Volume 40, Number 3
March 1997
Interactive Article

G. Rees Cosgrove, M.D., Fred H. Hochberg, M.D., Nicholas T. Zervas, M.D., Francisco S. Pardo, M.D., Raul F. Valenzuela, M.D., Paul Chapman, M.D.

Departments of Neurosurgery (GRC, NTZ, PC), Neurology (FHH, RFV), and Radiation Oncology (FSP), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

OBJECTIVE: This report describes the clinical evaluation of a novel stereotactic radiosurgical device for interstitial irradiation of malignant brain tumors.

METHODS: Fourteen patients with cerebral lesions less than 3.5 cm in greatest diameter were treated with a single fraction of stereotactic interstitial irradiation (average, 12.5 Gy). Clinical evaluation, Karnofsky Performance Scale ratings, and neuroimaging studies were obtained at 6-week intervals postoperatively to assess treatment response. Reduction or stabilization of tumor size on follow-up imaging was accepted as local control, whereas tumor enlargement indicated local failure.

INSTRUMENTATION: This battery-powered miniature x-ray generator device produces low-energy x-ray photons that are attenuated rapidly within tissue. A dose decline rate proportional to 1/r³ yields extremely sharp dose fall-off curves with minimal exposure to surrounding tissue. Dose rates of 200 cGy per minute are possible, allowing for the administration of 12.5 Gy to a lesion 3 cm in diameter in less than 1 hour.

RESULTS: Local control (stabilization or reduction in lesion size) was obtained in 10 of the 13 patients with tumors with follow-up of 1.5 to 36 months (mean, 12 mo). Of three patients with radiographic progression, recurrence was symptomatic in only one. All patients tolerated the procedure well, and most patients were discharged home the day after treatment. No new neurological deficits were noted after biopsy and irradiation.

CONCLUSIONS: Preliminary experience with this novel radiosurgical device has demonstrated its feasibility and safety. Clinical efficacy of this technique is now under investigation in an international multicenter study.

(Neurosurgery 40:518-525, 1997)

Key words: Brachytherapy, Brain tumor, Interstitial irradiation, Radiation therapy, Radiosurgery, Stereotaxy

Interstitial irradiation has been used for the treatment of neoplasia in many organ systems, and the word "brachytherapy" (therapy at short range) was introduced to differentiate this from standard long-range external beam radiation treatment or "teletherapy." The ability to place radioactive sources into brain tumors using stereotactic techniques allows brachytherapy to be applied in neuro-oncology, of which the therapeutic objective is to accurately deliver a high dose of radiation to a well-defined tumor volume with minimal exposure to surrounding brain structures. A variety of radioactive isotopes are available, each characterized by a specific half-life, energy, and activity level. Interstitial brachytherapy using conventional radioisotopes has been effective in controlling growth of primary and secondary tumors, but all isotopes require special precautions for storage, handling, shielding, and disposal and all suffer radioactive decay over time.

We describe our initial clinical experience using a battery-powered miniature x-ray generator that can be placed stereotactically into intracranial tumors to deliver a single fraction of high-dose interstitial radiation in less than 1 hour. The possible future clinical applications of this novel device are discussed.

PATIENTS AND METHODS

Device description

The photonic radiosurgical system (PRS II; Photoelectron Corporation, Lexington, MA) contains a miniature low-energy x-ray point source capable of delivering a prescribed therapeutic radiation dose directly to small brain lesions. The detailed physical and dosimetric properties of the device have recently been reported (2, 7). Initial evaluation of the device in animal models demonstrated focal radionecrotic lesions in both liver and brain for a range of doses and has been previously reported (Beatty J, unpublished data).

Operation of the system is directed from a low-voltage electronic control box that contains a 9.6-V rechargeable nickel-cadmium battery as the power source. Battery operation and packaging of all high-voltage components within a grounded housing result in a compact device with total electrical isolation for the safety of the patient. The device itself weighs 3.8 pounds and is designed to be compatible with current stereotactic frames (Fig. 1). It contains a step-up converter that can amplify the 9.6 V supplied by the battery to 40 kV and an internal electron gun, which creates a 40-uA electron beam (~0.5 mm wide). The beam is accelerated through a high-voltage field (range, 15-40 kV in 5 kV increments), and it then passes through a deflection chamber to the control beam position and is thus assured beam straightness. After traveling down the evacuated, magnetically shielded, rigid probe (3 mm in diameter and 100 mm in length), the electron beam strikes a thin gold foil target (0.5 u) at the probe tip, producing x-ray photons whose effective energies are in the 10 to 20-keV range. The gold foil is thick enough to stop the electrons but thin enough to allow the x-rays thus generated to pass through. The last 20 mm of the probe tip is constructed from beryllium, which is transparent to these low energy x-ray photons. The x-rays are emitted from the tip in a spherical symmetrical pattern, resulting in a dose rate in tissue of up to 120 Gy per hour at a 10-mm radius. Two scintillation counters monitor radiation and are positioned on the stereotactic frame to detect the small number of photons that pass through the cranium and compare these to the expected treatment levels. Although 99.9% of the energy created by the electron collision with the gold foil is in the form of heat and approximately 0.1% is generated as x-rays, hyperthermia was excluded as a possible tumoricidal factor in animal experiments by limiting the power of the electron beam to maintain the temperature at the tumor margin at less than 42°C.

Because the photons generated are low in energy, their absorption characteristics are different from high-energy brachytherapy sources. The "soft x-rays" of the device are attenuated rapidly within tissue, and a dose decline rate of approximately 1/r³ is obtained rather than 1/r² seen for standard higher energy interstitial radioactive sources. The resultant 30% dose reduction per millimeter of unit tissue creates an extremely steep dose fall-off, allowing as much as 35 Gy to be administered per hour to a 30-mm-diameter intracranial lesion with minimal dose to the scalp and only background levels to personnel more than 2 m away from the patient. This background exposure has been measured at approximately 5 to 10 mrem per hour, and, therefore, no special shielding of the patient or health care personnel is required.

Treatment technique

Before the procedure, a preliminary treatment plan was devised for each patient based on tumor size, location, and presumed histological type. Lesion dimensions were estimated from pretreatment contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) and combined with dose/depth and isodose curves to determine the optimal radiation treatment plan. The probe tip position, beam voltage, and current were then used to calculate the duration of treatment required to administer a prescribed dose of between 10 and 15 Gy (average, 12.5 Gy) to the periphery of the tumor with a 2-mm margin.

The instrument is designed for use with stereotactic frames. After fixation of the frame to the patient, stereotactic CT with contrast enhancement was performed using 1.5-mm contiguous slices through the tumor. The anteroposterior, lateral, and vertical dimensions of the tumor were determined and target coordinates calculated for the center of the lesion. The distance from the center of the lesion to the scalp surface bilaterally was also recorded to calculate the expected surface dose for comparison to actual surface dose during treatment. A standard stereotactic biopsy was then performed through a burr hole, and specimens from the target were submitted for pathological analysis. All procedures were performed under local anesthesia with intravenous sedation to minimize patient discomfort.

If intraoperative frozen section analysis confirmed the diagnosis of tumor, then irradiation was instituted. First, the biopsy needle track was expanded slightly to accommodate the probe tip (3 mm), using a graduated series of dilators. The housing was then mounted on the frame and advanced along the biopsy track to the target coordinates (Fig. 2). Treatment radiation monitors were then inserted into the side carrier rings of the frame to confirm expected surface dose during treatment. Treatment was initiated by activation of the device at the prescribed voltage and current parameters for the calculated time interval. On completion of the treatment, the probe was removed and the incision closed in a standard fashion.

Patient population

After animal studies were completed to determine the effects of this kind of irradiation on tissue, Food and Drug Administration approval was obtained for a Phase I study. The protocol was approved by the Massachusetts General Hospital Subcommittee on Human Studies and between December 16, 1992, and December 3, 1993, 14 patients were treated to establish the safety of the device. Case selection was limited to those patients who were thought to have either primary or secondary malignant brain tumors and not to be suitable for conventional surgical treatment. The lesions had to be 3.5 cm or less in greatest dimension and supratentorial in location. All patients had to be in general good health with a Karnofsky Performance Scale rating of 70 or greater and with an expected survival time of more than 4 months. Patients who were in poor general health or who had received previous radiation therapy or chemotherapy within 4 weeks of enrollment in the study were excluded. Brain stem or cerebellar lesions and tumors with significant cyst formation, hemorrhage, or calcification were also excluded.

All patients underwent detailed clinical evaluation, Karnofsky Performance Scale rating, and contrast-enhanced CT or MRI before treatment. Immediate posttreatment CT was performed within 24 hours in all cases to exclude perioperative complications. All patients were asked to return at 6-week intervals for follow-up clinical evaluation, Karnofsky Performance Scale rating, and imaging studies to document any change in lesion size. Tumor response was graded independently by a neuroradiologist with direct measurement of the maximal tumor dimensions as seen on the last posttreatment MRI study and compared to pretreatment studies. Reduction or stabilization of the tumor size was accepted as local control, whereas enlargement of the tumor indicated local failure. Radiological and clinical outcomes were measured at the last follow-up visit or at the time of death. When possible, positron emission tomographic scans were obtained to measure metabolic changes in the lesions and surrounding tissue. If the tumor showed signs of progression at any time after treatment, alternative methods of intervention were used as was clinically necessary. Patients who had not received whole brain radiation therapy (WBRT) before treatment were given 30 Gy in 10 fractions after treatment.

RESULTS

Ten men and four women (age range, 37-81 yr; mean age, 63 yr) underwent treatment. The baseline clinical characteristics and outcome of each patient are outlined in Table 1. Follow-up has ranged from 1.5 months to more than 36 months (mean, 12 mo). Lesions ranged in size from 10 to 35 mm (mean, 21 mm) in greatest diameter and were located in various lobes. Single doses of radiation between 10 and 20 Gy (mean, 12.5 Gy) were administered, with average treatment times of 23 minutes (range, 7-45 min). Twelve patients had metastatic lesions, and one patient had a primary central nervous system (CNS) lymphoma. One patient (Patient 4) was thought to have a malignant glioma, based on clinical presentation, radiological findings, and intraoperative pathological analysis. Subsequent pathological evaluation suggested that the abnormal glial cells and necrosis were not caused by tumor but were probably reactive astrocytes adjacent to an area of ischemic necrosis in the anterior caudate area. The patient seemed to suffer no adverse effects from treatment, and his condition remained unchanged from his preoperative state.

All patients tolerated the procedure well, and most patients were discharged home the day after treatment. No new neurological deficits were noted after biopsy and irradiation. There were no infections, and no acute increase in peritumoral edema was observed on follow-up imaging studies. Patients who underwent positron emission tomography postoperatively demonstrated decreased metabolism within the tumor but no decrease in metabolism in the surrounding tissue. Patient 4 experienced a small hematoma (<1 cm) after multiple biopsies at the target site. The hematoma was clinically silent but was detected by post-treatment CT. Three patients developed mild steroid myopathy secondary to prolonged dexamethasone use. Patient 3 developed leukoencephalopathy after intrathecal methotrexate. Two patients with cerebral metastases had received prior WBRT, whereas the remainder received 3000 cGy in 10 fractions within 2 weeks of treatment with the photonic radiosurgical system.

Local control of the lesion was obtained in 10 of the 13 patients with tumors (Fig. 3). Tumor progression was observed in three patients during follow-up, although symptomatic recurrence of the treated tumor was evident in only one patient. In Patients 1 and 7, slight tumor enlargement was noted on routine follow-up magnetic resonance images obtained at 3 and 10 months, respectively. The lesions were resected in both patients, and pathological analysis demonstrated central necrosis along with a thin rim of viable tumor tissue around the periphery of the lesion (Fig. 4). In Patient 9, there was clinical and radiological evidence of tumor progression 3.5 months after treatment and 2 months before the patient's death.

At the time of this report, all 12 patients with cerebral metastases had died (11 from systemic disease and 1 from distant CNS recurrence). Patient 4 remains alive and well with no new deficits related to the treatment, and Patient 3 has no evidence of recurrent lymphoma at the treatment site, although he has had distant CNS involvement.

DISCUSSION

The goal of any radiosurgical procedure is to accurately deliver a large single fraction of radiation to a small target volume while minimizing exposure to surrounding tissue (8). With external radiation sources, the desired dose/volume distribution is obtained when the focused beams intersect and summate at the target point after traversing cranial tissue from varied angles. Dose rates of approximately 1.0 to 2.0 Gy per minute yield treatment times generally less than 1 hour. Conventional interstitial brachytherapy obtains its desired dose/volume distribution by directly placing a radiation source in the tumor. Dose rates average 0.4 to 0.6 Gy per hour, and treatment typically takes many hours to several days. Radioisotopes with very low dose rates may require permanent implantation.

The major radiobiological advantage of interstitial brachytherapy is related to intratumoral placement of the radioactive isotope. The emitted dose is attenuated in tissue with increasing distance (1/r²) from the source (3). This inverse square property allows a high dose to be delivered to the tumor while minimizing exposure to the surrounding brain. Of two commonly used isotopes, iodine-125 generates low-energy photons (28-35 keV) but has a very low dose rate, typically requiring treatment times of several days. Iridium-192 emitshigh-energy photons (300-610 keV) and higher dose rates that can shorten treatment times but has less sharply defined dosimetry. These conventional radioactive isotopes have been effective in the treatment of certain brain tumors, but they decay in activity during storage and require special facilities and procedures for their safe handling and disposal. Protective shielding of health care personnel must also be considered.

This miniature x-ray generator has operational and dose characteristics that combine the short treatment times of external beam radiosurgery with the radiobiological advantages of interstitial brachytherapy. Unlike conventional radioisotopes, no special handling is required and the device does not undergo radioactive decay, so that its x-ray output remains constant over time. It generates only low-energy photons, which yield an extremely sharp dose/distribution curve, and minimal surrounding cerebral tissue is irradiated. Treatment times are typically less than 1 hour, so that it can create a radionecrotic lesion over a time period similar to that of external radiosurgical systems.

Our initial experience suggests that the device is relatively safe and well tolerated by patients. However, the probe tip must be placed into the tumor and this imparts a small but definite risk of hemorrhage or injury to surrounding brain. Given the need for tissue diagnosis before most forms of radiation treatment, however, this risk is minimized by inserting the probe at the time of stereotactic biopsy. There did not seem to be any significant acute, subacute, or chronic side effects of this high-dose irradiation, even in the patients with nonmetastatic disease. In the two patients who remained well 2 years after treatment, the lesioned areas appeared as low-signal intensity zones less than 10 mm in diameter on T1-weighted magnetic resonance images, without surrounding edema, enhancement, or significant white matter changes.

Potential inaccuracies involving target selection and volume determination exist with any radiosurgical system, but the extremely sharp dose distribution curves of this device require targeting accuracy. Opening of the cranial vault with shift of intracranial structures may introduce additional targeting error, and placement of the probe itself could displace the tumor volume. Difficulties may also arise with the requirement that therapeutic decisions are made intraoperatively when final pathological diagnosis is uncertain. Patients should not be treated unless the frozen section diagnosis is unequivocal.

Because the probe is currently designed for small spherical lesions with distinct margins, it seems ideally suited to treat metastatic brain tumors. WBRT in patients with cerebral metastases extends median survival time to between 3 and 6 months, depending on the type of primary cancer, extent of systemic disease, and a variety of other factors; however, the overall prognosis is poor (5). Patients with solitary cerebral metastases who undergo surgical excision plus WBRT experience improved overall survival (10-12 mo) and better local control rates, as compared to WBRT alone (9, 11, 12). Resection of multiple metastases may also lead to improved survival in those patients with controlled systemic disease (4), but resective surgery necessitates hospitalization and operative risk that could be minimized by less invasive techniques. Palliation of symptoms and improvement in long-term survival has already been demonstrated in patients with both new and recurrent solitary brain metastasis using iodine-125 implants (10). If this new device is similarly effective, it could represent an attractive alternative to conventional surgery in this population of patients. External radiosurgery has also been used in the treatment of cerebral metastases with success and is noninvasive (1, 6), but when tissue diagnosis is required, the ability to perform stereotactic biopsy and interstitial radiosurgery as one procedure could be advantageous and cost-effective.

It is not clear what role this device will have in the treatment of primary brain tumors. Malignant and even low-grade gliomas are generally larger than 3 cm at the time of diagnosis and tend to infiltrate locally along white matter tracts. However, the device may be of use in small, deep gliomas or recurrences and treatment plans incorporating multiple isocenters are feasible.

Perhaps the most useful role of the photonic radiosurgical system will be for intraoperative irradiation during open neurosurgical procedures in a manner similar to that used by other surgical specialties. The probe tip can be easily shielded to allow for unidirectional irradiation of resection cavities, tumor margins, dural attachments, or cranial base lesions. Conversely, sensitive neural structures could be shielded by thin radio-opaque metals to prevent radiation injury during treatment. It may have even broader application in other surgical subspecialties including urology, gynecology, orthopedics, and otolaryngology.

This miniature radiosurgical device is a new instrument in the neurosurgical armamentarium that gives neurosurgeons a primary role in treating intracranial lesions. It seems well suited for interstitial treatment of cerebral metastases, and preliminary experience has demonstrated its feasibility and safety. Clinical efficacy of this technique is now under investigation in an international multicenter Phase II study.

Investment disclosure

None of the authors have any financial interest in the Photonic Radiosurgical System or the Photoelectron Corporation.

ACKNOWLEDGMENTS

A number of researchers were helpful in this project, including Paul Okunieff, M.D., Peter Biggs, Ph.D., John Beatty, Kenneth Gall, Rudolfo Hakim, M.D., William Butler, M.D., and Griffith Harsh IV, M.D. We also thank Ken Davis for reviewing all the radiological studies. This work was supported with funds from the Photoelectron Corporation, the Massachusetts General Hospital Corporation, and the Neurosurgical Service Research Endowment.

Received, May 20, 1996.
Accepted, October 16, 1996.
Reprint requests: G. Rees Cosgrove, M.D., F.R.C.S.(C), Massachusetts General Hospital, 15 Parkman Street, Suite 331, Boston, MA 02114.

REFERENCES

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3. Bernstein M, Gutin PH: Interstitial irradiation of brain tumors: A review. Neurosurgery 9:741-750, 1981.
4. Bindal R, Sawaya R, Leavens M, Lee JJ: Surgical treatment of multiple brain metastases. J Neurosurg 79:210-216, 1993.
5. Cairncross JG, Kim JH, Posner JB: Radiation therapy for brain metastases. Ann Neurol 7:529-541, 1980.
6. Coffey RJ, Flickinger JC, Bissonette DJ, Lunsford LD: Radiosurgery for solitary brain metastases using the cobalt-60 gamma unit: Methods and results in 24 patients. Int J Radiat Oncol Biol Phys 20:1287-1295, 1992.
7. Dinsmore M, Harte KJ, Sliski AP, Smith DO, Nomikos PM, Dalterio MJ, Boom AJ, Leonard WF, Oettinger PE, Yanch JC: A new miniature x-ray source for interstitial radiosurgery: Device description. Med Physics 23:45-52, 1996.
8. Hudgins WR: What is radiosurgery? Neurosurgery 23:272-273, 1988.
9. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, MacDonald JS, Young B: A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494-500, 1990.
10. Prados M, Leibel S, Barnett CM, Gutin P: Interstitial brachytherapy for metastatic brain tumors. Cancer 63:657-660, 1989.
11. Smalley SR, Laws ER Jr, O'Fallon JR, Shaw E, Schray M: Resection for solitary brain metastases: Role of adjuvant radiation therapy and prognostic variables in 229 patients. J Neurosurg 75:531-540, 1992.
12. Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JHC, Hoekstra FH, Tans JTJ, Lambooij N, Metsaars AL, Wattendorf AR, Brand R, Hermans J: Treatment of single brain metastasis: Radiotherapy alone or combined with neurosurgery. Ann Neurol 33:583-590, 1993.

COMMENTS

The authors describe a miniature x-ray generator device that is capable of the stereotactically directed radiation of a spherical target volume. This information in this article constitutes Phase I data and comprises a technological report of a device that has been described at several recent meetings. The device seems to have scientific and intellectual merit; the issue is whether it has clinical usefulness in comparison with currently existing technologies. Almost all of the patients also receive conventional fractionated radiation therapy. "Boost irradiation" techniques must show significant improvement in both morbidity rates and outcomes to find a niche in our neurosurgical armamentarium. Radiosurgery has certainly done that, showing scientific evidence in both retrospective and prospective trials. Because patients with metastatic brain cancer survive longer, it will be limited to the presence or absence of systemic disease control rather than the presence or absence of a central nervous system metastasis. The same tumor that can be treated by this technology is ideally treated by closed cranial, noninvasive stereotactic radiosurgery. A cost-effectiveness analysis would be very valuable, especially in comparison to presently available techniques. The authors present their scientific pursuit of the technology. I hope that future publications will demonstrate the role of the photonic radiosurgical system in lesions outside of the central nervous system.

This miniature radiosurgery device looks like a by-product of the starwars program, i.e., a radiosurgical tool powered by a 9-volt battery that promises to be a substitute for expensive linear accelerators/gamma-units on the one side and of radioactive implants on the other side. As with interstitial radioactive implants, the method requires the temporary placement of a photon-emitting probe into the target volume. As with other radiosurgical procedures, a precise knowledge of the relationship between the radiation dose, the volume treated, and the subsequent response of normal tissue surrounding the lesion is a prerequisite. The dose administered has a steep dose gradient. It is more confined, as compared with standard radiation therapy, and lacks the penumbra of external focused beam radiosurgery. As with interstitial radiosurgery using iodine-125 implants, there is no beam traversing normal brain tissue. In all stereotactic irradiation procedures, a high dose is delivered to a relatively small target volume. The local dose application results in a radionecrosis that signifies both radiation toxicity and desired treatment effect, i.e., precise and complete tissue destruction (1). In physical terms, the photon energy is very similar to iodine-125 interstitial implants. Dose homogeneity is not of concern.

It was a logical step to use the photon radiosurgery probe for solitary brain metastases, which are comprised of ideally spherical small volumes that are well demarcated from surrounding normal brain. Radiosurgical methods here find optimal geometric conditions. Various methods have been used, such as conformal stereotactic radiotherapy, external beam radiosurgery, and interstitial radiosurgery (2). Radiosurgery can be used to effectively treat solitary brain metastasis with less invasiveness, dissection of normal tissue with lower morbidity, and with less expense compared to open surgery. The present small series also demonstrates that solitary brain metastasis can be controlled with photon radiosurgery alone, thereby avoiding surgery and/or postponing whole brain radiotherapy.

Other indications of photon radiosurgery in the brain are conceivable; above all is the intraoperative irradiation of resection cavities of gliomas, for the sterilization of secreting glial pseudocysts and (with partial shielding of the probe tip) even for more complex volumes close to critical structures. It has to be shown, however, that the advantages and effects of high-dose rate photon irradiation equal or outweigh those of continuous low-dose rate interstitial irradiation.

1. Larsson B: Radiobiological fundamentals in radiosurgery, in Steiner L (ed): Radiosurgery: Baseline and Trends. New York, Raven Press, 1992, pp 3-14.
2. Ostertag CB, Kreth FW: Interstitial iodine-125 radiosurgery for cerebral metastases. Br J Neurosurg 9:593-603, 1995.

This article describes the first clinical experience with patients treated with the new photonic radiosurgical system, which is a cleverly engineered miniature, battery-powered linear accelerator that can be stereotactically placed directly into brain tumors for the delivery of interstitial radiotherapy. The treatment plan is based on a preoperative assessment of the shape and volume of the tumor, as revealed by computed tomographic or magnetic resonance imaging studies combined with the assumption of perfect stereotactic placement of the probe. Of course, perfect placement is very difficult in a biological system, and when using a single point source with very rapid dose fall-off with distance (as opposed to an array of radioactive sources used in conventional brachytherapy), even small errors in placement can result in significant "cold spots" and consequent treatment failures. As the authors point out, that the insertion of the probe could potentially displace the tumor makes probe placement an even more critical issue. One could envision the use of orthogonal x-rays to verify the position of the source intraoperatively, as is routinely done during brain tumor brachytherapy procedures with interstitial isotopes.

The role for this device in the treatment of brain tumors is still unclear. The authors think that its best use might be in the treatment of brain metastases, but the option of (noninvasive) radiosurgery for these tumors would be the obvious first choice. Whether this new technology could provide cost-effective treatment in the very uncommon situation in which biopsy is required has yet to be determined. The authors suggest that another use for the photonic radiosurgical system might be the intraoperative irradiation of tumor resection beds, but dedicated intraoperative electron accelerators or the new portable electron generators designed for this purpose, with their ability to deliver homogeneous dose to targets of various sizes, will likely be the first choice for this application.

The relative role of surgery and radiation therapy in the treatment of brain tumors is evolving, and, unfortunately, the debate has been partially hijacked by the purveyors of costly equipment who have a financial agenda. It is imperative that experienced neurosurgeons impartially and rigorously evaluate new technology to define its role in the neurosurgery armamentarium. All countries are experiencing considerable pressure to reduce health expenditure, and it is essential that neurosurgeons can demonstrate to the health economists the benefits of any new technology.

In this report, the authors evaluate the photonic radiosurgical system in which a miniature low-energy x-ray point source is capable of delivering a prescribed therapeutic radiation dose directly to small brain lesions. The radiobiological characteristics seem ideal for small spherical metastatic tumors, and the treatment as described for the 14 patients seems to have been well tolerated. As described, the therapy delivered by this apparatus may be particularly useful for small deep metastatic tumors that are not well situated for surgical excision and for which the "pressure" effects of the tumor can be controlled with steroid therapy. My major concern is the accuracy of the placement of the relatively blunt end of the probe in the center of the tumor, particularly if the tumor has a much firmer consistency than the adjacent brain and if it has a tough capsule.

The authors allude to the exciting possibilities for intraoperative radiation using this equipment, and I think it is likely that it will find a useful role for intraoperative radiation for cranial base tumors, dural attachments, and tumor margins, as suggested. This might be achieved with the development of new probe tips or shielding of the presently designed model.

A major consideration must be the relative merits of the photonic radiation system, which is essentially an interstitial irradiation device, compared with the presently used radiosurgery systems. The authors have an excellent opportunity to be able to impartially evaluate the system, and they provide sound advice as to its role in neurosurgery. Further studies are eagerly awaited.

This article is must reading for anyone who thought Stanford's robotically manipulated, radiosurgical "backpack," LINAC, represented impressive miniaturization. A Phase I investigation in which 14 patients were treated intraoperatively with a stereotactically positioned miniature x-ray generator, this study demonstrates the feasibility and safety of a new device for interstitial irradiation.

As with brachytherapy seed implantation as well as radiosurgery with external energy sources, the therapeutic effect is primarily ablation of tissue within a treatment volume. Application to metastatic lesions and the provocative suggestion of adjunctive use during open resection may prove to be of value. The limitations of surgical resection imposed by the infiltrative nature of malignant gliomas unfortunately will also apply to this new approach. Potential difficulties arising from the need for intraoperative diagnosis and treatment decisions are acknowledged. The potential benefits, particularly when the device is used at the time of otherwise necessitated stereotactic biopsy, are well articulated by the authors. The relative merits of this technology vis-à-vis alternative approaches remain to be assessed, although radiosurgery's noninvasiveness and greater flexibility in the treatment of more irregularly shaped tumors may give it the same edge it enjoys relative to interstitial seeds.

Please submit your thoughts or comments to William Chandler, Internet Moderator at wchndlr@umich.edu.

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