Bruce Lulu

Preliminary Clinical Experience with Linear Accelerator-based Spinal Stereotactic Radiosurgery

A prototype device called an extracranial stereotactic radiosurgery frame was used to deliver stereotactic radiosurgery, with a modified linear accelerator, to metastatic neoplasms in the cervical, thoracic, and lumbar regions in five patients. In all patients, the neoplasms had failed to respond to spinal cord tolerance doses delivered by standard external fractionated radiation therapy to a median dose of 45 Gy (range, 33-65 Gy/11-30 fractions). The tumors were treated with single-fraction stereotactic radiosurgery with the spinal stereotactic frame for immobilization, localization, and treatment. The median number of isocenters was one (range, one to five) with a median single fraction dose of 10 Gy (range, 8-10 Gy) with median normalization to 80% isodose contour (range, 80-160%). There has been a single complication of esophagitis to date from radiosurgery of a tumor involving the C6-T1 segments; the esophagitis resolved with medical therapy. Median follow-up in this group of patients has been 6 months (range, 1-12 mo). To date, there has been no radiographic or clinical progression of the treated tumor in any patient. Two patients have died from systemic metastatic disease. In the three surviving patients, there has been computed tomographic- or magnetic resonance-documented regression of the treated tumor with a decrease of thecal sac compression with a median follow-up of 6 months (range, 3-14 mo). These five patients represent the first clinical application of stereotactic radiosurgery in the spine. The results suggest that extracranial radiosurgery may be suitable for the treatment of paraspinal neoplasms after external fractionated radiation therapy, even in the face of spinal cord compression.

Stereotactic radiosurgery as an adjunct to surgery and external beam radiotherapy in the treatment of patients with malignant gliomas

PURPOSE To evaluate the efficacy and toxicity of a stereotactic radiosurgery boost as part of the primary management of a minimally selected population of patients with malignant gliomas. METHODS AND MATERIALS Between June, 1991 and January, 1994 a stereotactic radiosurgery boost was given to 30 patients after completion of fractionated external beam radiotherapy. The study population consisted of 22 males and 8 females, with a range in age at treatment from 5 to 74 years (median: 54 years). Tumor volume ranged from 2.1 to 115.5 cubic centimeters (cc) (median: 24 cc). Histology included 17 with glioblastoma multiforme, 10 with anaplastic astrocytoma, 1 with a mixed anaplastic astrocytoma-oligodendroglioma, and 2 with a gliosarcoma. A complete resection was performed in 9 (30%) patients, while 18 (60%) underwent a subtotal resection, and 3 (10%) received a biopsy only. Fractionated radiation dose ranged from 44 to 62 Gy, with a median of 59.4 Gy. Prescribed stereotactic radiosurgery dose ranged from 0.5 to 18 Gy (median: 10 Gy), and the volume receiving the prescription dose ranged from 2.1 to 158.7 cc (median: 46 cc). The volume of tumor receiving the prescription dose ranged from 70-100% (median: 100%). One to four (median: 2) isocenters were used, and collimator size ranged from 12.5 to 50 mm (median size: 32.5 mm). The median minimum stereotactic radiosurgery dose was 70% of the prescription dose and the median maximum dose was 200% of the prescription dose. RESULTS With a minimum follow-up of 1 year from radiosurgery, 7 (23%) of the patients are still living and 22 (73%) have died of progressive disease. One patient died of a myocardial infarction 5 months after stereotactic radiosurgery. Follow-up for living patients ranged from 12 to 45 months, with a median of 30 months. The 1- and 2-year disease-specific survival from the date of diagnosis is 57 [95% confidence interval (CI) 39 to 74%] and 25% (95% CI 9 to 41%), respectively (median survival: 13.9 months). No significant acute or late toxicity has been observed. CONCLUSION Stereotactic radiosurgery provides a safe and feasible technique for dose escalation in the primary management of unselected malignant gliomas. Longer follow-up and a randomized prospective trial is required to more thoroughly evaluate the role of radiosurgery in the primary management of malignant gliomas.

Treatment of malignant gliomas with interstitial irradiation and hyperthermia

A Phase I study of interstitial thermoradiotherapy for high-grade supratentorial gliomas has been completed. The objective of this trial was to test the feasibility and toxicity of hyperthermia induced by ferromagnetic implants in the treatment of intracranial tumors. The patient population consisted of 16 males and 12 females, with a median age of 44 years and a median Karnofsky score of 90. Nine patients had anaplastic astrocytoma while 19 had glioblastoma multiforme. Twenty two patients were treated at the time of their initial diagnosis with a course of external beam radiotherapy (median dose 48.4 Gy) followed by an interstitial implant with Ir-192 (median dose 32.7 Gy). Six patients with recurrent tumors received only an interstitial implant (median dose 40 Gy). Median implant volume for all patients was 55.8 cc and median number of treatment catheters implanted per tumor was eighteen. A 60-minute hyperthermia treatment was given through these catheters just before and right after completion of brachytherapy. Time-averaged temperatures of all treatments were computed for sensors located within the core of (> 5 mm from edge of implant), and at the periphery of the implant (outer 5 mm). The percentage of sensors achieving an average temperature > 42 degrees C was 61% and 35%, respectively. Hyperthermia was generally well tolerated; however, there have been 11 minor toxicities, which resolved with conservative management, and one episode of massive edema resulting in the death of a patient. In addition, there were three major complications associated with the surgical implantation of the catheters. Preliminary survival analysis shows that 16 of the 28 patients have died, with a median survival of 20.6 months from diagnosis. We conclude that interstitial hyperthermia of brain tumors with ferromagnetic implants is feasible and carries significant but acceptable morbidity given the extremely poor prognosis of this patient population.

Interstitial thermoradiotherapy of brain tumors: Preliminary results of a phase I clinical trial

A Phase I clinical trial has been initiated to determine the feasibility, tolerance, and toxicity of interstitial thermoradiotherapy in the treatment of high-grade supratentorial brain gliomas. Hyperthermia was delivered by means of thermally-regulating ferromagnetic implants afterloaded into stereotactically placed plastic catheters. Heat treatments were given immediately before interstitial irradiation; in addition, five patients received a second heat treatment at the completion of brachytherapy. The desired target temperature for the 60-minute hyperthermia session was between 42 degrees C and 45 degrees C. Following hyperthermia, the catheters were afterloaded with Ir-192, which delivered a variable radiation dose of 14-50 Gy depending on the clinical situation. Interstitial irradiation was supplemented with external beam radiotherapy (40-41.4 Gy) in patients with previously untreated tumors. A total of 14 patients (4 males, 10 females) have been treated to date on this protocol. Eleven of the patients had a diagnosis of glioblastoma multiforme, whereas three had anaplastic astrocytoma. The mean implant volume was 61.5 cm3 (range: 9-119 cm3); the median number of interstitial treatment catheters implanted was 19 (range: 7-33). Continuous temperature monitoring was performed by means of multisensor thermocouple probes inserted in the center as well as in the periphery of the tumor. Of the 175 monitored intratumoral points, 83 (47%) had time-averaged mean temperatures of greater than 42 degrees C, and only 12 sensors (7%) exceeded a temperature of 45 degrees C. Among the 19 heat treatments attempted, there have been four minor acute toxicities, all of which resolved with conservative medical management and one major complication resulting in the demise of a patient. These preliminary results indicate that ferromagnetic implants offer a promising new approach to treating brain tumors with hyperthermia.

A Prototype Device for Linear Accelerator-Based Extracranial Radiosurgery

A prototype frame for accurate stereotactic localization and linear accelerator (LINAC)-based treatment of extracranial targets was developed. The ECRSF is designed to employ either spinal or skeletal osseous fixation to immobilize the area of interest and then encircle the targeted region with a traditional orthogonal, three-axis system. A series of experiments (n = 5) with semi-radiolucent calibration targets (n = 15) and computed tomography (CT) scanning using the EC showed that a mean localization error of 0.98 +/- 0.22 mm was obtainable in the last two and most accurate series of experiments with these targets (n = 8). Using the LINAC to irradiate these same targets demonstrated an overall radiation treatment accuracy ranging from 1.4 to 2.0 mm. This discrepancy between localization error and overall radiation treatment error can be explained by a lack of isocentricity of the LINAC treatment which is typically less than 1 mm and can be as low as 0.5 mm. These data demonstrate that extracranial stereotactic radiosurgery is now technically feasible and that the accuracy of such treatment would be acceptable for clinical treatment.

The use of stereotactic radiosurgical boost in the treatment of medulloblastomas

PURPOSE Starting in 1992, we began using a stereotactic radiosurgical (SRS) boost for the treatment of medulloblastomas. Four patients ranging in age from 7 to 42 years old have since been treated and are the subject of this retrospective study. METHODS AND MATERIALS All patients were initially treated with a maximally debulking surgery and external beam radiotherapy, which were then followed by a stereotactic radiosurgical boost using a modified 6 MeV linear accelerator. Radiosurgical boost doses ranged from 4.50 to 10.0 Gy. Target volumes ranged from 1.1 to 8.1 cc. The procedure was well tolerated with minimal acute toxicities. RESULTS All four patients are alive without evidence of recurrence (at 8 to 35 months). Acute nausea and vomiting was elicited during the radiosurgical procedure in the first patient treated. We have since begun premedicating patients with antiemetics or treating under general anesthesia. Late complications consisted of panhypopituitarism in one patient, which was thought to be attributable to the previous course of whole-brain radiotherapy. We have not observed any incidence of radionecrosis in this small cohort of patients. CONCLUSIONS Our preliminary results with the use of radiosurgery for medulloblastomas are optimistic, and we would like to suggest the inclusion of a radiosurgery boost in future clinical trials for treatment of this disease.

Stereotactic biopsy of intracranial brain lesions: High diagnostic yield without increased complications: 65 consecutive biopsies with early postoperative CT scans

Diagnostic yield and complication rate were analyzed for a series of 65 consecutive stereotactic biopsies of intra-axial brain lesions. The diagnostic yield was 98.5 ± 1.5% and the complication rate was 1.5%. A median number of 14 biopsies (range 1–48) were taken per lesion. The biopsy sites followed a clockwise pattern, going from the superficial margin to the center and the deep margin of the lesion with respect to the inner table of the skull. A side window cannula biopsy needle was used. All patients underwent immediate postoperative CT scans within 4 h of biopsy to rule out intracranial complications. All patients were discharged within 24 h after biopsy, unless medical reasons unrelated to the biopsy required further hospitalization. We attribute the high diagnostic yield in our series to the high number of systematically taken biopsies per lesion. The higher number of biopsies did not lead to an increase in complications. From our experience, it appears safe to discharge patients the same day or within 24 h after a stereotactic biopsy if the postoperative CT shows no complication. Stereotactic biopsy could often safely be performed on an outpatient basis.

The use of gold foil wrapping for radiation protection of the spinal cord for recurrent tumor therapy

PURPOSE The development of a technique to provide sufficient radiation protection to previously irradiated spinal cord in such a manner that interstitial brachytherapy can be conducted after resection of a recurrent tumor and decompression of the cord. METHODS AND MATERIALS A technique was developed that uses multiple layers of gold foil that are applied around the thecal sac and nerve root sleeves to produce an enveloping radiation shield after resection of recurrent tumor. Once the layers of gold foil are in place, interstitial I125 seeds are permanently placed in the bed of the tumor resection to prevent any recurrence from microcellular disease. The technique is described and its application in the case of a 28-year-old with a third recurrence of chondrosarcoma after external fractionated radiation therapy at the second to the fourth thoracic segments is reviewed. RESULTS This technique has been used in this first patient. An additional tumor dose of 120.0 Gy was delivered to the tumor bed while the spinal cord was calculated to receive only 1% of the dose over the life span of the implant. To date, this dose of radiation has prevented tumor recurrence for more than 18 months of follow-up. CONCLUSION This technique of multiple layers of gold foil shielding over the spinal cord and nerve roots has the potential to be a useful tool for the shielding of a previously irradiated spinal cord in the setting of resection of recurrent tumor. It may also have a wider application to a number of other radiosensitive tumors where interstitial brachytherapy may be useful to provide additional treatment after external fractionated radiation therapy.

A Comparison of Survival Between Radiosurgery and Stereotactic Implants for Malignant Astrocytomas

The purpose of this paper is to compare the survival of three groups of patients with high grade supratentorial gliomas who were treated on three sequential protocols with surgical resection, external beam fractionated radiotherapy and a boost to the residual contrasting enhancing mass by either interstitial brachytherapy (IB, n = 33), by interstitial thermoradiotherapy (IT, n = 25) or by stereotactic radiosurgery (SRS, n = 19). The primary aim of this study was to evaluate the role of different boosting techniques in the initial management of primary brain tumors. External beam radiotherapy doses were escalated from one study to the next so that the median doses given to the IB, the IT, and the SRS groups were 41.4 Gy, 48.4 Gy, and 59.4 Gy, respectively. The median dose of interstitial irradiation or stereotactic radiosurgery, were 40 Gy, 32.2 Gy and 10 Gy, respectively, for the same groups. Follow-up was such that all living patients had been followed for a minimum of 30, 27, 4 months in the IB, IT, and SRS groups, respectively; hence, twelve-month survival was 52% (95% CI: 34%-69%), 80% (95% CI: 64%-96%), and 51% (95% CI: 24%-78%) in the same respective groups. Using a multivariate Cox proportional hazards model, treatment with IT conferred a survival advantage over IB (p = 0.029). Furthermore, survival of patients treated with SRS did not significantly differ from that of patients treated with an implant with or without hyperthermia.(ABSTRACT TRUNCATED AT 250 WORDS)

TREATMENT PLANNING OF TEMPLATE-GUIDED STEREOTAXIC BRAIN IMPLANTS

We have initiated a Phase I clinical trial of interstitial hyperthermia induced with inductively heated ferromagnetic implants in combination with Ir-192 implants for glioblastomas and anaplastic astrocytomas of the brain. For speed and accuracy of the implant procedure, and to control the radiation and thermal dose, a stereotaxic frame is used to position a template. We have modified the Brown-Roberts-Wells frame to be used with a variety of templates which we designed. On the morning of the implant procedure, a CT scan is done, and a CT-based treatment plan is then completed before the patient goes to the operating room. We also describe the CT-based treatment planning system developed to accommodate the template-guided implant and illustrate its clinical use.