Management of brain metastatic tumor
Clinical analysis of management of brain metastatic tumor with MASEP- Gamma System
Yuan ShuBin, Liang Xin, Wen Wu, Feng HuaiZhi, Zhou YanQiong, He YueJun, Li XueMei, Wang YongJun
Gamma system management & research center of Air-force ChengDu hospital
[Outline] Objective: Retrospective analysis of method and therapeutic effect of brain metastatic tumor (BMT) managed with MASEP-gamma system (GK).
Methods: 262 cases with brain metastatic tumor were treated using GK, of which 182 cases with 276 nidi was paid follow-up visit. Among 39 cases with single metastatic tumor, 21cases were with mere gamma system radiosurgery (GKR) and 18 cases treated with GKR plus whole brain radiotherapy (WBRT). Whole brain radiotherapy was undergone before and after GKR to 143 cases with multiple metastatic tumors. Results: 182 cases were followed up for 6 to 28 months, of which 110 (60.49%) complete remission, 62 (34.1%) partial remission, 7 (3.8%) with no improving and 3 (1.7%) deterioration. Survival time ranged from 3 to 28 months (mean 14 months). 76 cases (41.8%) survived exceeding 12 months, 82 cases (45.1%) survived exceeding 24 months. There was no significant difference between two managements as to 39 cases with single metastatic tumor (P>0.05).
Conclusion: Brain metastatic tumor treated with GKR proved safety, high efficiency, little complication, reliable curative effect, living quality enhancing and survival time prolonging. Single or less than 3 metastatic tumors could cure by one-time treatment or interval treatments with GKR, which avoiding side effect of whole brain radiotherapy (WBRT).
[Key words] Brain metastatic tumor (BMT) Gamma system (GK) Whole brain radiotherapy (WBRT)
Brain metastatic tumor was a frequent intracranial malignant tumor. From August 2001 to December 2003, 1280 cases with intracranial diseases was treated with Rotated Gamma system (MASEP,China) ,including 262 cases with brain metastatic tumor ,which accounted for 20.5% of 1280 cases , 25.5% of intracranial tumor and 51.5% of intracranial malignant tumor. In this paper we retrospectively reviewed 182 cases with a follow up ranged from 6 to 28 months.
Materials and Methods
182 (112 males and 70 females) consecutive patients� age ranged from 22 to 83( mean 51.3), of which 109 patients (59.9%) above 50 .99 lung caners (54.4%),56 alimentary tract tumors(30.7%), 7 nasopharyngeal carcinomas (3.8%),5 renal carcinomas (2.7%), 5 breast tumors(2.7%) and 10 tumors with unknown original focus(5.9%) were studied. 39 patients (21.4%) had single brain metastatic tumor. 143 patients(78.6%)had multiple brain metastatic tumor, totaled in 276 nidi, of which 223 nidi(80.8%)located in cerebrum,28 (10.1%)in cerebellum and 25 (9.1%) in brainstem.
55 of 182 cases was removed original focus, 12 of 182 cases underwent brain metastasectomy before GKR.
Gamma system Radiosurgery: 39 single metastatic tumors were irradiated using 40%~50% isodose curve,with marginal dose 15~25Gy(mean 23.8�4.3Gy) and central dose 30~58GY(mean 42.5�8.6Gy). 9 cases , tumor size >3cm in diameter, were irradiated twice with 1~3 days� interval. 18 cases underwent whole brain radiotherapy after GKR.
143 multiple metastatic tumors(no less than 2 foci)were irradiated using 40%~50% isodose curve,with marginal dose 12~25Gy(mean 19.7�6.1Gy) and central dose 24~58GY(mean 32.5�9.7Gy). 5 cases were irradiated twice with 1~3 days� interval. All cases underwent whole brain radiotherapy after GKR. In 22 recurred cases ,16 cases underwent twice irradiation , 4 cases underwent thrice irradiation and 2 cases underwent four times irradiation with GKR.
3. Evaluation of therapeutic effect
MRI or CT was performed per 2~3 months after GKR. Curative effect and prognosis of brain metastatic tumor were appraised by evaluation criterion of World Health Organization (WHO), accordingly. Evaluation of therapeutic effect was listed as followed: Complete remission: tumor disappeared for no less than 1 month; Partial remission :tumor shrank no less than 50%; No improving: tumor shrank less than 50% or accreted less than 25%;Deterioration:mono- or multi-focus accreted more than 25% in size.
182 cases were followed up for 6 ~ 28 months (mean 14.5 months). According to clinical symptom and physical sign , 127 cases (69.8%)with complete remission, 48 cases (26.1%)with partial remission and 7 cases (4.2%)with no improving were recorded .Scanned by MRI and CT, 110 cases (60.49%)with complete remission, 62 cases(34.1%) with partial remission,7 cases(4.2%) with no improving and 3 cases(1.7%) with deterioration were recorded, too. Rate of tumor growth control was 94.5%. Survival time ranged from 3 to 28 months (mean 12.9�3.6 month). 76 cases(41.8%) survived exceeding 12 months ,82 cases (45.1%)survived exceeding 24 months. 4 cases (2.2%)died within 3 months, 8 cases died within 6 months,12 cases (6.6%) died within 12 months and 76 (41.7%)cases died within 24 months .6 cases(3.3%) had local cystido-necrosis complication.
39 cases with single metastatic tumor were treated with single GK or GK plus whole brain radiotherapy (WBRT) (seen Table 1)
Intracranial metastasis happened in 30%~50% tumor all of the body1,2.Posner JB presumed that survival time of brain metastatic tumor ,manifested by clinical symptom , would no longer than one month without management. Surgical intervention and whole brain radiotherapy ,by which 70%~90% cases would palliated ,were major therapeutic tool to brain metastatic tumor; however, 50%~70% patients survived within half year and 15% of them survived more than one year after tumor resection3 . Furthermore, it was difficult to undergo surgical therapy for multiple brain metastatic tumors, and side effect of whole brain radiotherapy could hardly improve living quality. Therefore, exploring a lower-risk approach, with curative effect surpassing surgery and radiotherapy, was a common concerned issue. Since the first time application by Kihstrom L in 1975,GKR was, as many studies and cases reported, proved an ideal method to manage brain metastatic tumor with safety, few complication, and reliable curative effect, significant enhancement of living quality and prolongation of survival time. Research data manifested that, in recent 10 years, the cases of brain metastatic tumor cured with GKR increased more than 10,000 per year. Till December 2003, the cases of brain metastatic tumor treated with Leksell Gamma Knife were 81859, accounting for 32.5% managements with GK and 78.0% managements of all malignant tumors in the world, contemporaneously. We managed 262 cases with GK from August 2001 to December 2003, accounted for 20.5% managements with GK, 25.5% managements of intracranial tumor and 51.5% managements of all malignant tumors, contemporaneously.
Good therapeutic effect of GK lied in radiation biological character of brain metastatic tumor, which was as an early reaction tissue. Commonly, brain metastatic tumor was located at the juncture of grey matter and white matter and not easy to cause nervous functional disturbance; in addition, the tumor had distinct boundary and irradiation field of vision covered whole tumor easily .High-dose single dissection of GK was rapidly effective and achieved ideal control of tumor growth. Theoretically, local control rate of GK to brain metastatic tumor was 81.5%~100%6-8.In our study, of 182 cases with 6~28 months follow up, there was 94.5% of local control rate with 41.8% survived no less than 12 months , 45.1% survived no less than 24 months. A thyroid follicular adenocarcinoma, original focus was dissected in 1981. In August 2002, intracranial metastasis of this follicular adenocarcinoma was found with metastatic focus located at white matter of left top cerebrum and invaded into right and left body of lateral cerebral ventricle, manifested headache, dizzy and paralyzed right limbs. After irradiated with GK using 40% isodose curve,with marginal dose 14Gy and central dose 35Gy, clinical symptom obviously relieved and patient could walk on foot up and down six floors within one month, tumor significantly shrunken scanned with MRI within 3 months. Reiradiation was performed with GK ,using 50% isodose curve,with marginal dose 14Gy and central dose 28Gy, no novel metastatic focus was found in intracalvarium for 24 months.
Another advantage of GK was that multiple foci of brain metastatic tumor underwent therapy simultaneously. The number of foci managed at one time by GK depended on focus size and position, hydropsy degree of brain tissue around tumor and general state of health. Voges J,et al found that9,after accelerator radiosurgery therapy, threshold dose of radiolesion of normal brain tissue around target area was 10Gy .When volume of brain tissue ,covered by 10Gy isodose curve ,no more than 10ml, radiation damage incidence rate was zero; while volume more than 10 ml , incidence rate up to 23.7%. Effective marginal dose was 18~25 Gy and higher than radiation tolerance dose, of small field of vision and single irradiation, of normal brain tissue around target area. As an early reaction tissue of brain metastatic tumor, it became quickly effective treated with GK , acute intracranial hydropsy was rapidly relieved after tumor growth under control and hydropsia subsided around carcinoma .Gamma system was characterized as high focus percision ,descended and steep dose curve, which could reduce radiation lesion of normal brain tissue around target area. We discovered that ,as to multiple brain metastatic foci less than 2cm in diameter , 3~6 foci could be therapy at one time, using 40%~50% isodose curve with marginal dose 16~18Gy. Regarding to multiple foci with 3~5cm interval ,in order to avoid multiple foci being treated separately,and thus decrease normal brain tissue damage by superposition of radiation ,we scheduled same dose program and regulated irradiation weight to assure each focus center received optimal radiation dose and normal brain tissue around focus received minimum radiation dose, simultaneously.
There was no significant difference between two managements as to 39 cases with single metastatic tumor (P>0.05), of which 21 case underwent mere GK irradiation, 18 cases underwent GK irradiation plus whole brain radiotherapy. For certain complications and inability to prevent secondary metastasis of whole brain radiotherapy 10, single metastatic tumor or 2~3 multiple metastatic tumors with diameter less than 3cm could undergo single or twice irradiation with high dose GK only. At the same time, it would achieve ideal tumor local control rate.
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