Workshop on Advanced Technologies in Radiation Oncology
description
Transcript of Workshop on Advanced Technologies in Radiation Oncology
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