Radiation Doses To Normal Tissues During Craniospinal Irradiations Biology Essay

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Abstract:

Craniospinal irradiation is considered an important constituent of the multidesplinary approach in the treatment of medulloblastoma. It is a complex radiotherapy technique, patients who are treated successfully usually live long periods. Every effort should be done to decrease the radiotherapy related side effects, especially with the currently available 3D conformal radiotherapy planning system in our department.

This dosimetric study is aiming to report the results of analysis of doses received by target volumes and organs outside the target volumes during treatment of medullblastoma patients. Also aiming at comparing the doses reaching to the eyes and the lens with the use of different shielding methods.

Ten children recent diagnosis of high risk medulloblastoma (large residual >1.5 cm, M0) were included in the study after reviewing the pathology. All of them were subjected to MRI brain and spine together with CSF cytology three weeks after surgery. They were subjected to fixation, conventional simulation, followed by CT simulation. The scans will be transferred to the treatment planning system. The brain, spinal canal, and different normal tissue will be outlined.

For the cranial fields, parallel opposed fields were used with the isocentre of the fields in the mid-plan in the centre of the brain, and behind the eyes. For the spinal field, the full length was opened to the desired position to treat the spine by asymmetric jaws. The inferior border of the cranial field was matched to the superior border of the spinal field using collimator and couch rotation of the cranial field. Sensitive tissues close to the target volume was shielded using either MLCS or blocks.

The dose prescribed was 36 Gy/20 fractions for cranial and spinal regions. The reference point was placed in the centre of the cranial and spinal fields. The maximum, minimum and mean dose to each anatomic structure were computed using dose volume histograms by summing the cranial and spinal treatment plans. All patients gave informed consent that we can study their plan and do research on it

Introduction

Medulloblastoma constitutes 15-20% of all childhood central nervous system tumors. The median age at diagnosis is usually 6 years. The most common site of origin is the vermis and the 4th ventricle. The presence of large residual tumor > 1.5 cm or cerebro-spinal metastasis identifies high risk patients (1).

Reduced-dose (23.4 Gy) craniospinal irradiation (CSI) in combination with weekly vincristine, followed by a boosting of the dose to the posterior fossa up to 55.8 Gy followed by adjuvant systemic chemotherapy in the form of vincristine, CCNU, and cisplatin yield a Progression-free survival of 79% at 5 years and is considered the state of art for standard risk medulloblastoma patients.(2)

Higher radiotherapy dose to the CSI 36-39 Gy is usually considered for M0 cases (>1.5 cm residual without cranio-spinal metastasis).(2)

Craniospinal axis irradiation (CSI) is considered the corner stone in the treatment of medulloblastoma. It is a complex technique with very irregular clinical target volume (CTV). It is executed in two phases, the whole brain and neuraxis are treated in the initial phase. The site of the 1ry tumor is boosted in the 2nd phase(3).

A number of techniques are applied to improve dose homogeneity across the junction between the cranial and the spinal fields; including either direct abutment of the fields or the introduction of a gap with or without a moving junction. Effort had been made to decrease the dose to the lens, thyroid, heart, GIT, and gonads and to decrease the possible late effects of radiotherapy in those long living patients.

Several new modalities and techniques are now available aiming at more precise coverage of the target volume (spinal canal & brain) and more sparing of the organs at risk, including the use of CT simulators, better fixation facilities , the use of conformal radiotherapy and IMRT.(4)

Since the introduction of our new linear accelerator (Elekta) and treatment planning system (Precise Elekta) with many displaying and evaluation software tools 5 years ago in our department we became more able to give better radiotherapy to those patients.

Aim of this study:

This dosimetric study is aiming at reporting the results of analysis of doses received by target volumes and organs at risk (OAR) during treatment of high risk medullblastoma patients. Also we will compare the dose reaching to the lens with the use of different shielding methods.

Materials and methods:

Ten children with recent diagnosis of high risk medulloblastoma (large residual >1.5 cm, M0) were included in the study after reviewing the pathology. All of them were subjected to MRI brain and spine together with CSF cytology three weeks after surgery. All of these patients were planned to receive whole craniospinal irradiation (CSI) concomitant with weekly vincristin starting 4 weeks after surgery. All patients gave informed consent that their plan will be studied and will be subjected to research.

All patients received craniospinal irradiation (CSI) with a lateral parallel opposed fields to the head and a matched posterior spine field, with moving of the junction 1cm every 7 fractions (The position of the lower cranial border and upper spinal field were shifted).

The cranial fields were treated iso-centrically while the spinal field was treated at fixed SSD.

An immobilization mask was fabricated from thermoplastic material for each patient. The patients were simulated from the top of the head to the mid-pelvis using CT scan. During simulation, patients were placed in prone position with neck extended so that a posteriorly oriented spine field could exit below the mandible.

CT spacing was 3mm for the brain and 5mm for the spine. Patients were marked with sagittal and lateral laser lines during the verification, simulation and subsequent treatment.

The CT scans were then transferred to Precise Elekta treatment planning system where spinal canal and brain were contoured as the target volumes. Organs at risk and other normal tissues were also contoured. They include lenses, eyes, optic nerves, heart, lung, liver and kidneys. Care was taken to ensure that the brain contour included the cribriform plate. Then the treatment fields were designed for treatment.

The energies of the photon beams were 4MV & 6MV for cranial and spinal fields respectively.

For the cranium, parallel opposed fields were used with two isocenters for each patient one behind the eye and the other in the centre of the brain. The cranial fields include whole brain and extended caudally as long as the shoulder permits with 1 cm above shoulder to allow moving junction. In order to generate the field aperture for the cranial fields, the multi-leaf collimator was automatically positioned with the inside corner of the aperture 0.5cm from the contoured brain then MLC leaves were adjusted.

Because the inferior divergence of the cranial fields may overlap into the spinal cord, a couch rotation of 6-80 was added to eliminate such divergence. Also a collimator rotation of 8-100 on the lateral cranial fields was done to match the divergence of the superior spinal field edge.

So couch and collimator rotation in lateral cranial fields were applied to effectively have all three field edges from both lateral brain ports and the posterior spine port to meet at the cervical junction as a single plane. So the dose homogeneity at the craniospinal junction was achieved.

For the spinal field, a single posterior long thin spinal field was used. It should cover the whole spine. The posterior spine field was simulated; the superior border of the spinal field touches the inferior border of the cranial field. The full length was opened to the desired position to treat the spine by asymmetric jaws. If the distance from 2nd cervical vertebra to the base of the spine (2nd sacral vertebra) was more than 39cm then the treatment was carried out at extended SSD. SSD was 100cm in 8 patients and 110cm and 120cm in two other patients.

For the cranial fields, the averaged field size was 20x20cm. For the spinal field, the length ranged from 26cm -38cm. The width of the spinal field ranged from 4-8cm.

MLCS and or cerrobend shielding blocks were used to shield eyes, lenses and other sensitive tissues close to the target volume as kidneys and lungs. For each patient, four planes were created; Plan 1, the isocenter of the cranial fields was placed in the center of the brain and MLCs were used to shield the eyes and lenses. In Plan 2 the isocenter was behind the eyes and MLCs were used to shield the eyes and lenses. In Plan 3 the isocenter was behind the eyes and shielding block was used to shield the eyes and lenses. In Plan 4 the isocenter was in the center of the brain and shielding block was used to shield the eyes and lenses.

The dose prescribed was 36 Gy/20 fractions for cranium and spine regions. For cranial dose prescription, the dose was normalized to the centre of the brain. For spinal cord dose prescription the dose was normalized to the centre of the field at the anterior surface of the spinal cord to achieve good coverage (95%) as the dose is low at the anterior surface of the spinal cord. The delivered MU of the spinal fields ranged from 190-300 and for the cranial field ranged from 95-108Mu.

For each plane of each patient the added dose plan function was used to check the dose coverage of the combined cranial and spinal dose plans. Then the four plans for each patient were compared using visual inspection of the dose distribution, dose volume histogram and dose volume histogram parameters. These parameters were listed and analyzed statistically using excel sheet and SPSS (version11) Wilcoxon signed Ranks test

Results:

Radiation doses to target volumes and organs at risk during CSI (Table 1):

By reviewing the treatment planning and dose volume histograms of all 10 patients, the followings were the results as regards the dose distribution of the target volumes (brain & spinal canal) and organs at risk:

As regards the target volumes;

Brain was covered in all cases by 95% of the dose. The minimum dose received by any of the treated patients was 34.2 Gy while the maximum dose received was 40.3Gy (still within the brain tolerance).

The spinal cord was covered in all cases by 95% of the dose. The minimum dose received by the spinal cord in any of the treated patients was 34.2 Gy, while the maximum dose was 41.4Gy (still within spinal cord tolerance).

As regards organs at risk (OARs):

The average of the mean dose received by the whole liver for all patients was 18% of the prescribed dose i.e. 641 cGy, with a dose range from 504-828cGy.

The average of the mean dose received by any of the kidneys was 8% of the prescribed dose i.e. 280 cGy with a dose range from 72-612 cGy.

The average of the maximum dose received by the heart of the treated patients was 94.5% of the prescribed dose i.e. 34Gy, with the dose ranges from 33-34.9 cGy

The average of the dose that 20% of the lungs received is 10% of the prescribed dose i.e. 360cGy with the dose ranges from 180cGy-540cGy.

The average of the maximum dose of optic nerve was 98.5% of the prescribed dose i.e. 36Gy, with the dose ranges from 34-37Gy. The maximum dose is still below the maximum point dose for the optic nerve.

The average of the body maximum dose was 118% of the prescribed dose i.e 42Gy, with the dose ranges from 40 and 45 Gy; this maximum point was in the back muscles (still within the tolerance of the muscle).

Table 1: Radiation doses in percentage for target volumes and organs at risk during CSI:

Patients

Brain min

Brain max

Cord min

Cord max

Liver mean

R. k. mean

L. k. mean

Heart max

Heart mean

Lung D20%

Optic max

Body max.

1

96

107

95

115

16

5

5

97

51

10

99

124

2

95

109

96

113

18

5

10

92

54

10

99

115

3

96

106

97

115

17

8

7

95

50

8

101

117

4

95

110

96

111

14

9

7

95

55

8

101

117

5

95

111

95

110

20

4

4

92

39

15

100

113

6

95

112

95

113

16

3

5

95

49

8

95

119

7

95

112

95

115

22

14

2

93

51

5

95

125

8

95

109

95

110

23

11

13

95

54

12

104

112

9

95

106

98

113

17

14

17

97

56

15

97

119

10

95

110

96

109

15

8

8

94

50

9

97

118

min

95

106

95

109

14

3

2

92

39

5

95

112

max

96

112

98

115

23

14

17

97

56

15

104

125

average

95.2

109.2

95.8

112.4

17.8

8.1

7.8

94.5

50.9

10

98.8

117.9

Median

95.5

109.5

96.5

111

17.5

8

7.5

94

50.5

9.5

99.5

117.5

Average = mean of the means.

Table 2 .Radiation doses in cGy for target volumes and organs at risk during CSI

Patients

Brain min

Brain max

Cord min

Cord max

Liver mean

R. k. mean

L. k. mean

Heart max

Heart mean

Lung D20%

Optic max

Body max.

1

3456

3852

3420

4140

576

180

180

3492

1836

360

3564

4464

2

3420

3924

3456

4068

648

180

360

3312

1944

360

3564

4140

3

3456

3816

3492

4140

612

288

252

3420

1800

288

3636

4212

4

3420

3960

3456

3996

504

324

252

3420

1980

288

3636

4212

5

3420

3996

3420

3960

720

144

144

3312

1404

540

3600

4068

6

3420

4032

3420

4068

576

108

180

3420

1764

288

3420

4284

7

3420

4032

3420

4140

792

504

72

3348

1836

180

3420

4500

8

3420

3924

3420

3960

828

396

468

3420

1944

432

3744

4032

9

3420

3816

3528

4068

612

504

612

3492

2016

540

3492

4284

10

3420

3960

3456

3924

540

288

288

3384

1800

324

3492

4248

Min

3420

3816

3420

3924

504

108

72

3312

1404

180

3420

4032

Max

3456

4032

3528

4140

828

504

612

3492

2016

540

3744

4500

average

3427

3931

3448.8

4046

640.8

291.6

280.8

3402

1832

360

3556.8

4244

Median

3438

3942

3474

3996

630

288

270

3384

1818

342

3582

4230

Average = mean of the means

As regard eyes & lenses:

The dose received by the eyes and lenses using two different shielding techniques and using two different positioning for brain isocenters:

Four plans were carried out, they are

Plan 1 isocenter is in the center of the brain with using MLCs shielding.

Plan 2 isocenter is behind the eyes with using MLCs shielding

Plan 3 isocenter is behind the eyes with using block shielding.

Plan 4 isocenter is in the center of the brain with using block shielding

The mean dose received by the right and left eyes and the maximum dose received by the right and left lens were listed and compared for the four plans. (Tables 3-6):

Plan 1 & 2:

Plan 2 shows lower doses to eyes and lenses compared to plan 1

In plan 2, the average of the mean dose of the right and left eyes was 46% & 45% compared with 53% & 52% in plan 1 (table 3). In plan 2 the average of the maximum dose of the right and left lens was 38% & 41% compared with 44% & 48% in plan1( table 5). So using MLCs to shield the eyes & lenses with putting the isocenter behind the eyes shows lower doses than putting the isocenter in the center of the brain.

Plan 3 & 4: plan 4 shows lower doses to eyes and lens compared to plan 3

In plan 3, the average of the mean dose of the right and left eyes was 32 & 31.5% compared with 30.5% & 30% in plan 4 (table 3). The average of the maximum dose of the right and left lens was 15.5% & 11% compared with 13% & 11% in plan 4(table 5). So using block to shield the eyes with putting isocenter behind the eyes or in the center of the brain shows no significant difference (both show low doses to eyes and lenses)

Plan 2 & 3: plan 3 shows lower doses to eyes and lenses compared to plan 2

In plan 2, the average of the mean dose of the right and left eyes was 46% & 45% compared with 32% & 31.5% in plan 3 (table3). The average of the maximum dose of the right and left lens was 38% & 41% compared with 15.5% & 11% in plan 3( table5). So putting the isocenter behind the eyes with block shielding shows low doses to eyes and lenses than putting the isocenter behind the eyes with using MLCs shielding.

Plan 1 & 3: Plan 3 shows lower doses to eyes and lenses compared to plan 1

In plan 1, the average of the mean dose of the right and left eyes was 53% & 52% compared with 32% & 31.5% in plan 3(table 3). In plan 1, the average of the maximum dose of the right and left lens was 44% & 48% compared with 15.5% & 11% in plan 3 (table5). so putting the isocenter behind the eyes with block shielding shows lower doses than putting the isocenter in the center of the brain with using MLCs shielding

Plan 1 & 4: plan 4 shows lower doses to eyes and lenses compared to plan 1

In plan 1, the average of the mean dose of the right and left eyes was 53% & 52% compared with 30.5% & 30 % in plan 4(table 3). The average of the maximum dose of the right and left lens was 44% & 48% compared with 13% & 11% in plan 4(table 5). So putting the isocenter in the center of the brain with using block shielding shows lower doses than putting the isocenter in the center of the brain with using MLCs shielding.

The mean dose to both eyes and the maximum point dose to both lenses for these plans were assessed and analyzed statistically using Wilcoxon signed rank test. We found that there is a significant difference in sparing the eyes and the lenses between plan 1 & 2, between plan 2 & 3, between plan1 & 3 and between plan 4 & 1 (P values <0.05 for all). On the other hand, there is no significant difference between plan 3 & 4. Both show low doses to eyes and lenses (P values>0.05).

Table 3, The mean dose received by the eye in % for four different planes using two different brain isocenters and different shielding methods

Rt eye

mean dose

Lt eye

mean dose

patients

plan 1

plan2

plan3

plan4

plan 1

plan2

plan3

plan4

1

31

31

12

12

33

23

12

13

2

70

56

36

32

57

41

21

19

3

77

68

46

48

60

55

32

35

4

46

41

30

24

50

42

36

30

5

65

64

50

49

51

47

34

30

6

33

32

17

18

24

26

15

11

7

38

20

18

11

37

27

19

13

8

62

57

46

49

75

72

59

60

9

43

38

29

25

61

52

37

40

10

65

55

37

37

74

61

50

47

min%

31

20

12

11

24

23

12

11

max%

77

68

50

49

75

72

59

60

average

53

46.2

32.1

30.5

52.2

44.6

31.5

29.8

Median

46

41

30

25

54

44.5

33

32.5

Average = mean of the means

Table 4, The mean dose received by the eye in cGy for four different planes using two different brain isocenters and different shielding methods

Rt eye

mean dose

Lt eye

mean dose

patients

plan 1

plan2

plan3

plan4

plan 1

plan2

plan3

plan4

1

1116

1116

432

432

1188

828

432

468

2

2520

2016

1296

1152

2052

1476

756

684

3

2772

2448

1656

1728

2160

1980

1152

1260

4

1656

1476

1080

864

1800

1512

1296

1080

5

2340

2304

1800

1764

1836

1692

1224

1080

6

1188

1152

612

648

864

936

540

396

7

1368

720

648

396

1332

972

684

468

8

2232

2052

1656

1764

2700

2592

2124

2160

9

1548

1368

1044

900

2196

1872

1332

1440

10

2340

1980

1332

1332

2664

2196

1800

1692

min

1116

720

432

396

864

828

432

396

max

2772

2448

1800

1764

2700

2592

2124

2160

average

1908

1663.2

1155.6

1098

1879.2

1605.6

1134

1072.8

Median

1656

1476

1080

900

1944

1602

1188

1170

Average = mean of the means.

Table 5; The maximum dose received by the lenses in % for 4 different planes using two different isocenters and different shielding methods:

Rt lens

max dose

Lt lens

max dose

patients

plan 1

plan2

plan3

plan4

plan 1

plan2

plan3

plan4

1

24

29

12

12

41

33

12

13

2

69

59

10

11

37

23

10

11

3

93

80

53

28

75

54

12

12

4

23

17

23

20

77

60

10

10

5

53

56

12

12

60

45

12

11

6

18

19

6

7

38

46

10

10

7

17

17

7

10

9

12

7

9

8

34

29

11

11

62

68

23

17

9

36

30

11

11

20

19

9

7

10

70

46

10

8

60

49

9

8

min%

17

17

6

7

9

12

7

7

max%

93

80

53

28

77

68

23

17

average

43.7

38.2

15.5

13

47.9

40.9

11.4

10.8

Median

35

38

11

11

41

45.5

10

10.5

Average = mean of the means.

Table 6; the maximum dose received by the lenses in cGy for 4 different planes using two different isocenters and different shielding methods

Rt lens

Max. dose

Lt lens

Max dose

patients

plan 1

plan2

plan3

plan4

plan 1

plan2

plan3

plan4

1

864

1044

432

432

1476

1188

432

468

2

2484

2124

360

396

1332

828

360

396

3

3348

2880

1908

1008

2700

1944

432

432

4

828

612

828

720

2772

2160

360

360

5

1908

2016

432

432

2160

1620

432

396

6

648

684

216

252

1368

1656

360

360

7

612

612

252

360

324

432

252

324

8

1224

1044

396

396

2232

2448

828

612

9

1296

1080

396

396

720

684

324

252

10

2520

1656

360

288

2160

1764

324

288

min

612

612

216

252

324

432

252

252

max

3348

2880

1908

1008

2772

2448

828

612

average

1573.2

1375.2

558

468

1724.4

1472.4

410.4

388.8

Median

1260

1368

396

396

1476

1638

360

378

Discussion:

This dosimetric study was conducted to report the results of analysis of doses received by target volumes and organs at risk during treatment of ten children with high risk medullblastoma treated with craniospinal irradiation concomitant with chemotherapy at our department. Also we compared the dose reaching to the eyes and the lens with the use of two different shielding methods and two different positions for brain isocenter.

As regards the target volume; the minimum dose received by the brain in any of the treated patients was 34.2Gy and the maximum dose received was 40.3Gy. The median of the maximum dose received by the brain was 39.4 Gy while the median of the minimum dose received by the brain was 34.38 Gy.

The minimum dose received by the spinal cord by any of the treated patients was 34Gy, and the maximum dose was 41.4Gy, The median of the maximum dose received by the cord was 39.96 Gy while the median of the minimum dose received by the brain was 34.74 Gy.

These results are closely related to the results published by Darunee Tongwan in his dosimetric analysis of craniospinal irradiation in the supine position comparing four different techniques, where the median dose received by the brain was 36.91Gy and the median dose received by the spine was 38.12 Gy. (5)

As regards organs at risk, starting with the liver, the median dose received by the whole liver for all patients was 17.5% of the prescribed dose i.e. 630 cGy, with a dose ranges between 504-828cGy. This was similar to darunee's study in which the dose to the liver ranged from 533-698 cGy with a median dose of 576 cGy.

Considering the kidneys, the median dose received by the right and left kidneys were 8 and 7.5% of the prescribed dose i.e. 288 and 270 cGy to the right and left kidney respectively with a dose range between 72-612 cGy, which is nearly identical to the median dose received by the kidneys in darunee's study.

In the present study, the maximum dose received by the heart in any of the treated patients was 34.9Gy, with the mean dose ranged between 14.04 Gy and 20.16 Gy. This is in agree with, the dose received by the heart in darunee's study, which ranged from 14,00-19,00 Gy.

In darunee's study, the lungs received a dose ranging from 413-565 cGy with a median dose of 476 cGy. This is nearly the same in our study where the dose received by 20% of the lungs ranged from 180-540 cGy with a median dose of 342 cGy.

In this study, the average of the mean dose received by the right and left eyes was 53% and 52% of the prescribed dose when using plan 1 (MLC and isocenter in the center of the brain), this was improved to 46% and 45% for both right and left eyes when the isodose was moved to just behind the eyes and keeping using of MLCs for shielding (plan 2). On the other hand, using blocks for shielding was associated with dramatic improvement in the mean dose reaching the eyes i.e. 32% , 31.5% to right and left eyes respectively when using ( plan 3) & 30.5% , 30% respectively when using ( plan 4).

So, by using blocks for shielding instead of MLCs there was a dramatic decrease in the dose reaching the eyes. The mean dose to the eyes was reduced by up to 42%

In the present study, the average of the maximum dose received by the right and left lens was 44% and 48% of the prescribed dose when using plan 1 (MLC used and the isocenter is in the center of the brain), this was improved to 38% and 41% for both right and left lens when the isocentre was moved to just behind the eyes and keeping using of MLCs for shielding (plan 2). On the other hand, using blocks for shielding was associated with dramatic improvement in the maximum dose reaching the lens i.e. 15.5 % , 11% to right and left lenses respectively when using ( plan 3) & 13% , 11% respectively when using ( plan 4). The max. dose to the lens was reduced by 70% & 77% for the right & left lens respectively.

Our results were similar to the results obtained by Kalapurakal et al in his study evaluating the adverse effect of the use of multileaf collimator on the dose received by the lens in children with leukemia receiving cranial irradiation where the dose to the lens was increased by about 64% and 72% when using MLC without shielding blocks(6).

The fact that the use of MLCs was associated with increase the dose to the lens was also recognized by vijay et al (7) evaluating shielding of the whole brain by three different methods in 10 children receiving whole brain irradiation and reaching the conclusion that the use of conformal planning and shielding using MLCs will lead to better coverage of the PTV by the 95% isodose curves but higher dose to the eyes and lenses

The dose to the lens was also evaluated in the study done by Cochran et al (8) evaluating the dose to the lens during craniospinal irradiation using protons and showing that angling the cranial proton beam 15-20 degree posteriorly will lead to substantial decrease in the dose received by the lens by nearly 50%.

But still our results were away from the results shown by pakisch et al (9) who showed that the dose to the lens was reduced to 4% only from the described midplan dose with use of combination of angulation of the couch, placement of additional eye blocks close to the surface, and angulation of the gantry during prophylactic cranial irradiation and with the use of 8 MV photon beams.

Conclusion:

From the above motioned study we can conclude that, the dose of radiation received by the target volume and the organs at risk during craniospinal irradiation of children with high risk medulloblastoma with the use of our new linear accelerator and treatment planning system Elekta & Precise Elekta is nearly identical to other studies and is reaching its target (OARs are within normal tissue tolerance).

As regards the dose to the lenses, using block shielding shows lower doses to eyes and lenses regardless to the position of isocenter, on the other hand, with the use of MLCs for shielding, the isocenter should be behind the eye not in the center of the brain as this shows lower doses to eyes and lenses. If we use the isocenter in the brain so we should use block.

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