CPT
ProtonProton--
Radiotherapy:Radiotherapy:Overview
of Clinical
Indications
Eugen B. Hug
(with emphasis
on indications
treated
at PSIFor comprehensive
clinical
reviews: ESTRO or PTCOG
seminars)
HUG 11/07
CPT
Complication-free
Tumor Control
Complication
–Free Survival
CPT
Complication-free
Tumor Control
Complication
free survival
CPT
Proton-Radiotherapy for skull base tumors:
2
Lomax, Phys. Med. Biol. 44:185- 205, 1999
brainstembrainstem
tumortumor
((targettarget volume)volume)
CPT
1973
—Massachusetts General Hospital und Harvard Cyclotron, Boston und Cambridge, USA
EarlyEarly
clinicalclinical
Phase: Phase: ProofProof
of of SafetySafety
and and EfficacyEfficacy
CPT
Early “biologic models”
(Long-term outcomes data):
•eye tumors (uveal
melanomas)
•skull base tumors
•paraspinale
tumors of various histologies
•Unresectable sarcomas
= = excellentexcellent
tumortumor
modelsmodels, , butbut
lowlow
incidenceincidence
ParadigmParadigm
of of protonproton
therapytherapy
in the in the 7070‘‘s and 80s and 80‘‘s: s:
Increase Increase tumortumor
dose = increase in dose = increase in locallocal
tumortumor
controlcontrol
and Cureand Cure
CPTProton RT
• Uveal
Melanomas
G. Goitein
•Chordomas and Chondrosarcomas
C. Ares
•Skull Base
and Paraspinal
C. Ares / E. Hug
•Sarcomas
• (occasional Pediatrics,
Prostate-Ca)
B. Timmermann
Proton Radiation Therapy since the ’70s and ’80s –
the longest follow up data
CPT
• Primary
skull base
tumors:
•Chordoma, Chondrosarcoma
•Secondary
infiltration
from intracranial
tumors:
•Meningioma
•Secondary
infiltration
from
primary H&N tumors:
•Nasopharynx CA,
• Paranasale
Sinus CA,
•Adenoid-cystic
CA
•A.o.
Tumors of the base of skull (examples)
Nasopharynx Ca
CPT5-
year
Loc
alC
ontr
olra
tes(
%)
20
40
60
80
100
20 40 60 80 100
Chordomas of the Base of Skull
Dose [ Gy (RBE)]
MGH 1999PSI 2007LLUMC 1999
GSI
Romero 1993Zorlu
2000
SRT –
Heidelb. 2000
C-Ions
Photons
Protons
CPT5-
year
Loc
alC
ontr
olra
tes(
%)
20
40
60
80
100
20 40 60 80 100
Chordomas of the Base of Skull
Dose [ Gy (RBE)]
MGH 1999PSI 2007LLUMC 1999
GSI
Romero 1993Zorlu
2000
SRT –
Heidelb. 2000
C-Ions
Photons
Protons
Small Chordomas Small Chordomas Chondrosarcomas Chondrosarcomas
High dose High dose CC--ionsions
CPT Proton Radiotherapy:
-
Results of the early
clinical
era-
High-dose
and/or hypofractionated therapy concepts
increased
tumor
control
compared
to conventional
photon
RT by
approx. 10 approx. 10 ––
30 % 30 %
.. and for the .. and for the firstfirst
time time offeredoffered
curescures
for for selectedselected, , previouslypreviously
uncurableuncurable
tumors tumors
(chondrosarcomas (chondrosarcomas fromfrom
2525--30% to 80% at 10 years)30% to 80% at 10 years)
Examples: Skull Base Chordomas, Chondrosarcomas and adenoid
Cystic
Carcinomas, subgroups
of Uveal
Melanomas, Unresectable Sarcomas.
CPT
High-capacity
patient
treatmentsAdditional clinical
Indications:
1.
Exploring high-frequeny
diseases
(prostate, lung)2.
New emphasis
on Normal tissue
sparing
(pediatrics)
ClinicalClinical
Phase of the 90Phase of the 90‘‘s: s: Start of Start of hospitalhospital--basedbased
Proton Proton
RadiotherapyRadiotherapyIntroductionIntroduction
of Gantryof Gantry
Loma
Linda,
1991
CPTProtons for Prostate
Ca:
Multiple comparisons
published
Difference
mainly
in decreased
Integral Dose
Combined rectal dose–volume curves for proton therapy and intensity-
modulated radiotherapy (IMRT) (n
= 20 plans)
Volume Comparison of Proton Therapy and Intensity-Modulated Radiotherapy for Prostate Cancer Vargas et al,IJROBP
2008, 70(3):744
CPT Prostate Ca > 12 000 Patients treated
•
Patients•
Stage
•
35•
1A/1B
•
314•
1C
•
291•
2A
•
248•
2B
•
283•
2C
•
50•
3
•Loma
Linda University MedicalCenter (Drs. Rossi, Slater
)
•1255 patients treated between10/91 and 12/97•Patients had
no prior
surgery
or hormonal therapy•74-75 CGE at 1.8 –
2.0 CGE
per fraction•Follow-up
mean
63 mos.,
median 62 mos. (range
1-132)
CPT
Prostate Cancer-LLUMC 10 YEAR Effect of Initial PSA on Disease-free Survival
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Years post Proton Radiation
Dis
ease
-fre
e Su
rviv
al (
%)
< 4.14.1 -
10.010.1 -
20.020.1 -
50.0
90%81%
62%
p =.0001
43%
CPT Treatment Morbidity RTOG Scale
Grade 2 Grade 3 & 4
GI
GU
Total
3.5%
5.4%
9%
0
0.3%
0.3%
CPT
Comparison of Conventional-Dose vs High-Dose Conformal Radiation Therapy in Clinically Localized Adenocarcinoma of the Prostate: A randomized controlled trialZietman AL et al. JAMA 2005; 294:1233-1239
•1996 -1999•393 patients enrolled•2 US academic institutions (LLUMC and HCL/MGH)•Stage T1b through T2b prostate cancer •Prostate-specific antigen (PSA) levels less than 15 ng/mL. Median PSA level was 6.3 ng/ml
•Median follow-up was 5.5 (range, 1.2-8.2) years.
Prospective, randomized
trial:
CPT
PROG 9509T1b-2b prostate cancer
PSA <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 GyE
Total prostate dose 79.2 GyE
r a n d o m i z a t i o nACR/RTOG
Randomized
Trials:
protons versus
protons
CPT
Copyright restrictions may apply.
Zietman, A. L. et al. JAMA 2005;294:1233-1239.
Freedom From Biochemical Failure (ASTRO Definition) Following Either Conventional-Dose (70.2 GyE) or High-Dose (79.2 GyE) Conformal
Proton / Photon Radiation Therapy
CPT
Copyright restrictions may apply.
Zietman, A. L. et al.JAMA 2005;294:1233-1239.
Acute and Late Genitourinary and Gastrointestinal (Rectal) Morbidity, by Assigned Radiation Therapy Dose and Toxicity Grade
Authors’
conclusions:
Men with clinically localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation. This advantage was achieved without any associated increase in RTOG grade 3 acute or late urinary or rectal morbidity.
CPT
Copyright restrictions may apply.JAMA 2008;299:899-900.
incorrect
2005corrected
2008
JAMA 2008: Correction
Authors
discovered
incorrect
coding
in data
base:
IntendedIntended: biochem. failure
= 3 successive
PSA increases
(ASTRO Def.)
CodedCoded::
biochem. Failure
= any
3 failures
Result: higher
# of pts. incorrectly
coded
as failures
79%
91%
CPT
A Phase III Trial Employing Conformal Photons with Proton Boost in Early-stage Prostate Cancer: Conventional Dose (70.2 GyE) Compared to High-dose Irradiation (79.2 GyE): Long-term Update analysis of Proton Radiation Oncology Group (PROG)/American College of Radiology (ACR) 95-09 Zietman AL, Rossi C, et al. IJROBP 2009, 75:3, S11 –
ASTRO
•Median follow-up: 8.9 years.
Randomized
Trials:
protons versus
protons
CPTZietman, A. L. et al. IJROBP 2009;75:3, S11
Freedom From Biochemical Failure (ASTRO Definition –
with backdating) Following Either Conventional-Dose (70.2 GyE) or High-Dose (79.2 GyE)
Conformal Proton / Photon Radiation Therapy
•70.2 vs. 79.2 GyE: 10-year BF rates
(ASTRO) 35.3% vs. 16.3 % (p=0.0001)
•Low –risk: 29% vs. 6.1% (p=0.0001)
•Intermed. Risk: 44.6 vs. 28.6% (p=0.06)
•No diff. in OS: 83.4 vs. 78.4% (p=0.45)
•No diff. in high Grade, late toxicity
(> Gr. 3): overall
2.1%
•Higher
toxicity, if
Grade 2 included: (> Gr. 2): 29.4 vs. 39.4% (p=0.045)
Authors’
conclusions:
This RCT shows a long-term advantage in terms of freedom from biochemical failure for men with low and intermediate risk prostate cancer receiving high-dose vs. conventional dose conformal radiation delivered with mixed proton and photon beams. This advantage was achieved without any associated increase in Grade >3 late urinary or rectal morbidity.
CPT Status of Proton-Radiotherapy for Carcinoma of Prostate:
•Thus far a conservative approach
•Similar dose levels and fractionation regimen compared to modern photon RT (IMRT, IGRT, SBRT etc.)
•Similar rates of tumor control –
as had to be expected
•indications of decreasing rates of severe side effects for protons.
••approx. 50% of all patients treated world wide approx. 50% of all patients treated world wide
with Protons are treated for prostate CAwith Protons are treated for prostate CA
CPT
The conservative
approach
for Prostate
Ca continues:
„New“
Protocol
for early-stage Prostate
Ca at LLUMC:
60 Gy (RBE) at 3 Gy / 60 Gy (RBE) at 3 Gy / fractfract..
ReducesReduces
treatment time treatment time fromfrom
45 frct. 45 frct. In 9 In 9 weeksweeks
(81 (81 GyEGyE
at 1.8) to 20 frct. at 1.8) to 20 frct.
In 4 In 4 weeksweeks
CPT
The conservative
approach
for prostate
Ca continues
unabated:
„New“
Protocol
for early-stage Prostate
Ca at LLUMC:
60 Gy (RBE) at 3 Gy / 60 Gy (RBE) at 3 Gy / fractfract..
AlreadyAlready
donedone
with with photonphoton--RTRTPrimaryPrimary
goalgoal
reduce reduce TxTx--timetime, , economiceconomic
concernsconcerns
Very Very conservativeconservative
hypofractionationhypofractionationcomparedcompared
to to CyberknifeCyberknife
(King et al. IJROBP, 73(4), 2009(King et al. IJROBP, 73(4), 20097.25 Gy x 5 = 36.25Gy)7.25 Gy x 5 = 36.25Gy)
WhereWhere
is the is the „„hypothesishypothesis--drivendriven
trialtrial““????
CPT
Proton Therapy for Proton Therapy for MalignanciesMalignancies of the of the ChestChest
and Thorax:and Thorax:
Breast-CA
(Non-Small
Cell) Lung
CA
Mesothelioma
CPT
ParticleParticle
Therapy for Therapy for MalignanciesMalignancies
of the of the ChestChest
and and Thorax:Thorax:
BreastBreast--CACA: :
Partial Partial BreastBreast
RTRT
Whole
Breast
/ Chestwall
+/-
regional LN RT
(Non-Small
Cell) Lung
CA
Mesothelioma
CPTPartial Breast
(accelerated) Irradiation:
The goal: replace
„whole
breast“
RT for low-risk
breast
Ca patients
MammoSite
Interstitial
Brachytherapy
CPT
Helical
Tomotherapy: Kainz K, Med. Coll. Wisconsin, IJROBP 74(1):275, 2009
Protons: Kozak
K at MGH, IJROBP 65(5), 2006
IMRT: Jagsi
R, U. Michigan, IJROBP, in press
Partial Breast
(accelerated) Irradiation
…plus intraoperative
RT
CPT
•
Phase I/II trial. 20 women
with T-1 breast
Ca, neg. margins
after lumpectomy
•PTV: lumpectomy
cavity
plus 1.5-2.0 cm, minimum
5mm distance to surface/skin
•32 Gy(RBE) total dose: 4 Gy (RBE) B.I.D. over
4 days
•1-3 field arrangements
overall, 1 field treated per day
only
•„Skin dose per field approached
maximum
dose“, Single field per day
= full
4 Gy skin
dose. (MGH, passive scatttering
)
•Observation: Median F/U 12 months
(8-22)
increased
acute
toxicity:
80% moderate to severe
skin
color
changes
22% severe
moist
desquamation
Accelerated
Partial-Breast
Proton Therapy: Initial MGH Experience
KozakKozak, , TaghianTaghian
et al. IJROBP 66(3):691, 2006et al. IJROBP 66(3):691, 2006
Proton Therapy for Proton Therapy for BreastBreast
Ca:Ca:
CPT
„Despite
significant
resolution
of acute
skin
toxicities
by 6 months, concerns
persist“
Authors
suggest:
•Multiple field arrangements,
•fields should not overlap
at skin,
•all fields treated per fraction
Accelerated
Partial-Breast
Proton Radiotherapy: Initial MGH Experience
KozakKozak, , TaghianTaghian
et al. IJROBP 66(3):691, 2006et al. IJROBP 66(3):691, 2006
Note: acute
toxicity
did
not translate
into
early-late
toxicity
CPT
ParticleParticle
Therapy for Therapy for MalignanciesMalignancies
of the of the ChestChest
and and Thorax:Thorax:
BreastBreast--CACA: :
Partial Breast
RT
WholeWhole
BreastBreast
/ / ChestwallChestwall
+/+/--
regional LN RTregional LN RT
(Non-Small
Cell) Lung
CA
Mesothelioma
CPT
3D-CRT IMRT IMPT
PTV1 scenario – Whole Breast only
3D-CRT IMRT IMPT
PTV2 scenario – Whole Breast, MSC, LSC and AxIII
3D-CRT, IMRT, IMPT Comparison
for local
and locoregional
breast
RT (Ares for PSI, IJROBP Epub
2009)
Scenario
#1:Whole
breast
Scenario
#2:Whole
breast,
axillary LN, supraclav. LN
CPT
Scenario
#3:Whole
breast,
axillary LN, supraclav. LNIMC
PTV3 scenario – Whole Breast, MSC, LSC, AxIII and IMC
3D-CRT IMRT IMPT
CPT
0 20 40 60 80 100
Right breast mean
Heart V22.5
Heart V5
Right lung V20
Right lung V5
Left lung V20
Left lung V5
Mean dose (%) +/- SD
IMPTIMRT3D-CRT
OAR‘smean
doses
+/-
SD
Loco-regional
RT (PTV-3) comparison
CPT
Planned
Pilot-Study
at PSI:
Proton Therapy for Breast
Ca requiring loco- regional
Irradiation
Eligibility criteria (draft version)
•female patients, •non metastatic left-sided breast cancer
with ≥
4
positive axillary lymph nodes
• ( indication for inclusion of IMC nodes: •internal quadrant tumors, •or positive IMC uptake on lymphoscintigraphy•or positive CT or PET-CT, •or biopsy proven positive IMC nodes)
CPT
ParticleParticle
Therapy for Therapy for MalignanciesMalignancies
of of the the ChestChest
and Thorax:and Thorax:
Breast-CA
((NonNon--SmallSmall
CellCell) ) LungLung
CACA
Mesothelioma
CPT
•Proton radiotherapy only•68 patients, •T1 (29 patients) and T2 (39 patients), NO,MO• medically inoperable Non-small-cell Lung CA •
Dose: 51 cobalt Gray equivalent (CGE) in 10
fractions over 2 weeks. Subsequently 60 CGE in 10 fractions.•Median follow-up time 30 months
Hypofractionated Proton Radiotherapy for Stage I Lung Cancer. Bush et al . Chest 126(4), 2004
Proton-Radiotherapy for early
Stage
Lung
Cancer
Before
PRT
After PRT
CPT
Hypofractionated Proton Beam Radiotherapy for Stage I Lung Cancer.
Bush et al . Chest 126(4), 2004
•No symptomatic pneumonitis or late esophageal or cardiac toxicity•3-year local control: 74%; 3-year disease-specific survival: 72%•Local tumor control T1 vs T2 tumors = 87% vs 49%•Trend toward improved survival.
87%
CPTEffect
of dose on Overall Survival:
3-year OS-rate
55% (60CGE) versus
27% (51 CGE) (p=0.03)
Present
LLUMC-
Protocol:
70 CGE / 10 frct. ( approx. 100 Gy at 2 Gy/frct)
CPTStudies on stage II and III NSCLC
First Author
Year Tx-
type
Pt. # Frct. dose (Gy)
Frct. #: Total dose(Gy)
% tumor
< 3cm
% medic. Inop.
Median FU in months (range)
STAGE II
Xia 2006 SBRT 18 7 10 70 42% 100% 27 (24-54)
Salazar 2008 SBRT 9 13 4 52 75% 100% 38 (2-84)
STAGE III
Rowell 2004 CCR 1065 NR various 45-70 NR NR various
Auperin 2007 CCR 1205 NR various 49-66 NR NR various
Bush 1999 Proton 8 1.8-
5.1
10-41 51-74 44% NR 14 (3-44)
Shioyam
a
2003 Proton 8 2-6 7-32 49-93 32% NR 30 (18-153)
CPT
CarbonCarbon--IonIon
Therapy for
NSC-Lung
Ca
CPT
Total129 pats
Clinical Study on Carbon Beam Therapy for Stage I Non-Small Cell Lung Cancer
(From: H. Tsjii, NIRs, Japan)
DoseDose--escalationescalation
Dose recommended90GyE
72 GyE
59.4GyE59.4GyE64.864.872.072.079.279.286.486.490.090.095.495.4
68.4GyE68.4GyE72.072.075.675.679.279.2
72GyE 52.8GyEfor stage IA
60.0GyEfor stage IB
9 fr
/ 3 wks50 pats
Single- dose
84 pats
4 fr
/ 1 wk79 pats
9 fr
/ 3 wks34 pts
18 fr
/ 6 wks47 pats
9303
Phase I/III(1994)
9701
Phase I/II(1997)
9802
Phase �(4/99 -
11/00)
0001
Phase I/II(12/00 -
11/03)
0201
Phase I/II(12/03 ~)
28GyE30343638404244
CPTLocal Control vs. Carbon Ion Dose
for Different Fractionations in NSCLCLo
cal C
ontr
ol(%
)
GyE
: 9 Fr.: 18 Fr.: 4 Fr.
1.0
0.5
00 20 40 60 80 100
9 Fr18 Fr.
4 Fr.1 Fr.
Patients’
data
30 GyE(TCP=0.95)
CPT
Total DoseGy(RBE) No. 6mo. 12mo. 18mo. 24mo. 30mo. 36mo.
28.0 6 100.0 66.7 50.0 50.0 50.0 50.032.0 27 96.2 72.9 72.9 68.8 64.8 64.834.0 34 100.0 79.1 69.2 69.2 65.4 65.436.0 18 100.0 94.4 94.4 94.4 94.4 94.438.0 14 100.0 92.3 92.3 92.3 92.340.0 15 100.0 86.7 86.7 79.4 68.142.0 15 100.0 85.7 85.7 85.744.0 30 100.0 90.8 79.4
Local Control in Single Fraction Treatment of Stage I NSCLC
Currently, single fraction of 46GyE is being evaluated.
CPTLocal Control of Single Fraction C-ion RT(#0201)
<34.0GyE vs. >36.0GyE
0
.2
.4
.6
.8
1
0 10 20 30 40 50 60 70
Months after RT
36�44GyE (n=105):84.3%
28�34GyE (n=67):52.5%
P=0.0014
CPT
Single fraction34GyE
Pneumonitis appeared corresponding to the high dose area.
From: Dr. Tsujii –
ESTRO Teaching course 2009
CPTParticleParticle
Therapy for Therapy for MalignanciesMalignancies
of the of the
ChestChest
and Thorax:and Thorax:
(Non-Small
Cell) Lung
CA –
present
status
Protons: evolving, essentially
only few
data, passive scattering only, active
scanning technology presently
not solved
(except
possibly
by using anesthesia)
Carbon
Ions: very promising
data, outstanding
effort
from
NIRS, needs
to be
confirmed
–
specifically
toxicity
profile
a)
Peripheral
lung
lesions: multiple modalities
offer
good local control
(particles, SBRT, Cyberknife, Tomotherapy) –
area
of
great
progress
compared
to standard
EBRT. Local
Control
IA > 80%, lesser
LC for IB. ? Added
benefit
for particles?
b)
Central lung
/ mediastinum: remains
a challenge
for photons mainly
due
to V5-V20, MLD –
dose. Excellent opportunity
for
particles.
c)
The co-morbid patient: reduced
lung
function
due
to chronic lumonary
disease (asthma, emphysema
etc.) with little
functional
reserve
to spare –
opportunity
for particles
CPT
ParticleParticle
Therapy for Therapy for MalignanciesMalignancies
of of the the ChestChest
and Thorax:and Thorax:
Breast-CA
(Non-Small
Cell) Lung
CA
MesotheliomaMesothelioma
CPT
chrysotile
Asbestos Asbestos
fibre
From Asbestosis
to
Mesothelioma
From Asbestos
to Mesothelioma
CPT
Standard Therapy for Mesothelioma:Standard Therapy for Mesothelioma:
„„TrimodalityTrimodality
Therapy / Therapy / TripleTriple
TherapyTherapy““
•Surgery
(Extrapleural pneumonectomy)
•Chemotherapy
•Radiotherapy
CPT
IMRT-Plan
from
MDAnderson
CC)
Conventional
XRT (Plan from
R. Cameron, UCLA, 2004)
Radiotherapy for Mesothelioma
CPT Comparison
of Patterns of Failure
After Extrapleural Pneumonectomy With or Without Adjuvant
Therapy (Sugarbaker, 1997)
VariableSugarbaker1997
Lung
Cancer Study Group [1991]
Cleveland Clinic
[1994]
TreatmentEPP, CAP, RT EPP EPP or P, CT
Median follow-up
(mo) 18 14 Not reported
No. of patients evaluable
for recurrence 46 17 18
% of patients with recurrence 54% 76% 67%
Recurrence
site
Local
% of all patients 35% 41% 56%
% of recurrences 67% 54% 83%
Abdomen
% of all patients 26% 29% Not stated
% of recurrences 50% 38%
Contralateral thorax
% of all patients 17% 29% Not stated
% of recurrences 33% 38%
Distant
% of all patients 8% 35% 28%a
% of recurrences 17% 46% 42%a
Mesothelioma: high failure
rate after triple-therapy
Recent
series: approx. 30%
CPT
6 / 13 patients developed
FATAL pneumonitis after 54 Gy with IMRT
IJROBP 2006
Mesothelioma: risk
of contralateral lung
damage by IMRT
CPTMesothelioma: IMRT / Proton comparison
U. Zürich / PSI collaborationKrayenbühl, Hartmann, Cziernik, Lomax
(IJROBP
submitted)
IMRT Protons
CPT
Mesothelioma: IMRT / Proton comparison U. Zürich / PSI collaboration
Krayenbühl, Hartmann, Cziernik, Lomax
CPT
IMRT PT Mean
difference p-value
V95 (PTV1) [%] 96.0 ±
2,9 96,2 ±
2.66 0.24 0.3
V105 (PTV1) [%] 4.8 ±
5.1 2.61 ±
2.12 -2.19 0.2
V95 (PTV2) [%] 94,6 ±
4.0 95.32 ±
1.27 0.73 0.2
V105 (PTV2) [%] 36.1±
20.7 33.42 ±
17.51 -2.64 0.2
IMRT PT Mean
difference p-value
D2 (spinal cord) [Gy] 15.1 ±
6,6 3.71 ±
3.98 -11.4 < 0,01
D2 (spinal cord) [Gy] 35.6 ±
3.9 28.61 ±
2.98 -7.0 < 0,01
Dmean (ipsi. kidney) [Gy] 11,4 ±
6.1 7.04 ±
4.04 -4.3 0.8
V15 (ipsi. Kidney) [%] 25.4 ±
13.7 18.62 ±
10.37 -6.8 0.02
Dmean (heart) [Gy] 26,5 ±
6,2 5.99 ±
4.64 -20.8 < 0,01
V45 (heart) [%] 5.8 ±
2,0 2.3 ±
3.39 -3.5 0.47
Dmean (lung) [Gy] 9,6 ±
2.7 0.35 ±
0.42 -9.3 < 0,01
V5 (lung) [%] 67.7 ±
20.3 1.04 ±
1.83 -66.7 < 0,01
V13 (lung) [%] 24.1 ±
16.2 0.4 ±
0.8 -23.7 0.04
V20 (lung) [%] 9.4 ±
6.8 0.2 ±
0.5 -9.2 0.04
Mesothelioma: IMRT / Proton comparison
U. Zürich / PSI collaboration
Krayenbühl, Hartmann, Cziernik, Lomax
CPT
2 2 legslegs
of of
Proton Radiation Therapy Proton Radiation Therapy
High Dose Tumor application
Reduction
of low-dose
volume of normal tissues
CPTOrbital Rhabdomyosarcoma: Protons versus Photons
Hug, et al. IJROBP, 47, 2000
Hein, Hug et al. IJROBP 62, 2005
PhotonsPhotons ProtonsProtons
CPTOrbitales
Rhabdomyosarkom: Protonen
versus Photonen
Hug, et al. IJROBP, 47, 2000
Hein, Hug et al. IJROBP 62, 2005
PhotonenPhotonen ProtonenProtonen
CPT
Comparative dose distributions for 9-field photon intensity-modulated photon (IMXT) and 3-field intensity-modulated
protonradiation
(IMPT) treatment plans for a patient with pelvic Ewing’s sarcoma.
(Courtesy of A.R. Smith and A.J. Lomax, in Delaney, Cancer Control, 2005)
IMPTIMXT
IMXT
-
IMPT
The Integral Dose Differential
CPT
Comparative dose distributions for 9-field photon intensity-modulated photon (IMXT) and 3-field intensity-modulated
protonradiation
(IMPT) treatment plans for a patient with pelvic Ewing’s sarcoma.
(Courtesy of A.R. Smith and A.J. Lomax, in Delaney, Cancer Control, 2005)
IMPTIMXT
IMXT
-
IMPT
The Integral Dose Differential
CPTPediatric Proton--
Radiotherapy
CPT
ReductionReduction
of the of the „„irradiated volumeirradiated volume““( Integral Volume ) ( Integral Volume )
= = ReductionReduction
of Late Effectsof Late Effects
ImprovedImproved
Quality of LifeQuality of Life==
ReducedReduced
riskrisk
of of inductioninduction
of Second of Second MalignancyMalignancy
(Scanning Technologie )(Scanning Technologie )
Protons for Pediatric Malignancies
–
the accepted
paradigm
CPT Proton RTProton RT
•
after >35 years and > 60 000 patients treated no single disease entity ever treated with protons was later found unsuitable
•no publication has raised the issue of unexpected acute or late toxicity. (exception: Taghian
et al., PBRT)
•The initial concept of physical dose distribution and biologic effectiveness has not been called into question by clinical results
•Proton-Radiotherapy has therefore successfully passed any reasonable requirements for treatment safety and feasibility.
CPT
Proton-RT: Status of Clinical Evidence
Proton RT
•Retrospective single-institution reports
•Prospective data accumulation
•Phase I and Phase II studies
WhatWhat
aboutabout
the the „„evidenceevidence““? ? WhatWhat
aboutabout randomizedrandomized, , prospectiveprospective
trialstrials??
CPT
Randomized
trial
photons
versus
protons:•Has not been
done, EXCEPT:
•MGH/HCL Prostate
trial: 67.2 Gy photons
vs. 75.6 Gy protons/photons, T3 and T4
Randomized
Trials: protons versus
protons•PROG 9509: Prostate
CA, mixed
photon/proton
versus
mixed
photon/proton
dose escalation:
•MGH + LBL+ LLUMC Chordoma and Chondrosarcoma – Skull Base and C-spine
randomized
protocol
(PROG)
•MGH/MEEI/HCL: Uveal
Melanoma, dose de-escalation trial
70 vs. 50 Gy(RBE)
„Level 1“
Evidence
for Proton Therapy (?)
CPT Proton RTProton RT
••Introduction of new radiotherapy technology has Introduction of new radiotherapy technology has thus far never required randomized trials as long as thus far never required randomized trials as long as safety and at least equivalency with prospect of safety and at least equivalency with prospect of superior outcomes have been demonstrated. superior outcomes have been demonstrated. (Examples: IMRT, Tomotherapy, (Examples: IMRT, Tomotherapy, CyberknifeCyberknife))
CPTThe ConfusingConfusing
World of Precision-
RT
CPTThe ConfusingConfusing
World of Precision-
RT
Clinical
trial required
Clinical
trial required
Clinical
trial required
CPTThe ConfusingConfusing
World of Precision-
RT
Clinical
trial required
Clinical
trial required
Clinical
trial required
CPT
THANK YOU !THANK YOU !
..more
on trials
and the ethics
of trials
on Wednesday
