Radioterapia guidata dalle immagini (IGRT)

1. XXIII Corso Residenziale di Aggiornamento
Moderna Radioterapia e Diagnostica per Immagini: dalla
definizione dei volumi alla radioterapia «adaptive»
Il glossario per il corso:
IGRT
V. Frascino, A. R. Alitto, A. Nardangeli,
A. Castelluccia, M. Rapisarda

2. PREVIOUSLY
FRACTIONATED-RT
IMAGE-BASED-RT
• Diagnosis
(months ... years)
• Response evaluation
• Staging
• Target definition
• Planning
AFTER
• Tumor recurrence
Theragnostic Imaging
• Late toxicity
(biologically optimized dose
prescription)
•Early toxicity
Follow-UP
Bentzen SM, Radiother Oncol. 2005 Dec;77(3):227-30. Epub 2005 Nov 21

3. PREVIOUSLY
• Diagnosis
• Staging
• Target definition
• Planning
FRACTIONATED-RT
IMAGE-BASED-RT
IMAGE- GUIDED-RT
AFTER
(months ... years)
• Response evaluation
• Tumor recurrence
Theragnostic Imaging
• Late toxicity
(biologically optimized dose
prescription)
•Early toxicity
Follow-UP
Bentzen SM, Radiother Oncol. 2005 Dec;77(3):227-30. Epub 2005 Nov 21

4. In general, most tumors are radioresistant
if they are not in the treatment beam

5. Local Control
Target Definition
Dose Delivery
Optimized dose
distribution
Accuracy in hitting
the target
?

6. IGRT: Definition
“IGRT is defined as external beam radiation
therapy with positional verification
using imaging prior to each treatment
fraction…”
“IGRT includes, but is not limited to, 3DCRT,
IMRT,
stereotactic radiosurgery, stereotactic RT, and
brachytherapy…
RTOG Research Plan 2002-2003 IGRT Committee Report Michalski J, Purdy JA, Gaspar L, et al
Int J Radiat Oncol Biol Phys 2001; 51:60-5
Image Guided Radiation Therapy Guidelines: ATC QA subcommittee report October 18, 2009

7. IGRT: Definition
IGRT is the use of the image in the actual
treatment room as a tool for tracing and
verification of the tumour volume immediately
before or during treatment.
RTOG Research Plan 2002-2003 IGRT Committee Report Michalski J, Purdy JA, Gaspar L, et al
Int J Radiat Oncol Biol Phys 2001; 51:60-5
Image Guided Radiation Therapy Guidelines: ATC QA subcommittee report October 18, 2009

8. IGRT
Indication
• Target moving
• Positioning
• Tumor shrinkage or expansion
• Changes in tumor’s shape and surrounding
anatomy
Jaffray et al. Int J Radiat Oncol Biol Phys 1999 Oct 1;45(3):773-89.

9. IGRT: Rationale
SM
ITV
ITV
CTV
CTV
OAR
CTV
OAR
OAR
SETUP ERRORS
DELETION
ORGAN MOTION
REDUCTION/
COMPENSATION

10. IGRT: Rationale
SM
ITV
ITV
CTV
CTV
OAR
OAR
•
Target Dose
•
OAR Dose
CTV
OAR

11. IGRT: Rationale
Use of more collimated techniques
Target missing risks

12. IGRT: Rationale
ESBRT
Random Errors

13. IGRT
 History
 Different technical solution and role of
TSRM
Clinical applications
 Our Experience

14. IGRT:
(r)evolution of in-room
imaging
Radiotherapy has always been “image-guided”
Search for a compromise between:
• adequate coverage of the target
• Organ at risk saving
Uncertainties in
planning &
Errors
Benefits reduction
delivery

15. Gammagraphy
 Portal image for treatments performed by
gamma-ray COBALTO 60
 Films used:
• Kodak TL ( therapy localizzation)
• Kodak TV ( therapy verification)

16. After LINAC
Portal images were uncommon
• Poor combination dose/sensitive of the film
• Source dimension for Cobalto-therapy
Poor image quality
…used for set-up check
Haus et al., A technique for imaging patient treatment area during a therapeutic radiation exposure, Radiology 170; 97:653-6

17. 50’s-60’s

18. When the LINAC comes…
Field-setup errors depend on patient,
treatment site and set-up complexity
The concept of “diagnostic” quality image is
considered in the structure of the machine
 impossibility of a daily control due to the use of the film
 lack of tools for a quantitative comparison between
simulation and portal images
Byhardt et al. Weekly localizzation films and detection of field placement errors, Int J Radiat Oncol Biol Phys 1978; 4:881-7

19. Traditional Portal Imaging

20. Electronic Portal Imaging
Electronic Portal Imaging Device (EPID)
“Digital technology
instrument for treatment
field monitoring”
Use of BONY LANDMARKS

21. Actually…
Volumetric Imaging 3D:
Cone Beam-CT (CBCT)
PARENCHYMA
visualization

22. To be continued…

24. Directly installed on
GANTRY

25. Directly installed on
GANTRY

26. Directly installed on
GANTRY
TOMOTHERAPY
Il fascio di radiazione emesso che
Il fascio di radiazione emesso che
attraversa il paziente viene direttamente
attraversa il paziente viene direttamente
raccolto da un rivelatore allo Xeno che
raccolto da un rivelatore allo Xeno che
permette la ricostruzione di immagini 3D,
permette la ricostruzione di immagini 3D,
per l’individuazione del target, prima di
per l’individuazione del target, prima di
ogni singolo trattamento.
ogni singolo trattamento.

27. An RX-tube permanently positioned
in the bunker in order to obtain a
reference image

28. A TC positioned in the bunker with
the linear accelerator

29. A TC positioned in the bunker with
the linear accelerator

30. Optical devices: Surface Imaging
A 3D imaging of patient’s body
surface is created by camera units,
using laser system.

31. To allow the alignment
and the control of the
respiratory movements
without using markers
and further exposure.

32. Ultrasounds –
especially for pelvic tumors

33. Optical Devices :
Optical tracking system
Using infrared cameras to determine the
position of markers situated on patient and to
localize spatial coordination for the treatment.

37. …There is a continuous upgrade
of systems and softwares…

38. … In order to obtain and process
images of increasing quality…

39. …Using more and more
advanced techniques and new
aquisition modality…

40. … with different times and work
tasks in everyday life…

41. … requiring an important
training and a continuous
collaboration with medical
staff… In order to obtain the
same target…

42. IGRT protocols are…

43. • Toxicity
reduction
• Dose
escalation
• Local control
improvement
• Margin
reduction
Bujold et al, Semin Radiat Oncol 22:50-61, 2012

44. Prostate: protocols
Off line:
-Dose escalation
-Volumes and margins
reduction
-OAR sparing
On line:
-13%
target
increasing
-5% benefit
dose
Zelefsky et al. (W. Beaumont Hosp), Int Radiat Oncol Biol Phys, 50 (5): 1226-1234, 2001
Brabbins D et al. (W. Beaumont Hosp), Int Radiat Oncol Biol Phys, 61 (2): 400-408, 2005
Ghilezan M et al., Int Radiat Oncol Biol Phys, 60 (5): 1602-1610 2004

45. Prostate: protocols
•
Without IGRT: decreasing of biochemical control for rectal
distension and dose coverage (rectal distension and bladder filling)
•
Repeated CBCT at the beginning of the treatment course: effective in
reducing setup errors and safety margins.
• The additional gain by daily imaging and online correction may be
smaller compared to the step from no IGRT to offline IGRT
•
Low toxicity rate with CBCT and possibility of dose escalation
Boda-Heggemann et al, Strahelenther Onkol; 2011, 187: 284-91

46. Prostate: protocols
G. S. Mageras and J. Mechalakos – Sem. in Rad. Onc, 2007, 17: 268.277

47. Prostate: clinical outcomes
• Clinical outcomes improvement with high dose
IGRT in localized prostate cancer
• 3-year LC (IGRT=186 pts vs IMRT=190 pts; PD 86.4Gy):
– Low-intermediate risk: ND
– High risk: 97,7% vs 77,7% (p=0.05)
• Chronic toxicity (from G2):
– GU: 10.4% vs 20% (p=0.02)
– GI: 1% vs 1.6% (p=0.81)
Zelefsky et al. (W. Beaumont Hosp), Int Radiat Oncol Biol Phys, 84 (1): 125-29, Sept 2012

48. Prostate: clinical outcomes
•
Adaptive IGRT impact on biochemical failure caused by the bias of
rectal distension
– 5 years BC: 89% (p<0.001)
• Low risk: 96%
• Intermediate/High risk: 83%
Chronic
Toxicity
Grades >= 3
(%)
GU
15.5
4.3
GI
•
Grades >= 2
(%)
21.2
2.9
No statistical differences in stratification by RV
Parks SS et al., Int Radiat Oncol Biol Phys, 2012 Jul 1, 83(3):947-52

49. Liver
• CBCT to examine residual positioning of liver (SBRT) with
breathing controll
• Intrafraction organ motion and measurement uncertainty
contribute to residual error
• Residual error of more than 5 mm occurred 1/3 of patients
• Volumetric image guidance would improve correction
accuracy (better target and OAR visualization)
G. S. Mageras and J. Mechalakos – Sem. in Rad. Onc, 2007, 17: 268.277
Hawkins et al, IJROBP 2006, 66:610-619

50. Lung
Boda-Heggemann et al, Strahelenther Onkol; 2011, 187: 284-91

51. Lung:EPI and CBCT
LR: Good correlation
CC & AP: EPI understimated setup error
Borst et al, IJROBP, 2007, 68 (2): 555-561

52. Lung: protocols
G. S. Mageras and J. Mechalakos – Sem. in Rad. Onc, 2007, 17: 268.277

53. Lung: protocols
• Daily pre-treatment imaging (CBCT kV) with correction
of setup errors is required before SBRT:
– To avoid target underdosage
– To frameless setup
• Safety margins
• A multiinstitutional analysis of more than 400 pts
treated with CBCT-based SBRT:
– 2 y LC of 92%
– Low toxicity
Boda-Heggemann et al, Strahelenther Onkol; 2011, 187: 284-91
Grilss et al, JCO 2010, Elekta Collaborative Lung Research Group

54. SBRT body radiotherapy stageI NSCLC
for early for stage
Stereotactic
Stereotactic body radiotherapy for early stage NSCLC
# of patients RT dose
and FU
Local
control
CSS / OS
Zimmermann
2007
68
17 months
3 Fx 12.5Gy
@ 65%
88%
73% / 53%
Lagerwaard
2008
216
12 months
Risk adapted
Guckenberger
2009
41
18 months
Risk adapted
Ricardi
2009
62
28 months
Fakiris
2009
Baumann
2009
High preci
Retrospe
@ 3 years
 3D-CT
 4D-CT
@ 2 years
- / 64%
@ 2 years
All treated
84%
59% / 37%
@ 3 years
@ 3 years
3 Fx 15Gy
@ 80%
88%
73% / 51 %
70
50 months
3 Fx 20-22Gy
@ 80%
88%
57
35 months
3 Fx 15Gy
@ 65%
92%
ESTRO IGRT teaching course 2011
@ 3 years
93%
@ 3 years
@ 3 years
@ 3 years
@ 3 years
82% / 43 %
@ 3 years
88% / 60 %
@ 3 years
ESTRO

55. SBRT for early stage
High precision radiotherapy for advanced stage NSCLC
Liao IJROBP 2010
Retrospective comparison for advanced stage NSCLC
 3D-CT / 3D-CRT:
 4D-CT / IMRT:
n=318
n=91
All treated with 63Gy
OS
ESTRO IGRT teaching course 2011
Toxicity

56. CNS
• Hypofractionated RT with kV IG: head frame vs
thermoplastic mask
– Lesions smaller than 5 mm: 22% intrafraction motion
with 1-2 mm shift without invasive immobilization
– Larger tumors: treated with similar accuracy
• Daily IGRT and verification of setup correction
• Same LC and less toxicity
Bujold et al, Semin Radiat Oncol 22:50-61, 2012
Boda-Heggemann et al, Strahelenther Onkol; 2011, 187: 284-91

57. H&N
•
Weight loss
•
Shrinkage and regression of primary tumor and nodal
disease and healthy tissues
•
Sites of variability
G. S. Mageras and J. Mechalakos – Sem. in Rad. Onc, 2007
Zhang et al,IJROBP, Vol. 64(5), 1559–1569, 2006

58. H&N
• Mean reduction of parotyds volumes: 28%
• Medial shift linked with weight loss
• Significative anatomic changes: after 3-4 weeks
• Dmean at the end of treatment>10%
• Margin reduction: benefit of 22%
• Volumetric daily reduction of omolateral parotyd of 1%
• Motion of 3-4 mm at the end of treatment
Barker et al, IJROBP 2004
WU Q et al, IJROBP 2009
Castadot P et al, RO 2010
Kuo et al, AJCO 2006

59. H&N protocols
• 24 patients (802 fractions) treated with daily IG on a
helical tomotherapy unit
• Many protocols
• Residual setup errors reduce with increasing frequency
of IG for head-and-neck cancer patients. The inability to
reduce random setup errors for fractions that are not
image guided results in notable residual setup errors.
Zeidan et al, IJROBP. 2007 Mar 1;67(3):670-7

60. H&N protocols
Zeidan et al, IJROBP. 2007 Mar 1;67(3):670-7

61. H&N protocols
• 56 pt with H&N cancers- CBCT
• Average displacements calculated on the first 5 or 10
CBCT shifts
• Uncorrected: 4.8 ± 1.4 mm (40,8% fractions >5mm
off target; pts with daily errors>5mm 35.7%)
• Five CBCT: 3.9 ± 1.3 mm (19% fractions fractions >5
mm off target; pts with daily errors>5mm 14.3%)
• Ten CBCT: 3.7 ± 1.1 mm (not improvement)
Zumsteg et al, IJROBP 2012, June, 83(2): 712-719

62. H&N protocols
Zumsteg et al, IJROBP 2012, June, 83(2): 712-719

63. IGRT …

64. IGRT: Our Experience
PROSTATE
STEREO-BODY

65. IGRT: Our Experience Rational
PROSTATE

66. IGRT: Our Experience Rational
PROSTATE
STEREO-BODY

67. Flow chart
Stereobody IGRT
Set-up
+ TC
CBCT
TC
+
fusione
PT
provv
TC
+
fusione
1
2
3
4
5
PT
def
CBCT
CBCT
CBCT
CBCT
SBRT SBRT SBRT SBRT SBRT
6
Days
7
8
9
10

68. IGRT PROSTATE: UCSC Experience
TC
CBCT
+
CBCT
+
PT
CBCT
+
2 TC
CBCT
+
CBCT
CBCT
CBCT
CBCT
CBCT
CBCT
IGRT
IGRT
IGRT
IGRT
IGRT
IGRT
IGRT
IGRT
IGRT
IGRT
1
2
3
4
5
6
7
1° PT
5 CBCT al TPS
CBCT
CBCT
CBCT
CBCT
CBCT
IGRT
IGRT
IGRT
IGRT
IGRT
11
2° PT
12
13
14
15
8
9
2° Personalised
PT
10
Days
PT = treatment plan
TC = computed tomography
CBCT = cone beam CT
TPS = treatment planning system
..……
41
Days

69. First Day of RT: 5 CBCT

70. From the 5 CBCT: PTV IGRT
PTV1-PTV2 IGRT
Margini al CTV1-CTV2 IGRT:
3 mm in ogni direzione
Vs
PTV1-PTV2
12 mm Caudale
2 mm Craniale
7 mm Circonferenziale

71. Comparison between PTV e
PTV IGRT
PTV
PTV IGRT

72. IGRT- KV
SET-UP ERROR

73. IGRT- CONE BEAM TC
O
R
G
A
N
M
M
O
T
I
O
N

76. IGRT PROSTATE: UCSC Experience
CONCLUSION
1) Statistically significant
reduction (-14%) of the PTV1
(prostate); no statistically
significant difference of the
PTV2 (vescichette seminali)
2) Rectal and bladder toxicity wereless
than whom of patient treated with no IGRT
technique.

77. CONCLUSION (1)

78. CONCLUSION (2)
MRIgRT
(MRI-guided radiotherapy)
•MR-linacs
•MR-guided brachytherapy
•MR for proton therapy
The Holy Grail
Alternative solutions to the standard patient setup
The geometrical accuracy of MR images is critical
Lagendijk, 2008 Raaymakers, 2008 Raaymakers, 2009
Van der Heide, 2012, in press

79. CONCLUSION (3)
From IGRT…
Image guided Radiation Therapy
…to BIG- RT
Biological-Guided RT
temporal changes in anatomy
…temporal modifications of the tumor biology
during radiotherapy