC (2000) Radiosurgery for hemangiomas of the cavernous sinus and orbit: technical case report. Neurosurgery 47(3):778–783 20. Nakamura N, Shin M, Tago M, Terahara A, Kurita H, Nakagawa K, Ohtomo K (2002) Gamma knife radiosurgery for cavernous hemangiomas in the cavernous sinus. Report of three cases. J Neurosurg 97(5 Suppl):477–480. doi:10.3171/jns.2002.97.sup plement5.0477 21. Peker S, Kilic T, Sengoz M, Pamir MN (2004) Radiosurgical treatment of cavernous sinus cavernous haemangiomas. Acta Neurochir (Wien) 146(4):337–341. doi:10.1007/s00701-0040231-6 (discussion 340) 22. Khan AA, Niranjan A, Kano H, Kondziolka D, Flickinger JC, Lunsford LD (2009) Stereotactic radiosurgery for cavernous sinus or orbital hemangiomas. Neurosurgery 65(5):914–918. doi:10.1227/01.NEU.0000356987.98197.71 (discussion 918) 23. Hori S, Hayashi N, Nomoto K, Sato H, Hayashi T, Nagai S, Nishikata M, Endo S (2010) Cavernous sinus cavernous hemangioma largely extending into the sella turcica and mimicking pituitary adenoma: case report. Neurol Med Chir (Tokyo) 50(4):330–332 24. Wang X, Mei G, Liu X, Dai J, Pan L, Wang E (2012) The role of stereotactic radiosurgery in cavernous sinus hemangiomas: a systematic review and meta-analysis. J Neurooncol 107(2):239–245. doi:10.1007/s11060-011-0753-8 25. Wang X, Liu X, Mei G, Dai J, Pan L, Wang E (2012) Phase II study to assess the efficacy of hypofractionated stereotactic radiotherapy in patients with large cavernous sinus hemangiomas. Int J Radiat Oncol Biol Phys 83(2):e223–e230. doi:10.1016/j. ijrobp.2011.12.051
