Continuous low dose rate brachytherapy with high activity iodine-125 seeds in the management of...

Inr J. Radmlion Oncology Bid Phys., Vol. 25. pp. 325-328 0360.3016193 $6.00 + .Xl Printed in the U.S.A. All rights reserved. Copyright 0 1993 Pergamon Press Ltd.

??Brief Communication

CONTINUOUS LOW DOSE RATE BRACHYTHERAPY WITH HIGH ACTIVITY IODINE-125 SEEDS IN THE MANAGEMENT OF MENINGIOMAS

PRADEEP P. KUMAR, M.D.,* ARUN A. PATIL, M.D.,+ LYAL G. LEIBROCK, M.D.,+

WEI-KOM CHU, PH.D.,* HON-WEI SYH, PH.D.,* GAYLE F. MCCAUL, RTT, CMD* AND MICHAEL A. REEVES, B.S.R.T., (R,T) CMD*

University of Nebraska Medical Center, Omaha, NE 68 198- 1045

The purpose of this study was to evaluate if meningiomas can he effectively treated with hrachytherapy using permanent implantation of high activity I-125 seeds. Thirteen patients with intracranial meningiomas were treated by means of permanent stereotactic implantation of one or more high-activity I-125 seeds. The physical characteristics of I-125 enabled us to deliver a minimum tumor dose ranging from 100 Gy to 500 Gy at a low dose rate of 5 cGy to 25 cGy per hr. Indications for this procedure included recurrence after initial surgery or as primary modality of treatment in patients who were not candidates for surgery. All 13 patients are alive at a median follow-up of 25 months. Nine of 13 patients achieved complete resolution of the tumor and in the remaining four, more than 50% reduction in tumor volume was noted at the last follow-up. No late complications were observed. We conclude from this initial data that localized high dose irradiation delivered at a low dose rate using I-125 permanent implantation is an effective, safe, and simple method in the treatment of both recurrent and primary intracranial meningiomas.

Meningioma, Low dose rate irradiation, I-125 stereotactic brachytherapy.

INTRODUCIION

Meningiomas account for 13 to 18% of all primary intra- cranial tumors and for approximately 25% of intraspinal tumors. In the latter group, they are second to the schwannomas in incidence. They occur at any age but are mainly neoplasms of adults, most cases occurring be- tween 20 and 60, with a peak incidence around the age of 45. In the cranial cavity the female to male ratio is 2 to 1 and in the spine 4 to 1 (15, 19).

The most frequent sites of intracranial meningiomas are the parasagittal region followed by lateral cerebral convexity. A significant number arise from the falx cerebri often extending on both sides of the dura to form a dumb- bell shaped mass that excavates the frontal lobes.

Another notable group that may present a formidable surgical problem originates at the base of the brain, in particular from the sphenoid ridge and from the tuber- culum sellae. Other sites include the olfactory grooves, the cerebellopontine angle, and the 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 mag- num. In all these situations the tumor tends to be related to a major dural sinus. In the spinal canal, the thoracic

region is more frequently implicated than other levels. Other primary sites of meningiomas are intraventricular and orbital ( 14).

Meningiomas are characteristically benign, they are slow growing, circumscribed, and do not invade the com- pressed brain. However, this absence of invasiveness does not apply to other adjacent tissue elements, which makes total surgical extirpation of these tumors difficult. In 1972, Rubinstein (14) wrote; treatment of meningiomas is en- tirely surgical, radiation plays no part. However, following surgery alone the probability of recurrence after complete resection has been reported as 7- 10% at 5 years and 20- 22% at 10 years. After incomplete removal the rate of recurrence increases to 26-31% at 5 years and 55-74% at 10 years. Fifteen years after subtotal resection, only 9% are free of recurrence without adjuvant therapy (1,3, 13).

The results of Taylor et al., ( 17) as well as those of other investigators (3, 12, 16, 18) have clearly demonstrated that post-operative radiation therapy improves long-term local control of subtotal resected or recurrent meningio- mas. Taylor et al., reported a 1 O-year survival rate of 8 1% for patients who received post-operative radiation therapy compared with 49% for patients in the non-irradiated group with subtotal resection. The lo-year survival rate for treatment of recurrence was 89% for patients who re-

* Division of Radiation Oncology. + Division of Neurosurgery.

325

Reprint requests to: P. P. Kumar, M.D. Accepted for publication 24 July 1992.

326 I. J. Radiation Oncology 0 Biology 0 Physics Volume 25. Number 2, 1993

ceived radiation compared with 43% for re-operated pa- All of the remaining 11 patients had their implants per- tients without additional radiation therapy. formed stereotactically under local anesthesia.

Different methods of irradiating the meningiomas were described in the literature, from conventional fractionated dose to stereotactic single high dose external radiation therapy as well as continuous low-dose rate irradiation with high activity I-125 seeds (4, 10, 17). We report our experience with high activity I- 125 seeds in the manage- ment of both recurrent and primary intracranial menin- giomas.

The determination of the number of seeds, their activ- ity, and location to be implanted into each tumor was accomplished by developing pre-implant 3-dimensional CT based treatment planning. Uniform tumor dose was achieved by implanting a single seed into spherical tumors, two seeds into oval tumors, and three seeds into irregular tumors. The minimum tumor dose delivered in this series ranged from 100 Gy to 500 Gy at a low dose rate of 5 cGy to 25 cGy per hr over the life time of the radionuclide.

METHODS AND MATERIALS

Between 1984 and 1990 we treated thirteen intracranial meningiomas with one or more high activity I- 125 seeds (Table 1). The age of our patient group ranged from 25 years to 90 years with a median age of 68 years. The female to male ratio is 5: 1, which is higher than reported before. Six of our thirteen patients had one surgical removal of their meningioma and patient #I in Table 1 underwent surgery twice. Of these seven patients who were treated post-operatively, four were for late recurrences (cases 2, 3, 10, and 11 in Table 1) and three were for incomplete resection (cases 1, 8 and 12 in Table 1). The remaining six patients, following stereotactic biopsy to establish the diagnosis had implantation as the primary modality of treatment because of their age or some medical contrain- dication for surgery.

We present a case who had a large irregular residual tumor requiring the placement of three high activity I- 125 seeds.

Cuse report

The first two patients in Table 1 had their implants under direct vision following craniotomy prior to the availability of stereotactic equipment at our institution.

(Case 8, Table 1) A 25-year-old white male initially presented in July of 1989 with two episodes of seizures and vomiting. Clinically, the patient had no neurologic deficit. CT and MRI of the head revealed a large contrast enhancing tumor in the left cerebellopontine (CP) angle displacing the brain stem and the basilar artery to the right. The tumor also extended anteriorly involving the left cavernous sinus. An attempt was made to remove the tumor surgically. Because of the extent of the tumor only partial removal was accomplished. Post-operatively, the patient developed right-sided hemiplegia and left third cranial nerve palsy. On microscopic examination, the tu- mor was consistent with meningioma. By October of 1989, the patient started having severe headaches. Repeat CT of the head showed persistent tumor (Fig. 1) with new

Table 1. High activity I-125 brachytherapy in 13 patients with meningiomas

Age/sex Tumor site Year of Initial Date of

diagnosis treat implant

No. of seeds Tumor X activity dose Tumor

(mCi) (Gray) response Present status

1. 29/M

2. 39/F

3. 72/F

4. 17/F

5. 81/F 6. 90/F

7.

8. 9.

10. 11.

12. 13.

59/F

25/M 79/F

68/F 25/F

54/F 86/F

Left posterior clinoid

Tuberculum sellae

Left sphenoid wing

Right C.P. angle

Left C.P. angle Right C.P.

angle Left optic

nerve Left C.P. angle Right C.P.

angle Left C.P. angle Right sphenoic

wing Left clivus Tuberculum

sellae

1983 s, S

1978 S

7/ 1 l/84 1 x 10.4 100 CR Alive at 88 months

1 O/30/84 1 x 10.0 100 CR Alive at 85 months

1971 S 517186 1 x 15.0 250 CR Alive at 66 months

1988 - 213188 2 x 10.0 200 PR Alive at 45 months

1988 - 5/ 18/88 2 x 8.0 200 CR Alive at 43 months 1989 - 317189 I x 10.0 200 PR Alive at 32 months

1989 1 O/20/89 1 x 14.5 200 CR Alive at 25 months

1989 S 10/27/89 3 x 12.0 200 CR Alive at 25 months 1989 - 1 l/13/89 2 X 6.0 100 PR Alive at 25 months

1986 S 514190 2 x 12.8 140 CR Alive at 18 months 1987 S 6126190 2 x 7.5 200 CR Alive at 17 months

1990 S g/8/90 1 x 15.0 500 CR Alive at 15 months 1990 1 J/5/90 2 x 5.0 100 PR Alive at 12 months

S = Surgery; CR = Complete Response; PR = Partial Response.

I- I25 brachytherapy of meningiomas 0 P. P. KUMAR et al. 321

Fig. I. Post-implant CT scan of the head with contrast showing a large left CP angle meningioma displacing the brain stem and basilar artery (arrow) to the right. Note the tumor extending anteriorly into the left cavernous sinus. The three high activity I- 125 seeds (arrow-heads) are seen.

Fig. 3. CT scan of the head with contrast 7 months post-implant showing complete resolution of the tumor. The decayed I-125 seeds are in place. The basilar artery (arrow) returned almost to its normal position.

development of hydrocephalus. A ventriculoperitoneal shunt was placed to relieve hydrocephalus. At the same sitting, the tumor was implanted stereotactically with three 12 mCi I- 125 seeds. The tumor received a minimum tu- mor dose of 200 Gy ( 10 cGy per hr isodose line) over the life time of the radionuclide (Fig. 2). Repeat CT of the head with contrast done in May of 1990 showed complete resolution of the tumor (Fig. 3).

Fig. 2. Post-implant CT of the head with the cGy/hr isodose lines super-imposed. The tumor received 200 Gy (10 cGy/hr isodose line) over the life time of the radionuclide.

RESULTS

Nine of the 11 patients (82%) without calcification in their meningiomas achieved complete resolution of the tumor. The minimum time to achieve complete response was 3 months which is equal to the average life of the radionuclide. In the remaining four patients, two with calcification and two without calcification, the response was partial. Of the meningiomas with calcification, only the non-calcified component of the tumor regressed leav- ing the calcified component intact. In all of our partial responders the regression was more than 50% of the orig- inal size.

Only the first two patients who had their implants fol- lowing craniotomy remained in the hospital over 5 days. All of the other 11 patients who had their implants stereo- tactically under local anesthesia were only detained over- night for observation. No acute or late complications re- lated to this technique of brachytherapy were observed.

DISCUSSION

We have come a long way since Rubinstein wrote in 1972 that radiation plays no part in the treatment of me- ningiomas. With improved teletherapy technology and treatment planning, the role of radiotherapy in the man- agement of intracranial meningiomas changed from little therapeutic benefit as reported by Ring et al., (5) to sig- nificant benefit as reported by Taylor et al., ( 17). The next challenge is to find out how this can best be accomplished other than with conventional fractionated external beam therapy. Recently Engerhart et al., (4) reported favorable

328 I. J. Radiation Oncology 0 Biology 0 Physics Volume 25. Number 2, 1993

results with stereotactic single high-dose radiation of in- tracranial meningiomas. We reported our initial experi- ence with high activity I-125 brachytherapy of CP angle meningiomas (10). From our experience we believe there are several advantages with our technique.

With I-125 brachytherapy, the dose distribution can be tailored to fit the tumor shape by selecting seed placement at desired locations. The stereotactic implantation of I- 125 seeds is verifiable at each step of the procedure on the CT screen, making the treatmint more accurate. The procedure is done under local anesthesia and usu- ally takes an hour. The patient is detained in the hos- pital overnight for observation. Therefore, this tech- nique is simple and highly cost effective. Tolerance of normal tissues to continuous low-dose irradiation is much higher than to conventional frac- tionated or single high-dose irradiation (2, 7, 9, 1 1). No acute or late complications were noted in our pa- tient population.

1.

2.

I.

2.

3.

4.

5.

6.

7.

8.

9.

Benign meningiomas are slow growing and well cir- zumscribed. Biologically, tumors with long doubling Limes are best treated with continuous low-dose rate Irradiation. This is because the probability of damaging the slowly dividing cells as they pass through their vul- nerable phase of cell cycle is much better with contin- JOUS low-dose irradiation than with conventional ‘ractionated or single high-dose irradiation (6). rumors in the central nervous system, especially at :he skull base, are in close proximity to cranial nerves, zerebral blood vessels, and the brain stem. A tight do- ;imetry is of vital importance while treating tumors in :his region. I-125, because of its low gamma energy, 3roduces a steep dose gradient permitting delivery of 1 high tumor dose with a low dose to adjacent struc- Lures (8).

CONCLUSION

In conclusion, we believe that all the above mentioned advantages combined with a complete response rate of 82% makes stereotactic I- 125 brachytherapy an effective modality in the management of both primary as well as residual and/or recurrent skull base meningiomas.

REFERENCES

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