Rotary Gamma system (GS) for 2895 Clinical Cases
Rotary Gamma system (GK) for Neurosurgery (Analyses of 2895 Clinical Cases)
Yu Xin,Liu Zhonghui,Zhou Xuedong,Chen Ling,Du Jixiang,Hu Yong,Yi Weidong,Yuan Shubiao,Zhong Qiang,Li Cuining
Gamma system Center of navy general hospital Beijing China
[Outline] Objective: To evaluate the efficacy and safety of GK for neurosurgery. Methods: first we evaluated the efficacy and safety of GK using animal models. According to these data of animal models, 2895 cases with intracranial diseases were treated in our center using GK since recent 7 years. The population consisted of 1491 males and 1404 females. The mean age was 44.1 years. Etiological data of the 2895 patients were as follows: 1322 intracranial benign tumors, of which pituitary tumors 540, meningiomas 312, craniopharyngioma 185, and acoustic neuroma 113; 864 malignant tumors, of which gliomas 351, cerebral metastatic tumor 460; 319 ateriovenous malformations (AVMs); 250 functional neurological diseases. In this article we were concerned about 3 categories as follows to evaluate GK for neurosurgery: GK techniques for all diseases including therapeutic models, irradiation dose, and stereotactic methods; primary evaluation the efficacy of GK for all kinds of brain tumors; analyses of operation complications and side effects including mechanisms and managements.
Results: cure and amelioration were achieved for some selective benign diseases as follows: pituitary tumor, meningioma, acoustic neuroma, AVMs, craniopharyngioma etc; extending patient抯 survival and improving patient抯 life quality were for some malignant tumors as follows: cerebral metastatic tumor, glioma. Rate of concomitant brain edema after GK was 0.73%.
Conclusions: we conclude gamma system, a concomitance with the developments of modern high-techs, is a precise, versatile and effective operation instrument for brain diseases, which makes many brain diseases free from mankind. However, serious and deadly complication may be involved with inappropriate usage, so we must strictly follow its operation procedures, precisely locate operation targets, carefully plan irradiation dose, regularly follow up patients, and duly manage possible complications, then best outcome are deserved.
[Key words] stereotactic radiosurgery, gamma system, intracranial disease, therapy, complication, prevention.
Conventional surgery is still the chief option for intracranial space-occupying diseases; however a new treatment modality should be alternative for those lesions with complex anatomic structure and in deep brain, inclining to be involved with serious complications while gamma system is a safe and effective substitution for conventional surgery to those patients. Gamma system is based on stereotactic techniques to irradiate lesions with converging beams of highly focused ionizing radiation. With its advantages of noninvasiveness, gamma system is especially viable for indications as follows: older patients, multiple local lesions, residue and recurrence. Between December 1996 and December 2003, 2895 patients with intracranial space-occupying lesions were treated in our center using GK and we reported as follows:
1. Rotary gamma system structure and data of animal models
OUR rotary gamma system develops from static gamma system in Sweden and is designed by Chinese scientists. 30 gamma radiation sources and 4 groups of automatically rotatable collimators in different size controlled by computers are substitute for 201 gamma radiation sources and four groups of collimators in different size (4?8?14?18mm). Collimators synchronously follow sources when they circulate so as to precisely deliver gamma radiation from sources to the center of globe and converge. Besides two parts above, each gamma system therapy unit consists of treatment planning computer system, image system, and sterotactic helmet.
Before we applied GK to clinical medicines, we had verified its reliability, safety, and effectiveness on animal models with gods and rats. We determined different biological reactions after radiation with different dose and different size collimators and explored mechanisms of injury after stereotactic radiosurgery. The results of animal models were accordant with other literatures.
2. Application to clinical medicine.
With the excellent performances of OUR gamma system demonstrated by animal models, it was introduced into clinical applications. Between December 1996 and December 2003, 2895 patients with intracranial space-occupying lesions were treated in our center using GK. The population consisted of 1491 males and 1404 females. The mean age was 44.1 years. Etiological data of the 2895 patients were as follows: 1322 intracranial benign tumors (45.66%), 864 malignant tumors (29.84%), 428 cerebral vascular diseases (14.87%) 250 functional neurological diseases (8.63%), and 31 other diseases (1.07%). Details go as follows.
2.1 Treatment for AVMs:
AVMs were our chief indication for GK and had best outcomes, especially for those with small size located in deep brain. In 7 years, 428 cerebral vascular diseases (14.78%) were treated in our center using GK, of which 319 cases (74.53%) were AVMs and 109 cases (25.47%) were cavernous hemangiomas. Indications of AVMs for GK are as follows: 1) AVMs are located in eloquent functional areas and neurological deficits are likely involved with conventional surgery and embolization therapy. 2) The mean diameter was no more than 3cm. 3) The residues after conventional surgery or embolization therapy. 4) Patients are unable to tolerant conventional surgery or embolizaiton for their physical morbidities. 5) Patients insist on GK.
The mean central dose was 37.5Gy (range 5-50Gy) and the mean peripheral dose was 19Gy (range 13-25Gy).10 we found that the rate of obliteration was significantly raised when we used multiple isodose centers to distribute irradiation uniformly encompassing AVMs niduses. In this group, 254 AVMs were followed up at least 24 months; the rate of complete obliteration was 60.2% and 80.5% with 1 year and 2 years of follow-up respectively; the smaller the nidus the earlier complete obliteration; nearly all AVMs with a single feeding artery were complete obliteration in 1 year after GK surgery (figure2). It was reported by Steiner et al11 that 403 of 503 AVMs followed up for 2 years after radiosurgery were complete obliteration (80%). Coffey et al12 reported of 121 cases the rate of complete obliteration was 72 two years later after GK surgery. Flicknger et al13 reported of 197 AVMs, with peripheral dose of 16-20Gy, the rate of complete obliteration was 70%~90% one year later after radiosurgery. According to our experiences and reports from other scholars.A conclusion can be made that GK was safe and effective for AMVs with few complications and most patients can be permanently cured using this method.
2.2 Treatment for brain benign tumor:
Cerebral benign tumors located in deep brain or skull base are chief indication of GK. With high resolution MRI involved in the orientation of target, lesions can be depicted directly and clearly, irradiation dose can be exactly planed, and safety can be ensured. So GK surgery is a precise, effective and noninvasive operation for brain tumor.
2.2.1 Treatment for acoustic neuroma(AN)
GK was first used to treat acoustic neuroma in 1969, since then, especially after CT or MRI was applied, ten thousands cases have been treated using GK and have good outcomes14.15. The indication of acoustic neuroma for GK is as follows: 1) Tumor diameter<2.5cm. 2) Residues after microsurgery. 3) Bilateral tumors and small size. 4) Infirm older patients or patients unable to tolerant general anesthesia with small or middle size. Acoustic neuroma is characteristic of benignity and slow growth. Only if tumor growth is under control, new signs of compression or involved with cranial nerve will not be present. The principles of GK to treat AN is that first tumor stops to grow and then tumor shrinks and necroses, which is a long term procedure. So GK for AN is reasonable16. Norien et al16 reported that: of 400 patients with AN treated using GK, the rate of tumor control at 1, 2, 4, 10years follow-up was 32%, 40%, 64%, 91% respectively.
In our study, 113 patients with AN were treated using GK, accounting for 8.54% of benign tumors. The population consisted of 64 males and 49 females. The mean age was 48.38 years (range (10-85years). 105 patients had unilateral lesion and 8 patients had bilateral lesions. The mean peripheral dose was 13Gy (range 9~24Gy). The mean central dose was 37.5Gy (range 20~65Gy). Because the borders of tumors were clear, more attention about dose planning was focused on the protection of brain stem and prevention brain edema. 6 patients underwent ventricle-shunting operation; 10 patients had hearing reduction in some extent. No patients had acute irradiation reaction. The rate of symptoms relief was 80% and the rate of tumor control was 59.42% during 1~4years of follow-up after radiosurgery (Figure 3).
2.2.2 Treatment for meningiomas (MG)
Microsurgery resection is still best option for MG. Since Kandziolka et al (1991) first reported that GK was used to treat MG, the GK surgery for MG has been developed widely all around the world. The indications of MG for GK were as follows: 1) Tumors located in internal sphenoid crests or sponge sinus inaccessible for conventional surgery or apt to involved in neurological deficits.2) Older patients intolerant to craniotomy. 3) Base residues after conventional surgery18.19. Duma20 assumed the indication of MG for GK as follows: small, in deep brain, and border clear, or residues base and bed. In our study, 312 patients had MG, accounting for 10.77% of all patients and 23.06% of benign tumors; most of MGs are located in pyramis, skull base, sponge sinus or other sites inaccessible for conventional surgery; the mean tumor volume were 7.2cm3 (range 2.5-30cm3); 46 of 312 patients were postoperative recurrence; 35 of 312patients were too old to tolerate surgery(>70 years); 231 patients had been followed for 1~6 years and the rate of tumor control( tumor stops to grow) was 92.64%(214 cases).
2.2.3 Treatment for pituitary tumors (PT)
Since GK was first used to manage PT in 1986, it has been accepted an effective method for PT21.22. Between December 1996 and December 2003, 540 patients with pituitary tumors were treated in our center using GK, accounting for 40.84% of benign tumors. The population consisted of 212 males and 328 females. The mean age was 44.39 years (range 10~83years). Etiological data of the 540 patients were as follows: 310(57.04%) of 540 tumors were microadenoma( diameter=1.0cm); tumor diameter of 119 tumors (22.04%) ranged from 1.0cm to 2.0cm; 110 tumors (20.56%) were recurrence or residue after surgery. Prescription dose was as follows: the mean central dose was 32.7Gy (range 17~66.7Gy); the mean peripheral dose was 13.5Gy (range 8.5~30Gy); the mean percentage of isodose line was 45 %( range 35%~60%). The mean isodose centers were 4 (range 1-13) with collimators diameter in 4~8mm. In our study, during 1~3 months after radiosurgery , no patients had side effects or complications and no patients had optic cross injury or optic nerve injury; 458 patients were followed up for 6months-5years;268 of 310 microadenomas were followed and rate of tumor control was 98.13(263 cases). 130 of 230 big adenomas were followed and rate of tumor control was 95.26 %( 181 cases) (Figure4).
Our experiences went as follows: the best indication of GK for PT was the small adenoma located in pituitary fossa without implication of optic nerve and optic cross because it is easy to precisely focus without damage to normal pituitary functions. Although it is not viable for a big adenoma, GK is still a appeasable method for patients who are unable to tolerate surgery or unsuitable for surgery if we divide the period of treatment. We suggest careful irradiation dose be applied to protect optic systems. After the feasible first irradiation dose is applied to reduce tumors, then in 3~6 later the second therapy can be followed. The indications of PT for GK we use are as follows: 1) parts of residues after microsurgery implicating sponge sinus; 2) residues of massive tumor after the decompressing of optic cross using surgical resection; 3) microadenomas; 4) recurrence of endocrine adenomas after surgery or extraradiotherapy, especially for ACTH cell adenomas on condition of protection of normal pituitary; 5) PRL cell adenomas residues after surgery.
2.2.4 Treatment for craniopharyngiomas
185 patients with craniopharyngiomas were treated in our center using GK, accounting for 6.39% of 2895 tumors and 13.99% of benign tumors. The population consisted of 106 males and 79 females. The mean age was 25.74 years (range 3~74years). The nature of the tumor was classified as solid in 74, cystic in 42, and mixed in 69 cases. For cyst, cyst formation after surgery and mix with large cyst, intracavitary irradiation was initially applied and then GK was applied to obliterate solid part with excellent outcome. We designed to use GK in combination with intracavitary irradiation in a single treatment to treat 90 mixed tumors as follows: The male/female ratio was 53:37. The mean age was 38.9years (range 3~70years). The mean period of history was 50months (range 1~252). Surgical treatments prior to GKS included craniotomy resection for 1 or 2 times but recurrence in 34, extracranial irradiation in 17, insertion of a VP shunt in 9, pure intracyst radionuclide irradiation in 20 cases. Material and methods of combination treatment were as follows: large solid and small cyst mix in 40, small solid and large cyst mix in 33,and multiple cysts and small solid in 13 cases; The mean volume of tumors was 14.5ml (range 1.4~49 ml); GK was first used to treat solid part, and then cyst fluid was extracted out, finally p32 nuclide was infused into cyst; the mean central irradiation dose was 27.5Gy (range 20~40Gy); the mean peripheral irradiation dose was 12Gy (range 8~20Gy); if the volume of cyst viscera was more than 30ml, the tumor was drained for at least 2 or 3 days to reduce the tumor volume and then drugs were infused into cyst ;in 1~3 months later after radiosurgery no patients had serious complications or injury of optic nerve and hypothalamus;60 patients were followed for 2~4 years (mean 2.5years) Results of combination treatment were as follows: 45 of 60 patients (75%) had excellent tumor control(disappeared and decreased); 10 of 60 patients (16.67%) had good tumor control(decreased and unchanged); 5 of 60 patients (8.33%) had poor tumor control(tumor enlarged and aggressive eyesight decreased); the total rate of tumor control was 92.5%23.24. Our data of patients and results were accordant to those from Prasad et al25.
2.3 Treatment for malignant brain tumors
864 patients with malignant cerebral tumors were treated in our center using GK, accounting for 29.84% of all tumors. Etiological data of patients were as follows: gliomas 351(40.62% of malignant tumors), cerebral metastatic tumor 460(53.24% of malignant tumors), and other malignant tumors 53( 6.14% of malignant tumors)
2.3.1 Treatment for metastatic tumors
Metastatic brain tumors, a serious malignant central nerve disease in neurosurgery, are rising at rate of morbidity only inferior to gliomas in malignant brain tumors. The aggressive and multiple lesions always have bad outcomes and short-term survivals. 460 patients with metastatic brain tumors were treated in our center using GK. Materials and methods were as follows: 184 of 460 patients had single focus, 190 patients had 2~4 focuses( 655 focuses), and 86 patients had 5~12 focuses( 614 focuses were treated using GK); The male/female ratio was 266:194; The mean age was 56.89years(range17~81years); data of original focuses were as follows: lung cancer in 285 cases, other cancers in 113 cases from kidney, breast, recta, stomach, esophagus, larynx, and thyroid., and original focuses of 62 (13.48%) cases were not found before radiosurgery; data of irradiation dose were as follows: the mean percentage of isodose line was 45% (range 35~60%), the mean central dose was 37.5Gy (range 20~42.5Gy), the mean peripheral dose was 12.9Gy( range 14~15Gy); 246 patients were followed after radiosurgery, of whom survival term of 143 patients(58.1%) was 12 months and survival term of 69 patients(58.1%) was 24 months. Rate of local tumor control at 1 and 2 years of follow-up was 87.4%(125/143)and 75.4%(52/69), respectively. It was reported by Moriarty et al26 that good outcome was achieved for 357 metastatic brain tumors with 643 tumor lesions, which consisted of single, dual and more than three focuses at rate of 60%, 20% and 20% ,respectively. Flickinger et al27 reported that 116 patients were treated using GK, of which 51 patients using GK alone and 65 patients using GK in combination with extraradiotherapy; the rate of local tumor control was 85%, the mean survival term was 11 months, and rate of tumor control at 2 years was 67�8%.
Our evaluation of GK for metastatic brain tumors was that: not only short term outcome was good but also multiple lesions incurable in past time still could be treated using GK and both survival term and life quality were improved; new recurrent lesions could be treated using GK again after the first radiosurgery. Of new recurrent patients 1 or 2 years later after the first radiosurgery, 22 patients underwent the second GK therapy and 8 patients underwent the third GK therapy. No patients had serious brain edema or cerebral hemorrhage. 2~3 months later after radiosurgery tumor shrinkage or disappearance could be detected while brain edema around obviously abated (Figure6). So GK should be advocated as an effective method to treat brain metastatic tumors.
2.3.2 Treatment for gliomas
Recently more and more reports28-30 concerned about GK for gliomas were published. Initially, most therapeutic studies for gliomas using GK were confined to lower grade tumor (I~II grade), however its therapeutic indications have been expanded to some extent, but it is still in clinical probations and long term outcome is still being observed. The indications of gliomas for GK we use are as follows: 1) I~II grade tumor with location inaccessible for conventional surgery; 2) tumor diameter is no more than 35mm and tumor boundary is clear; 3) tumor basement after surgery; 4) patients are unable to tolerate convention surgery, radiotherapy or chemotherapy and insist on GK therapy. Results of our study showed that some I~II grade gliomas had good short-term outcome(disappeared or inactive) and patients� manifestations ameliorated after combination treatment with GK surgery, however, boundaries of some gliomas aggressively enlarged to form a larger lesion, so GK must be weighed for gliomas carefully according to its indications31.
2.4 Complications after GK surgery
Main complications after GK surgery include reactive brain edema, seizure, and hemorrhage with lower possibility. When lesions are located in cortex, postoperative antiepilepsy medications and cortisone for 2~3 weeks are necessary for patients to prevent seizure. There two categories involved with brain edema after GK surgery as follows: acute reactive brain edema is one of the two categories, which only accounts for minority and can be treated using feasible cortisone and dehydration agents. The other is delayed brain edema, which occurs generally in 3, 6 months or more later after GK surgery, so patients should be regularly followed up using CT or MRI and be managed in time according their conditions with comprehensive treatment including dehydration. Data of complications in our study were shown in table1. The characters of brain edema after GK surgery are as follows: located in tumor periphery, in different degree, without serious clinical symptoms or initial symptoms aggression. Most complications present 1 or 2 months later after GK surgery, of which the most can be cured in time with dehydration agents. Craniotomy decompression is unnecessary unless signs of high intracranial pressure are confirmed. Data from table1 showed most brain edema is middle tumor peripheral edema, and could be cured using dehydration agents. No patients died or had brain hernia induced by serious brain edema. So patients should be followed up when clinical conditions become aggressive and timely dehydration agents and cortisone can contribute to an excellent outcome. In our study no patient died or had hemorrhage.
Table1 brain edema after gamma system surgery between December 1996 and December 2003 Aohai gamma system center navy general hospital
Etiology Number of cases(unit) Number of edema(unit) Rate of brain edema (%)
AVM&CHM 428 3 0.70
Benign tumor 1322 3 0.23
Glioma 351 7 1.99
BMT 460 5 1.09
FBD 250 2 0.8
Other 84 1 1.19
Total 2895 21 0.73
Note: AVM: ateriovenous malformation, CHM: cavernous hemangiomas, BMT: brain metastatic tumor, FBD: functional brain disease
Data of an unusual case in our study with acute brain edema after GK surgery are reported as follows: a female patient(45 years old)was diagnosed AVMs with chief complaint of sensible seizure and left leg weakness. A 2.5cm AVM was detected in the left external parietal lobe by MRI. On August 28, 1997 she underwent GK surgery and its procedure was fluent. The prescription irradiation dose was follows: central dose was 40Gy, peripheral dose was 20Gy and the percentage of isodose line was 50%. She had focal seizure 2 hours later after GK surgery, acute CT examination showed no hemorrhage then she was prescribed dehydration agents and cortisone continuously. But in 20 days later after GK, peripheral tumor edema was detected by MRI and she was admitted to our ward. Although she had been treated using dehydration agents and cortisone, aggressive edema deterioration was showed on repeated MRI, and on 50 days after GK, brain edema obviously enlarged and left limb weakness became aggressively deteriorated. On 5 months later after GK surgery brain edema peaked without manifestation deterioration and seizure recurrence. Her left limb muscle power was graded in the second level. Brain edema began to fade away on 8 months later after GK surgery and meanwhile her left limb gradually resumed. She underwent MRI followed-up at 12, 20, 32months after GK surgery while her brain edema fade away and AVMs completely obliterated.
From the case above, once the reactive brain edema is confirmed, active and continuous dehydration in combination with other comprehensive treatments is necessary for an outcome while craniotomy is not advocated unless high ICP is definitive because reactive brain edema develops very slowly
Figure1 Results of animal models: (A)lesion on animal 1 month later after irradiation with 180Gy. (B) necrosis and cell degeneration in pathology
Figure2. The comparison between preradiosurgery and postradiosurgery with gamma system of an AVM DSA image. A and B: the A-P DSA image and lateral DAS image of AVM after embolization, residue of magnitude AVM located in right thalamencephalon after embolization on A and B. C and D: the A-P DSA image and lateral DAS image of AVM 24 months later after gamma system, AVM complete obliteration
Figure3 Female, 65 years old, right vestibular schwannoma. (A) Before gamma system therapy (B) 1 years after gamma system therapy. MRI showed tumor shrinkage and necrosis in tumor center
Figure4 male, 38 years old. (A) Before gamma system therapy; (B) 2 years after gamma system therapy. MRI showed tumor obliteration.
Figure5 male, 36 years old, craniopharyngioma. (A) Before gamma system therapy; (B) 2 years after gamma system therapy. MRI showed tumor obliteration.
Figure6 male, 35 years old. Multiple metastatic brain tumors from lung cancer. (A) Before Gamma system therapy; (B) 1 year after gamma system therapy. CT showed tumors obliteration with lower density lesion. Presentations of patients were free.
Figure7 Acute brain edema after gamma system therapy: occurrence, development, an
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