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Radiothérapie Hypofractionnée et
Cancer de Prostate
JM Hannoun-Levi
Cercle des Oncologues Radiothérapeutes du Sud / Centre Antoine Lacassagne
2ème Congrès du CORS – Juan les Pins – 26/06/09
# fractions
Hypofractionated RT
Accelerated Non Accelerated
treatment time treatment time =
dose/fraction total dose
# fractions
Hypofractionated RT
Accelerated Non Accelerated
dose/fraction total dose
treatment time treatment time =
Rationnal
Patient
Tumor
RT department
Quality of lifeTime for recovering professional life
Treatment coast
Biological considerationsDose escalation
Therapeutic index
linac time # treated pts
treatment delay
Rationnal
Patient
Tumor
RT department
Quality of lifeTime for recovering professional life
Treatment coast
Biological considerationsDose escalation
Therapeutic index
linac time # treated pts
treatment delay
Rationnal
Patient
Tumor
RT department
Quality of lifeTime for recovering professional life
Treatment coast
Biological considerationsDose escalation
Therapeutic index
linac time # treated pts
treatment delay
Rationnal
Patient
Tumor
RT department
Quality of lifeTime for recovering professional life
Treatment coast
Biological considerationsDose escalation
Therapeutic index
linac time # treated pts
treatment delay
Development
• Biological considerations
• Dose escalation in prostate cancer
• Small volume
• Clinical data
• Conclusion
Development
• Biological considerations
• Dose escalation in prostate cancer
• Small volume
• Clinical data
• Conclusion
Development
• Biological considerations
• Dose escalation in prostate cancer
• Small volume
• Clinical data
• Conclusion
Development
• Biological considerations
• Dose escalation in prostate cancer
• Prostate motion
• Clinical data
• Conclusion
Development
• Biological considerations
• Dose escalation in prostate cancer
• Prostate motion
• Clinical data
• Conclusion
Development
• Biological considerations
• Dose escalation in prostate cancer
• Prostate motion
• Clinical data
• Conclusions
Development
• Biological considerations
• Dose escalation in prostate cancer
• Prostate motion
• Clinical data
• Conclusions
α/ Dose range
(Gy)
Normal Tissue
Response OTT* D/f**
Low
High
1 to 5
10 to 20
Late
Early
& Tumors
+
+++
+++
+
Sensitivity to
* OTT: Overall Treatment Time** D/f: Dose per fraction
α/ Dose range
(Gy)
Normal Tissue
Response OTT* D/f**
Low
High
1 to 5
10 to 20
Late
Early
& Tumors
+
+++
+++
+
Sensitivity to
* OTT: Overall Treatment Time** D/f: Dose per fraction
2///*' dDD
D’: biologic equivalent dose (Gy)D : physical delivered dose (Gy)d : dose per fraction for D (Gy)d’ : dose per fraction for D’ (Gy)
For dose/fraction < 8 GyFor dose/fraction < 8 Gy
Development
• Biological considerations
• Dose escalation in prostate cancer
• Prostate motion
• Clinical data
• Conclusions
HypothesisHigher RT Doses will cause late flattening of K-M curves
through a reduction in local persistence of disease
Time After RT
%Fr
ee O
f Fa
ilure
Low RT Dose
[ [
Morgan PB, et al. IJROBP 2007;67:1074
Time After RT
%Fr
ee O
f Fa
ilure
Low RT Dose
[ [
Morgan PB, et al. IJROBP 2007;67:1074
Early drop due to
micrometastatic disease
HypothesisHigher RT Doses will cause late flattening of K-M curves
through a reduction in local persistence of disease
Time After RT
%Fr
ee O
f Fa
ilure
Low RT Dose
[Late drop due
to local persistence of
disease
[
Morgan PB, et al. IJROBP 2007;67:1074
Early drop due to
micrometastatic disease
HypothesisHigher RT Doses will cause late flattening of K-M curves
through a reduction in local persistence of disease
HypothesisHigher RT Doses will cause late flattening of K-M curves
through a reduction in local persistence of disease
Time After RT
%Fr
ee O
f Fa
ilure
High RT Dose
Low RT Dose
[Late drop due
to local persistence of
disease
[
Morgan PB, et al. IJROBP 2007;67:1074
Early drop due to
micrometastatic disease
PSA Era Randomized Dose Escalation Trials
Authors (yr) # pts Dose (Gy) FFBF p-value
Kuban (2008)* 151 78 78%(10yr) 0.004150 70 59%(10yr)
Zietman (2005) 195 79.2 80%(5 yr) <0.001197 70.2 61%(5 yr)
Peeters (2006) 333 78 64%(5 yr) 0.02331 68 54%(5 yr)
Dearnaley (2007) 422 74 71%(5 yr) 0.0007421 64 60%(5 yr)
*Nadir+2 FFBF; Neoadjuvant AD 3-6 mo.
PSA Era Randomized Dose Escalation Trials
Authors (yr) # pts Dose (Gy) FFBF p-value
Kuban (2008)* 151 78 78%(10yr) 0.004150 70 59%(10yr)
Zietman (2005) 195 79.2 80%(5 yr) <0.001197 70.2 61%(5 yr)
Peeters (2006) 333 78 64%(5 yr) 0.02331 68 54%(5 yr)
Dearnaley (2007) 422 74 71%(5 yr) 0.0007421 64 60%(5 yr)
*Nadir+2 FFBF; Neoadjuvant AD 3-6 mo.
Hypofractionated RT
Development
• Biological considerations
• Dose escalation in prostate cancer
• Prostate motion
• Clinical data
• Conclusions
Sigmoid Flexure
Ischial Tuberosities
PP
R R
Not corrected for motion
B B
Prostate motion according to the rectum vacuity
Courtesy of Alan Pollack
Sigmoid Flexure
Ischial Tuberosities
PP
R R
Not corrected for motion
B B
Prostate motion according to the rectum vacuity
Courtesy of Alan Pollack
Development
• Biological considerations
• Dose escalation in prostate cancer
• Prostate motion
• Clinical data
• Conclusions
Results of Prospective Phase II“Soft” Hypofractionation Studies (EBRT)
Miles EF et al. Semin Radiat Oncol 2008;18:41
Ongoing Randomized Trials of“Soft” Hypofractionation (EBRT)
Miles EF et al. Semin Radiat Oncol 2008;18:41
Results of ProspectiveHypofractionation Boost Studies (HDR)
Risk Authors (yr) Groups Median Dose (Gy)
EBRT HDR
Median
follow-up (yr)
5-year
Biochemical
control rate (%)*
Low Elau (2000)
Galalae (2004)
Demanes (2005)
T1-2b, SG =6, PSA<10
T1-2b, SG =6, PSA<10
T1-2b, SG =6, PSA<10
50 12-16
46-50 16-30
36 22-24
6
5
7.25
96
96
90
Inter. & high Elau (2000)
Martinez (2002)
Galalae (2004)
Demanes (2005)
Martinez (2009)
T2c-3, SG 7-10, PSA >15
Intermediate : 1/2 factors
High : 3 factors
T2c-3, SG 7-10, PSA =10
T = 2b, SG =7, PSA =10
Intermediate : 1 factor
High : =2 factors
T2b-c, SG 7, 10<PSA =20
T3, SG 8-10, PSA > 20
T = 2b, SG =7, PSA =10
50 12-16
46 23
46-50 16-30
36 22-24
40 24
6
4
5
7.25
5.8
72
49
87
88
69
87
69
85 (82*)
*ASTRO definition** 10-year biochemical control rate
Fractionation
schedule
Tech Dose/fx #fxs TD
Gy 1.5
α/β
3 10
Madsen
Stanford
Martinez
Demanes
Mark
CK
CK
HDR
HDR
HDR
6.70
7.20
9.50
7.25
7.50
5
5
4
6
6
33.50
36.25
38.00
43.50
45.00
78.5
90.6
119.4
108.8
115.7
65.0
74.3
95.0
89.2
94.5
46.6
52.1
61.8
62.5
65.6
Different fractionation schedules using“Hyper” Hypofractionated regimens with
CK or HDRBT
Development
• Biological considerations
• Dose escalation in prostate cancer
• Prostate motion
• Clinical data
• Conclusions
Quality of lifeTime for recovering professional life
Treatment coast
Rationale for Accelerated and Hypofractionated Treatments for Prostate Cancer
Quality of lifeTime for recovering professional life
Treatment coast
Biological considerationsDose escalation
Therapeutic index
Rationale for Accelerated and Hypofractionated Treatments for Prostate Cancer