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Stereotactic fractionated radiotherapy for the treatment of benign meningiomas
Int. J. Radiation Oncology Biol. Phys., Vol. 66, No. 4, Supplement, pp. S3–S6, 2006 Copyright © 2006 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/06/$–see front matter
doi:10.1016/j.ijrobp.2005.11.031
SRS/SRT SUPPLEMENT
STEREOTACTIC FRACTIONATED RADIOTHERAPY FOR THE TREATMENT OF BENIGN MENINGIOMAS CHARLES CANDISH, F.R.C.R.,* MICHAEL MCKENZIE, F.R.C.P.C.,* BRENDA G. CLARK, PH.D.,† ROY MA, F.R.C.P.C.,* RICHARD LEE, PH.D.,† EMILY VOLLANS, M.SC.,† JAMES ROBAR, PH.D.,‡ ERMIAS GETE, PH.D.,† AND MONTY MARTIN, F.R.C.P.C.§ *Departments of Radiation Oncology, †Medical Physics, and §Radiology, BC Cancer Agency, Vancouver, British Columbia, Canada; ‡Department of Medical Physics, Nova Scotia Cancer Centre, Halifax, Nova Scotia, Canada Purpose: To assess the use of stereotactic fractionated radiotherapy (SRT) for the treatment of meningiomas. Methods and Materials: Between April 1999 and October 2004, 38 patients underwent SRT. Of 34 patients (36 tumors) assessed, the median age was 53 years. The indication was primary treatment in 26 cases (no histology) and postoperative in 10 cases. The most common sites were cavernous sinus (17), optic nerve (6), and cerebellopontine angle (5). The median gross target volume and planning target volume were 8.9 cm3 and 18.9 cm3, respectively. Stereotactic treatment was delivered with 6-MV photons with static conformal fields (custom-made blocks, 9 patients, and micromultileaf collimator, 25 patients). Median number of fields was six. The median dose prescribed was 50 Gy (range, 45–50.4 Gy) in 28 fractions. The median homogeneity and conformality indices were 1.1 and 1.79, respectively. Results: Treatment was well tolerated. Median follow-up was 26 months with 100% progression-free survival. One patient developed an area of possible radionecrosis related to previous radiotherapy, and 2 men developed mild hypogonadism necessitating testosterone replacement. The vision of 5 of 6 patients with optic pathway meningiomas improved or remained static. Conclusions: Stereotactic fractionated radiotherapy for the treatment of meningiomas is practical, and with early follow-up, seems to be effective. © 2006 Elsevier Inc. Stereotactic radiotherapy, Meningioma, Micromultileaf collimator.
stereotactic fractionated radiotherapy (SRT), stereotactic radiosurgery, intensity-modulated radiotherapy (IMRT), and proton beam therapy have all been used for the treatment of benign meningiomas. These techniques have enabled improved conformation of the treatment volume to the target, which, for meningiomas, is often small, of complex shape, and close to critical structures such as the brainstem, pituitary, and optic chiasm. Stereotactic fractionated radiotherapy, in particular, combines the localization benefits of stereotactic radiosurgery with the radiobiologic benefits of fractionation. Using a relocatable stereotactic headframe for accurate immobilization and localization, image fusion for accurate target delineation and treatment planning with multiple, static, conformal noncoplanar beams, treatment plans with SRT are of high precision and conformality. Previous authors have demonstrated encouraging early results with SRT for base of skull meningiomas (7–9). We present our experience of SRT for the treatment of benign meningiomas using static conformal fields.
INTRODUCTION Meningiomas account for 13% to 26% of all intracranial neoplasms (1). The majority are benign (90%) and undoubtedly, for accessible meningiomas, the treatment of choice is surgical excision of the tumor and its dural tail with excellent local control rates (2). However, due to their location many meningiomas are unresectable despite advances in neurosurgical technique. Considerable debate remains as to the most optimal treatment for these patients (3). In the absence of symptoms, observation may be appropriate, but for patients with multiple cranial nerve palsies treatment is usually recommended to prevent symptomatic progression. Such patients commonly have either base of skull/cavernous sinus or optic pathway tumors. Treatment with radical radiotherapy for these patients has shown high rates of progression-free and overall survival and visual control (4 – 6). There have been dramatic changes in the last decade in radiation treatment planning techniques. Techniques such as Reprint requests to: Michael McKenzie, F.R.C.P.C., Radiation Therapy Program, BC Cancer Agency, 600 W 10th Ave, Vancouver, BC, Canada V5Z 4E6. Tel: (604) 877-6000; Fax: (604)
877-0505; E-mail: [email protected] Received July 27, 2005. Accepted for publication Nov 23, 2005. S3
S4
I. J. Radiation Oncology
●
Biology
●
Physics
Volume 66, Number 4, Supplement, 2006
Fig. 1. Planning magnetic resonance imaging of a patient with a bilateral cavernous sinus meningioma treated with seven fields to obtain conformation of the 90% isodose around the planning target volume (yellow contour). The brainstem as an organ at risk is also contoured (purple).
METHODS AND MATERIALS Between April 1999 and October 2004 38 patients underwent SRT. Four patients were excluded from analysis as circular arcs were used for treatment (2 patients) and the stereotactic component of the treatment was only as part of a boost (2 patients). Thirty-six tumors in 34 patients were treated. The median age was 53 years (range, 29 –76 years). The indication was primary therapy in 26 cases (no histology available but characteristic neuroradiology), immediately postoperatively in 4 cases, and at progression after previous surgery in 6 cases. When available, the histology was benign, graded as I on the World Health Organization scale (10). The tumor site was skull base in 23 cases (cavernous sinus 17, sphenoid 2, petro-clival 1, anterior clinoid 1, foramen magnum 1, supraclinoid 1), optic nerve in 6 cases, cerebellopontine angle in 5, olfactory groove in 1, and posterior tentorium in 1. For treatment planning and delivery, patients were immobilized in a relocatable stereotactic headframe (BrainLAB AG, Heimstetten, Germany) with associated bite-block, occipital impression, and facial Aquaplast. The planning computed tomography (CT) with contrast (Picker 5000; Marconi) included all six fiducial markers and orbits (slice thickness, 1.5–2 mm). A contrast-enhanced magnetic resonance imaging (MRI) was performed in the treatment position, and axial T1-weighted images postcontrast were used to fuse with the planning CT images. The gross tumor volume was contoured based on both MRI and CT appearances with a median volume of 8.9 cm3 (range, 0.6 –38.4 cm3). A margin of 2 mm was added to generate the planning target volume (PTV). The median PTV was 18.9 cm3 (range, 2.0 – 46.5 cm3). Treatment planning was undertaken using BrainSCAN software (versions 3.5–5.02; BrainLAB AG). The aim was to encompass 99% of the PTV by the 90% isodose using static conformal fields. Figures 1 and 2 show an example of a patient with a bilateral cavernous sinus meningioma treated with seven such fields. Treatment was delivered using 6-MV photons (Varian CL21EX). The median number of fields
used was six (range, 4 –10). Conformation was by means of custommade blocks in 9 cases (25%) and a micromultileaf collimator (m3) in 27 cases (75%). The median dose delivered was 50 Gy (range, 45 Gy–50.4 Gy) over 28 fractions (range, 25–29). The dose prescription point was 85% in 1 patient, 90% in 16 patients, and 100% in 19 patients. The Radiation Therapy Oncology Group conformality index (11) was calculated for each case (CI90% ⫽ Volume encompassing 90%/PTV). The median CI90% for this series was 1.79 (range, 0.98 – 3.52). The Radiation Therapy Oncology Group homogeneity index (11) defined as the ratio of maximum dose to prescription dose was calculated for each plan. The median homogeneity index was 1.06 (range, 1.01–1.18). Clinical follow-up involved 6-monthly review and
Fig. 2. Seven static fields using a micromultileaf collimator were used to treat the meningioma shown in Fig. 1.
SRT for benign meningiomas
MRI until 2 years and then annual follow-up and imaging thereafter. Full endocrine and ophthalmic follow-up is mandatory for our patients.
RESULTS The median follow-up was 26 months (range, 2 months to 58 months). During this period there have been no episodes of clinical or radiologic progression and 100% overall survival. Acute effects were minimal, with 10 patients reporting symptoms of a mild headache, 11 patients reporting minimal nausea, and 11 patients feeling mildly fatigued. Only 2 patients necessitated a prescription of corticosteroids for radiation-induced edema. There were no serious early side effects. With a median follow-up of only 26 months, late effects cannot as yet be fully assessed. At present, 2 patients have low testosterone levels (biotestosterone level at 2.8 nmol/L and ⬍1.2 nmol/L, respectively [normal ⬎2.9 nmol/L]). These patients were aged 52 and 66 years, respectively at the start of radiotherapy, and their site of disease was close to the pituitary fossa (right sphenoid and right cavernous sinus) such that the 90% isodose covered a significant proportion of the pituitary fossa. Due to these results and symptoms of lethargy, both have started testosterone replacement therapy. All other measures of pituitary function were normal. One patient, who received treatment for synchronous meningiomas (right cerebellopontine angle and posterior tentorium) and who had previous surgery and radiotherapy to the cerebellum (43.4 Gy in 28 fractions) for a low-grade glioma, has developed an abnormal area in the brachium pontis, which is being observed as possible radiation-induced change. The patient is well, however, with no radiologic evidence of necrosis. Of the 6 patients with optic nerve meningiomas (median follow-up, 28.5 months), 5 have controlled vision (3 improved, 2 static). One patient at 58 months has a minor decrease in ipsilateral acuity with associated retinal changes compatible with radiotherapy. MRI findings are stable with no evidence of progression of the primary tumor. DISCUSSION Radical radiotherapy using innovative techniques is undoubtedly effective for the treatment of inoperable or recurrent meningioma. This study, showing 100% progressionfree survival at a median follow-up of 26 months, is comparable to previous reports of stereotactic fractionated radiotherapy for meningiomas (7–9). Selch et al. (7) reported a 3-year progression-free survival of 97.4% in 45 patients treated for benign meningiomas of the cavernous sinus, using comparable planning techniques to our group. Jalali et al. (8) with a median follow-up of 21 months has reported no recurrences in 41 patients. Two of their patients developed hypopituitarism as in our study. The largest study to date has been by Debus et al. (9). A total of 189 patients with a median follow-up of 35 months have been followed. In patients with benign meningiomas local control was
●
C. CANDISH et al.
S5
excellent, with only 3 patients recurring. The median PTV for patients in this study was significantly higher than ours (52.5 cm3 vs. 18.9 cm3). Single fraction stereotactic radiosurgery has also been used extensively to treat skull base meningiomas with similar high levels of local control. Lee et al. (12) reported a series of 159 patients with cavernous sinus meningiomas treated with gamma-knife radiosurgery (median volume, 6.5 cm3) showing local control of 93% with a median follow-up of 35 months. Linear accelerator– based radiosurgery is equally effective. Shafron et al. (13) treated 70 benign meningiomas (mean PTV, 10.0 cm3) with a mean follow-up of 23 months showing a 100% control rate. In our study, although the tumor volumes were relatively small in comparison to previous SRT studies, the majority were in proximity to the optic apparatus, and thus, on this factor alone, patients were thought to be unsuitable for stereotactic radiosurgery. Other innovative radiotherapy techniques have also been used to treat meningiomas. IMRT allows improved conformation of the target as a result of the variance in the fluence across multiple beams. Uy et al. (14) treated 40 patients with predominately skull base meningiomas with IMRT. Cumulative 5-year progression-free survival was 93%. Pirzkall et al. (15) treated 20 patients with benign skull base meningiomas of complex shape. With a median follow-up of 36 months, there was 100% local control. The natural evolution of these radiotherapy planning techniques is to now consider intensity-modulated stereotactic radiotherapy utilizing the localization/immobilization benefits of the stereotactic frame and the potential conformation benefit of IMRT, for example with dynamic micromultileaf collimation (16, 17). In a replanning study of 10 patients with skull base meningiomas, Baumert et al. (17) described improved PTV coverage and a decrease in the dose to organs at risk with intensity-modulated stereotactic radiotherapy. Whether this has a therapeutic gain for patients is yet to be demonstrated. For this study, our measure of conformality was with the Radiation Therapy Oncology Group conformality index (CI90%). There are potential limitations with this definition, as this index does not account for the position of the PTV within the high-dose treatment area. These limitations are discussed in detail elsewhere (18, 19). However, as our planning protocol necessitates 99% coverage of the PTV by the 90% isodose, a geographical miss is unlikely. Therefore CI90% is valid, in our eyes, as a measure of conformality. The median CI90% in this series at 1.79 is comparable to previous reports (7). Longer follow-up is required to assess the late toxicity of SRT. Two patients in this series developed mild hypogonadism, which may have been related to the radiotherapy. Continued endocrine follow-up is recommended life-long for all patients. Indeed, in one retrospective review of postoperative radiotherapy for meningiomas (20), 5 of 140 patients developed complications 20 months or more after radiotherapy. In addition, the safety of IMRT needs to be confirmed. One patient in the study by Uy et al. of IMRT (14) developed fatal brainstem necrosis.
S6
I. J. Radiation Oncology
●
Biology
●
Physics
CONCLUSIONS This study has shown that SRT for the treatment of benign meningiomas is practical, safe, and with early follow-up seems to be effective. Although further follow-up
Volume 66, Number 4, Supplement, 2006
is required, this series complements previous work demonstrating the efficacy of SRT for base of skull and optic pathway meningiomas. Any therapeutic gain from other innovative planning techniques such as dynamic arcs or IMRT needs to be proven against SRT.
REFERENCES 1. Whittle I, Smith C, Navoo P, et al. Meningiomas. Lancet 2004;363:1535–1543. 2. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 1957;20: 22–39. 3. Mirimanoff R. New radiotherapy technologies for meningiomas: 3D conformal radiotherapy? Radiosurgery? Stereotactic radiotherapy? Intensity-modulated radiotherapy? Proton beam radiotherapy? Spot scanning proton radiation therapy. . .or nothing at all? Radiother Oncol 2004;71:247–249. 4. Nutting C, Brada M, Brazil L, et al. Radiotherapy in the treatment of benign meningiomas of the skull base. J Neurosurg 1999;90:823– 827. 5. Pourel N, Auque J, Bracard S, et al. Efficacy of external fractionated radiation therapy in the treatment of meningiomas: A 20 year experience. Radiother Oncol 2001;61:65–70. 6. Baumert B, Villa S, Studer G, et al. Early improvements in vision after fractionated stereotactic radiotherapy for optic nerve sheath meningioma. Radiother Oncol 2004;72:169 – 174. 7. Selch M, Ahn E, Laskari A, et al. Stereotactic radiotherapy for treatment of cavernous sinus meningiomas. Int J Radiat Oncol Biol Phys 2004;59:101–111. 8. Jalali R, Loughrey C, Baumert B, et al. High precision focused irradiation in the form of fractionated stereotactic conformal radiotherapy (SCRT) for benign meningiomas predominately in the skull base location. Clin Oncol 2002;14:103–109. 9. Debus J, Wuendrich M, Pirzkall A, et al. High efficacy of fractionated stereotactic radiotherapy of large base of skull meningiomas: Long term results. J Clin Oncol 2001;19:3547– 3553. 10. Louis DN, Scheithauer BW, Budka H, von Deimling A, Kepes JJ. Meningiomas. In: Kleihus P, Cavence WK, editors. Pathology and genetics of tumours of the nervous system: World
11. 12. 13. 14. 15.
16. 17.
18. 19. 20.
Health Organization classification of tumours. Lyons, France: IARC Press; 2000. p. 176 –184. Shaw E, Kline R, Gillin M, et al. Radiation Therapy Oncology Group: Radiosurgery quality assurance guidelines. Int J Radiat Oncol Biol Phys 1993;27:1231–1239. Lee JYK, Niranjan A, McInerney J, et al. Stereotactic radiosurgery providing long-term tumour control of cavernous sinus meningiomas. J Neurosurg 2002;97:65–72. Shafron DH, Friedman WA, Buatti JM, et al. Linac radiosurgery for benign meningiomas. Int J Radiat Oncol Biol Phys 1999;43:321–327. Uy NW, Woo SY, The BS, et al. Intensity-modulated radiation therapy (IMRT) for meningioma. Int J Radiat Oncol Biol Phys 2002;53:1265–1270. Pirzkall A, Debus J, Haering P, et al. Intensity-modulated radiotherapy (IMRT) for recurrent, residual, or untreated skull-base meningiomas: Preliminary clinical experience. Int J Radiat Oncol Biol Phys 2003;55:362–372. Benedict SH, Cardinale RM, Wu Q, et al. Intensity-modulated stereotactic radiosurgery using dynamic micro-multileaf collimation. Int J Radiat Oncol Biol Phys 2001;50:751–758. Baumert B, Norton I, Davis J. Intensity-modulated stereotactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominately in the skull base. Int J Radiat Oncol Biol Phys 2003;57:580 –592. Lomax NJ, Scheib SG. Quantifying the degree of conformity in radiosurgery treatment planning. Int J Radiat Oncol Biol Phys 2003;55:1409 –1419. Paddick I. A simple scoring ratio to index the conformity of radiosurgical treatment plans. J Neurosurg 2000;93(Suppl. 3):219 –222. Goldsmith BJ, Wara WM, Wilson CB, et al. Postoperative irradiation for subtotally resected meningiomas: A retrospective analysis of 140 patients treated from 1967 to 1990. J Neurosurg1994;80:195–201.
doi:10.1016/j.ijrobp.2005.11.031
SRS/SRT SUPPLEMENT
STEREOTACTIC FRACTIONATED RADIOTHERAPY FOR THE TREATMENT OF BENIGN MENINGIOMAS CHARLES CANDISH, F.R.C.R.,* MICHAEL MCKENZIE, F.R.C.P.C.,* BRENDA G. CLARK, PH.D.,† ROY MA, F.R.C.P.C.,* RICHARD LEE, PH.D.,† EMILY VOLLANS, M.SC.,† JAMES ROBAR, PH.D.,‡ ERMIAS GETE, PH.D.,† AND MONTY MARTIN, F.R.C.P.C.§ *Departments of Radiation Oncology, †Medical Physics, and §Radiology, BC Cancer Agency, Vancouver, British Columbia, Canada; ‡Department of Medical Physics, Nova Scotia Cancer Centre, Halifax, Nova Scotia, Canada Purpose: To assess the use of stereotactic fractionated radiotherapy (SRT) for the treatment of meningiomas. Methods and Materials: Between April 1999 and October 2004, 38 patients underwent SRT. Of 34 patients (36 tumors) assessed, the median age was 53 years. The indication was primary treatment in 26 cases (no histology) and postoperative in 10 cases. The most common sites were cavernous sinus (17), optic nerve (6), and cerebellopontine angle (5). The median gross target volume and planning target volume were 8.9 cm3 and 18.9 cm3, respectively. Stereotactic treatment was delivered with 6-MV photons with static conformal fields (custom-made blocks, 9 patients, and micromultileaf collimator, 25 patients). Median number of fields was six. The median dose prescribed was 50 Gy (range, 45–50.4 Gy) in 28 fractions. The median homogeneity and conformality indices were 1.1 and 1.79, respectively. Results: Treatment was well tolerated. Median follow-up was 26 months with 100% progression-free survival. One patient developed an area of possible radionecrosis related to previous radiotherapy, and 2 men developed mild hypogonadism necessitating testosterone replacement. The vision of 5 of 6 patients with optic pathway meningiomas improved or remained static. Conclusions: Stereotactic fractionated radiotherapy for the treatment of meningiomas is practical, and with early follow-up, seems to be effective. © 2006 Elsevier Inc. Stereotactic radiotherapy, Meningioma, Micromultileaf collimator.
stereotactic fractionated radiotherapy (SRT), stereotactic radiosurgery, intensity-modulated radiotherapy (IMRT), and proton beam therapy have all been used for the treatment of benign meningiomas. These techniques have enabled improved conformation of the treatment volume to the target, which, for meningiomas, is often small, of complex shape, and close to critical structures such as the brainstem, pituitary, and optic chiasm. Stereotactic fractionated radiotherapy, in particular, combines the localization benefits of stereotactic radiosurgery with the radiobiologic benefits of fractionation. Using a relocatable stereotactic headframe for accurate immobilization and localization, image fusion for accurate target delineation and treatment planning with multiple, static, conformal noncoplanar beams, treatment plans with SRT are of high precision and conformality. Previous authors have demonstrated encouraging early results with SRT for base of skull meningiomas (7–9). We present our experience of SRT for the treatment of benign meningiomas using static conformal fields.
INTRODUCTION Meningiomas account for 13% to 26% of all intracranial neoplasms (1). The majority are benign (90%) and undoubtedly, for accessible meningiomas, the treatment of choice is surgical excision of the tumor and its dural tail with excellent local control rates (2). However, due to their location many meningiomas are unresectable despite advances in neurosurgical technique. Considerable debate remains as to the most optimal treatment for these patients (3). In the absence of symptoms, observation may be appropriate, but for patients with multiple cranial nerve palsies treatment is usually recommended to prevent symptomatic progression. Such patients commonly have either base of skull/cavernous sinus or optic pathway tumors. Treatment with radical radiotherapy for these patients has shown high rates of progression-free and overall survival and visual control (4 – 6). There have been dramatic changes in the last decade in radiation treatment planning techniques. Techniques such as Reprint requests to: Michael McKenzie, F.R.C.P.C., Radiation Therapy Program, BC Cancer Agency, 600 W 10th Ave, Vancouver, BC, Canada V5Z 4E6. Tel: (604) 877-6000; Fax: (604)
877-0505; E-mail: [email protected] Received July 27, 2005. Accepted for publication Nov 23, 2005. S3
S4
I. J. Radiation Oncology
●
Biology
●
Physics
Volume 66, Number 4, Supplement, 2006
Fig. 1. Planning magnetic resonance imaging of a patient with a bilateral cavernous sinus meningioma treated with seven fields to obtain conformation of the 90% isodose around the planning target volume (yellow contour). The brainstem as an organ at risk is also contoured (purple).
METHODS AND MATERIALS Between April 1999 and October 2004 38 patients underwent SRT. Four patients were excluded from analysis as circular arcs were used for treatment (2 patients) and the stereotactic component of the treatment was only as part of a boost (2 patients). Thirty-six tumors in 34 patients were treated. The median age was 53 years (range, 29 –76 years). The indication was primary therapy in 26 cases (no histology available but characteristic neuroradiology), immediately postoperatively in 4 cases, and at progression after previous surgery in 6 cases. When available, the histology was benign, graded as I on the World Health Organization scale (10). The tumor site was skull base in 23 cases (cavernous sinus 17, sphenoid 2, petro-clival 1, anterior clinoid 1, foramen magnum 1, supraclinoid 1), optic nerve in 6 cases, cerebellopontine angle in 5, olfactory groove in 1, and posterior tentorium in 1. For treatment planning and delivery, patients were immobilized in a relocatable stereotactic headframe (BrainLAB AG, Heimstetten, Germany) with associated bite-block, occipital impression, and facial Aquaplast. The planning computed tomography (CT) with contrast (Picker 5000; Marconi) included all six fiducial markers and orbits (slice thickness, 1.5–2 mm). A contrast-enhanced magnetic resonance imaging (MRI) was performed in the treatment position, and axial T1-weighted images postcontrast were used to fuse with the planning CT images. The gross tumor volume was contoured based on both MRI and CT appearances with a median volume of 8.9 cm3 (range, 0.6 –38.4 cm3). A margin of 2 mm was added to generate the planning target volume (PTV). The median PTV was 18.9 cm3 (range, 2.0 – 46.5 cm3). Treatment planning was undertaken using BrainSCAN software (versions 3.5–5.02; BrainLAB AG). The aim was to encompass 99% of the PTV by the 90% isodose using static conformal fields. Figures 1 and 2 show an example of a patient with a bilateral cavernous sinus meningioma treated with seven such fields. Treatment was delivered using 6-MV photons (Varian CL21EX). The median number of fields
used was six (range, 4 –10). Conformation was by means of custommade blocks in 9 cases (25%) and a micromultileaf collimator (m3) in 27 cases (75%). The median dose delivered was 50 Gy (range, 45 Gy–50.4 Gy) over 28 fractions (range, 25–29). The dose prescription point was 85% in 1 patient, 90% in 16 patients, and 100% in 19 patients. The Radiation Therapy Oncology Group conformality index (11) was calculated for each case (CI90% ⫽ Volume encompassing 90%/PTV). The median CI90% for this series was 1.79 (range, 0.98 – 3.52). The Radiation Therapy Oncology Group homogeneity index (11) defined as the ratio of maximum dose to prescription dose was calculated for each plan. The median homogeneity index was 1.06 (range, 1.01–1.18). Clinical follow-up involved 6-monthly review and
Fig. 2. Seven static fields using a micromultileaf collimator were used to treat the meningioma shown in Fig. 1.
SRT for benign meningiomas
MRI until 2 years and then annual follow-up and imaging thereafter. Full endocrine and ophthalmic follow-up is mandatory for our patients.
RESULTS The median follow-up was 26 months (range, 2 months to 58 months). During this period there have been no episodes of clinical or radiologic progression and 100% overall survival. Acute effects were minimal, with 10 patients reporting symptoms of a mild headache, 11 patients reporting minimal nausea, and 11 patients feeling mildly fatigued. Only 2 patients necessitated a prescription of corticosteroids for radiation-induced edema. There were no serious early side effects. With a median follow-up of only 26 months, late effects cannot as yet be fully assessed. At present, 2 patients have low testosterone levels (biotestosterone level at 2.8 nmol/L and ⬍1.2 nmol/L, respectively [normal ⬎2.9 nmol/L]). These patients were aged 52 and 66 years, respectively at the start of radiotherapy, and their site of disease was close to the pituitary fossa (right sphenoid and right cavernous sinus) such that the 90% isodose covered a significant proportion of the pituitary fossa. Due to these results and symptoms of lethargy, both have started testosterone replacement therapy. All other measures of pituitary function were normal. One patient, who received treatment for synchronous meningiomas (right cerebellopontine angle and posterior tentorium) and who had previous surgery and radiotherapy to the cerebellum (43.4 Gy in 28 fractions) for a low-grade glioma, has developed an abnormal area in the brachium pontis, which is being observed as possible radiation-induced change. The patient is well, however, with no radiologic evidence of necrosis. Of the 6 patients with optic nerve meningiomas (median follow-up, 28.5 months), 5 have controlled vision (3 improved, 2 static). One patient at 58 months has a minor decrease in ipsilateral acuity with associated retinal changes compatible with radiotherapy. MRI findings are stable with no evidence of progression of the primary tumor. DISCUSSION Radical radiotherapy using innovative techniques is undoubtedly effective for the treatment of inoperable or recurrent meningioma. This study, showing 100% progressionfree survival at a median follow-up of 26 months, is comparable to previous reports of stereotactic fractionated radiotherapy for meningiomas (7–9). Selch et al. (7) reported a 3-year progression-free survival of 97.4% in 45 patients treated for benign meningiomas of the cavernous sinus, using comparable planning techniques to our group. Jalali et al. (8) with a median follow-up of 21 months has reported no recurrences in 41 patients. Two of their patients developed hypopituitarism as in our study. The largest study to date has been by Debus et al. (9). A total of 189 patients with a median follow-up of 35 months have been followed. In patients with benign meningiomas local control was
●
C. CANDISH et al.
S5
excellent, with only 3 patients recurring. The median PTV for patients in this study was significantly higher than ours (52.5 cm3 vs. 18.9 cm3). Single fraction stereotactic radiosurgery has also been used extensively to treat skull base meningiomas with similar high levels of local control. Lee et al. (12) reported a series of 159 patients with cavernous sinus meningiomas treated with gamma-knife radiosurgery (median volume, 6.5 cm3) showing local control of 93% with a median follow-up of 35 months. Linear accelerator– based radiosurgery is equally effective. Shafron et al. (13) treated 70 benign meningiomas (mean PTV, 10.0 cm3) with a mean follow-up of 23 months showing a 100% control rate. In our study, although the tumor volumes were relatively small in comparison to previous SRT studies, the majority were in proximity to the optic apparatus, and thus, on this factor alone, patients were thought to be unsuitable for stereotactic radiosurgery. Other innovative radiotherapy techniques have also been used to treat meningiomas. IMRT allows improved conformation of the target as a result of the variance in the fluence across multiple beams. Uy et al. (14) treated 40 patients with predominately skull base meningiomas with IMRT. Cumulative 5-year progression-free survival was 93%. Pirzkall et al. (15) treated 20 patients with benign skull base meningiomas of complex shape. With a median follow-up of 36 months, there was 100% local control. The natural evolution of these radiotherapy planning techniques is to now consider intensity-modulated stereotactic radiotherapy utilizing the localization/immobilization benefits of the stereotactic frame and the potential conformation benefit of IMRT, for example with dynamic micromultileaf collimation (16, 17). In a replanning study of 10 patients with skull base meningiomas, Baumert et al. (17) described improved PTV coverage and a decrease in the dose to organs at risk with intensity-modulated stereotactic radiotherapy. Whether this has a therapeutic gain for patients is yet to be demonstrated. For this study, our measure of conformality was with the Radiation Therapy Oncology Group conformality index (CI90%). There are potential limitations with this definition, as this index does not account for the position of the PTV within the high-dose treatment area. These limitations are discussed in detail elsewhere (18, 19). However, as our planning protocol necessitates 99% coverage of the PTV by the 90% isodose, a geographical miss is unlikely. Therefore CI90% is valid, in our eyes, as a measure of conformality. The median CI90% in this series at 1.79 is comparable to previous reports (7). Longer follow-up is required to assess the late toxicity of SRT. Two patients in this series developed mild hypogonadism, which may have been related to the radiotherapy. Continued endocrine follow-up is recommended life-long for all patients. Indeed, in one retrospective review of postoperative radiotherapy for meningiomas (20), 5 of 140 patients developed complications 20 months or more after radiotherapy. In addition, the safety of IMRT needs to be confirmed. One patient in the study by Uy et al. of IMRT (14) developed fatal brainstem necrosis.
S6
I. J. Radiation Oncology
●
Biology
●
Physics
CONCLUSIONS This study has shown that SRT for the treatment of benign meningiomas is practical, safe, and with early follow-up seems to be effective. Although further follow-up
Volume 66, Number 4, Supplement, 2006
is required, this series complements previous work demonstrating the efficacy of SRT for base of skull and optic pathway meningiomas. Any therapeutic gain from other innovative planning techniques such as dynamic arcs or IMRT needs to be proven against SRT.
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