A study on the effect of set up errors

and organ motion in patients treated

with IMRT for prostate cancer
B. Saracino, V. Landoni

S.C. Radioterapia
Laboratorio di Fisica Medica e Sistemi Esperti
I.F.O. Istituto Regina Elena, Roma

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer

Radiotherapy is one of the most important and evolving

therapeutic strategies in localized prostate cancer

Dose escalation studies employing the newest techniques

(conformal therapy and IMRT) have shown to improve
local control and DFS in patients with favourable,
intermediate and unfavourable prognosis

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer

The probability of tumor control (TCP) is a function of

the dose received by CTV, whilst the probability of
normal tissue complication (NTCP) is a function of the
dose absorbed by organs at risk (ORs)
TCP and NTCP are dose-dependent and the doseresponse relationships are described by sigmoid-shaped
curves
3

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer

Clinical data have shown that the amount of rectal and

bladder wall receiving high doses is significantly lower
employing IMRT than in patients treated with conventional
3DRT
As rectal and bladder toxicities exhibit a volume-effect, even
high dose IMRT allows a decrease of acute and late toxicities
ORs
4

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer
Tumor control curves are usually at the lower dose levels
relative to normal tissue toxicity curves
The decrease of the amount of ORs within the treatment
field induces a translation of NTCP curve toward the high
dose region
This allows the treatment of the tumor with high doses in
a dose escalation program, without a significant increase
of toxicity of the organs at risk

3D-CRT:

TCP/NTCP Model
1.0

Dose Escalation with 3D-IMRT

Conventional
Radiotherapy

Tumor Control Probability

0.8

0.6

0.4

0.2

3D-IMRT

Prescribed Dose

Prescribed Dose
6

Normal Tissue Complication Probability

Hypothetical Model

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer
IMRT is a dose-delivery technique that provides high
gradient dose distributions
An adequate level of treatment accuracy is mandatory in
IMRT dose-escalation studies, in order to define the
extent of the safety margins and DVHs constraints
Treatment accuracy depends on both daily repositioning
uncertainties and random internal organ motion
7

Study design
IMRT

adequate immobilization system

accuracy and set-up reproducibility
evaluation of internal organ motion
Matching portal images on DRR
(reference anatomical structures)

C.T. scans taken also at the middle and at the end of RT course
Contours re-outlined

DVH evaluation

Safety margin for PTV

8

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer

Patients selection:
12 patients at intermediate risk prostate cancer,
without clinical evidence of lymph node and distant
metastases entered our study

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer
Technical procedures:

Baseline C.T. simulation in prone position in a customized

immobilization cradle, including the whole trunk and with a
wedge cushion under the ankles

C.T. scans were acquired with a spiral C.T. and the slides were
reconstructed at 5 mm increments

Digitally reconstructed radiographs (DRR) generated from C.T.

data were used as reference images
10

Baseline C.T. simulation in prone position in a

customized immobilization cradle with a wedge
cushion under the ankles

11

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer
Technical procedures:

The pubic symphysis and the ischiatic bone on L-L DRR, the ilium
bone, the ileo-pubic branch and the ischio-pubic branch on A-P
DRR were chosen as reference structures

The evaluation of set-up errors was achieved by means of daily

orthogonal portal images

An online matching of the anatomical structures on portal images

allowed a daily isocenter check
12

Comparison between reference images (DRR)

and orthogonal portal images

13

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer
Technical procedures:
The evaluation of organ motion was achieved by means of two
further C.T. scans taken on each patient during radiation therapy
course
The volumes of interest (CTVs and ORs) were re-contoured
In order to eliminate intra-observer variability, CTVs and ORs
were always outlined by the same radiation oncologist
The new data were transferred to the planning system and the
dose distribution was recalculated by using the original beams
parameters
14

CTVs volumes outlined on three T.C. scans

CTV (A-P view)

CT 1
CT 3
CT 2

CTV (L-L view)

15

Comparison between rectal wall volumes

outlined on the three C.T. scans
Rectum (A-P view)

Rectum (L-L view)

CT 1
CT 3
CT 2

16

Modification of volumes of interest and

shifts of internal organs

CT 1
CT 3
CT 2

17

DISTRIBUTION OF SYSTEMATIC SET UP ERRORS IN THE

THREE DIRECTIONS

LATERAL

ANTERIOR-POSTERIOR

CRANIO-CAUDAL
*J.C. Stroom et al.: Geometrical uncertainties, radiotherapy planning margins, and ICRU-62 report; Radiotherapy and Oncology 64 (2002) 75-83.

18

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer
Results and conclusions:
Our study has shown that the mean shift for the population of the
treatment isocentre with respect to the planning one in the 3
directions was less than 2 mm

Errors within 2 mm did not significantly influence the behaviour of

both CTV and rectal wall DVHs
Therefore, margins adopted for PTV seem to be adequate
19

Volumes (cm3) of rectal wall, CTV and PTV to rectal wall intersection
calculated from baseline, intermediate and final CT scan

Volumes (cm3)

rectal wall

CTV

PTV to rectal wall intersection

patient

initial

intermediate

final

initial

intermediate

final

initial

intermediate

final

32,56

27,37

32,08

82,54

63,67

61,00

9,29

3,93

2,71

38,89

37,27

39,51

56,98

58,59

57,58

5,39

5,55

4,81

30,21

29,66

31,03

52,64

53,28

51,97

3,25

3,64

2,55

31,72

24,98

32,92

61,23

43,81

52,11

8,14

5,08

6,68

53,79

56,28

69,58

63,09

70,05

71,44

6,03

5,85

4,03

34,69

32,81

42,53

59,98

62,49

69,24

2,97

2,78

3,20

42,59

49,40

49,64

93,39

82,22

93,16

6,44

5,46

6,27

39,06

52,61

55,68

74,95

76,79

58,93

5,69

2,26

5,88

29,95

47,68

50,00

87,96

72,42

71,65

3,81

8,82

5,84

10

43,18

44,88

49,17

43,11

34,08

42,23

3,22

2,22

3,23

11

29,42

43,18

45,43

95,11

102,8

97,84

4,82

5,42

4,03

12

33,58

37,85

40,12

99,92

108,5

96,84

2,97

3,25

3,3

median value

34,14

40,52

43,98

69,02

66,86

65,12

5,11

4,51

4,03

std deviation

7,23

10,27

11,08

18,87

21,81

18,56

2,08

1,89

1,47

20

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer
Results and conclusions:
The analysis of CTV and rectal wall volumes has shown
a slight decrease of CTV (prostate and seminal vesicles)
by tumor cell killing

a slight increase of rectal wall by aedema and

congestion, during the treatment course
21

A study on the effect of set-up errors and organ

motion in patients treated with IMRT for
prostate cancer
Toxicity:
Acute toxicity:

Gr 1

Gr 2

Gr 3

Rectal

4 (33%)

3 (25%)

Vesical

5 (42%)

3 (25%)

1 (8%)

No late rectal or vesical toxicity was found

22

RATIONALE FOR TREATMENT PLANNING

IMRT plans were developed
using Helios 6.3 on
CadPlan v 6.3.5

Five field sliding window

technique

20-30%
40-50%
60-70%
80-90%

90-100%
100-105%

23

RATIONALE FOR TREATMENT PLANNING

Prescription: 80 Gy in 40 fractions to the ICRU reference point,
with percent minimum and maximum dose to the PTV of 95% and
107% respectively. Dose-volume constraints on normal tissues
were: doses of 70 Gy (V70) and of 40 Gy (V40) to less than
35% and 60% of rectal wall volume respectively and doses of 70
Gy (V70) and of 50 Gy (V50) to less than 50% and 70% of
bladder volume respectively.
Treatment was delivered by 15 MV photon beams from VARIAN
2100CD linear accelerators, all equipped with Millenium (0.5 cm
leaf width) multileaf collimators (MLC).
24

EFFECT OF SET UP ERRORS ON DVHs

Original plan was recalculated with the isocentre

shifted from the original one of a quantity equal to the
systematic error measured
Random errors were assumed averaging to zero

25

EFFECT OF SET UP ERRORS ON DVHs

V%

1.8 MM IN ANTERIOR
DIRECTION

100
90
80

3.4 MM IN CRANIAL
DIRECTION

70
60

init ial rect al wall

50
recalculat ed CTV

40
30

recalculat ed rect al
wall
init ial CTV

20
10
0

10

20

30

40

50

60

70

80 Gy 90

26

EFFECT OF ORGAN MOTION ON DVHs

At the middle and at the end of treatment, two more CT scans

were taken on each patient (i.e. intermediate and final)

The volumes of interest were re-contoured by the same radiation

oncologist and the new data transferred to the planning system

Dose distribution was recalculated on the new CT data by using

the original beam parameters.

27

EFFECT OF ORGAN MOTION ON DVHs

CTV DVHs

planning CTV (from initial treatment plan)

V%

treatment CTV (from recalculated plans)

100
90
80

Planning DVHs
dose to the 50% of CTV: from 76.8 to 81.2 Gy
dose to the whole CTV: from 75.6 to 84.8 Gy
Treatment DVHs
dose to the 50% of CTV: from 75.6 to 81.6 Gy
dose to the whole CTV: from 54.4 to 85.6 Gy

70
60
50
40
30
20
10
0
50

55

60

65

70

75

80

85

Gy

90

planning rectal w all (from initial treatment plan)

treatment rectal w all (from recalculated plans)

V%

RECTAL WALL DVHs

Planning DVHs
median V70 = 26.3 5.8 %
median V40 = 67.4 9.8 %
Treatment DVHs
median V70 = 26.0 11.1 %
median V40 = 69.4 12.8 %

100
90
80
70
60
50
40
30
20
10
0
0

10

20

30

40

50

60

70

80

28

Gy

90

FREQUENCY HISTOGRAMS OF V70 AND V40 VALUES

No time dependance
PERCENTAGE RECTAL
WALL RECEIVING 70 Gy
V70 moves beyond the maximum
initial volume constraint obtained of
35 % in 5 out of 12

PERCENTAGE RECTAL
WALL RECEIVING 40 Gy

V40 moves beyond the maximum

initial volume constraints obtained of
85 % in 3 patients out of 12
29

RADIOBIOLOGICAL ANALISYS
NORMAL TISSUE COMPLICATION PROBABILITY

NTCP was calculated from normalized DVHs obtained converting the

total physical dose into the biologically equivalent total dose normalized to

2 Gy per fraction according to the Lyman-Burman-Kutcher model.[1]

NTCP

1
2

exp t

D TD50(v)
m * TD50(v)

V
Vref

/ 2 dt
Vref = whole organ;
v = fraction of volume irradiated with a dose D;
TD50(1) = tolerance dose that gives 50%
probability of damage for whole organ
irradiation;
m = parameter that gives the slope of the doseresponse curve;
n = parameter that gives the dependance of
TD50 on the fraction of volume irradiated;

TDv TD1 v n
[1] Burman C., Kutcher G.J., Emami B., and Gotein M. Fitting of normal tissue tolerance data to an analytic function.
Int. J. Radiation Oncology Biol. Phys. 1991; 21: 123-135.

30

RADIOBIOLOGICAL ANALISYS
NORMAL TISSUE COMPLICATION PROBABILITY

We assumed a/b = 3 Gy for rectum and we used the recently fitted

parameters of TD50=81.9 Gy, n=0.23 and m=0.19 [2]. These
parameters were calculated for a group of patients with minimum
follow-up of 18 months and considered as bleeders if showing
grade 2 late complication according to a slightly modified
RTOG/EORTC scoring system.
[2]: T.Rancati, Fiorino C., Gagliardi G.M. et al. Analysis of clinical complication data on late rectal bleeding: fitting to
different NTCP models.Abstracts of ESTRO. Geneva 12-18 Sept 2003.

31

RADIOBIOLOGICAL ANALISYS
TUMOR CONTROL PROBABILITY

TCP was calculated by using the Poisson model without taking into account tumor
repopulation. Since patients recruited for this study were those classified at the

intermediate risk group (i.e. PSA=10-20 ng/ml, or Gleason 7 ,or stage T2b) we
fitted clinical data for external beam irradiation reported by Fowler et al. [1].

TCP

exp vi exp a b Di /N Di
i

= initial density of clonogenic cells; Di = total dose delivered to the volume vi ;

N = number of fractions; a and b : parameters of the linear-quadratic model for cell survival
[1] Fowler J., Chappel R. and Ritter M. Int. J. Radiation Oncology Biol. Phys. 2001; 50: 1021-1031.

32

RADIOBIOLOGICAL ANALISYS
TUMOR CONTROL PROBABILITY

The number of clonogenic cells (N0) was estimated by using a Matlab

code according to Starev et al. [2]. For a = 0.0391 Gy-1 and a/b = 1.5
Gy our esteem was N0 =253 34
A mean prostate volume of 72.58 18.87 cm3 was estimated from our
patient population, giving a mean clonogenic cellular density

= 3.48 1.37 cells/cm3

TCPs were calculated by assuming a costant clonogenic cellular
density and taking into account each patients CTV volume
[2] Stavrev P., Nemierko A., Stavreva N., M. Goitein. The Application of Biological Models to Clinical Data.
Physica Medica April-June 2001; vol. XVII: 71-82.

33

TCP AND NTCP CALCULATED FROM PLANNING AND

TREATMENT DVHS

TCP (%)

TCP (%)

TCP (%)

NTCP norm (%)

NTCP norm (%) NTCP norm (%)

patient

(planning)

(intermediate)

(final)

(planning)

(intermediate)

(final)

86,08

88,03

88,20

11,04

6,49

2,94

87,60

88,27

87,95

8,25

6,92

5,69

87,30

89,51

89,37

5,16

10,02

4,27

87,67

92,49

90,42

11,61

15,01

5,32

85,60

81,18

85,96

4,85

11,60

0,58

87,58

86,99

86,05

4,09

3,25

10,32

76,56

83,42

82,16

5,47

10,68

10,35

78,28

73,45

59,18

9,37

3,76

3,92

83,96

83,63

87,22

7,55

22,14

19,16

10

89,31

93,98

92,44

6,56

4,33

11,52

11

71,27

68,27

70,85

6,62

14,43

6,24

12

80,95

77,81

81,46

3,95

5,95

3,44

mean TCP

mean TCP

mean NTCP

mean NTCP

planning

treatment

planning

treatment

83.515.57

83.627.53

7.042.58

7.864.65

34

PERCENTAGE DEVIATION
FROM INITIAL NTCP
VALUE
Variations in NTCP are mostly limited to
within 10 % of the initial value. In only
one patient the intermediate and final
NTCP showed values of 11.6 % and 14. 6
% higher than the initial one

PERCENTAGE DEVIATION
FROM INITIAL TCP
VALUE
Variations in TCP are mostly
limited to within 5% of the
initial value. In only one patient
final TCP was 19.1 % lower than
initial one
35

Results and conclusions

DVH modification due to organ motion is more considerable than
that produced by set-up errors
Contrary to the latter, which can be easily detected and quantified
by precise measurement of the shift between rigid structures (i.e.
pelvic bones), organ motion does not occur by a simple translation
of rigid organs but involves several other mechanisms of organ
modification, such as changes in volume, shape and position
produced by different levels of organs filling
Furthermore, the level of bladder filling can easily be controlled
before each treatment session, whilst rectal filling depends on
several factors (diet, individual intestinal habits, etc.)
36

Results and conclusions

The analysis of DVHs has shown that CTVs were irradiated by a

homogeneous dose distribution and are not influenced by organ

motion, whilst larger shifts of the rectal wall were observed

There arent significant differences between initial and late TCP

values, whilst the percent deviation from initial values was larger for
NTCP

37

Results and conclusions

Longer follow-up will be necessary to further substantiate our

considerations:

The prediction of a grade 2 toxicity of 10%, despite the rectal wall

modifications
The prediction of the 83% local control, despite the CTV motion

38