Gamma Knife radiosurgery for numerous brain metastases: is this a safe treatment?

Gamma Knife (GK) radiosurgery has recently been employed in patients with numerous brain metastases (METs), even those with 10 or more lesions. However, cumulative irradiation doses to the whole brain (WB), with such treatment, have not been determined.

Since the GammaPlan ver. 5.10 (ver. 5.31 is presently available, Leksell GammaPlan) became available in November 1998, 92 GK procedures have been performed for 80 patients with 10 or more brain METs at our facility. The median lesion number was 17 (range: 10–43) and the median cumulative volume of all tumors was 8.02 cc (range: 0.46–81.41 cc). The median selected dose at the lesion periphery was 20 Gy (range: 12–25 Gy). Based on these treatment protocols, the cumulative irradiation dose was computed.

The median cumulative irradiation dose to the WB was 4.71 (range: 2.16–8.51) Gy. The median brain volumes receiving >2 Gy, >5 Gy, >10 Gy, >15 Gy, and >20 Gy were 1105 (range 410–1501) cc, 309 (46–1247) cc, 64 (13–282) cc, 24 (2–77) cc, and 8 (0–40) cc, respectively.

The cumulative WB irradiation doses for patients with numerous radiosurgical targets were not considered to exceed the threshold level of normal brain necrosis.     

Dosimetric and radiobiological evaluation of dose distribution perturbation due to head heterogeneities for Linac and Gamma Knife stereotactic radiotherapy

INTRODUCTION: In SRT/SRS, dedicated treatment planning systems are used for the calculation of the dose distribution. The majority of these systems utilize the standard TMR/OAR formalism for dose calculation as well as they usually neglect any perturbation due to head heterogeneities. The aim of this study is to examine the errors due to head heterogeneities for both absolute and relative dose distributions in stereotactic radiotherapy. MATERIALS AND METHODS: Dosimetric measurements in phantoms have been made for linac stereotactic irradiation. CT-based phantoms have been used for Monte Carlo simulations for both linac-based stereotactic system and Gamma Knife unit. Absolute and relative dose distributions have been compared between homogeneous and heterogeneous media. DVH and TCP results are presented for all cases. RESULTS: The maximum absolute dose difference at the isocenter was 2.2% and 6.9% for the linac and Gamma Knife respectively. The impact of heterogeneity in the target DVH was minor for the linac technique whereas considerable difference was observed for the Gamma Knife treatment. This was reflected also to the radiobiological evaluation, where the maximum TCP difference for the linac system was 2.7% and for the Gamma Knife was 4%. DISCUSSION AND CONCLUSIONS: The errors rising from the existence of head heterogeneities are not negligible especially for the Gamma Knife which uses lower energy beams. The errors of the absolute dose calculation could be easily eliminated by implementing a simple heterogeneity correction algorithm at the TPS. Nevertheless, the errors for not taking into account the lateral electron transport would require a more sophisticated approach and even direct Monte Carlo calculation.     

Use of the Leksell Gamma Knife for localized small field lens irradiation in rodents

For most basic radiobiological research applications involving irradiation of small animals, it is difficult to achieve the same high precision dose distribution realized with human radiotherapy. The precision for irradiations performed with standard radiotherapy equipment is +/-2 mm in each dimension, and is adequate for most human treatment applications. For small animals such as rodents, whose organs and tissue structures may be an order of magnitude smaller than those of humans, the corresponding precision required is closer to +/-0.2 mm, if comparisons or extrapolations are to be made to human data. The Leksell Gamma Knife is a high precision radiosurgery irradiator, with precision in each dimension not exceeding 0.5 mm, and overall precision of 0.7 mm. It has recently been utilized to treat ocular melanoma and induce targeted lesions in the brains of small animals. This paper describes the dosimetry and a technique for performing irradiation of a single rat eye and lens with the Gamma Knife while allowing the contralateral eye and lens of the same rat to serve as the "control". The dosimetry was performed with a phantom in vitro utilizing a pinpoint ion chamber and thermoluminescent dosimeters, and verified by Monte Carlo simulations. We found that the contralateral eye received less than 5% of the administered dose for a 15 Gy exposure to the targeted eye. In addition, after 15 Gy irradiation 15 out of 16 animals developed cataracts in the irradiated target eyes, while 0 out of 16 contralateral eyes developed cataracts over a 6-month period of observation. Experiments at 5 and 10 Gy also confirmed the lack of cataractogenesis in the contralateral eye. Our results validate the use of the Gamma Knife for cataract studies in rodents, and confirmed the precision and utility of the instrument as a small animal irradiator for translational radiobiology experiments.     

Radiation exposure during head repositioning with the automatic positioning system for gamma knife radiosurgery

PURPOSE: To measure radiation exposure to a patient during head repositioning with the automatic positioning system (APS) for Gamma Knife radiosurgery. METHODS AND MATERIALS: A 16-cm diameter spherical solid phantom, provided by the manufacturer, was mounted to the APS unit using a custom-made holder. A small-volume ionization chamber (0.07-cm(3) volume) was placed at the center of the phantom. We recorded the temporal variation of ionization current during the entire treatment. Measurements were made for 3 test cases and 7 clinical cases. RESULTS: The average transit time between successive shots, during which the APS unit was moving the phantom for repositioning the shot coordinates, was 20.5 s for 9 cases. The average dose rate, which was measured at the center of the phantom and at a point outside the shot location, was 0.36 +/- 0.09 cGy/min when the beam output was approximately 3.03 Gy/min for the 18-mm collimator helmet. Hence, the additional intracranial radiation dose during the APS-driven head repositioning between two successive shots (or APS transit dose) was 0.12 +/- 0.050 cGy. The APS transit dose was independent of the helmet size and the position of shots within the phantom relative to the measurement point. CONCLUSION: The head repositioning with the APS system adds a small but not negligible dose to the dose expected for the manual repositioning method.     

Pulmonary hilar stereotactic body radiation therapy in the rat

Stereotactic Body Radiation therapy (SBRT) is an emerging modality of treatment for early stage non-small cell lung carcinoma. Concerns have arisen related to increased toxicities for medial tumors. We have developed a model of high dose, hypofractionated radiotherapy to the pulmonary hilum using the Leksell Gamma-Knife. Sprague-Dawley rats received hypofractionated SBRT to the unilateral lung hilum using a custom immobilization device on the Gamma Knife. Each animal was individually scanned, treatment planned, and treated with either two 4 mm or one 8 mm collimated shots at escalating doses of 20, 40, and 80 Gy to the 50% isodose volume, encompassing the right mainstem bronchus. All animals were carefully followed post-treatment and imaged by plain film and CT. In addition, histopathological analysis of all rats was performed at selected time points. Animals treated with 4 mm collimated shots demonstrated no appreciable changes on plain films or sequential, follow-up CT scans, or histopathologically. Animals irradiated with the 8 mm collimator were less active, gained weight at a reduced rate, and demonstrated histopathological changes in 7/34 animals six months post-irradiation. Cellular atypia and interstitial pneumonitis were found, three of the seven of the animals showed clear bronchial damage and two showed vascular damage. Significant volume and time effects were found. Utilizing a novel Gamma Knife based animal model to study SBRT toxicity, it was found that the bronchus will tolerate small volumes of very high dose radiotherapy. It was postulated that radiation of the surrounding support stroma and normal tissue are important in the etiology of bronchial or hilar damage.     

Radiation-induced epilation due to couch transit dose for the Leksell gamma knife model C

PURPOSE: To determine the cause of epilation at the top of the head for 2 patients with acoustic neuromas after undergoing fractionated radiosurgery with the Leskell Gamma Knife model C. This epilation was unexpected, because the treatment planning program stated the dose at this location was <0.1 Gy. METHODS AND MATERIALS: The radiation dose along a central axis, parallel to the couch, from the helmet's focus to the helmet cap was measured during couch transit. RESULTS: Transit doses of 4.4 cGy/shot at 10 cm and 5.6 cGy/shot at distances >15 cm from the helmet's focus were measured. It was estimated that the 2 patients with epilation received approximately 6-7 Gy to the scalp. A shield was constructed and shown to reduce the transit dose by as much as 60%. CONCLUSION: The design of the helmet allows the uncollimated beams to reach areas of the patient, superior to the target, just before and after couch docking with the housing. For treatment involving a large number of shots (i.e., fractionation), off-target doses < or = 8 Gy can result. For these cases, the transit dose should be considered and some form of additional shielding should be used.     

Application of normoxic polymer gels in 3D-dosimetry for radiosurgery

The aim of this study was to describe the manufacture of normoxic polymer gels, to characterize their dose response relationship, to optimize MR imaging parameters in order to minimize the standard deviation in the measured dose and to use the gel in a dose verification experiment in radiosurgery. The normoxic polymer gel used is simple to manufacture under normal atmospheric conditions and is characterized by a linear dose relationship up to 40 Gy. MR imaging was performed using 2-dimensional (20) single spin echo pulse sequences with two different echo times. The imaging parameters were optimized in order to minimize the standard deviation of the measured transversal relaxation rate R2 and to achieve a geometrical resolution of 1.5 mm. Comparisons of calculated and measured relative 3D dose distributions using a multi isocentric irradiation with Gamma Knife B showed a good overall agreement of both the isodose levels and the differential and cumulative dose volume histograms. The standard deviation in the measured dose was approximately 9% at 30 Gy. The evaluation according to the gamma criterion showed that 96% of the dose voxels remained within a spatial uncertainty of 1.5 mm and a dose uncertainty of 8%.     

Risk analysis of Leksell Gamma Knife Model C with automatic positioning system

PURPOSE: This study was conducted to evaluate the decrease in risk from misadministration of the new Leksell Gamma Knife Model C with Automatic Positioning System compared with previous models. METHODS AND MATERIALS: Elekta Instruments, A.B. of Stockholm has introduced a new computer-controlled Leksell Gamma Knife Model C which uses motor-driven trunnions to reposition the patient between isocenters (shots) without human intervention. Previous models required the operators to manually set coordinates from a printed list, permitting opportunities for coordinate transposition, incorrect helmet size, incorrect treatment times, missing shots, or repeated shots. RESULTS: A risk analysis was conducted between craniotomy involving hospital admission and outpatient Gamma Knife radiosurgery. A report of the Institute of Medicine of the National Academies dated November 29, 1999 estimated that medical errors kill between 44,000 and 98,000 people each year in the United States. Another report from the National Nosocomial Infections Surveillance System estimates that 2.1 million nosocomial infections occur annually in the United States in acute care hospitals alone, with 31 million total admissions. CONCLUSIONS: All medical procedures have attendant risks of morbidity and possibly mortality. Each patient should be counseled as to the risk of adverse effects as well as the likelihood of good results for alternative treatment strategies. This paper seeks to fill a gap in the existing medical literature, which has a paucity of data involving risk estimates for stereotactic radiosurgery.     

体部伽玛刀治疗202例肺癌临床疗效观察

目的：探讨体部伽玛刀治疗肺癌的近期疗效。方法：采用OUR—QGD型体部伽玛刀治疗肺部肿瘤202例，根据病灶的三维形状及病人的身体状况确定靶点数目、治疗次数及分次剂量。P1v覆盖95％以上CTV，等剂量曲线50％-85％，中位值61．81％，Ⅲ周边照射总剂量2800eGy-5500eGy，分割处方剂量350eGy-800eGy，重复治疗4—12次。结果：治疗后随诊3至15个月，胸痛症状止痛有效率为94．93％。189例病人进行疗效评价，CR29例（15．34％），PR113例（59．79％），NC36例（19．05％），PD11例（5．82％），稳定率为94．18％。病理类型以小细胞未分化癌疗效最佳。肿瘤体积≤30cm^3者较肿瘤体积〉30cm^3者治疗效果明显为好。肿瘤分期早期病人治疗效果较好，中晚期病人经过放射治疗可以减轻临床症状。治疗中与治疗后发生的副反应及放射性损伤均较小。结论：体部伽玛刀治疗肺癌可以使肿瘤局部得到准确的高剂量照射，近期疗效显著，安全可行。     

体部立体定向放射治疗112例非小细胞肺癌近期疗效观察

目的观察立体定向放射治疗（SBRT）非小细胞肺癌的近期疗效和放射副反应。方法 112例非小细胞肺癌患者行伽玛刀放疗,50%的处方剂量线完全覆盖PTV,60%～70%剂量线包裹95%以上GTV,照射剂量以50%剂量线作为处方剂量,3～12 Gy/次,总剂量40～60 Gy,1～3周完成治疗。结果治疗后3～16个月所有患者得到随访,中位随访时间11个月,其中完全缓解（CR）率29.5%（33/112）,部分缓解（PR）率为60.7%（68/112）,总有效率为90.2%（101/112）。6个月和1年的局控率分别为98.8%（80/81）、92.3%（36/39）,生存率分别为100%（81/81）、94.9%（37/39）;放射性肺炎为其主要并发症,发生率为9.8%（11/112）。结论 LUNATM-260型伽玛刀作为1种新的SBRT设备,能够有效地提高非小细胞肺癌的局部控制率和生存率,且并发症发生率低。     

A brain tumor dose escalation protocol based on effective dose equivalence to prior experience

Purpose: The current study describes the design of a dose escalation protocol for conformal irradiation of primary brain tumors that preserves the safe experience of a previous, sequential dose escalation scheme while enabling the delivery of substantially higher effective doses to a central target volume.Methods and Materials: Normalized isoeffective composite dose distributions were formed for 20 patients treated on the original protocol (which specified three progressively smaller planning target volumes [PTVs]) using the linear quadratic model (here corrected to equivalent 2 Gy fractions using α/β = 10 Gy). These distributions were investigated and a new protocol was designed to preserve a similar level of efficacy and lack of toxicity for the outer volumes, but allowing a higher dose to the inner PTV. Treatment plans were then investigated to determine if the objectives of the new protocol were achievable. In particular, plans that simultaneously achieved all biological treatment planning objectives (all fields treated each day) were investigated. Finally, the success of the protocol design was demonstrated by analysis of the effective dose distributions of 10 patients treated using the new protocol.Results: The composite normalized isoeffective minimum doses to the outer PTVs (PTV3 and PTV2) in the original protocol were close to 60 Gy and 75 Gy, respectively, and these values are specified as the minimum doses to those volumes for the new protocol. Homogeneity requirements to maintain equivalence for the outer target volume domains are: not more than 25% of [PTV3 exclusive of PTV2] >75 Gy; and not more than 50% of [PTV2 exclusive of PTV1] >85 Gy. Treatment plans using multiple noncoplanar arrangements of beams and static intensity modulation treat all volumes at each session. DVHs of the normalized isoeffective dose distributions reveal the equivalence of the new protocol plans to the sequential plans in the previous protocol as well as the ability to achieve a higher dose of 90 Gy to the isocenter of PTV1 (+/- 5% homogeneity required).Conclusion: The ability to incorporate past experience through use of the linear quadratic model in the design of a new dose escalation protocol is demonstrated.     

Dose-volume analysis of different stereotactic radiotherapy mono-isocentric techniques

Several stereotactic irradiation techniques, using Linacs with the patient in lying and sitting position and a Gamma Knife Unit, were compared with regard to mono-isocentric three-dimensional dose distributions. Three types of target volumes, a sphere and two ellipsoids, were used for the comparisons. All three targets were centered on a real head, reconstructed from transversal CT scans. The ARTEMIS 3D Treatment Planning System, developed by the Tenon Hospital, Paris, was used for the dosimetry and the dose-volume histogram (DVH) calculation. For the comparative study, several quantitative parameters were used, derived from the dose-volume histogram calculation. Differential DVHs were plotted for each target volume and beam arrangement. Irradiation techniques were compared by deriving quantitative parameters from the DVHs such as mean and integral dose delivered to the target and normal tissue irradiated, as well as by the relative volume of the examined areas. All techniques used in this study produced very similar dose distributions. The small differences confirm the capability of the studied techniques to produce the same irradiation effects. By changing from the spherical target shape to a more elliptical shape, more of the normal tissue was irradiated with higher doses. For elliptical cases we therefore identified a need for more conformal stereotactic planning.     

Quantitative changes of metabolic and bioenergetic parameters in experimental tumors during fractionated irradiation

Purpose: Previous studies with rat rhabdomyosarcomas indicate that during fractionated irradiation profound alterations of the tumor microvasculature and the oxygenation status occur when the total dose exceeds 45 Gy. At this dose a destruction which included all structures of the vessels and a significant worsening in tumor oxygenation were found. The aim of the present study was to analyze whether these effects of fractionated irradiation on the microvasculature and on tumor oxygenation also induce changes in the bioenergetic and metabolic status in the tumors during radiation treatment.

Methods and Materials: R1H rhabdomyosarcomas of the rat implanted into the flank were irradiated with ⁶⁰Co-γ-rays using 5 fractions of 3 Gy per week over 5 weeks. During this irradiation schedule, tumors were investigated each week for the microregional distributions of glucose, lactate, and ATP concentrations. For this, tumors were rapidly excised, shock-frozen and quantitative bioluminescence measurements were performed on tumor tissue sections.

Results: ATP concentrations remained unchanged during fractionated irradiation up to a total dose of 45 Gy. Above this dose, a significant decrease in ATP levels was observed. Lactate concentrations changed only slightly during irradiation whereas glucose levels increased continuously over the whole irradiation period.

Conclusions: During fractionated irradiation of R1H tumors with a total dose of 75 Gy, the bioenergetic and metabolic status of the tumors changed considerably. This became most obvious once a dose of 45 Gy had been achieved. The severe energy depletion and worsening of tumor oxygenation might be the result of destruction of tumor blood vessels as has been described previously in the same tumor model. The modification of the tumor micromilieu appears to be an important parameter in the responsiveness of tumor cells to radiation and for local tumor control.     

Comparison of different radiation types and irradiation geometries in stereotactic radiosurgery

Recent interest in stereotactic radiosurgery of intracranial lesions, and the development of stereotactic irradiation techniques has led to the need for a systematic and complete comparison of these methods. A method for conducting these comparisons is proposed and is applied to a set of currently-used stereotactic radiosurgical techniques. Three-dimensional treatment planning calculations are used to compare dose distributions for several different radiation types and irradiation geometries. Calculations were performed using charged particles (H, He, C, and Ne ions) and the irradiation geometry currently used at Lawrence Berkeley Laboratory. Photons in the Gamma Knife configuration and the Heidelberg Linac arc method are used. The 3-dimensional dose distributions were evaluated by means of dose-volume histograms and integral doses to the target volume and to normal brain. The effects of target volume, shape and location are studied. The charged particle dose distributions are more favorable than those of the photon methods. The differences between charged particles and photons increase with increasing target volume. The differences between different charged particle species are small, as are the effects of target shape and location.     

旋转式伽玛刀治疗55例听神经瘤分析

目的;分析伽玛刀（γ刀）治疗听神经瘤的疗效及适应证,并发症发生的原因及预防,方法：采用OUR－XGD旋转式伽玛刀治疗听神经瘤55例,肿瘤平均直径2．9cm,平均肿瘤边缘剂量14Gy,中心剂量33．6Gy,平均采用 等剂量曲线为48．7％,平均等中心点为4．7个,随访12－35个月,结果：肿瘤缩小41．8％,肿瘤稳定无增大50．9％,合计肿瘤生长控制率92．7％,肿瘤增大7．3％,听神经保护率40％,面神经保护率89．8％,无死亡病例,结论：γ刀治疗听神经瘤具有较高的肿瘤生长控制率,死亡纺极小,且可保护颅神经功能,是一种有效的治疗方法。