Radiothérapie Hypofractionnée et Cancer de Prostate JM Hannoun-Levi Cercle des Oncologues Radiothérapeutes du Sud / Centre Antoine Lacassagne 2 ème Congrès

$Page 1: Radiothérapie Hypofractionnée et Cancer de Prostate JM Hannoun-Levi Cercle des Oncologues Radiothérapeutes du Sud / Centre Antoine Lacassagne 2 ème Congrès$
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

# fractions

dose/fraction total dose

# fractions

Hypofractionated RT


# fractions

Hypofractionated RT

Accelerated

treatment time


# fractions

Hypofractionated RT

Accelerated Non Accelerated

treatment time treatment time =




# fractions

Hypofractionated RT

Accelerated Non Accelerated


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


Treatment coast


Therapeutic index


treatment delay

Rationnal

Patient

Tumor

RT department


Treatment coast


Therapeutic index


treatment delay

Rationnal

Patient

Tumor

RT department


Treatment coast


Therapeutic index


treatment delay

Durée duTTT

Dose/fraction(Total dose)

Volume

3D Hypofractionnated RT

Overall Treatment Time

Overall treatment time

Dose / fraction

Volume

High doseSmall volume

Short time

Volume



Development

• Biological considerations

• Dose escalation in prostate cancer

• Small volume

• Clinical data

• Conclusion

Development



• Small volume

• Clinical data

• Conclusion

Development



• Small volume

• Clinical data

• Conclusion

Development



• Prostate motion

• Clinical data

• Conclusion

Development



• Prostate motion

• Clinical data

• Conclusion

Development



• Prostate motion

• Clinical data

• Conclusions

Development



• Prostate motion

• Clinical data

• Conclusions

?=

Biological Equivalent Dose @ 2 Gy

?=

Biological Equivalent Dose @ 2 Gy


Sur

vivi

ng c

ell f

ract

ion

Dose (Gy)

Sur

vivi

ng c

ell f

ract

ion

Dose (Gy)

α/ ↔ Fractionation sensitivity

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

Efficacy

Toxicity

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

α/

Late respondingnormal tissue

Tumor

α/

Late respondingnormal tissue

Tumor

α/

Brenner DJ, Hall EJ. IJROBP 1999;43:1095

1.5 3


1< < 5α/

Hypofractionated RT

Development



• 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

[ [


Early drop due to

micrometastatic disease



Time After RT

%Fr

ee O

f Fa

ilure

Low RT Dose

[Late drop due

to local persistence of

disease

[


Early drop due to






Time After RT

%Fr

ee O

f Fa

ilure

High RT Dose

Low RT Dose

[Late drop due

to local persistence of

disease

[


Early drop due to


Haz

ard

Haz

ard

Haz

ard

All P

atients<

74 G

ray>

74 G

ray

Morgan PB et al. IJROBP 2007;67:1074

Haz

ard

Haz

ard

Haz

ard

All P

atients<

74 G

ray>

74 G

ray


Haz

ard

Haz

ard

Haz

ard

All P

atients<

74 G

ray>

74 G

ray


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



• Prostate motion

• Clinical data

• Conclusions


Bladder & Rectal Volume Changes During RT

Antolak JA et al. IJROBP 1998;42:661

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

Consequences of prostate motion

de Crevoisier et al, IJROBP 2005;62:965

Consequences of prostate motion

de Crevoisier et al, IJROBP 2005;62:965

Hypofractionated RT

Development



• Prostate motion

• Clinical data

• Conclusions


Technical aspect

Technical aspect

RCMI +/- AT

Technical aspect

RCMI +/- AT CyberKnife

Technical aspect

RCMI +/- AT Curie HDDCyberKnife

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

High Dose Rate Brachytherapy

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



• Prostate motion

• Clinical data

• Conclusions

Rationale for Accelerated and Hypofractionated Treatments for Prostate Cancer


Treatment coast



Treatment coast


Therapeutic index


Biological considerations

1< < 5α/

= 3

Biological considerations

1< < 5α/

= 3

Dose escalation


Hypofractionated RT for Prostate Cancer

« Soft » « Hyper »?


Documents

Radiothérapie Hypofractionnée et Cancer de Prostate JM Hannoun-Levi Cercle des Oncologues Radiothérapeutes du Sud / Centre Antoine Lacassagne 2 ème Congrès