0360-3016190 $3.00 + .OO CopyrIght !e’1990 Pergamon Press plc
Int. .I Rudrol~un Oncolo~,~ Bid Phys, Vol. 19. PP. lO?l-1026 Pnnted in the U.S.A. All rights reserved.
0 Technical Innovations and Notes STEREOTACTIC SINGLE HIGH DOSE RADIATION THERAPY OF BENIGN INTRACRANIAL MENINGIOMAS
RITA ENGENHART,
M.D.,’
BERND WOWRA,
BERNHARD N. KIMMIG, M.D.,3
M.D.,
VOLKER STURM, M.D.,4
PH.D.,’ KARL-HEINZ
GERHARD VAN KAICK, M.D.’
AND MICHAEL WANNENMACHER, ‘University
HOVER, PH.D.,*
M.D.,
M.D.’
Clinic of Radiology. Dept. Radiotherapy. 6900 Heidelberg: 2German Cancer Research ‘University Clinic of Neurosurgery. Heidelberg: and %niversity Clinic of Neurosurgery,
Center, Heidelberg: Cologne
Seventeen patients with intracranial meningiomas were treated with single high dose irradiation at the German Cancer Research Center in Heidelberg. Indications for radiosurgery includedunresected tumors, gross disease remaining despite surgery, and recurrences. Therapy was carried out by a technique using multiple non-coplanar arc irradiations from a 15 MeV linear accelerator. This technique coupled with secondary tungsten collimators allowed a high concentration of the dose in the target volume with an extremely steep dose gradient at the field borders. The patients were treated with a single irradiation dose ranging from 10 to 50 Gy (mean of 29 Gy). Four of 17 patients died: one death was tumor-related and not attributable to the treatment, one died of a treatment related complication, and two patients died of intercurrent diseases. The remaining 13 of the 17 patients with a median follow-up time of 40 months have no evidence of tumor relapse. Late severe side effects include five patients with a large area of brain edema, three of which were concurrent with tumor necrosis. We conclude from these initial data that single high doses of irradiation concentrated to the tumor volume by stereotaxic methods can achieve local tumor control. It is also clear from these data that the effective therapeutic dose range must be better defined. Radiosurgery, Stereotaxic
radiation, High dose irradiation, Meningiomas.
INTRODUCTION
The results of Taylor rt al. (I 8) as well as those of other groups (2, 9, 15, 19) have clearly demonstrated that postoperative radiation therapy improves long-term local control of subtotal resected or recurrent meningiomas. The actuarial determinate survival rate was also significantly improved by postoperative radiation therapy. Taylor et a/. reported a 1O-year survival rate of 8 1% for patients who received postoperative radiation therapy compared with 49% for patients in the non-irradiated group with subtotal resection. The 1O-year survival rate for treatment of recurrence was 89% for patients who received radiation compared with 43% for reoperated patients without additional radiation therapy. Our study differs from other reports in that we have treated our patients with a single high dose of radiation delivered stereotactically to the tumor volume. Note that
Meningiomas constitute approximately 15% of all intracranial and 25% of all intraspinal neoplasms. They are most commonly detected in the fifth decade of life and there is a clear predominance in women ( 12, 2 1). Standard treatment is surgical resection. Some meningiomas, especially those in the sphenoidal ridge or parasellar regions, recur even when extirpation seems to be complete. Following surgery alone, the probability of recurrence after complete resection has been reported as 710% at 5 years and 20-22% at 10 years. After incomplete removal, the rate of recurrence increases to 26-37% at 5 years and 55-74% at 10 years. Fifteen years after subtotal resection, only 9% are free of recurrence without adjuvant therapy (1, 2, 10).
Presented at the 3 1st Annual Meeting of the American Society for Therapeutic Radiology and Oncology. San Francisco, CA, l-6. October 1989. Reprint request to: Rita Engenhart M.D.. Radiologische
Universitatsklinik, Abt. Strahlentherapie, Im Neuenheimer 400, D-6900 Heidelberg, FRG. Accepted for publication 26 April 1990.
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1. J. Radiation Oncology 0 Biology 0 Physics
the patient population in this study had an extraordinarily unfavourable prognosis since all patients had a macroscopical tumor residual and 6 of 17 patients were unresectable. In this paper we review the results from 17 patients with meningiomas who were treated by this method.
METHODS
AND
MATERIALS
We used a commercial 15 MeV linear accelerator* which had been mechanically adjusted so that the stereotactically defined coordinates could be equated with a high degree of accuracy to the isocenter of a multiple noncoplanar arc irradiation (5). After vertical gantry rotation through an arc of 140”, the treatment couch with the patient rotated horizontally through the isocenter. Secondary cylindrical tungsten collimators+ were used to reduce the penumbra and were adaptable to target volumes with field diameters ranging from 10 to 54 mm. The superposition of the multiple irradiation fields delivers spherical dose distributions with steep dose gradients (7-l 5%/mm) at the margin of the target volume (5. I 1). If the calculated spherical dose distribution was unsatisfactory, an additional collimator of different diameter and an additional isocenter could be chosen until only the tumor volume was covered in an acceptable manner (Fig. 1). During the diagnostic and therapeutic procedure. the patient’s skull was firmly fixed in a Riechert-Mundinger stereotactic head frame.+ A CT-adapted localization device+ attached to the base ring allowed the stereotactic coordinate system to be calculated ( 17). For 3-dimensional treatment planning, thin CT-slices (~2 mm) had to be taken from the region between the skull base and the top of the head. A computer program* allowed the precise calculation of the target point coordination and the definition of target volume, collimator size. and isodose distribution (13). Once the tumor localization procedures were completed. the patient was transferred to the treatment couch of the linear accelerator. A removable target positioning device+ fitted to the base ring allowed the target point to be adjusted to the isocenter of the irradiation facility within stereotactic precision (I 1 mm).’ Patient srlrction A total of 17 patients with diagnoses of intracranial meningiomas were treated with a single high dose stereotactic irradiation. Histological results were available in all patients. Confirmation of benign meningioma was obtained in all 17 patients. The series included 14 females and 3 males with ages varying from 41 to 74 years with a mean age of 54 years. The locations of the intracranial meningioma are summarized in Table 1, and the distri* Mevaton
77, Siemens AG. Erlangen, West Germany. + Available by F. L. Fischer, Freiburg, West Germany. * STP planning system distributed by F. L. Fischer. Freiburg, West Germany.
October 1990. Volume 19. Number 4
bution of patients in Table 2. Four patients had unresectable meningiomas located in the petroclival area and in the sphenoid ridge. Of 13 patients who had undergone previous surgery, 6 were known to have had gross residual tumor masses after primary resection and 7 were referred with recurrences. In two cases. the patient was referred for irradiation of unresectable recurrences. Two patients had undergone a second partial resection. Two patients were referred for additional irradiation after three and four subtotal resections. Another patient was referred for post surgical irradiation after six recurrences and seven subtotal resections. All 17 patients with intracranial meningiomas were treated with single high doses under stereotactic conditions. Four patients received radiosurgery as initial therapy for unresectable meningiomas and two patients for unresectable recurrences. Six patients were irradiated in the postoperative period lasting until 6 months after surgery, and five patients were irradiated after 1 to 7 subtotal resections for recurrent disease. The maximum single dose within the tumor volume ranged from 10 to 50 Gy with a mean dose of 29 Gy. The collimators were set for each treatment so that the 80% isodose contours matched the outline ofthe target volume. The individual dose chosen depended on tumor volume. localization. and radiosensitivity of critical structures in the vicinity of the tumor. The mean field diameter was 40 mm and ranged from 18 to 52 mm. To minimize the risk of radiation-induced damage to surrounding healthy brain tissue, in four patients second and in one patient a third isocenter and collimators were used to adapt the tumor volume to the target volume. The entire treatment, including the CT-examination and 3-D planning procedure, usually took 3 to 4 hr depending on the shape of the target volume, the number of collimators used, and the size of the collimator opening. The stereotaxic photon beam irradiation procedure normally lasted about 30 minutes. All patients received a prophylactic administration of 20 mg steroids dexamethasone 2 hr before being irradiated. The patients were discharged from hospital 2 days after treatment.
RESULTS CT or MRI follow-up examinations were performed periodically. An increase in tumor mass visualized on CT or MRI was taken as evidence of recurrent disease. The median follow-up period after irradiation was 40 months (ranging from I to 60 months). If the four early deaths are excluded, the remaining 13 patients have a disease free follow-up period of more than 32 months (ranging from 32-60 months). One patient with a large inoperable q Fischer Co. Ltd.. Freiburg. West Germany.
Single high dose irradiation of meningiomas 0 R. ENCENHART etul.
(4
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I. J. Radiation Oncology 0 Biology 0 Physics
Table 1. Intracranial sites of 17 meningiomas treated by radiosurgery Tumor
site
No. of patients
Sphenoid ridge Parasellar region Clivus and brainstem Falx Optic nerve sheath Ccrcbellar pontine angle
8 3 2 9 ;
I 17
Total
meningioma located in the petroclival area died I month after radiosurgery from inferior herniation attributed to a VP shunt occlusion. At the time of referral, this patient was in very poor clinical condition and thus received a maximum dose of I2 Gy to a target volume of about 30 cm3. Another patient died of a treatment-related complication. This patient was suffering from a large recurrence located in the parasellar region. A maximum target dose of 35 Gy was delivered to a volume of 73.6 cm3. A large perifocal edema was detected by CT 4 months later. The neurological symptoms increased progressively and the patient died 8 months after therapy from herniation attributable to radiation induced tumor necrosis. The deaths of the two other patients were neither tumor- nor treatment-related. One patient died from coronary infarction 23 months after treatment. The patient with multiple recurrences and seven operations died from pseudomona sepsis 3 months after radiation therapy. The remaining I3 patients treated for intracranial meningioma are alive and free of clinical and radiographic signs of tumor regrowth. CT or MRI scanning has verified either a stability (1 1 cases) or a gradual decrease in tumor size (2 cases). Five out of seven treated with radiosurgery for gross disease had a partial resection of the recurrence. The clinical course of these patients is summarized in Table 3. Acute treatment-related discomfort included headaches, nausea (which subsided usually within 2 days after treatment), and a temporary alopecia. Late complications occurred in eight patients between 5 and 18 months. Transient neurological deprivation was recorded in five patients between 5 and 8 months and in two patients could be attributed to a reversible perifocal edema. Two additional patients had persistent perifocal edema probably related to the radiation-induced tumor necrosis. These two patients are being treated with 6-12 mg dexamethasone daily. and are currently free of neurological problems. Six months after the radiation treatment another patient who was referred with a third recurrence complained of head-
Fig. I. Transverse,
coronal
and sagittal CT-reconstructions
October 1990. Volume 19. Number
4
aches, vomiting, hemianaesthesia. and a spastic hemiparesis. A CT scan taken at time of neurologic deterioration revealed an expansive lesion with hypo- and hyperdensity areas. One field of 30 mm in diameter was selected for treatment and 50 Gy was stereotaxically delivered in a single dose. The neurological deficiencies increased progressively despite treatment with steroids and surgical intervention was necessary. Histological examination of the surgical specimen revealed a radionecrosis of brain parenchyma around the treated necrotic tumor. After surgery, there has been a progressive improvement in neurologic function and the patient continues to lead a productive life. Another patient with a recurrence involving the optic nerve who had decreased visual acuity after surgery lost total vision 5 months after irradiation. This patient had received a maximum of 35 Gy to a target volume of 10.5 cm3 and has remained recurrence free for 50 months. DISCUSSION 11 tracranial meningiomas are generally benign, wellbounded. and slow-growing tumors. The location of the tumor determines the clinical complaints as well as the surgical accessibility. Over 90% of intracranial meningiomas are located supratentorially. The standard treatment for meningiomas is complete resection. Simpson first described five different grades of resection. From complete macroscopic excision (grade 1) to decompression or biopsy (grade 5) ( 14). Local control and long-term survival correlate well with this Simpson-grade. Recurrence rates after complete resection increases with time form 7%) after 5 vears to 32% after IO years, for incomplete removal from ;6% after 5 vears to 74% after IO years. About 10% of all diagnosed meningiomas are unresectable and are. for that reason, suitable for primary radiotherapy. However. meningiomas generally are regarded as poorly responsive to radiation therapy. Several articles with controversial results have been reported in recent years. King et al. reported little therapeutic benefit of radiation therapy to unresectable meningiomas (6). In contrast, Taylor et ul. ( 18) reported a recurrence rate after subtotal resection alone of 69%~ ( 19/29) which was reduced to 15% (3/l 3) by postoperative radiation therapy. Taylor et al. ( 18) further showed that in patients who received surgery alone for recurrent meningiomas. the local control rate was 30% after IO years. For patients who received additional radiation after resection, the local control rate was 89%. These data as well as other retrospective studies (3, 19. 20) have clearly shown that radiation therapy following subtotal resection or given for the treatment of recurrences
of a meningioma
located in the sphenoid
CT-slices show the fixation of the patient in the stereotactic head frame and the CT-localization
ridge. The
device used for
calculation of the stereotactic coordinates. The target volume is outlined by white points. Two different collimators focused to different isocenters were used to fit the treatment volume close to the target volume. The 80%~isodose contour surrounds the target volume. The isodose contours displayed are 80%. 50% and 30%.
Single high dose irradiation of meningiomas 0 R.
delays or prevents further recurrences and in turn has a favorable effect on absolute survival. Our experience with 17 intracranial benign meningiomas differs with regard to the radiation technique. Normally, a dose of 50 to 55 Gy in daily fractions of 1.8 Gy or 2 Gy is delivered and well-tolerated by the normal brain tissue. In this series of patients. percutaneous single high doses ranging from a maximum of 10 to 50 Gy were applied under stereotactic conditions with collimated narrow beams. The precise stereotactic localization of the tumor and a steep dose gradient outside the target volume allowed the administration of high doses with a reduced probability of damage to adjacent normal brain tissue. Certainly the patient population in this study had an extraordinarily unfavourable prognosis. All patients had a macroscopical tumor residual, of which 7 patients underwent 2 to 7 subtotal excisions for recurrent diseases and 6 of 17 patients were unresectable at time of irradiation. The majority of recurrences are clinically and radiographically manifested between the 2nd and 4th year postoperatively. Therefore, with the current median follow-up period in our study of just 40 months. we cannot draw any hard conclusions concerning arrest, remission. or recurrence-free survival. We can conclude, however. that in our series of patients. the meningiomas responded to single high irradiation doses at least on a par with what might be expected from conventional fractionated irradiation. The high rate oftumor necrosis observed indicates that the stereotaxic delivery and the dose of radiation were effective. However, the rate of brain damage seems relatively high in our study when compared to that observed in the treatment of arteriovenous malformations (AVM) in which similar or higher doses were used (3,4, 7, 8, 16). This might not be expected in view of the steep fall-off in
Table 2. Patient distribution and resection type according Simpson’s classification ( 18) No. of patients Average age (years) Primary disease Unresectable disease (grade 5) Partial resection (grade 4) Recurrent disease Unresectable disease (grade 5) Partial resection (grade 4)
to
l7(f= l4.m=3) 54 (4 I-74) 10 4 6 7 2 5
1025
ENGENHART rt al.
Table 3. Time to relapse after surgery compared with outcome after radiosurgery
No. of patient
1 2 3 4 5 6 7
No. of recurrence (months) 6 1 2 2
I 1 3
Time to relapse after surgery
Simpson grade of resection
Follow-up after RT (months)
5 IO 13 14 39 58 60
4 4 4 5 4 5 4
3 ID 8TR 36 RF 45 RF 50 RF 33 RF 41 RF
ID = Intercurrent death: TR = Treatment lapse free survival: RT = Radiation therapy.
related: RF = Re-
dose at the margins of the target volume. Thus one explanation might be that the chosen target volume included a significant amount of healthy brain parenchyma. However, the dose of radiation as well as the target volume are probably not the only factors contributing to these late effects. Prior surgery, anatomic location, and the presence or absence of neurological deficits are also parameters that should be taken into consideration. The tissues in and around an arteriovenous malformation may be nonfunctional and sclerotic as implied by a surrounding gliosis, and therefore less radiosensitive. Additionally, as larger meningiomas have a tendency to have a central necrosis, the brain blood barrier may be compromised, leading to an increased incidence of edema before therapy and as seen in one patient, a possible increase in intensity following radiation. This does not occur with AVM’s because there is no tendency for central necrosis. Based on our present experience, intracranial meningiomas can be treated by high single radiation therapy with good expectations for prolonged disease-free survival. It is still too early to draw definitive conclusions regarding the optimum dose and target volume. However, based on our results and within the framework of a limited 3-year follow-up. single doses of 20 to 30 Gy are sufficient to arrest further tumor growth. As radiation-induced complications are no doubt related to dose and target volume. to minimize the rate of undue neurologic side effects. we currently avoid single doses above 30 Gy and a target volume larger than 40 cm3. For enlarged meningiomas, conventional fractionated radiation therapy should be considered.
REFERENCES I. Adegbite,
A. B.; Khan, M. 1.; Paine, K. W. E.: Tan, L. K. The recurrence of intracranial meningiomas after surgical treatment. J. Neurosurg. 58:5 1-56; 1983. 2. Carella, R. J.: Ransohoft. J.; Newall, J. Role of radiation therapy in the management of meningioma. Neurosurgery 10:332-339; 1980.
3. Engenhart, R.; Kimmig, B.: Wowra, B.; Sturm. V.; Hover, K. H.; Schneider, S.; Wannenmacher, M. Stereotaktische Einzeitbestrahlung cerebraler Angiome. Radiologe 29:2 19223; 1989. 4. Fabrikant, J. I.; Lymann. J. T.: Hosobuchi, Y. Stereotactic heavy-ion Bragg peak radiosurgery for intracranial vascular
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5.
6.
7.
8. 9.
10.
1L.
12.
13.
I. J. Radiation Oncology ??Biology 0 Physics
disorders: method for treatment of deep arteriovenous malformations. Br. J. Radio]. 57:479-490: 1984. Hartmann, G. H.; Schlegel, W.; Sturm, V.: Kober. B.; Pastyr. 0.; Lorenz. W. J. Cerebral radiation surgery using moving field irradiation at a linear accelerator facility. Int. J. Radiat. Oncol. Biol. Phys. 11:1185-1192: 1985. King, D.; Chang, C.: Pool, J. Radiotherapy in the management of meningiomas. Acta Radio]. Ther. Phys. Biol. 5:2633: 1966. Kjellberg. R. N.; Davis. K. R.; Lyons, S. L.; Butler, W.: Adams. R. D. Bragg peak proton-beam therapy for arteriovenous malformations of the brain. Clin. Neurosurg. 3 1: 248-290; 1983. Leksell. L. The stereotaxic method and radiosurgery of the brain. Acta Chir. Scan. 1023 16-3 19; 195 1. Mesic, J.: Hanks. G.: Doggett, S. The value of radiation therapy as an adjuvant to surgery in intracranial meningiomas. Am. J. Clin. Oncol (CCT) 9(4):337-340; 1986. Mirimanoff, R.: Dosoretz. D.: Linggood, R.; Ojemann. R.: Martuza. R. Meningioma analysis of recurrence and progression following nemosurgical resection. J. Neurosurg. 62: 18-24: 1985. Rhein, B.: Klevenz, N.: Mlurer. K.; Hover, K. H.; Lorenz, W. J. Dosimetrische Eigenschaften von 15 MeV Photonen bei der Ausblendung kleiner Felder ( IO-40 mm) fur die externe stereotaktische Bestrahlung. In: Bergmann, H. S., ed. Medizinische Physik 87 Annual Scientific Meeting. ISBN 3-9252 18-04-I. NC: Deutsche Gesellschaft fur Medizinische Physik; 1987:655-660. Russel, D. S.; Rubenstein. L. J. Pathology of tumors of the nervous system, 4th edition. London: Edward Arnold: 1977: 66-9 I. Schlegel, W.: Scharfenberg. H.: Doll, J.; Hartmann. G.;
October 1990. Volume 19. Number 4
14.
15.
16.
17.
18.
19.
20.
21.
Sturm, V.; Lorenz, W. J. Three dimensional dose planning using tomographic data. In: Proc. of the Eight Int. Conference on the Use of Computers in Radiation Therapy IEEE Comp. Society. Silver Spring, MD: IEEE Comp. Sot. Press; 1984:191-196. Simpson, D. The recurrence of intracranial meningiomas after surgical treatment. J. Neurol. Neurosurg. Psychiat. 20: 22-39; 1957. Solan. M.: Kramer, S. The role of radiation therapy in the management of intracranial meningiomas. Int. J. Radiat. Oncol. Biol. Phys. 11:675-677; 1985. Steiner, L. Radiosurgery in cerebral arteriovenous malformation. In: Fein, J.. Flamm. E., eds. Textbook of cerebrovascular, Vol. 4, Surgery. Berlin, Heidelberg, New York: Springer Verlag; 1986:l 161-1215. Sturm. V.; Pastyr. 0.: Schlegel, W.; Scharfenberg. H.; Zabel. H. J.; Netzeband. G.; Schabbert, S.; Berberich, W. Stereotactic computer tomography with a modified RiechertMundinger device as the basis for integrated stereotactic neuroradiological investigations. Acta Neurochir. 64:87102: 1983. Taylor, B.: Marcus, R.: Friedman, W.; Ballinger, W.: Million. R. The meningioma controversy: postoperative radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 15:299-304; 1988. Wara. W. M.; Sheline, G. E.: Newmann, H.: Tonsend, I.: Boldrey, E. Radiation therapy of meningiomas. Am. J. Rontgenol. 123:453-458: 1975. Yamashita. J.: Handa. H.; Iwaki, K.; Abe, M. Recurrence of intracranial meningiomas, with special reference to radiotherapy. Surg. Neural. 14:33-40: 1980. Ziilch, K. J. Brain tumors. Their biology and pathology, 2nd edition. New York: Springer-Pub. Co.: 1965: 187.
Int. .I Rudrol~un Oncolo~,~ Bid Phys, Vol. 19. PP. lO?l-1026 Pnnted in the U.S.A. All rights reserved.
0 Technical Innovations and Notes STEREOTACTIC SINGLE HIGH DOSE RADIATION THERAPY OF BENIGN INTRACRANIAL MENINGIOMAS
RITA ENGENHART,
M.D.,’
BERND WOWRA,
BERNHARD N. KIMMIG, M.D.,3
M.D.,
VOLKER STURM, M.D.,4
PH.D.,’ KARL-HEINZ
GERHARD VAN KAICK, M.D.’
AND MICHAEL WANNENMACHER, ‘University
HOVER, PH.D.,*
M.D.,
M.D.’
Clinic of Radiology. Dept. Radiotherapy. 6900 Heidelberg: 2German Cancer Research ‘University Clinic of Neurosurgery. Heidelberg: and %niversity Clinic of Neurosurgery,
Center, Heidelberg: Cologne
Seventeen patients with intracranial meningiomas were treated with single high dose irradiation at the German Cancer Research Center in Heidelberg. Indications for radiosurgery includedunresected tumors, gross disease remaining despite surgery, and recurrences. Therapy was carried out by a technique using multiple non-coplanar arc irradiations from a 15 MeV linear accelerator. This technique coupled with secondary tungsten collimators allowed a high concentration of the dose in the target volume with an extremely steep dose gradient at the field borders. The patients were treated with a single irradiation dose ranging from 10 to 50 Gy (mean of 29 Gy). Four of 17 patients died: one death was tumor-related and not attributable to the treatment, one died of a treatment related complication, and two patients died of intercurrent diseases. The remaining 13 of the 17 patients with a median follow-up time of 40 months have no evidence of tumor relapse. Late severe side effects include five patients with a large area of brain edema, three of which were concurrent with tumor necrosis. We conclude from these initial data that single high doses of irradiation concentrated to the tumor volume by stereotaxic methods can achieve local tumor control. It is also clear from these data that the effective therapeutic dose range must be better defined. Radiosurgery, Stereotaxic
radiation, High dose irradiation, Meningiomas.
INTRODUCTION
The results of Taylor rt al. (I 8) as well as those of other groups (2, 9, 15, 19) have clearly demonstrated that postoperative radiation therapy improves long-term local control of subtotal resected or recurrent meningiomas. The actuarial determinate survival rate was also significantly improved by postoperative radiation therapy. Taylor et a/. reported a 1O-year survival rate of 8 1% for patients who received postoperative radiation therapy compared with 49% for patients in the non-irradiated group with subtotal resection. The 1O-year survival rate for treatment of recurrence was 89% for patients who received radiation compared with 43% for reoperated patients without additional radiation therapy. Our study differs from other reports in that we have treated our patients with a single high dose of radiation delivered stereotactically to the tumor volume. Note that
Meningiomas constitute approximately 15% of all intracranial and 25% of all intraspinal neoplasms. They are most commonly detected in the fifth decade of life and there is a clear predominance in women ( 12, 2 1). Standard treatment is surgical resection. Some meningiomas, especially those in the sphenoidal ridge or parasellar regions, recur even when extirpation seems to be complete. Following surgery alone, the probability of recurrence after complete resection has been reported as 710% at 5 years and 20-22% at 10 years. After incomplete removal, the rate of recurrence increases to 26-37% at 5 years and 55-74% at 10 years. Fifteen years after subtotal resection, only 9% are free of recurrence without adjuvant therapy (1, 2, 10).
Presented at the 3 1st Annual Meeting of the American Society for Therapeutic Radiology and Oncology. San Francisco, CA, l-6. October 1989. Reprint request to: Rita Engenhart M.D.. Radiologische
Universitatsklinik, Abt. Strahlentherapie, Im Neuenheimer 400, D-6900 Heidelberg, FRG. Accepted for publication 26 April 1990.
1031
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1. J. Radiation Oncology 0 Biology 0 Physics
the patient population in this study had an extraordinarily unfavourable prognosis since all patients had a macroscopical tumor residual and 6 of 17 patients were unresectable. In this paper we review the results from 17 patients with meningiomas who were treated by this method.
METHODS
AND
MATERIALS
We used a commercial 15 MeV linear accelerator* which had been mechanically adjusted so that the stereotactically defined coordinates could be equated with a high degree of accuracy to the isocenter of a multiple noncoplanar arc irradiation (5). After vertical gantry rotation through an arc of 140”, the treatment couch with the patient rotated horizontally through the isocenter. Secondary cylindrical tungsten collimators+ were used to reduce the penumbra and were adaptable to target volumes with field diameters ranging from 10 to 54 mm. The superposition of the multiple irradiation fields delivers spherical dose distributions with steep dose gradients (7-l 5%/mm) at the margin of the target volume (5. I 1). If the calculated spherical dose distribution was unsatisfactory, an additional collimator of different diameter and an additional isocenter could be chosen until only the tumor volume was covered in an acceptable manner (Fig. 1). During the diagnostic and therapeutic procedure. the patient’s skull was firmly fixed in a Riechert-Mundinger stereotactic head frame.+ A CT-adapted localization device+ attached to the base ring allowed the stereotactic coordinate system to be calculated ( 17). For 3-dimensional treatment planning, thin CT-slices (~2 mm) had to be taken from the region between the skull base and the top of the head. A computer program* allowed the precise calculation of the target point coordination and the definition of target volume, collimator size. and isodose distribution (13). Once the tumor localization procedures were completed. the patient was transferred to the treatment couch of the linear accelerator. A removable target positioning device+ fitted to the base ring allowed the target point to be adjusted to the isocenter of the irradiation facility within stereotactic precision (I 1 mm).’ Patient srlrction A total of 17 patients with diagnoses of intracranial meningiomas were treated with a single high dose stereotactic irradiation. Histological results were available in all patients. Confirmation of benign meningioma was obtained in all 17 patients. The series included 14 females and 3 males with ages varying from 41 to 74 years with a mean age of 54 years. The locations of the intracranial meningioma are summarized in Table 1, and the distri* Mevaton
77, Siemens AG. Erlangen, West Germany. + Available by F. L. Fischer, Freiburg, West Germany. * STP planning system distributed by F. L. Fischer. Freiburg, West Germany.
October 1990. Volume 19. Number 4
bution of patients in Table 2. Four patients had unresectable meningiomas located in the petroclival area and in the sphenoid ridge. Of 13 patients who had undergone previous surgery, 6 were known to have had gross residual tumor masses after primary resection and 7 were referred with recurrences. In two cases. the patient was referred for irradiation of unresectable recurrences. Two patients had undergone a second partial resection. Two patients were referred for additional irradiation after three and four subtotal resections. Another patient was referred for post surgical irradiation after six recurrences and seven subtotal resections. All 17 patients with intracranial meningiomas were treated with single high doses under stereotactic conditions. Four patients received radiosurgery as initial therapy for unresectable meningiomas and two patients for unresectable recurrences. Six patients were irradiated in the postoperative period lasting until 6 months after surgery, and five patients were irradiated after 1 to 7 subtotal resections for recurrent disease. The maximum single dose within the tumor volume ranged from 10 to 50 Gy with a mean dose of 29 Gy. The collimators were set for each treatment so that the 80% isodose contours matched the outline ofthe target volume. The individual dose chosen depended on tumor volume. localization. and radiosensitivity of critical structures in the vicinity of the tumor. The mean field diameter was 40 mm and ranged from 18 to 52 mm. To minimize the risk of radiation-induced damage to surrounding healthy brain tissue, in four patients second and in one patient a third isocenter and collimators were used to adapt the tumor volume to the target volume. The entire treatment, including the CT-examination and 3-D planning procedure, usually took 3 to 4 hr depending on the shape of the target volume, the number of collimators used, and the size of the collimator opening. The stereotaxic photon beam irradiation procedure normally lasted about 30 minutes. All patients received a prophylactic administration of 20 mg steroids dexamethasone 2 hr before being irradiated. The patients were discharged from hospital 2 days after treatment.
RESULTS CT or MRI follow-up examinations were performed periodically. An increase in tumor mass visualized on CT or MRI was taken as evidence of recurrent disease. The median follow-up period after irradiation was 40 months (ranging from I to 60 months). If the four early deaths are excluded, the remaining 13 patients have a disease free follow-up period of more than 32 months (ranging from 32-60 months). One patient with a large inoperable q Fischer Co. Ltd.. Freiburg. West Germany.
Single high dose irradiation of meningiomas 0 R. ENCENHART etul.
(4
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I. J. Radiation Oncology 0 Biology 0 Physics
Table 1. Intracranial sites of 17 meningiomas treated by radiosurgery Tumor
site
No. of patients
Sphenoid ridge Parasellar region Clivus and brainstem Falx Optic nerve sheath Ccrcbellar pontine angle
8 3 2 9 ;
I 17
Total
meningioma located in the petroclival area died I month after radiosurgery from inferior herniation attributed to a VP shunt occlusion. At the time of referral, this patient was in very poor clinical condition and thus received a maximum dose of I2 Gy to a target volume of about 30 cm3. Another patient died of a treatment-related complication. This patient was suffering from a large recurrence located in the parasellar region. A maximum target dose of 35 Gy was delivered to a volume of 73.6 cm3. A large perifocal edema was detected by CT 4 months later. The neurological symptoms increased progressively and the patient died 8 months after therapy from herniation attributable to radiation induced tumor necrosis. The deaths of the two other patients were neither tumor- nor treatment-related. One patient died from coronary infarction 23 months after treatment. The patient with multiple recurrences and seven operations died from pseudomona sepsis 3 months after radiation therapy. The remaining I3 patients treated for intracranial meningioma are alive and free of clinical and radiographic signs of tumor regrowth. CT or MRI scanning has verified either a stability (1 1 cases) or a gradual decrease in tumor size (2 cases). Five out of seven treated with radiosurgery for gross disease had a partial resection of the recurrence. The clinical course of these patients is summarized in Table 3. Acute treatment-related discomfort included headaches, nausea (which subsided usually within 2 days after treatment), and a temporary alopecia. Late complications occurred in eight patients between 5 and 18 months. Transient neurological deprivation was recorded in five patients between 5 and 8 months and in two patients could be attributed to a reversible perifocal edema. Two additional patients had persistent perifocal edema probably related to the radiation-induced tumor necrosis. These two patients are being treated with 6-12 mg dexamethasone daily. and are currently free of neurological problems. Six months after the radiation treatment another patient who was referred with a third recurrence complained of head-
Fig. I. Transverse,
coronal
and sagittal CT-reconstructions
October 1990. Volume 19. Number
4
aches, vomiting, hemianaesthesia. and a spastic hemiparesis. A CT scan taken at time of neurologic deterioration revealed an expansive lesion with hypo- and hyperdensity areas. One field of 30 mm in diameter was selected for treatment and 50 Gy was stereotaxically delivered in a single dose. The neurological deficiencies increased progressively despite treatment with steroids and surgical intervention was necessary. Histological examination of the surgical specimen revealed a radionecrosis of brain parenchyma around the treated necrotic tumor. After surgery, there has been a progressive improvement in neurologic function and the patient continues to lead a productive life. Another patient with a recurrence involving the optic nerve who had decreased visual acuity after surgery lost total vision 5 months after irradiation. This patient had received a maximum of 35 Gy to a target volume of 10.5 cm3 and has remained recurrence free for 50 months. DISCUSSION 11 tracranial meningiomas are generally benign, wellbounded. and slow-growing tumors. The location of the tumor determines the clinical complaints as well as the surgical accessibility. Over 90% of intracranial meningiomas are located supratentorially. The standard treatment for meningiomas is complete resection. Simpson first described five different grades of resection. From complete macroscopic excision (grade 1) to decompression or biopsy (grade 5) ( 14). Local control and long-term survival correlate well with this Simpson-grade. Recurrence rates after complete resection increases with time form 7%) after 5 vears to 32% after IO years, for incomplete removal from ;6% after 5 vears to 74% after IO years. About 10% of all diagnosed meningiomas are unresectable and are. for that reason, suitable for primary radiotherapy. However. meningiomas generally are regarded as poorly responsive to radiation therapy. Several articles with controversial results have been reported in recent years. King et al. reported little therapeutic benefit of radiation therapy to unresectable meningiomas (6). In contrast, Taylor et ul. ( 18) reported a recurrence rate after subtotal resection alone of 69%~ ( 19/29) which was reduced to 15% (3/l 3) by postoperative radiation therapy. Taylor et al. ( 18) further showed that in patients who received surgery alone for recurrent meningiomas. the local control rate was 30% after IO years. For patients who received additional radiation after resection, the local control rate was 89%. These data as well as other retrospective studies (3, 19. 20) have clearly shown that radiation therapy following subtotal resection or given for the treatment of recurrences
of a meningioma
located in the sphenoid
CT-slices show the fixation of the patient in the stereotactic head frame and the CT-localization
ridge. The
device used for
calculation of the stereotactic coordinates. The target volume is outlined by white points. Two different collimators focused to different isocenters were used to fit the treatment volume close to the target volume. The 80%~isodose contour surrounds the target volume. The isodose contours displayed are 80%. 50% and 30%.
Single high dose irradiation of meningiomas 0 R.
delays or prevents further recurrences and in turn has a favorable effect on absolute survival. Our experience with 17 intracranial benign meningiomas differs with regard to the radiation technique. Normally, a dose of 50 to 55 Gy in daily fractions of 1.8 Gy or 2 Gy is delivered and well-tolerated by the normal brain tissue. In this series of patients. percutaneous single high doses ranging from a maximum of 10 to 50 Gy were applied under stereotactic conditions with collimated narrow beams. The precise stereotactic localization of the tumor and a steep dose gradient outside the target volume allowed the administration of high doses with a reduced probability of damage to adjacent normal brain tissue. Certainly the patient population in this study had an extraordinarily unfavourable prognosis. All patients had a macroscopical tumor residual, of which 7 patients underwent 2 to 7 subtotal excisions for recurrent diseases and 6 of 17 patients were unresectable at time of irradiation. The majority of recurrences are clinically and radiographically manifested between the 2nd and 4th year postoperatively. Therefore, with the current median follow-up period in our study of just 40 months. we cannot draw any hard conclusions concerning arrest, remission. or recurrence-free survival. We can conclude, however. that in our series of patients. the meningiomas responded to single high irradiation doses at least on a par with what might be expected from conventional fractionated irradiation. The high rate oftumor necrosis observed indicates that the stereotaxic delivery and the dose of radiation were effective. However, the rate of brain damage seems relatively high in our study when compared to that observed in the treatment of arteriovenous malformations (AVM) in which similar or higher doses were used (3,4, 7, 8, 16). This might not be expected in view of the steep fall-off in
Table 2. Patient distribution and resection type according Simpson’s classification ( 18) No. of patients Average age (years) Primary disease Unresectable disease (grade 5) Partial resection (grade 4) Recurrent disease Unresectable disease (grade 5) Partial resection (grade 4)
to
l7(f= l4.m=3) 54 (4 I-74) 10 4 6 7 2 5
1025
ENGENHART rt al.
Table 3. Time to relapse after surgery compared with outcome after radiosurgery
No. of patient
1 2 3 4 5 6 7
No. of recurrence (months) 6 1 2 2
I 1 3
Time to relapse after surgery
Simpson grade of resection
Follow-up after RT (months)
5 IO 13 14 39 58 60
4 4 4 5 4 5 4
3 ID 8TR 36 RF 45 RF 50 RF 33 RF 41 RF
ID = Intercurrent death: TR = Treatment lapse free survival: RT = Radiation therapy.
related: RF = Re-
dose at the margins of the target volume. Thus one explanation might be that the chosen target volume included a significant amount of healthy brain parenchyma. However, the dose of radiation as well as the target volume are probably not the only factors contributing to these late effects. Prior surgery, anatomic location, and the presence or absence of neurological deficits are also parameters that should be taken into consideration. The tissues in and around an arteriovenous malformation may be nonfunctional and sclerotic as implied by a surrounding gliosis, and therefore less radiosensitive. Additionally, as larger meningiomas have a tendency to have a central necrosis, the brain blood barrier may be compromised, leading to an increased incidence of edema before therapy and as seen in one patient, a possible increase in intensity following radiation. This does not occur with AVM’s because there is no tendency for central necrosis. Based on our present experience, intracranial meningiomas can be treated by high single radiation therapy with good expectations for prolonged disease-free survival. It is still too early to draw definitive conclusions regarding the optimum dose and target volume. However, based on our results and within the framework of a limited 3-year follow-up. single doses of 20 to 30 Gy are sufficient to arrest further tumor growth. As radiation-induced complications are no doubt related to dose and target volume. to minimize the rate of undue neurologic side effects. we currently avoid single doses above 30 Gy and a target volume larger than 40 cm3. For enlarged meningiomas, conventional fractionated radiation therapy should be considered.
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3. Engenhart, R.; Kimmig, B.: Wowra, B.; Sturm. V.; Hover, K. H.; Schneider, S.; Wannenmacher, M. Stereotaktische Einzeitbestrahlung cerebraler Angiome. Radiologe 29:2 19223; 1989. 4. Fabrikant, J. I.; Lymann. J. T.: Hosobuchi, Y. Stereotactic heavy-ion Bragg peak radiosurgery for intracranial vascular
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disorders: method for treatment of deep arteriovenous malformations. Br. J. Radio]. 57:479-490: 1984. Hartmann, G. H.; Schlegel, W.; Sturm, V.: Kober. B.; Pastyr. 0.; Lorenz. W. J. Cerebral radiation surgery using moving field irradiation at a linear accelerator facility. Int. J. Radiat. Oncol. Biol. Phys. 11:1185-1192: 1985. King, D.; Chang, C.: Pool, J. Radiotherapy in the management of meningiomas. Acta Radio]. Ther. Phys. Biol. 5:2633: 1966. Kjellberg. R. N.; Davis. K. R.; Lyons, S. L.; Butler, W.: Adams. R. D. Bragg peak proton-beam therapy for arteriovenous malformations of the brain. Clin. Neurosurg. 3 1: 248-290; 1983. Leksell. L. The stereotaxic method and radiosurgery of the brain. Acta Chir. Scan. 1023 16-3 19; 195 1. Mesic, J.: Hanks. G.: Doggett, S. The value of radiation therapy as an adjuvant to surgery in intracranial meningiomas. Am. J. Clin. Oncol (CCT) 9(4):337-340; 1986. Mirimanoff, R.: Dosoretz. D.: Linggood, R.; Ojemann. R.: Martuza. R. Meningioma analysis of recurrence and progression following nemosurgical resection. J. Neurosurg. 62: 18-24: 1985. Rhein, B.: Klevenz, N.: Mlurer. K.; Hover, K. H.; Lorenz, W. J. Dosimetrische Eigenschaften von 15 MeV Photonen bei der Ausblendung kleiner Felder ( IO-40 mm) fur die externe stereotaktische Bestrahlung. In: Bergmann, H. S., ed. Medizinische Physik 87 Annual Scientific Meeting. ISBN 3-9252 18-04-I. NC: Deutsche Gesellschaft fur Medizinische Physik; 1987:655-660. Russel, D. S.; Rubenstein. L. J. Pathology of tumors of the nervous system, 4th edition. London: Edward Arnold: 1977: 66-9 I. Schlegel, W.: Scharfenberg. H.: Doll, J.; Hartmann. G.;
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