3726

Role of Brachytherapy in the Management of the Skull Base Meningioma Treatment of Skull Base Meningiomas

Pradeep P. Kumar, M.D.,* Angelo A. Pati l , M.D.,t Hon-Wei Syh, Ph.D.,* Wei-Kom Chu, Ph.D.,* and Michael A. Reeves, B.S.R.T., C.M.D.*

Background. The treatment of primary and recur- rent skull base meningiomas presents a formidable sur- gical problem.

Methods. Fifteen patients with primary and recur- rent skull base meningiomas were treated by means of interstitial irradiation with iodine 125 ( I T ) seed implan- tation. The physical characteristics of lZ5I enabled the au- thors to administer a minimum tumor dose ranging from 100 to 500 Gy at a low dose rate of 0.05-0.25 Gy per hour.

Results. All 15 patients are alive at a median follow- up of 29 months. Of the 15 patients, 2 with calcification and 2 without calcification achieved only partial re- sponses. The remaining 11 patients achieved a complete response. No early or late complications were observed.

Conclusions. From these data, the authors conclude that interstitial irradiation with '''I seeds is an effective, safe, and simple method in the treatment of both recur- rent and primary skull base meningiomas. Cancer 1993; 71~3726-31.

Key words: skull base meningiomas, iodine 125 intersti- tial irradiation, low-dose-rate iodine 125 brachytherapy, nonsurgical management of meningiomas.

Meningiomas account for 13-18% of all primary intra- cranial tumors and approximately 25% of intraspinal tumors. In the latter group they are secondary to the schwannomas. They occur in patients at any age but are mainly neoplasms of adults, with most cases occurring in patients between 20 and 60 years of age, with a peak incidence at approximately 45 years of age. For menin-

Presented at the 74th Annual Meeting of the American Radium Society, Orlando, Florida, April 11-15, 1992.

From the Divisions of *Radiation Oncology and INeurosurgery, University of Nebraska Medical Center, Omaha, Nebraska.

Address for reprints: I'radeep I'. Kumar, M.D., Radiation Oncol- ogy Service (1 14R), VA Medical Center, Mountain Home, TN 37684.

Accepted for publication October 5, 1992.

gioma in the cranial cavity, the female to male ratio is 2:l and in the spine 4:1.'v2

Meningiomas originate from cell elements that form the meninges and their derivatives in the menin- geal spaces. They may arise from dural fibroblasts and pial cells, but most of them stem from arachnoid cells, in particular, those packing the arachnoid villa, which protrude as finger-like projections into the walls of the dural veins and sinuses. This explains the preferential sites of origin of meningiomas, corresponding very closely to the points where the villa are normally the most numerous, that is, along the major dural venous sinuses and at the exits of the spinal nerve roots from their meningeal sleeves. The most frequent site of intra- cranial meningiomas is the parasagittal region, fol- lowed by the lateral cerebral convexity. A significant number arise from the falx cerebri, often extending on both sides of the dura to form a dumbbell-shaped mass that excavates the frontal lobes.

Another notable group of meningiomas that may present a formidable surgical problem originate at the base of the brain, in particular from the sphenoid ridge and the tuberculum sellae. Other sites include the olfac- tory grooves, cerebellopontine angle, and petrous ridge of the temporal bone. In the latter case, the tumor is attached to the tentorium cerebelli. Another site in the posterior fossa (fortunately rare) is the region of the foramen magnum. In all these situations the tumor tends to be related to a major dural sinus. In the spinal canal, the thoracic region is implicated more frequently than other levels. Other primary sites of meningiomas are intraventricular and orbitaL3

Meningiomas are characteristically benign; they are slow growing, circumscribed, and do not invade the compressed brain. This absence of invasiveness, how- ever, does not apply to other adjacent tissue elements, which makes total surgical extirpation of these tumors difficult. In 1972, Rubinstein3 wrote that treatment of

Treatment of Skull Base Meningiomas/Kumar et al. 3727

meningiomas is entirely surgical and radiation therapy plays no part. After complete resection alone, however, the probability of recurrence has been reported to be 7-10% at 5 years and 20-22% at 10 years. After incom- plete removal, the rate of recurrence increases to 26- 37% at 5 years and 5574% at 10 years. Fifteen years after subtotal resection, only 9% of patients are free of recurrence without adjuvant the rap^.^-^

The results of Taylor et al.' and other investiga- tors5,8-10 have demonstrated clearly that postoperative radiation therapy improves long-term local control of subtotal resected or recurrent meningiomas. Taylor et al. reported a 10-year survival rate of 81% for patients who received postoperative radiation therapy com- pared with 49% for patients receiving subtotal resection without radiation therapy. The 10-year survival rate for treatment of recurrence was 89% for patients who re- ceived radiation therapy compared with 43% for pa- tients receiving further surgery without additional radi- ation therapy.

Different methods of irradiating the meningiomas were described in the literature, from conventional fractionated dose to stereotactic single high-dose exter- nal radiation therapy, as well as continuous low-dose- rate irradiation with high-activity iodine 125 (1251) seed^.^.",'^ We report our experience with high-activity '*'I seeds in the management of both recurrent and pri- mary skull base meningiomas.

Materials and Methods

Between 1984 and 1991, we treated 15 skull base men- ingiomas with one or more high-activity lz5I seeds (Ta-

ble 1). The patient ages ranged from 25 to 90 years, with a median of 67 years. The female to male ratio was 6.5:1, which is higher than reported previously. Seven of our 15 patients had one surgical removal of their meningioma, and Patients 1 and 15 in Table 1 had sur- gery twice,

Of these nine patients who were treated with lZ5I implantation postsurgically, four received this treat- ment for late recurrences (Patients 2, 3, 10, and 11 in Table 1) and five received it for incomplete resection. The remaining six patients had implantation as the pri- mary modality of treatment because of their age or some contraindication for surgery.

The first two patients in Table 1 received their im- plants under direct vision after craniotomy before the availability of stereotactic equipment at our institution. All of the remaining 13 patients acquired their implants stereotactically while under local anesthesia.

The determination of the number of seeds to be implanted into each tumor and their activity was ac- complished by developing preimplant treatment plan- ning. Uniform dose distributions were achieved by im- planting a single seed into spheric tumors, two seeds into oval tumors, and three seeds into irregular tumors. The minimum dose administered in this series ranged from 100 to 500 Gy at a low-dose rate of 0.05-0.25 Gy per hour over the average life of the radionuclide (87 days).

In this article, we present the cases of two patients: one treated for recurrence after two surgical removals (Patient 15, Table 1) and another who had extensive calcification in her meningioma, but was not a surgical candidate (Patient 6, Table 1).

Table 1. Summary of the Patients Who Underwent Iodine 125 Brachytherapy

Patient Age Year of Initial Date of seeds X activity dose Tumor no. (yr) Sex Tumor site diagnosis treatment implant (mCi) (Gy) response Current status

1 29 M Left posterior clinoid 1983 S,S 7/11/84 1 X 10.4 100 CR Alive at 92 mo 2 39 F Tuberculum sellae 1978 S 10/30/84 1 X 10.0 100 CR Alive at 89 mo 3 72 F Left sphenoid wing 1971 S 5/7/86 1 X 15.0 250 CR Alive at 70 mo 4 77 F Right CP angle 1988 - 2/3/88 2 X 10.0 200 PR Alive at 49 mo 5 81 F Left CP angle 1988 - 5/18/88 2 X 8.0 200 CR Alive at 47 mo 6 90 F Right CP angle 1989 - 3/7/89 1 X 10.0 200 PR Alive at 36 mo 7 59 F Left optic nerve 1989 - 10/20/89 1 X 14.5 200 CR Alive at 29 mo 8 25 M Left CP angle 1989 S 10/27/89 3 X 12.0 200 CR Alive at 29 mo 9 79 F Right CP angle 1989 - 11/13/89 2 X 6.0 100 PR Alive at 29 mo

10 68 F Left CP angle 1986 S 5/4/90 2 X 12.8 140 CR Alive at 22 mo 11 25 F Right sphenoid wing 1987 s 6/26/90 2 X 7.5 200 CR Alive at 21 mo 12 54 F Left clivus 1990 S 8/8/90 1 X 15.0 500 CR Alive at 19 mo 13 86 F Tuberculum sellae 1990 - 11/5/90 2 X 5.0 100 PR Alive at 16 mo 14 67 F Right CPangle 1990 S 1/25/91 2 X 5.5 200 CR Alive at 14 mo 15 31 F Olfactorygroove 1984 S ,S 7/18/91 1 X 6.0 100 CR Alive at 8 mo

No. of Tumor

S: surgery; CR: complete response; CP: cerebellopontile; P R partial response.

3728 CANCER Iune 1 , 2993, Volume 71, No. 11

Case Reports

Case 1

A 24-year-old woman with 6-month history of worsening vi- sion, headaches, and personality changes was seen in the Uni- versity Ophthalmology Department in September 1984. On examination, her vision with glasses was counting fingers at 6 feet in the right eye and 20/50 in the left eye. There was no improvement with pinhole. Refraction improved her vision in the right eye to 20/400 and did not improve vision in the left eye. Both pupils reacted to light with no afferent pupillary defect. The ocular motion was normal. The findings on slit lamp examination were unremarkable. The intraocular pres- sure was 20 mmHg in the right eye and 21 mmHg in the left eye. Fundoscopic examination showed edema of both disks. Goldman visual fields showed a central scotoma in the right eye, which broke out to the inferior nasal periphery. There was an inferior altitudinal visual field defect in the left eye.

A computed tomography (CT) scan of the head showed a large contrast-enhanced mass in the midfloor of the anterior cranial fossa consistent with meningioma (Fig. 1). A bifrontal craniotomy was performed on October 3, 1984, and the tu- mor was removed. The pathology report confirmed the diag- nosis of meningioma.

The patient was evaluated regularly with physical exami- nation and CT scans of the head. By August 1985 there was CT evidence of local recurrence. No additional treatment was contemplated, however, until January 1989, when the patient started having headaches and worsening vision in her left eye. Repeat CT scans of the head in October 1988 showed

Figure 2. Case 1. CT scan of the head with contrast, showing local recurrence 4 years after the first surgical removal of the meningioma.

progression of the local recurrence (Fig. 2 ) . On January 19, 1989, a second bifrontal craniotomy was performed and the tumor removed. After the operation, the patient lost vision completely in her left eye. Again, she was evaluated regularly with physical examination and CT scans of the head. By April 1990, she again had CT evidence of local recurrence. Nothing was done until July 1991, however, when the patient started having headaches. A repeat CT scan of the head in June 1991 showed local progression of the tumor (Fig. 3). On July 18,

Figure 1. Case 1. CT scan of the head with contrast, showing a 7 X 5 X 5 cm tumor arising from the floor of the olfactory groove. The tumor is extending superiolaterally, compressing the frontal lobes.

Figure 3. Case 1. CT scan of the head with contrast, showing local recurrence 2.5 years after the second surgical removal of the recurrent meningioma .

Treatment of Skull Base Meningiomas/Kumar e t al . 3729

1991, under stereotactic guidance, a single 6-mCi 12’1 seed was implanted into the center of the tumor. The tumor re- ceived 0.05 Gy per hour over the average life of the radionu- clide (87 days) (Fig. 4). A follow-up CT scan of the head in January 1992, 6 months after the implant, showed complete resolution of the tumor (Fig. 5 ) . The patient is alive and free of symptoms.

Case 2

A 90-year-old woman with a history of breast cancer was seen in the Neurology Department in March 1989. The pa- tient had become increasingly clumsy over the previous sev- eral months and had been falling quite frequently. The falls were not associated with syncope, incontinence, or any other postictal state. She also had intermittent headaches. Neuro- logic examination showed all cranial nerves to be intact, ex- cept there was diminished hearing in the right ear. There was no sensory or motor deficits. Her response to the finger-to- nose test was inaccurate with the left hand, but her response to the heel to shin test was accurate and symmetric. Rapid alternating movements were symmetric. Deep tendon re- flexes were 2/4 symmetric without clonus.

CT scans of the head showed a large tumor in the right cerebellopontile angle with central and peripheral calcifica- tions consistent with meningioma (Fig. 6). On March 7, 1989, under stereotactic guidance, needle biopsy of the tumor was performed and the histologic diagnosis of meningioma was confirmed. At the same operation, a 10-mCi 1251 seed was implanted into the center of the tumor. The tumor received 0.10 Gy per hour over the average life of the radionuclide (87

Figure 5. Case 1. Follow-up CT scan of the head with contrast, showing complete resolution of the tumor 6 months after the implant. The decayed 1251 seed (white arrowhead) is in place.

days) (Fig. 7). A follow-up CT scan of the head in April 1990, 13 months after the implant, showed complete calcification of the tumor with resolution of only the noncalcified part (Fig. 8). The patient is alive with persistent symptoms. No surgical intervention is contemplated because of the age of the patient and recurrent breast cancer in the chest wall.

Figure 4. Case 1. Postimplant CT scan of the head showing the high-activity 1251 seed in the center of the tumor (white arrowhead). The rad per hour isodose lines are superimposed.

Figure 6. Case 2. Noncontrast CT scan of the head, showing a 2 X 2 X 2 cm tumor in the right cerebellopontile angle with central and peripheral calcifications.

3730 CANCER June 1, 2993, Volume 71, No. 11

120

Figure 7. Case 2. Postimplant CT scan of the head, with the patient in the prone position (cerebellopontile-angle tumors are implanted with patient in prone position), showing the high-activity 1251 seed in the center of the tumor (white arrowhead). The rad per hour isodose lines are superimposed.

Results

Eleven of the 15 patients (73%) achieved a complete response and 4 had a partial response. In Patients 6 and 13 (Table l), there was extensive calcification in the meningioma before implantation. Only the noncalci- fied component of the tumor regressed, leaving the cal- cified component intact. If these 2 patients are excluded from our partial response data, then 11 of our 13 pa- tients (84%) achieved a complete response. The com- plete response was observed from 2 to 8 months after implantation (Fig. 9).

Figure 8. Case 2. Follow-up noncontrast CT scan of the head, showing calcification of the entire tumor with slight reduction in size 13 months after implantation.

fi

Y w

t i i 8

8 c

c

0 5 10 15

Time (months) Figure 9. Time-volume regression curves plotted for all the meningiomas treated with 1251 show that a complete response was observed from 2 to 8 months after implantation.

Only the first two patients who received their im- plants after craniotomy remained in the hospital more than 5 days. All of the other 10 patients who received their implants stereotactically while under local anes- thesia were detained overnight for observation. No acute or late complications related to this technique of brachytherapy were observed.

Discussion

We have come a long way since Rubinstein wrote in 1972 that radiation therapy plays no part in the treat- ment of meningiomas. With improved teletherapy tech- nology and treatment planning, the contribution of radi- ation therapy in the management of intracranial men- ingiomas changed from little therapeutic benefit, as reported by King et al.,13 to significant benefit, as re- ported by Taylor et aL7 The next challenge is to deter- mine how this can best be accomplished other than with conventional fractionated external-beam therapy. Recently, Engerhart et al.” reported favorable results with stereotactic single high-dose radiation therapy for intracranial meningiomas. We reported our initial expe- rience with high-activity lZ5I brachytherapy of cerebel- lopontile-angle meningiomas.” From our experience, we believe there are several advantages with our tech- nique:

1. Benign meningiomas are slow growing and well bordered. Biologically, tumors with long doubling times are best treated with continuous low-dose- rate irradiation. This is because the probability of

Treatment of Skull Base Meningiomas/Kumar et al. 3731

2.

3.

4.

5.

6.

damaging the slowly dividing cells as they pass through their vulnerable phase of cell cycle is much better with continuous low-dose irradiation than with conventional fractionated or single high-dose irradiati~n.'~ Tumors in the central nervous system, especially at the skull base, are in close proximity to cranial nerves, cerebral blood vessels, and the brain stem. A tight dosimetry is of vital importance while tu- mors are being treated in this region. I2'I, because of its low gamma energy, permits administration of a high tumor dose with a low dose to adjacent structures." With '"I brachytherapy, the dose distribution can be tailored to fit the tumor shape by simple seed placement at desired locations. The stereotactic implantation of 1251 seeds is verifi- able at each step of the procedure on the CT screen, making the treatment more accurate. The procedure is performed while the patient is under local anesthesia and usually takes 1 hour. The patient is detained in the hospital overnight for observation. Therefore, this technique is simple and highly cost-effective. Tolerance of continuous low-dose irradiation by normal tissues is much higher than with conven- tional fractionated or single high-dose irradia- tion.l6-I9 No acute or late complications were ob- served in our patient population.

Conclusions

In conclusion, we believe that all the above-mentioned advantages, combined with a complete response rate of 84%, make stereotactic I2'I brachytherapy a viable al- ternative primary modality in the management of intra- cranial meningiomas located at the skull base in pa- tients who are poor surgical candidates. Meningiomas with extensive calcifications do not regress after radia- tion therapy.

References

1. Russel DS, Rubinstein LJ. Pathology of tumors of the nervous system. 4th ed. London: Edward Arnold, 1977:66-91.

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Carella RJ, Ransohoft J, Newall J . Role of radiation therapy in the management of meningiomas. Neurosurgery 1980; 10:332-9. Mirimanoff R, Dosoretz D, Linggood R, Ojemann R, Martuza R. Meningiomas: analysis of recurrence and progression following neurosurgical resection. 1 Neurosurg 1985; 62:18-24. Taylor B, Marcus R, Friedman W, Ballinger W, Million R. The meningioma controversy: post-operative radiation therapy. Int ] Radiaf Oncol Biol Pbys 1988; 15299-304. Mesic J, Hanks G, Doggett S. The value of radiation therapy as an adjuvant to surgery in intracranial meningiomas. An] / Clin Oncol 1986; 9:337-40. Solan M, Kraner S. The role of radiation therapy in the manage- ment of intracranial meningiomas. Int ] Radint Oncol B i d Phys

Wara WM, Sheline GE, Newmann J, Tonsend I, Boldrey E. Radi- ation therapy of meningiomas. A I R 1975; 123:453-8. Engerhart R, Kimmig BN, Hover KH, Wowra B, Sturm V, Van- Kack G, et al. Stereotactic single high dose radiation therapy of benign intracranial meningiomas. Znt / Radiat Oncol Biol Pbys

Kumar PP, Good RR, Patil AA, Leibrock LG. Permanent high- activity iodine-125 in the management of petroclival meningio- mas: case reports. Neurosurgev 1989; 25:436-42. King D, Chang C, Pool J. Radiotherapy in the management of meningiomas. Acta Radio[ Ther Pbys Biol 1966; 526-33. Kumar PP. Cancer and state of the art in radiation oncology. Tbe Cancer Joitrnnl 1989; 2461-71. Kumar PP, Good RR, Leibrock LG, Mawk JR, Yonkers AJ, Ogren FP. High activity iodine-1 25 endocurie-therapy for recurrent skull base tumors. Cancer 1988; 61:1518-27. Bernstein M, Marotta T, Stewart P, Glen J, Resch L, Henkelman M. Brain damage from 1-125 brachytherapy evaluated by MR imaging, a blood-brain barrier tracer, and light and electron mi- croscopy in a rat model. / Neurosurg 1990; 73:585-93. Kumar PP, Good RR, Jones EO, Skultety M, Leibrock L, McComb RD. Contrast-enhancing computed tomography ring in glioblastoma multiforme after intra-operative endocurie- therapy. Cancer 1988; 61:1759-65. Kumar PP, Good RR, Leibrock LG, Patil AA, Bartone FF, Yonkers AJ, et al. Tissue tolerance to continuous low dose rate iodine- 125 irradiation. Endocurietb~rapy Hypertbennia Oncology

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