Workshop on Advanced Technologies in Radiation

OncologyHoward Sandler

Prostate Cancer

• Model for use of advanced technologies

• Common, long follow-up, simple geometric relationship to critical structures

Dose Limiting Toxicity

• Rectal toxicity

• What about bladder?

Garg, et al. IJROBP66:1294,2006

Late Morbidity from Early Proton Study – median FU 13 yrs

Gardner, et al. MGH J Urol167:123,2002

GI MorbidityGU Morbidity

Shipley, et al. IJROBP 32:3,1995

50.4 photon + 25.2 CGE proton

50.4 photon + 16.8 photon

RTOG 9406?

RTOG 9406

• 1084 patients from 34 institutions

• 36% had neoadjuvant hormonal rx

• By dose level, 5 yr OS is 89%, 87%, 88%, 89%, [95%*]

* 3-yr OS

RTOG 9406 – Biochemical ResultsDoselevel

Study Group n

3-Year RateASTRO

5-Year RateASTRO

3-Year RateNadir + 2

5-Year RateNadir + 2

I68.4 Gy

1 73 68% 58% 86% 69%

2 34 65% 55% 85% 67%

II73.8 Gy

1 95 82% 67% 90% 78%

2 112 48% 38% 78% 60%

3 94 52% 47% 78% 64%III

79.2 Gy

1 102 73% 59% 91% 70%

2 68 61% 52% 85% 73%IV74 Gy

1 115 79% 72% 93% 83%

2 142 65% 61% 74% 65%V78 Gy

1 119 83% - 84% -

2 101 74% - 78% -

RTOG 9406 – Toxicity

RTOG 9406 – Toxicity

• Grade 3+– By dose level– 4%, 4%, 5%, 7%, 10%

DVH

Dose-VolumeHistogram

Grade ≥2 Rectal Morbidity at 70 Gy

Huang, et al MD Anderson IJROBP 54:1314,2002

Rectal Bleeding Requiring Laser Treatment or Transfusion(3DCRT)

Peeters et al. IJROBP 61:1019, 2005

Peeters et al. IJROBP 64:1151, 2006

LKB Modelling of Dutch Study – Uses Entire DVHLKB Modelling of Dutch Study – Uses Entire DVHn = 0.13, TD50 81 Gy, m = 0.14, p=0.025

Peeters et al. IJROBP 66:11, 2006

Rectal ConstraintInstitution Rectal ConstraintUM <20% over 70, <50% over 50

FCCC <17% over 65, <35% over 40

Wash U <17% over 65, <35% over 40

Wisconsin <15% over 70

Duke <20% over 70

Jefferson <20% over 65, <40% over 50

ROC <20% over 65, <45% over 40

UCSF DVH-based

Mayo <15% over 70, <30% over 60, <50% over 50

64 Gy3 fieldConv – openConf – 16 mm GTV-block margin 90% coverageHD vol reduced by 40%Bladder toxicity NS

Modelling Data from Marsden Trial

• Dose-surface histograms– 79 pts available– Physical dose converted using α/β=3– 1000 points per contour (= points per slice)

Fenwick, et al IJROBP 49:473–480, 2001

Randomized Trials

• Of higher dose vs. lower dose?

Trial designNo hormonal therapy

PROG 9509

T1b-2b prostate cancerPSA <15ng/ml

Proton boost 19.8 GyE

Proton boost 28.8GyE

3-D conformal photons 50.4 Gy

3-D conformal photons 50.4 Gy

Total prostate dose

70.2 GyETotal prostate dose

79.2 GyE

r a n d o m i z a t i o n

Zietman, et al. JAMA2005;294:1233-1239

Morbidity?Morbidity?

Zietman, et al. JAMA2005;294:1233-1239

Dutch Study Points

• ASTRO no backdating• 21% had hormonal rx• 0 mm post PTV margin

from 68-78 Gy• Dose prescribed to

isocenter

Peeters et al. JCO 24:1990,2006

Randomized Trials

• Of altered fractionation vs. standard fractionation?

HypofractionationHypofractionation

Hypofractionated Randomized TrialHypofractionated Randomized Trial

• 16 Canadian regional centres

• 66 Gy in 33 fx vs. 52.5 Gy in 20 fx (2.62)

• Simple conformal rx

• Non-inferiority design with abs diff 7.5%

Lukka, et al. JCO 23:6132,2005

7% worse in short arm

T1c-2aGS <7PSA <10

73.8 Gy/41 Fx

70 Gy/28 Fx

RTOG 0415 Schema

n=800Endpoint is 5 Year BFFF Non-inferiority margin 7% (Control 85%, Exp 78%)

Other Hypofractionation Randomized Other Hypofractionation Randomized TrialsTrials

• CHHIP (Conv or Hypo High Dose IMRT)

– N=2200

– 3 arm study

– Standard vs. 2 hypofractionated arms

Randomized TrialsRandomized Trials

• Particle vs. photon?

– No PSA era trials

• MGH proton, RTOG neutron

Particle TherapyParticle Therapy

• Protons

– Bragg peak

– Concerns

• ‘Wide’ penumbra due to scattering

• Neutron dose unless proton IMRT (scanned beam) is used (from p,n reaction)

Carbon IonCarbon Ion•Higher LET - ?Better for more “resistant” tumors

•?Fewer fractions needed

“The promising results obtained with carbon radiotherapy need confirmation in controlled clinical trials with large patient numbers comparing carbon ion RT with photon IMRT and proton RT taking also into account toxicity and quality of life.”

Schulz-Ertner, et al Radiation Therapy With Charged Particles Semin Radiat Oncol 16:249,2006

Future Technologies/Areas for StudyFuture Technologies/Areas for Study

• Particle therapy

– Carbon vs. Proton vs. Photon IMRT

• Hypofractionation

– Can the low α/β model for prostate be verified?

• NTCP modelling

– Randomized trials can help

• Target motion

– Issue for all externally delivered, highly conformal dose approaches