Fractionated stereotactic radiotherapy with the Leksell Gamma Knife: feasibility study

IR ADIDTHERAPY a 0 ELSEVIER

NCDLDGY

Radiotherapy and Oncology 37 (1995) 108-l 16

Fractionated stereotactic radiotherapy with the Leksell Gamma Knife: feasibility study Gabriela Simonovh, Josef Novotnf, Josef Novotnq Jr., Vilibald Vladyka, Roman Li,%hk Hospital Na Homolce, Stereotactic and Radiation Neurosurgery Department, Roentgenova 2, ISI I9 Prague 5, Czech Republic

Received 18 November 1994;revision received 17 August 1995;accepted 29 August 1995

Abstract

The main aim of this study was to check feasibility of stereotacticradiotherapy,which is routinely practisedon linear accelerators,usinga fixed Leksellstereotacticframeand a LeksellGammaKnife. The study refersto the first experienceswith 48 patientstreatedby a fractionatedregimen(in 2-6 days).Isoeffectrelationshipscalculationsbasedon the linear-quadraticmodel and the levels of applied radiation doses,taking into account radiobiology of the tumour, tumour volume, critical structures surrounding the treated lesion and other factors are discussed.The procedure for quality control during the whole fractionated regimen is described. The study has shown that stereotactic radiotherapy with the Leksell Gamma Knife is feasible. However, only early effectscan be discussedand there are still questions remaining which should be carefully studied: tolerance dosesfor critical struc-

turesat fractionation,definition of an ‘ideal’ fractionation regimen,andjustification of the linear-quadraticmodelin the caseof stereotacticradiotherapy. Keyworcis:

Fractionated stereotactic radiotherapy; Isoeffect relationships calculations; Leksell Gamma Knife; Early and late re-

spondingtissues

1. Introduction Stereotactic radiosurgery (SR) is the treatment of small lesions (max. diameter 30 mm) in the brain using external beam radiation. The treatment is performed in one single high dose fraction. The beams are guided to the desired point within the brain using a very accurate, 3-dimensional imaging procedures [ 171. Stereotactic radiotherapy (SRT) is the treatment of small or medium lesions in the brain with fractionated regimens employing the stereotactic method. This procedure differs from conventional external beam radiotherapy (EBRT) in that the volume of the lesion is usually smaller, the number of fractions delivered is much smaller, and the dose per fraction is much larger. The strategy of stereotactic radiosurgery or radiotherapy is to use the delivery of a high radiation dose to a well-defined volume of the target lesion to * Corresponding author.

effect the desired biological result, while sparing adjacent normal tissues. SR with the Leksell Gamma Knife (LGK) has been in clinical use for more than 25 years. A single large dose given during the SR treatment is an adequate and effective treatment modality for small arteriovenous malformations (AVMs), functional disorders or benign tumours, with good results reported by many authors [ 11,20,22,26].The treatment of malignancies (only small limited volumes) with this method started in the late of 1980s.One single large dose has been also accepted as a proper treatment modality for small solitary brain metastaseswith minimal rate of complications [4,12,21]. However, from our own experience, when larger volumes (more than 10 cm3) or volumes with large collateral edema are treated, the occurrence of acute side effects (progression of edema and neurodeficit) increases.In addition, the basic radiobiological principles and experience of EBRT accumulated over the past 75 yearshas indicated improvement of the therapeutic ratio in the caseof fractionated regimens in the treatment of

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malignant tumours. Although there are differences between EBRT and SRT (especially with regard to the volume of treatment targets and in the quality of accessible dose distribution), the main biological principles should remain for the sameboth methods. Fractionated SRT with the LGK for small intracranial volumes can be a compromise between the large number of fractions in EBRT and a single large dose used during SR. The tolerance of normal glial and vascular tissues limits the dose that can be delivered in brain tumours. These tissues exhibit slow rate or absenceof sublethal radiation damage repair. Therefore, the tolerance of thesetissuesto irradiation may be increasedby reducing the dose per fraction. It is well known that the tolerance doses for critical structures in the brain using a fractionated regimen are larger than for single large doses. Since tumour death is influenced more by the total dose than the dose per fraction, fractionated regimens, in comparison with a single large dose, allow to apply higher total tumour doses and increase tumour local control without increasing complication rate. On the other hand, the small number of fractions should remain one of the potential advantagesof SR and SRT because large fractions are more effective at killing radioresistant tumours (e.g., malignant melanoma) whilst adding all the radiobiological advantages of fractionation. Linear quadratic formalism is a generally accepted tool in the field of radiotherapy for comparing the early and late effects of the different fractionation schemes [S-10,13,16,18]. Malignant tumours which, from a radiobiological point of view are early responding tumours, are tissues containing hypoxic cells. Normal brain tissues (critical structures) are typically late responding tissues,composedentirely of aerated cells. The radiobiological studies [8- 10,13,16,18]suggestbetter results in terms of therapeutic ratio between tumour control and complications with a fractionated regimen than with a single large fraction, which should be an important consideration in the treatment of brain malignancies. The main aim of this study was to check the feasibility of stereotactic radiotherapy, which is practised routinely on linear accelerators, using a fixed Leksell stereotactic frame and a Leksell Gamma Knife. As far as we know there is no systematic study dealing with the possibility of the use of the LGK for fractionated stereotactic radiotherapy.

tumour repopulation; (c) large number of fractions to allow reoxygenation of the hypoxic cells to make them more sensitive to the subsequent irradiation fractions and to maximise sparing of critical late-responding normal tissues. Although requirements (a) and (b) are mutually exclusive we can resolve them in the case of SR or SRT without the need for essential compromise in contrast with EBRT. Because SR and SRT of intracranial tumours with the LGK represents a special situation where excellent dose distributions can be obtained, the need for long overall treatment times to reduce early normal-tissue complications will rarely apply. Specifically, early skin or mucosal reactions are not a problem with intracranial SR and SRT [ 1,2,19]. Thus, short overall treatment times can be used despite requirement (a). Isoeffect relationships calculations based on the linear-quadratic (LQ) formalism [8- 10,13,16,18] were used for prediction of suitable treatment regimens. Mathematically it can be written

2. Metbod

BED = D(l + dl(ollp)) - 0.693(No. of cell doublings)ar (5)

SFd= exp(-crd - @d2)

(1)

where SFd is a surviving fraction of target cells after a dose per fraction d, the ratio CY//~ (the dose at which the cell killing by the linear and quadratic terms in Eq. 1 is equal) tends to be smaller for late-responding tissues ( - 2 Gy) and larger ( - 10 Gy) for early-responding tissues[8,10,16,18].Using LQ (Eq. l), one can expressthe effect E [10,13,18] of n fractions E = D(CY+ /%I)

(2)

where the total radiation dose D = nd. Dividing both sides of Eq. 2 by CY,biologically effective dose (BED) is obtained [ 11,161. The BED for radiosurgery dose (RD), in the caseof SR and for total fractionated dose (D) in the case of fractionated SRT can be expressed BED = RD(1 + RD/(a@)) BED = D(1 + d/(0//3))

(3) (4)

Eq. 4 is an approximation of the following more precise expression (Eq. 5) [16] where cell proliferation during treatment is included

2.1 Isoeffect relationships calculations

The optimal strategy for any radiotherapeutic regimen used for the treatment of malignancies requires [2,8,18,23,26]: (a) long overall times to reduce early normal-tissue sequelae; (b) short overall times to limit

Considering that overall treatment times are short (a few days), we can assume,for simplification of calculations, that the last term in Eq. 5 is negligible and use Eq. 4 [16]. Without this approximation, the D corresponding to an equivalent given RD would be slightly larger

110

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tion for each fraction must be guaranteed. It can be realised in several ways: (a) Attach the stereotactic frame again, perform a new stereotactic examination and make a new doseplan before eachfraction. This is the most accurate, but timeand cost-consuming method. (b) Use a relocatable stereotactic frame which makes it possible to use the identical position every time. At least two relocatable stereotactic frames are commercially available [13]. The Laitinen frame 1151provides fixation by meansof ear plugs and a nasal support, and the Gill-Thomas-Cosman frame which is stabilised with an oral appliance [7]. Fig. 1. Doses for fractionated sterotactic radiotherapy, in terns of tumour control (&!I) = IO Gy), providing the equivalent Biologically Effective Dose for Total Fractionated Dose (D) and Radiosurgery Dose (RD). (Calculated by using equation 3 and 4).

than that shown in Fig. 1. Using Eqs. 3 and 4 one can easily find relationship for D (as a solution of a quadratic equation) like a function of RD, n and ratio o/o. Ratio a@, in terms of tumour control, has been usedas a value for early-responding tissues(10 Gy). The LQ model can be probably used also for prediction of the treatment regimen for benign tumours if the proper or/@ratio is chosen (e.g., for meningiomas, 2 Gy) [8-10,13,16,18]. The relationship between D, RD and number of fractions, providing the equivalent BED is presented in Fig. 1. For every patient, radiosurgery dose (RD) was set first, and then the number of fractions n in which total fractionated dose (D) was delivered was decided depending on the histological type and the volume of the treated intracranial tumour, or other conditions such as limitation for critical structures and previous treatment (radiotherapy or neurotoxic chemotherapy) (see Table 1). The limit of RD in case of previous EBRT is dependent on total applied dose, irradiated volume and fractionated regimen. Detailed evaluation is based on LQ model and tolerance doses [3,6]. All treated patients were subjected to one fraction per day. Hyperfractionation, i.e., the use of more than one fraction per day is another challenge of SRT. 2.2. Stereotactic fixation and quality assurance during fractionated stereotactic radiotherapy with the LGK To achieve the same accuracy of delivering the prescribed absorbed dose during the whole course of fractionated SRT with the LGK, as for a single dose irradiation, high precision and reproducibility of irradia-

(c) Use a framelesssystem.Instead of the stereotactic frame the reference Iiducal markers (small metallic objects) are fixed to the patient’s skull bones, creating a permanent reference system. The target can then be precisely located with respect to the markers. The patient is immobilised using a thermoplastic mask, a head ring, or a relocatable frame. (d) A stereotactic frame is left on the patient’s head for the whole course of the stereotactic fractionated treatment (from the first to the last fraction). To ensure the required accuracy of dose delivery during each fraction to the target volume, a control procedure testing the unchangeableposition of the frame must be used during the treatment. An example of this method is given in ]231. Since the relocatable frame or reference markers are not available with the LGK system,and method (a) was discarded due to the complicated and time-consuming procedure, only method (d) could be used with the LGK system. Consequently, the Leksell stereotactic frame was attached and left on the patient’s head from the first to the last fraction (for our group of patients it was maximally 6 days, see Table 1). To guarantee the required precision of dose delivery, the position of the frame on the patient’s skull must be verified during the whole treatment regimen (2-6 days). The following independent control methods were developed and practised during fractionated treatment. Method 1 The Leksell Skull Scaling Instrument (Elekta Instrument, Sweden) was attached to the stereotactic frame fixed on the patient’s head to measurethe distances between the centre of the Leksell stereotactic space and certain significant points on the outer boundary of the patient’s skull. The skull scaling instrument is a partial sphere drilled with 24 holes at predefined points on its surface with guiding channels directed to the centre of

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Table 1 Survey of 48 patients treated by fractionated stereotactic radiotherapy with the Leksell Gamma Knife in Prague from April 1993until April 1995 No.

Site of tumour

volume (mm3) Total frac. dose at maximum WY)

Total frac. dose to margin GY)

% isodose

!3oIItary metastases 1 parietal left lung adenocarcinoma 2 occipital right renal adenocarcinoma 3 frontal right NSC lung carcinoma 4 parietal left lung adenocarcinoma 5 III.ventricle renal adenocarcinoma 6 skull base malignant melanoma I temporal right urinary bladder carcinoma 8 parasagital parietal right Ewing sarcoma 9 parietal right colorectal carcinoma 10 Parietal left NSC lung carcinoma 11 brain stem malignant melanoma 12 occipital right lung adenocarcinoma 13 parietal left lung squamous cell carcinoma 14 parietoccipital right mammary carcinoma 15 orbitae left Ewing sarcoma 16 temporal left malignant melanoma 17 parietal left NSC adenocarcinoma 18 parietal right NSC lung carcinoma 19 parietal right colorectal adenocarcinoma 20 parietal left lung adenocarcinoma 21 frontal right renal1cell adenocarcinoma 22 cerebellum colorectal adenocarcinoma 23 occipital right urinary bladder carcinoma 24 cerebellum left Grawitz 25 parietal right lung adenocarcinoma

35 400 9500 2500 6000 3750 10500 7700 15900 13700 5100 3400 9700 17600 23 600 740 17500 37 300 7700 23 100 3500 1800 17 loo 15800 8400 7100

36 55 48 50 *20 36 36 *24 42 40 30 40 40 38 28 36 42 40 36 l 33 40 38 44 50 *36

18 22 24 20 10 18 18 12 21 20 15 20 18 17 20 18 19 20 18 18 20 19 22 25 18

50 40 50 40 50 50 50 50 50 50 50 50 45 45 70 50 45 50 50 55 50 50 50 50 50

2 2 2 2 3 2 2 2 3 2 5 2 2 2 2 2 3 2 2 3 2 2 3 2 3

l.5c 0 0 0 0 Ilb 0 0 0 8,4’ 0 0 0 0 0 0 15b 0 0 0

Low grade ghmas (Grade I-11) I cerebellum 2 temporobasal right 3 parietal right 4 frontoparietal right 5 pineahs 6 frontoparietal right 7 temporal right 8 frontal right 9 temporal left 10 skull base 11 thalamus left 12 temporal left 13 parietal right

3000 18000 10550 26 100 3800 3500 7200 10200 2400 4600 3400 3400 5100

50 58 60 *32 50 230 50 l 30 50 50 53 55 *32

25 23 30 13 25 15 25 12 25 25 26,5 27,5 16

50 40 50 40 50 50 50 40 50 50 50 50 50

5 6 5 5 5 5 5 4 2 5 6 5 5

0 0 0 .O 15b 0 16’ 0 15b 0 loc 0 0

Meningiomas 1 skull base posterior 2 frontal left 3 sinus cavernosus right

15800 16500 3000

45 24 28

18 12 14

40 50 50

0 0 0

Pinerlomas I pinealis 2 pinealis 3 pinealis

4200 2400 25 600

48 50 l 30

24 25 13,5

50 50 45

0 15a 0

epifaringeal

10 150

52

26

50

0

Ependymomas 1 III ventricle

2800

50

25

50

0

No. of Total frac. dose to fractions critical structures WY)

0 0 0 0 0

Adenoma epifrvingis

I

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Table I (continued) No.

volume (mm3) Total frac. dose at maximum GY)

Site of tumour

Germiaomas 1 pinealis

Chordoma skullbase 1

1750

*46

13300

33

Total frac. dose to margin

No. of Total frac. dose to fractions critical structures (GY)

GY)

% isodose

23

50

5

0

165

50

3

13b

Ten patients (marked by *) had combined treatment with external beam fractionated radiotherapy before fractionated stereotactic radiotherapy. Ten patients had significant dose to the critical structure: Yhalamus, bbrain stem, coptic tract.

the stereotactic space. A special measurement probe marked with a scale graduated in millimetres which closely fit the measurementchannels was made and used for measurementsby its insertion into the holes until the tip of the probe came into contact with the patient’s scalp or skin (seeFig. 2). If the measured distances for all 24 points are identical (with tolerance < kO.5 mm) during the whole fractionated regimen (before each applied fraction) an unchanged position of the stereotactic frame is ensured. Method 2 A new stereotactic CT investigation (‘control’ investigation including a few slices through the target volume)

ti

A7

subsequentto the original one used for target localisation was performed. After definition of the coordinate system for a series of ‘control’ CT slices the following tests were performed: (a) the coordinates of the sameintracranial structures in both original ‘planning’ (used for treatment planning) and ‘control’ CT slicesin the caseof sliceswith identical (or nearly identical) z-coordinates were compared; (b) the original calculated treatment plan was superimposedon the ‘control’ CT imagesand the target volume coverage and doses to critical structures were comparedwith the original plan. This control procedure was performed on our treatment planning system (KULA and later on Leksell Gammaplan, Elekta Instrument, Stockholm). If the coordinates of the checked intracranial structures and the dose distribution (target volume coverage) are the same in both (‘planning’ and ‘control’) series of images then the position of the stereotactic frame is the same for both these investigations, and so the subsequentirradiation will be delivered with the same precision as the original one. If any changes are found in the position of the frame on patient’s skull a new detailed CT stereotactic investigation and a new doseplan have to be created.

point

Meusurement

MeasUrProbe in Contact with Skull

3. Results

Fig. 2. Schematically demonstration of the distancesmeasurementsin one point with the use of the leksell skull scaling instrument (ELEKTA INSTRUMENT, Sweden)and measurementprobe. Before each applied fraction there was tested all 24 measurementpoints and the distances compared with the previous results. In the case of the identical values for all control measurementsthe unchangeable position of the frame is guaranteed (figure from Leksell GammaPlan Users Manual, ELEKTA INSTRUMENT, 1994).

Forty-eight patients were treated from April 1993 until April 1995 with SRT using LGK (stmnnarised in Table 1). For the first 10 patients both Methods 1 and 2 were used to check the position of the stereotactic frame before each applied fraction, and no measurable changeswere detected. Based on the positive results of these tests it was decided, as a cost- and time-saving measure,to use Method 2 for all subsequentpatients in the case of fractionated regimens with three or more fractions. Method 2 was then applied only before the third and fifth fractions, and again no changes in the frame position during the whole fractionated course

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were found. Simultaneously, Method 1 was used for all treated patients before each applied fraction. In the case of any differences being detected in the frame position when only Method 1 was used, Method 2 was applied immediately. Since no changesof the stereotactic frame position were detected by either Method 1 or Method 2, for the whole group of our patients all fractionated treatments were thus delivered with high precision and reproducibility. For evaluation of acute and late toxicity in the patients treated by SRT it was decided to use the RTOG/EORTC scoring criteria [5,24]. Acute morbidity criteria are used to score the toxicity from radiation therapy and are relevant from day 1, the commencement of the therapy, until day 90 [5]. In our group of 48 patients, 46 had a score of 0 (no change) and two patients (patient no. 5 with a solitary brain metastasis from a renal cell carcinoma and patient no. 1 with meningioma; both had an occasional headache) had a score of 1 (capable of working, with minor neurological findings, no medical care needed). For the evaluation of late toxicity and complete treatment results, a minimum interval of l-5 years is necessary.The accurate grading of late toxicity can best be assessedwith the development of a longitudinal study, with pretreatment baseline tests followed by a series of reassessmentsat adequate and regular intervals. These reassessmentsare carried out at 2-month intervals for patients treated for solitary brain metastasis and at 6-month intervals for patients with low grade glial tumours, ependymomas and meningiomas. Three clinical examples of follow-up of patients treated by SRT with the LGK are presented here for illustration.

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The first is a patient with solitary brain metastasis from lung adenocarcinoma in left parietal region which was operated becauseof this indication 4 months before SRT with the LGK. The first symptoms were: ataxia, hemiparesis, headache and dysphasia. The patient was treated with irradiation of total fractionated dose to margin (TFDM) (the dose to the isodose curve (usually 50%)which fully covered defined treated target volume) of 20 Gy in two daily fractions (seeFig. 3 and Table 1; solitary metastases,patient no. 4). Pretreatment performance state Kamofsky value was 60%. At the time of the first CT control (2 months after irradiation) this had increased to 70%. Complete symptomatic response and regression of the collateral edema was apparent 2 months after SRT. Follow-up of this patient is 16 months and no acute or late toxicity was detected; the patient still has a score of 0 (RTOG and EORTC criteria) and a Kamofsky value of 70%. The second is an example of a patient with astrocytoma grade II in the right temporobasal region. The first symptom of this patient was seizure. TFDM, 23 Gy in six daily fractions (seeFig. 4 and Table 1, low grade gliomas, patient no. 2) was applied. Pretreatment performance state Kamofsky value was 80% and, after 6 months this was increasedto 100°/. Partial symptomatic response (seizures) occurred 6 months after SRT. Follow-up of this patient is 24 months and no acute or late toxicity has been detected; the patient still has a score of 0 and a Kamofsky value of 100%. The third is an example of a large solitary brain metastasis from lung adenocarcinoma in left parietal region. The first symptoms were: hemiparesis, headache and cerebral edema.The patient was treated by irradiation, TFDM, 18 Gy in two daily fractions (seeFig. 5 and

Fig. 3. Example of patient with solitary brain metastasistreated by SRT (seesolitary metastasespatient No. 4 in Table I). (a) stereobiopsy verified metastasisof lung adenocarcinoma in left parietal region. (b) control CT scan I6 months after SRT with the LGK (total fractionated doseto margin 20 Gy in 2 daily fractions).

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Fig. 4. Example of patient with astrocytoma grade II treated by SRT (see low grade gliomas patient No. 2 in Table 1) (a) stereobiopsy verified astrocytoma grade II in right temporobasal region. (b) control CT scan 24 months after SRT with the LGK (total fractionated dose to margine 23 Gy in 6 daily fractions).

Table 1, solitary metastases,patient no. 1). Pretreatment performance state Kamofsky value was 70% and, after 2 months, this was increased to 80%. Complete symptomatic response (headache and regression of the collateral edema)was at 2 months, and partial responseof the hemiparesis 1 month, after the SRT. Two small brain metastases(parasellar left and frontal left) were then discovered and treated by SR during the second year after the SRT. Follow-up of this patient is 24 months and no acute or late toxicity was detected; the patient has a score of 0 and a Kamofsky value of 80%.

4. Discussion The purpose of this paper was to study the feasibility of SRT with the Leksell stereotactic frame and LGK. Our attention was paid mainly to the following basic items: (a) identical positioning of the stereotactic frame during the entire fractionated regimen; (b) finding a model for correlation of radiosurgery dose to total fractionated dose delivered during SRT;

Fig. 5. Example of patient with sohatry brain metastasistreated by SRT (seesolitary metastasespatient No. 1 in Table I). (a) stereobiopsy verified metastasisof lung adenocsrcinoma in left parietal region. (b) control CT scan 24 months after SRT with the LGK (total fractionated dose to margine I8 Gy in 2 daily fractions).

G. Simonovri

(c) patient’s tolerance during regimen.

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the fractionated

The tests performed by Methods 1 and 2 showed very stable positioning of the frame in all 48 patients studied. Regular checks of the frame position can assure that subsequent irradiation of the lesion is performed with high precision and reproducibility. The LQ model seemsto be a good approximation for the total fractionated dose calculation of different fractionated regimens.There were no early effectsobserved. The application of the LQ model for benign tumours is in principle possible but the ar/@ratio for particular lesions is still not known with any accuracy. Fractionated SRT with the LGK was well tolerated by all our patients, and attachment of the stereotactic frame during the course of the fractionated regimen caused only minimal disturbances; also, there were no acute complications, such as skin infection or skin haemorrhage. Taking into account all radiobiological aspects,fractionated SRT can be used for the treatment of the following tumours: Solitary brain metastases(small volumes) Single high dose irradiation of pathological volumes with central necrosis, large volume and collateral edema (typically for fast-growing brain metastases)may have acute side effects caused by increase of edema and progression of neurodeticit. The fractionated regimen has a radioprotective effect not only for late, but also for the early, responding tissues. Low grade gliomas (small volumes up to maximum diameter 25 cm) SR with only one single high dose represents, on the basisof radiobiological experiencewith EBRT, a suboptimal treatment modality for glial tumours compared with SRT. With fractionated SRT it is possible to apply larger doses with a minimum of radiation-induced damage to surrounding intracranial structures. The main aim of this treatment modality is to increase local control and to decreasethe side effects of irradiation (especially late effects on surrounding brain structures) and to improve the patients’ quality of life. Meningiomas (fast growing with rapid progression of neurological symptomatology) Although benign tumours are in most casessuitable for SR, they can be appropriate for SRT if they have greater volumes, are located near critical structures, or when they are accompanied by larger collateral edema. Fractionation can then reduce radiation damage to surrounding tissuesand decreaseearly and late side effects. The use of the isoeffect relationship calculations mentioned above (Eqs. 3 and 4) can easily provide dose

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values and number of fractions (seeFig. 1) for any fractionated regimen. But it should not be applied without careful consideration of all parameters which can influence results of the treatment, such as histology and tumour volume, o//3 ratios for different tissues, tolerancelevels for critical structures, repair mechanism, etc. Unfortunately most of these factors are still not well known and will be the subject of the next detailed investigation. A trial study where strict rules for selection of patients, dose fractionation regimen, and reporting of early and late effects, will be the next step to prove the efficacy of this method. 5. Conclusion This study has proved that stereotactic radiotherapy with the LGK for some malignancies in the brain is feasible. The proper choice, preparation of patients for the treatment, and careful quality control during the course of therapy, are important parts of the whole procedure. Advantages of the SR and SRT methods can be summarised: (a) very accurate and reproducible treatment of lesions with a minimum dose to surrounding brain tissue, i.e., better control of tumour; (b) the possibility of subsequenttreatment in the case of recurrence or appearanceof new lesions, becausethe integral dose to the brain is very small; (c) minimum complication after treatment; (d) relatively short time of hospitalisation; (e) improvement of the patient’s quality of life during and after the treatment. For the full exploitation of the SRT method there are still questions remaining which should be carefully studied: (a) levels of tolerance doses for critical structures in the brain during SRT, (b) better knowledge of tumour lethal doses dependent on the number and size of fractions; (c) definition of an ‘ideal’ fractionated regimen for different brain malignancies; (d) justification of application of the LQ model for SRT and SR.

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