Interstitial thermoradiotherapy for recurrent brain tumors

Radiation Oncology, Biology, Physics October 1990, VOlUma 19, SUPPtement 1

204

153 STEREOTAXIC INTERSTITIAL MALIGNANT GLIOMAS

IODINE-125

P. Gutin, M.D., M.D., P. Sneed,

M.D., D. Larson, M.D., 8. Leibel, M.D., M. Prados, M.D., V. Levin, Weaver, M.D. P. Silver, B.A., K. Lamborn, Ph.D., T. Phillips, M.D.

W. Wara, M.D., K.

Brain Tumor Research Oncology, University Group (NCOG)

"BOOST"

IN THE INITIAL

MANAGEMENT

OF

Center and the Departments of Neurological Surgery and Radiation of California, San Francisco, and the Northern California oncology

Brachytherapy has proven the treatment of choice for selected recurrences of malignant gliomas. We tested the use of brachytherapy in the adjuvant treatment of these tumors when between Jan. 3, 1983 and Nov. 1 1989 we treated patients after biopsy or surgical resection of unifocal, supratentorial, and radiographically-circumscribed (eimplantable") glioblastoma multiforme (GM) or non-glioblastoma anaplastic astrocytoma (NOM) with external irradiation to the tumor volume (6000 rad), with concomitant hydroxyurea, followed by a stereotaxically-placed temporary implant with high-activity iodine-125 (5000 rad). Patients were then placed on a regimen of procarbazine, CCNU, and vincristine for 6 courses. Eighty-eight patients were entered into this NC00 protocol , with 4 dying during or immediately after external irradiation and 29 (22 GM , 7 NGM) not receiving an implant for various other reasons, the majority (62%) because the tumor had grown during irradiation. Twenty-five patients with NOM and 30 patients with GM received implants and are considered evaluable. At the time of analysis 56% of evaluable patients with NGU were alive with a median survival of 157 weeks while 43% of GM patients were alive with a median survival of 88 weeks. Twenty-five of the evaluable patients (45%) underwent reoperation after implant because of clinical deterioration and increasing steroid dependency. Other patients were treated with the same adjuvant brachytherapy regimen but were not registered with the NCOG because of geographic considerations. The median survival for the additional 27 patients with NGM was 142 weeks, and for the 50 with GM it was 83 weeks, both values close to those of patients registered with NCOG. Thirty-five patients with NGM and 33 with GM were uimplantablel~ but for various reasons were treated on another NCOG protocol of external beam irradiation given with bromodeoxyuridine (BUdR) infusion. Since these uimplantablee patients were treated concurrently with the brachytherapy patients, the two groups were compared. The median survival for the BUdR-treated patients with NGM was 199 weeks and that for those with GMwas 60 weeks. We conclude that for selected patients with GM, but not NGM, an interstitial eboostw is an advantage. Hyperthermia with brachytherapy is already being used at our center for selected recurrences of both GM _and NOM, and a trial integrating hyperthermia and brachytherapy into the adjuvant treatment of GM is being designed.

154 INTERSTITIAL

THERMORADIOTHERAPY

FOR RECURRENT

BRAIN TUMORS

PK Sneed, MD, PR Stauffer, MS, PH Gutin, MD, TL Phillips, MD, KA Weaver, Departments

of Radiation

Oncology

and Neurological

Surgery,

University

PhD, DA Larson, MD, PhD, WM Wara, MD

of California,

San Francisco

A Phase l/II interstitial thermoradiotherapy trial was instituted in June, 1987 for the treatment of recurrent Patients underwent stereotaxic implantation of brain malignant gliomas and recurrent solitary brain metastases. catheters after pre-planning using the Brown-Roberts-Wells stereotaxic system integrated with a CT scanner. Hyperthermia treatment was administered pre- and post- high-activity iodine-125 brachytherapy using 2450 or 915 MHz helical coil microwave antennas. The treatment goal was to heat as much of the tumor as possible to 42.506 for 30 minutes. Temperatures were mapped at 0.5 cm intervals approximately every IO minutes. Between 6/87 and l/90, 36 tumors in 35 patients (21 males, 14 females) were treated with interstitial irradiation and hyperthermia. Age ranged from 18-71 years (median 47 years) and KPS from 40-90% (median 80%). Histology included glioblastoma (16 tumors), anaplastic astrocytoma (13) melanoma (3), and adenocarcinoma (4). Tumor volume ranged from 1.7-61 .l cc. All patients had been treated with external beam radiation therapy with dose ranging from 39.0-80.0 Gy, given 2 months to 9 years earlier, and 3 patients had also undergone previous brain implants. The minimum tumor dose delivered with the present implant ranged from 47.6-61.8 Gy at a dose rate of 37-70 cGy/hr except for one patient with an initial KPS of 40% who received only 32.6 Gy. A total of 3-10 catheters were implanted, housing l-8 helical coil microwave antennas and l-3 fiberoptic thermometry probes. Sixty-seven hyperthermia treatments were delivered. Heating could be localized to small or large, superficial or deep tumors while sparing surrounding normal tissues. Heating success improved after allowing maximum tumor temperatures of up to 5OOC instead of only 45OC. Comparing the first 15 tumors with the next 21 tumors, steady-state temperatures of at least 42.5OC were attained in 45% of 269 vs. 67% of 350 tumor points, respectively (p = 0.005). Data will also be presented for T50 and T90 (the temperatures which 50% and 90% of the steady-state tumor temperatures exceeded). Complications were all reversible, including increased hemiparesis in 2 patients lasting 1 week and 1 month, transient worsening of neurologic deficits in 8 patients, 5 seizures, 1 scalp burn, and 3 infections. Of 29 evaluable 2-

205

Proceedings of the 32nd Annual ASTRO Meeting

month follow-up scans, 11 showed definite improvement in the radiographic appearance of the tumor, 4 were slightly improved, 7 were stable, and 7 showed apparent tumor progression. Nine patients have undergone reoperation for tumor and/or necrosis. All glioma patients who failed did so at the site of the treated lesion except for one patient with Median survival was 52 weeks overall and 40 weeks for the mixed glioblastoma and malignant ependymoma. patients with glioblastoma. Median survival has not yet been reached for the patients with anaplastic astrocytoma. Interstitial microwave brain hyperthermia is technically feasible. Toxicity is acceptable and CT-responses have been encouraging. Updated patient numbers and follow-up will be presented, and T90 temperatures will be correlated with outcome.

155 EVALUATION OF BROMODEOXYURIDINE IN GLIOBLASTOMA MULTIFORME: AN NCCC PHASE II STUDY T.L. Phillips, V.A. Levin, P.H. Gutin, R.L. Davis, C.B. Wilson, M.D. Prados, W.M. Wara, M.S. Flam and D.K. Ahn Departments

of Radiation

Oncology

and Neurosurgery,

University

of California,

San Francisco

In a study activated in 1983 and closed in 1987, the Brain Tumor Research Center (BTRC) of the University of California and the Northern California Cancer Center (NCCC), evaluated the effect of bromodeoxyuridine (BUdR) in the treatment of glioblastoma multiforme (GBM). A total of 160 patients were evaluable of 173 entered. Patients were to receive a BUdR infusion of 0.8 g/m2 daily over 24 hours for 4 days each of 6 weeks of radiotherapy directed to the tumor plus a margin delivering a total The total dose of BUdR received varied because of toxicity, infusion problems and patient of 60 Gy. Eligibility requirements included Karnofsky performance status (KPS) 1 70, biopsy or refusal. resection and central pathology review. Following radiotherapy with BUdR, patients received chemotherapy with procarbazine, CCNU and vincristine for 1 year. There was a male preponderance of 2:l in the group. Total resection was done in 16% and subtotal resection was done in 79% of patients. The mean Karnofsky score was 86%. The mean age was 52 years. Median survival was 390 days. Variables that influenced survival were: (1) cumulative BUdR dose (P=.OO6), (2) age (P=.OOl), and (3) KPS (P=.OOl). Increasing BUdR cumulative dose (g/m2) influenced survival significantly. The results were compared to the immediately preceding study in which low dose misonidazole was the sensitizer and in which the radiotherapy was similar. With 78 patients having similar attributes, the median survival was 370 days. Overall the results suggest a benefit of full dose BUdR over previous therapies. 156 HYPERFRACTIONATED David Linstadt University

IRRADIATION

FOR ADULTS

MD, David Larson MD, Michael

of California,

Hyperfractionated

WITH BRAINSTEM

Edwards MD, Michael

irradiation

appears to have improved

survival

However, the efficacy and safety of this technique

brainstem

tumors.

brainstem

gliomas using 100 cGy fractions

In 1984 the UCSF Department

7800 cGy (median dose 7200 cGy).

months).

times for surviving

Tumor histologies

astrocytoma,

patients ranging

included

5 moderately

The 3-year actuarial

actuarial local control rate of 48%. the actuarial tolerated:

is less well established

of Radiation Oncology

for adults with

began treating

adults with

between 4-69 months (median follow-up anaplastic

astrocytomas,

At the time of this analysis,

survival

Performance

or 3-year

was in excess of 5 years, while

was 31 months (134 weeks).

Karnofsky

8 patients had failed locally,

rate was 59%, with a corresponding median survival

33

1 highly anaplastic

There were no deaths due to complications

The projected

median time to progression

the mean pre-treatment

patients with brainstem

By the end of 1989, a total of 14 patients had been irradiated

and 8 which were unbiopsied.

illness.

for pediatric

given twice daily to total doses ranging between 6600-

with 5 dying as a result of recurrent tumor. intercurrent

Prados MD, William Wara MD

San Francisco

gliomas.

with follow-up

GLIOMAS

The treatments

were well

Status was 74% (range SO-SO%); at the