Fractionated Gamma Knife Radiosurgery Research Articles

Fractionated Gamma Knife radiosurgery for skull base meningiomas: a single-institution experience

OBJECTIVEGamma Knife radiosurgery (GKRS) has been successfully used for the treatment of intracranial meningiomas given its steep dose gradients and high-dose conformality. However, treatment of skull base meningiomas (SBMs) may pose significant risk to adjacent radiation-sensitive structures such as the cranial nerves. Fractionated GKRS (fGKRS) may decrease this risk, but until recently it has not been practical with traditional pin-based systems. This study reports the authors' experience in treating SBMs with fGKRS, using a relocatable, noninvasive immobilization system.METHODSThe authors performed a retrospective review of all patients who underwent fGKRS for SBMs between 2013 and 2018 delivered using the Extend relocatable frame system or the Icon system. Patient demographics, pre- and post-GKRS tumor characteristics, perilesional edema, prior treatment details, and clinical symptoms were evaluated. Volumetric analysis of pre-GKRS, post-GKRS, and subsequent follow-up visits was performed.RESULTSTwenty-five patients met inclusion criteria. Nineteen patients were treated with the Icon system, and 6 patients were treated with the Extend system. The mean pre-fGKRS tumor volume was 7.62 cm3 (range 4.57-13.07 cm3). The median margin dose was 25 Gy delivered in 4 (8%) or 5 (92%) fractions. The median follow-up time was 12.4 months (range 4.7-17.4 months). Two patients (9%) experienced new-onset cranial neuropathy at the first follow-up. The mean postoperative tumor volume reduction was 15.9% with 6 patients (27%) experiencing improvement of cranial neuropathy at the first follow-up. Median first follow-up scans were obtained at 3.4 months (range 2.8-4.3 months). Three patients (12%) developed asymptomatic, mild perilesional edema by the first follow-up, which remained stable subsequently.CONCLUSIONSfGKRS with relocatable, noninvasive immobilization systems is well tolerated in patients with SBMs and demonstrated satisfactory tumor control as well as limited radiation toxicity. Future prospective studies with long-term follow-up and comparison to single-session GKRS or fractionated stereotactic radiotherapy are necessary to validate these findings and determine the efficacy of this approach in the management of SBMs.

Frameless Fractionated Gamma Knife Radiosurgery with ICON™ for Large Metastatic Brain Tumors.

BackgroundRecently, a new generation of gamma knife radiosurgery (GKRS) equipped with a frameless immobilization system has encouraged the use of fractionated GKRS as an increasingly favorable treatment option. We investigated the preliminary outcome of efficacy and toxicity associated with frameless fractionated gamma knife radiosurgery (FF GKRS) for the treatment of large metastatic brain tumors.MethodsFifteen patients with 17 lesions were treated using FF GKRS and included in this study, because of the large tumor size of more than 10 cm3. FF GKRS was performed based on a thermoplastic mask system for 3 to 5 consecutive days.ResultsThe mean duration of clinical follow-up was 12 months (range, 4–24), and the local control rate was 100%. Tumor volume decreased in 13 lesions (76.5%), and remained stable in 4 lesions (23.5%). One patient was classified as new lesion development because of the occurrence of leptomeningeal seeding regardless of the tumor volume change. Compared with the initial volume at the time of FF GKRS, tumor volume change at the last follow-up was 62.32% ± 29.80%. Cumulative survival rate at 12 months was 93.3% ± 6.4%. One patient died during the follow-up period because of the progression of the primary disease. No patient showed radiation necrosis on the follow-up images.ConclusionDaily FF GKRS by gamma knife ICON™ revealed satisfactory tumor control rate and low morbidity, despite the short follow-up period. Further prospective studies and a longer follow-up of a large cohort of patients diagnosed with brain metastases are required to elucidate the effect of FF GKRS in brain metastases.

Single fraction and multisession Gamma Knife radiosurgery for craniopharyngioma.

The optimal management of residual or recurring craniopharyngioma is still a matter of debate even though adjuvant radiation therapy plays a crucial role. Aim of our study is to report the results of single fraction or multisession Gamma Knife radiosurgery (GKRS) in patients with craniopharyngioma. We included 50 consecutive patients treated from 1994 to 2016. All patients had at least one post GKRS magnetic resonance imaging reviewed at our center. Vital status of all patients was assessed at the end of 2016. There were 29 males (58.0%) and 21 females (42.0%). Mean age was 41.5 ± 2.8year. Single session GKRS was delivered in 29 patients (58.0%). The mean tumor volume was 2.15 ± 0.3cm3 and the mean prescription dose to the tumor margin was 14.3 ± 0.3Gy. During a mean follow-up of 74.6 ± 8.4months, seven patients (14.0%) had recurrence of disease. The 5- and 10-year recurrence-free survivals were 90.3% (95% CI, 81.0-99.6%) and 78.4% (95% CI, 59.9-96.9%), respectively. Multisession GKRS was not less effective than single fraction GKRS. Eighteen of the 28 patients (64.3%) had a tumor volume decrease of at least 10%. No serious side effects occurred after GKRS treatment, except for one case of mild visual worsening. GKRS was effective for controlling the growth of residual or recurrent craniopharyngioma. Serious side effects were uncommon. Multisession GKRS seems a very promising tool to allow performing GKRS even in patients with large residual or recurrent craniopharyngioma.

Fractionated Gamma Knife Radiosurgery as Initial Treatment for Large Skull Base Meningioma.

We present our experience on the hypofractionated Gamma Knife radiosurgery (FGKS) for large skull base meningioma as an initial treatment. We retrospectively reviewed 23 patients with large skull base meningioma ≥10 cm3 who underwent FGKS as the initial treatment option. The mean volume of tumors prior to radiosurgery was 21.2±15.63 cm3 (range, 10.09~71.42). The median total margin dose and marginal dose per fraction were 18 Gy (range, 15~20) and 6 Gy (range, 5~6), respectively. Patients underwent three or four fractionations in consecutive days with the same Leksell® frame. The mean follow-up duration was 38 months (range, 17~78). There was no mortality. At the last follow-up, the tumor volume was stationary in 15 patients (65.2%) and had decreased in 8 patients (34.8%). Six patients who had cranial neuropathy at the time of FGKS showed improvement at the last clinical follow-up. Following FGKS, 4 patients (17%) had new cranial neuropathy. The trigeminal neuropathy was the most common and all were transient. The mean Karnofsky Performance Status score at pre-FGKS and the last clinical follow-up was 97.0±10.4 points (median, 100) and 98.6±6.9 (median, 100) points, respectively. FGKS has showed satisfactory tumor control with functional preservation for large skull base meningiomas. Further prospective studies of large cohorts with long term follow-up are required to clarify the efficacy in the tumor control and functional outcome as well as radiation toxicity.

Emerging Indications for Fractionated Gamma Knife Radiosurgery.

Gamma Knife radiosurgery (GKRS) allows for the treatment of intracranial tumors with a high degree of dose conformality and precision. There are, however, certain situations wherein the dose conformality of GKRS is desired, but single session treatment is contraindicated. In these situations, a traditional pin-based GKRS head frame cannot be used, as it precludes fractionated treatment. To report our experience in treating patients with fractionated GKRS using a relocatable, noninvasive immobilization system. Patients were considered candidates for fractionated GKRS if they had one or more of the following indications: a benign tumor >10 cc in volume or abutting the optic pathway, a vestibular schwannoma with the intent of hearing preservation, or a tumor previously irradiated with single fraction GKRS. The immobilization device used for all patients was the Extend system (Leksell Gamma Knife Perfexion, Elekta, Kungstensgatan, Stockholm). We identified 34 patients treated with fractionated GKRS between August 2013 and February 2015. There were a total of 37 tumors treated including 15 meningiomas, 11 pituitary adenomas, 6 brain metastases, 4 vestibular schwannomas, and 1 hemangioma. At last follow-up, all 21 patients treated for perioptic tumors had stable or improved vision and all 4 patients treated for vestibular schwannoma maintained serviceable hearing. No severe adverse events were reported. Fractionated GKRS was well-tolerated in the treatment of large meningiomas, perioptic tumors, vestibular schwannomas with intent of hearing preservation, and in reirradiation of previously treated tumors.

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations on daily or alternate day schedule outside the linear quadratic model: Proof of concept and early results. A substitute to volume fractionation.

To evaluate the feasibility, safety and efficacy of dose fractionated gamma knife radiosurgery (DFGKRS) on a daily schedule beyond the linear quadratic (LQ) model, for large volume arteriovenous malformations (AVMs). Between 2012-16, 14 patients of large AVMs (median volume 26.5 cc) unsuitable for surgery or embolization were treated in 2-3 of DFGKRS sessions. The Leksell G frame was kept in situ during the whole procedure. 86% (n = 12) patients had radiologic evidence of bleed, and 43% (n = 6) had presented with a history of seizures. 57% (n = 8) patients received a daily treatment for 3 days and 43% (n = 6) were on an alternate day (2 fractions) regimen. The marginal dose was split into 2 or 3 fractions of the ideal prescription dose of a single fraction of 23-25 Gy. The median follow up period was 35.6 months (8-57 months). In the three-fraction scheme, the marginal dose ranged from 8.9-11.5 Gy, while in the two-fraction scheme, the marginal dose ranged from 11.3-15 Gy at 50% per fraction. Headache (43%, n = 6) was the most common early postoperative complication, which was controlled with short course steroids. Follow up evaluation of at least three years was achieved in seven patients, who have shown complete nidus obliteration in 43% patients while the obliteration has been in the range of 50-99% in rest of the patients. Overall, there was a 67.8% reduction in the AVM volume at 3 years. Nidus obliteration at 3 years showed a significant rank order correlation with the cumulative prescription dose (p 0.95, P value 0.01), with attainment of near-total (more than 95%) obliteration rates beyond 29 Gy of the cumulative prescription dose. No patient receiving a cumulative prescription dose of less than 31 Gy had any severe adverse reaction. In co-variate adjusted ordinal regression, only the cumulative prescription dose had a significant correlation with common terminology criteria for adverse events (CTCAE) severity (P value 0.04), independent of age, AVM volume, number of fractions and volume of brain receiving atleast 8 Gy of radiation. DFGKRS is feasible for large AVMs with a fair nidus obliteration rate and acceptable toxicity. Cumulative prescription dose seems to be the most significant independent predictor for outcome following DFGKRS with 29-30 Gy resulting in a fair nidus obliteration with least adverse events.

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations.

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations.

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations: A word of caution

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations: A word of caution

Fractionated gamma knife radiosurgery for large brain arteriovenous malformations.

Fractionated gamma knife radiosurgery for large brain arteriovenous malformations.

Is Fractionated Gamma Knife Radiosurgery a Safe and Effective Treatment Approach for Large-Volume (>10 cm3) Intracranial Meningiomas?

Even with great advances in surgery and improved clinical outcome, morbidity and mortality are still high for large-volume intracranial meningiomas (MNGs). Recently, Gamma Knife radiosurgery (GKS) has proven to be a safe and effective treatment for many patients with intracranial MNGs. However, single-session GKS may increase the risk of radiation-induced toxicity for large MNGs. Recently, fractionated GKS (FGKS) has been performed for an increasing number of patients with surgically high-risk and large intracranial tumors. In this study, we report our results on the efficacy and safety of FGKS for large MNGs. The authors performed a retrospective review of 70 patients who underwent GKS for large-volume (>10 cm3) intracranial MNGs between 2004 and 2015, with a minimum follow-up of 12 months. The authors classified these patients into 2 groups of single-session GKS, FGKS. The patients were followed by clinical examination and serial imaging with magnetic resonance imaging. In the single-session GKS group (42 patients), the median tumor volume was 15.2 cm3 (range 10.3-48.3 cm3); the median prescription dose was 12 Gy (range 8-14 Gy), and the median follow-up duration was 57.8 months (range 14.5-128.4 months). In the FGKS group (28 patients), the median tumor volume was 21 cm3 (range 10.2-54.7 cm3), and the median prescription was 7.5 Gy in 2 fractions (range 5-8 Gy), 6 Gy in 3 fractions (range 5-6.5 Gy), and 4.5 Gy in 4 fractions. The median follow-up duration for the FGKS group was 50 months (range 12.5-90.6 months). The overall 5-year tumor control rate was 92.9% in the FGKS group and 88.1% in the single-session GKS group. Fourteen (33.3%) symptomatic complications after single-session GKS were noted, including 5 cases of hemiparesis, 4 of seizure, 3 of peritumoral edema, and 2 of hydrocephalus. Two (7.1%) symptomatic complications after FGKS were noted, including 2 cases of hemiparesis. The FGKS group had higher progression-free survival (PFS) rate at 5 years (92.9% vs. 88.1%), but the differences did not reach statistical significance (P= 0.389). The patients in the FGKS group, however, experienced a lower complication rate compared with patients with a single-session GKS group (P= 0.017, hazard ratio, 5.7:1). When the large-volume (>10 cm3) intracranial MNGs are expected to have high morbidity after microsurgery and for patients that have a poor medical status for surgery, FGKS can be considered an alternative with good tumor control and lower complications rates compared with single-session GKS (P= 0.017).

Results of volume-staged fractionated Gamma Knife radiosurgery for large complex arteriovenous malformations: obliteration rates and clinical outcomes of an evolving treatment paradigm.

OBJECTIVE There are few reported series regarding volume-staged Gamma Knife radiosurgery (GKRS) for the treatment of large, complex, cerebral arteriovenous malformations (AVMs). The object of this study was to report the results of using volume-staged Gamma Knife radiosurgery for patients affected by large and complex AVMs. METHODS Data from 20 patients with large AVMs were prospectively included in the authors' AVM database between 2004 and 2012. A staging strategy was used when treating lesion volumes larger than 10 cm3. Hemorrhage and seizures were the presenting clinical feature for 6 (30%) and 8 (40%) patients, respectively. The median AVM volume was 15.9 cm3 (range 10.1-34.3 cm3). The mean interval between stages (± standard deviation) was 15 months (± 9 months). The median margin dose for each stage was 20 Gy (range 18-25 Gy). RESULTS Obliteration was confirmed in 8 (42%) patients after a mean follow-up of 45 months (range 19-87 months). A significant reduction (> 75%) of the original nidal volume was achieved in 4 (20%) patients. Engel Class I-II seizure status was reported by 75% of patients presenting with seizures (50% Engel Class I and 25% Engel Class II) after radiosurgery. After radiosurgery, 71.5% (5/7) of patients who had presented with a worsening neurological deficit reported a complete resolution or amelioration. None of the patients who presented acutely because of hemorrhage experienced a new bleeding episode during follow-up. One (5%) patient developed radionecrosis that caused sensorimotor hemisyndrome. Two (10%) patients sustained a bleeding episode after GKRS, although only 1 (5%) was symptomatic. High nidal flow rate and a time interval between stages of less than 11.7 months were factors significantly associated with AVM obliteration (p = 0.021 and p = 0.041, respectively). Patient age younger than 44 years was significantly associated with a greater than 75% reduction in AVM volume but not with AVM obliteration (p = 0.024). CONCLUSIONS According to the results of this study, volume-staged GKRS is an effective and safe treatment strategy for large, complex, cerebral AVMs for which microsurgery or endovascular approaches could carry substantially higher risks to the patient. Radiation doses up to 20 Gy can be safely administered. The time interval between stages should be shorter than 11.7 months to increase the chance of obliteration. High nidal flow and a patient age younger than 44 years were factors associated with nidus obliteration and significant nidus reduction, respectively.

Spontaneous intratumoural and intraventricular haemorrhage associated with a pilomyxoid astrocytoma in the hypothalamic/chiasmatic region

Pilomyxoid astrocytoma (PMA) is a rare, low-grade glioma that is recognised as a variant of pilocytic astrocytoma. There have been few reports on this pathologic entity presenting with spontaneous haemorrhage. In this study, we report a rare case of PMA in the hypothalamic/chiasmatic region presenting with intratumoural and intraventricular haemorrhage. An external ventricular drain was urgently inserted. A ventriculo-peritoneal shunt (VP) was undergone 4weeks thereafter. The patient received fractionated Gamma Knife radiosurgery in another hospital 3weeks after the VP shunt. Three months later, subtotal resection of the tumour was performed in our hospital via a pterional approach. The pathological diagnosis was PMA. Postoperatively, no adjuvant therapy was given, and the neurologic deficits were improved. However, the presentation of endocrine deficits remained. Notably, PMAs in the hypothalamic/chiasmatic region presenting with massive intratumoural and intraventricular haemorrhage may result in a severe condition and long-term impairment of endocrine function. Long-term follow-up is required to monitor the recurrence of the tumour and endocrinopathy.

Clinical outcome of neurofibromatosis type 2-related vestibular schwannoma: treatment strategies and challenges.

To discuss the appropriate treatment strategy for NF2-related vestibular schwannoma (VS) according to our experiences, we analyzed long-term clinical and radiological data focusing on NF2-related VS patients. Seventeen NF2-related VS patients were included. Based on their first management modality for VS, we classified these patients into the following four groups: microsurgery (MS), fractionated gamma knife radiosurgery (f-GKS), single session gamma knife radiosurgery (s-GKS), and conservative management (CM). Each patient was assessed for each separate ear. Changes of tumor volume and hearing status for 32 ears in 17 patients according to their first treatment modality were evaluated. The mean follow-up duration and tumor volume of the MS (4 ears, 4 patients), f-GKS (12 ears, 10 patients), s-GKS (8 ears, 7 patients), and CM (8 ears, 7 patients) groups were 3.9years and 1.6mL; 5.1years and 11.1mL; 8.4years and 5.6mL; and 6.1years and 1.6mL, respectively. Relatively lower local control rates were observed in the MS and the CM group (0 and 12.5%, respectively). On the other hand, better local control rates for follow-up periods of 5.1 and 8.4years were achieved in the f-GKS and the s-GKS groups (75 and 50%, respectively). However, hearing preservation in all treatment modalities could not be achieved effectively. Long-term preservation of hearing in at least one serviceable ear as well as tumor control should be considered for each patient. Therefore, a proper treatment option should be selected at the appropriate time according to clinical characteristics of individual patients.

Fractionated gamma knife radiosurgery for benign perioptic tumors: outcomes of 38 patients in a single institute.

BackgroundThis study was performed to evaluate the efficacy and safety of fractionated Gamma Knife radiosurgery (GKRS) for perioptic lesions.MethodsThirty-eight patients with perioptic tumors were treated at our institute from May 2004 to December 2008. All patients had a lesion in close contact with the optic apparatus. Twenty-four of these patients had undergone surgical resection before fractionated GKRS. Radiation was delivered in four sessions with 12 hours intervals between sessions. The mean target volume was 3,851 mm3 and the median cumulative marginal dose was 20 Gy. The median follow-up was 38.2 months. Visual acuity and visual fields were analyzed according to visual impairment score using the German Ophthalmological Society guidelines.ResultsTumor control was achieved in 35 (94.6%) of the 37 patients with available follow-up images. Progressive tumor growth was observed in two craniopharyngioma patients (5.4%). Favorable visual outcomes in the postoperative period were achieved in 94.7% of cases (36/38). Sixteen patients showed visual function after fractionated GKRS, twenty cases were stationary, and two patients showed visual function deterioration after GKRS.ConclusionGKRS is a safe and effective alternative to either surgery or fractionated radiotherapy for selected benign lesions that are adjacent to the optic apparatus.

Verification of Gamma Knife extend system based fractionated treatment planning using EBT2 film

This paper presents EBT2 film verification of fractionated treatment planning with the Gamma Knife (GK) extend system, a relocatable frame system for multiple-fraction or serial multiple-session radiosurgery. A human head shaped phantom simulated the verification process for fractionated Gamma Knife treatment. Phantom preparation for Extend Frame based treatment planning involved creating a dental impression, fitting the phantom to the frame system, and acquiring a stereotactic computed tomography (CT) scan. A CT scan (Siemens, Emotion 6) of the phantom was obtained with following parameters: Tube voltage--110 kV, tube current--280 mA, pixel size--0.5 × 0.5 and 1 mm slice thickness. A treatment plan with two 8 mm collimator shots and three sectors blocking in each shot was made. Dose prescription of 4 Gy at 100% was delivered for the first fraction out of the two fractions planned. Gafchromic EBT2 film (ISP Wayne, NJ) was used as 2D verification dosimeter in this process. Films were cut and placed inside the film insert of the phantom for treatment dose delivery. Meanwhile a set of films from the same batch were exposed from 0 to 12 Gy doses for calibration purposes. An EPSON (Expression 10000 XL) scanner was used for scanning the exposed films in transparency mode. Scanned films were analyzed with inhouse written MATLAB codes. Gamma index analysis of film measurement in comparison with TPS calculated dose resulted in high pass rates >90% for tolerance criteria of 1%∕1 mm. The isodose overlay and linear dose profiles of film measured and computed dose distribution on sagittal and coronal plane were in close agreement. Through this study, the authors propose treatment verification QA method for Extend frame based fractionated Gamma Knife radiosurgery using EBT2 film.

SU-E-T-398: Verification of Gamma Knife EXtend System Based Fractionated Treatment Planning Using EBT2 Film.

To present EBT2 film verification of treatment planning with the eXtend System, a relocatable frame system for multiple-fraction or serial multiple-session radiosurgery. A human head shaped phantom simulated the verification process for fractionated Gamma Knife (GK) treatment. Phantom preparation for eXtend Frame based treatment planning involved creating a dental impression, fitting the phantom to the frame system, acquiring a stereotactic computed tomography (CT) scan. A CT scan (Siemens, Emotion6) of the phantom was obtained with following parameters: Tube Voltage - 110 kV, Tube Current - 280 mA, pixel size - 0.5 mm × 0.5 mm and 1 mm slice thickness. A treatment plan with two 8 mm collimator shots and three sector blocking in each shot was made. Dose prescription of 4.0 Gy at 100% was delivered for the first fraction out of the two fractions planned. Gafchromic EBT2 film (ISP Wayne, NJ) was used as 2D verification dosimeter in this process. Films were cut and placed inside the film insert of the phantom for treatment dose delivery. Meanwhile a set of films from the same batch were exposed from 0 Gy to 12 Gy doses for calibration purpose. EPSON (Expression 10000XL) scanner was used for scanning the exposed films in transparency mode. Scanned films were analyzed with in-house made Matlab codes. Gamma index analysis of film measurement in comparison with TPS calculated dose resulted in high pass rates >90% for different tolerance criteria of 2%/2mm, 1%/1mm, and 0.5%/0.5mm. The isodose overlay and linear dose profiles of film measured and computed dose distribution on sagittal and coronal plane was in close agreement. Through this study we propose a treatment verification QA method for eXtend frame based fractionated Gamma Knife radiosurgery using EBT2 film. Acknowledgement: Authors acknowledge the help of Andre Micke, ISP for sharing his expertise on EBT2 film.

Early Decreased Tumor Volume Following Fractionated GammaKnife Radiosurgery for Metastatic Melanoma and the Role of “Adaptive Radiosurgery”

We report a case in which fractionated gamma knife radiosurgery was used to treat a metastatic melanoma lesion. The tumor demonstrated a rapid response to radiosurgery with an observable reduction in tumor volume between the second and third treatments, requiring a favorable modification in the third fractionated treatment. A 61-year-old woman presented with a frontal floor metastatic melanoma lesion that was located adjacent to the optic apparatus. Gamma knife radiosurgery was administered in three fractionated treatments of 6.5 Gy to the 50% isodose line in each case. Repeat imaging for the purpose of planning demonstrated that tumor volume at the time of the third treatment, 9 days following the first treatment, had decreased by 31%, resulting in a 21% decrease in the dose administered to the optic chiasm. A case of metastatic melanoma treated with fractionated GKRS is presented, in which a significant reduction in tumor volume was noted 9 days following the initial treatment. This case provides insight into the rate with which malignant neoplasms may respond to intermediate-dose hypofractionated GKRS, and lends support to the concept of "adaptive radiosurgery" as a means of optimizing radiation to an evolving target while minimizing collateral radiation to surrounding structures.

Fractionated gamma knife radiosurgery for optic nerve tumors: a technical report

The main purpose of this report is to demonstrate the effects of fractionated radiosurgery regimens in the management of optic gliomas MATERIALS and Two patients suffering from progressive loss of vision due to optic nerve gliomas were treated with Gamma Knife radiosurgery in three fractions within three consecutive days instead of a single dose regimen. Patients were followed for 42 and 39 months respectively. The treatment modality was well tolerated by the patients with radiological and neurological tumor control after 42 and 39 months of follow up. There were no additional complications. Fractionated regimens of Gamma Knife surgery offer a very good alternative for lesions such as optic glioma and optic nevre sheath meningioma.

Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study

Object. This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT). Methods. Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (≥ 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9–60 months). Six patients remained alive for 3 to 60 months. Conclusions. The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.