Transcript Ablatherm PowerPoint Presentation

Ablatherm®
HIFU
 Technology
 History
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
The HIFU Treatment
for Localized Prostate Cancer
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
HIFU TECHNOLOGY POWERED BY EDAP
Ultrasound Waves Generation
Physical Principle
HIFU
Treatment
Description
 Technology
 History
Plane transducer
ABLATHERM
 Device
 Treatment
Ultrasound waves emission by
transducer electro-mechanical
vibrations
CLINICAL
 Effects
Acoustical pressure
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/4
Tissue motion
Tissue heating
+
+
-
+
-
-
Focused Ultrasound Waves
Physical Principle
HIFU
Treatment
Description
 Technology
 History
ABLATHERM
Focused transducer
Emitting ultrasound waves
 Device
 Treatment
CLINICAL
 Effects
Acoustical pressure
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
2/4
Tissue heating
Over 85°C
Tissue Lesion Formation
Physical Principle
HIFU
 Technology
Treatment
Description
Thermal effects
 History
Temperature Simulation
ABLATHERM
INSERM U 556
 Device
+
 Treatment
3L/4
L/4
Cavitation effects
HIC Technology
CLINICAL
HIFU INDUCED CAVITATION
 Effects
 Results
HIGHLIGHTS
+
D
Time exposure
Thermal Dose Simulation
 Indications
INSERM U 556
 Benefits
 Positioning
=
3/4
Tissue lesion
Lesion
L = 24 mm max
D = 1.7 mm
Local Increase of Tissue Temperature
Physical Principle
HIFU
 Technology
Treatment
Description
Two different approaches to reach the destruction threshold :
 History
ABLATHERM
Temp.
Temp.
 Device
 Treatment
CLINICAL
 Effects
HIFU
 Results
HYPERTHERMIA
HIGHLIGHTS
 Indications
 Benefits
Time
 Positioning
High Temperature (>85 °C)
 Short Time (< 5 Sec.)

4/4
Time
Low Temperature (< 45 °C)
 Long Duration (>1 Hr)

Transducer Positioning
Physical Principle
HIFU
Treatment
Description
 Technology
 History
ABLATHERM
 Device
 Treatment
Precise lesion positioning
with Dynamic Focusing
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/2
Sparing of
surrounding tissue
Lesion Distribution within the Prostate
Physical Principle
HIFU
 Technology
 History
ABLATHERM
 Device
Treatment
Description
• Each shot consists of a burst of
ultrasound waves with a duration
of 5 seconds
 Treatment
• The focal volume is very small: 1924 mm in length by 1.7 mm in
diameter
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
• The firing head moves until the
whole targeted volume is treated
Treatment Simulation
2/2
History of the Ablatherm Project
HIFU
 Technology
• 1989:
Preliminary experiments on rats kidneys
and technology development
 History
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/2
• 1990:
Cancer treatment - feasibility: Dunning tumors
• 1991:
Endorectal approach - feasibility: canine prostate
• 1992:
Treatment safety - evaluation: human B.P.H.
• 1993:
Treatment efficacy - evaluation: PCa
• 1995:
Device safety improvements
• 1996:
European Multicentric Study
• 2000:
CE Mark Ablatherm®
CE Mark Ablatherm
CE Marked January 2000
HIFU
 Technology
 History
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
2/2
Device Description
General
Description
HIFU
 Technology
 History
ER
Probe
Command
Module
ABLATHERM
 Device
User Interface
 Treatment
Treatment
Module
Electronics
Imaging
and safeties
and Firing
RF Power
CLINICAL
 Effects
Probe
Module
System
Motors
 Results
Cooling
HIGHLIGHTS
 Indications
+ Disposable
 Benefits
 Positioning
1/1
Computer
Patient Support
Endorectal Probe
Endorectal Probe
General
Description
HIFU
 Technology
 History
ER
Probe
Imaging Position
ABLATHERM
 Device
 Treatment
The therapy transducer (focuses at
40 mm, operates at 3 MHz) and
CLINICAL
 Effects
the 7,5 MHz biplane imaging
 Results
probe are coupled in a latex
HIGHLIGHTS
 Indications
 Benefits
balloon filled with a coupling fluid
(AblasonicTM)
 Positioning
Firing Position
1/2
Imaging / Treatment Position
General
Description
HIFU
 Technology
 History
ABLATHERM
 Device
ER
Probe
Imaging Position
The targeted prostatic volume
is localized with the bi-plan
ultrasound imaging probe
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
High-energy ultrasound waves are
focused through the rectal wall
to the targeted prostate area
Firing Position
2/2
Click on one of the above
images for animation
Main Steps of a Treatment
Summary
Positioning
Treatment
HIFU
 Technology
 History
• Probe preparation (Ablapak® disposable)
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/1
• Patient installation (Immobilization)
• Prostate localization (Apex identification)
- Longitudinal imaging
- Transversal imaging
• Treatment (Safety controls)
• Patient removal
• Probe cleaning and disinfection
Patient Installation
(Immobilization)
Summary
HIFU
 Technology
 History
ABLATHERM
Positioning
Treatment
Patient positioned in right lateral
decubitus position
Patient movement
detector
 Device
Indicator light is ON
 Treatment
Infra-red light
CLINICAL
Reflector
 Effects
 Results
Patient
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/1
Treatment (Safety Controls)
Summary
Positioning
Treatment
HIFU
 Technology
 History
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
Main safety features
• Power / Firing sequence
• Probe position
• Patient movement
• Rectum position
• Temperature
 Indications
 Benefits
 Positioning
Click on the above image for an animation of the control interface
1/1
MRI performed day 2 after HIFU
Session
Imaging
HIFU
PSA/Followup
Conclusio
n
 Technology
 History
ABLATHERM
MRI shows the boundaries of the
necrotic tissue
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/2
The treated area appears as a
hypo-intense area surrounded by
a 6-8 mm thick ring of contrast
enhancement
Tissue Development
Imaging
HIFU
 Technology
PSA/Followup
Conclusio
n
Complete destruction of the
glandular tissue due to
 History
ABLATHERM
 Device
coagulation necrosis lesion
which reaches the capsula
 Treatment
and the periprostatic fat
CLINICAL
48 hours
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
The necrotic prostatic tissue
is replaced by a fibrotic
tissue (including the capsula)
3 months
2/2
Typical PSA after Ablatherm
Imaging
HIFU
PSA/Followup
Conclusio
n
 Technology
250
 History
1 HIFU Session
 Device
Complete response
after one HIFU
session
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/3
Nadir PSA reached
at 3 months
200
Last PSA 0.2 ng/ml
PSA (ng/ml)
ABLATHERM
150
Negative Biopsies
100
50
0
m-93
m-94
m-95
m-96
date
m-97
m-98
m-99
Multiple Ablatherm Sessions
Imaging
HIFU
PSA Followup
Conclusio
n
 Technology
50
 History
Partial treatment at
the first session
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
2/3
Last PSA
40
In case of rising
PSA, a second HIFU
session can be
performed
35
PSA (ng/ml)
 Device
2 HIFU Sessions
45
ABLATHERM
Positive
Biopsies
0,3
ng/ml
0 ng/ml
30
Negative
Biopsies
25
20
15
10
5
0
nov-95
nov-96
nov-97
Date
nov-98
Typical PSA after Ablatherm
Imaging
HIFU
PSA/Followup
Conclusio
n
 Technology
 History
ABLATHERM
 Device
 Treatment
Quality of life assessment (IPSS - QOL)*
• HIFU treatment does not adversely affect
the patient’s QOL
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
Available for analysis
Mean
Paired difference from baseline
Before
N= 491
1.59
After
N= 339
2.04
0.55
* Data collected in Munich (October 1, 2000)
• 52% of the patients with the same or an improved QOL
• Variation without clinical significance
3/3
Clinical Effects
Imaging
HIFU
 Technology
 History
PSA/Followup
Conclusio
n
With Ablatherm®, the urologist:
ABLATHERM
 Device
 Treatment

CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications

 Benefits
 Positioning

1/1
obtains a complete necrosis of prostate tumors in
the treated area without damaging the surrounding
tissues, and without adversely affecting QOL
has an early assessment of the treatment efficacy
(PSA nadir, histology…)
can repeat the treatment, since no maximum dose
exists
Evidence-based Efficacy
EM Study
HIFU
Long Term
Efficacy
Adverse
Events
Conclusio
n
 Technology
 History

Large cohort of patients: European Multicentric Study

Long term follow-up: Results from Lyon

Optimal Efficacy: Results from Munich

Minimal Morbidity: Results from Munich
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
Evidence-based Efficacy
EM Study
HIFU
Long Term
Efficacy
Adverse
Events
Conclusio
n
 Technology
 History

ABLATHERM
Ref: C. Chaussy, S. Thüroff, G. Vallancien, W. Wieland, H.J. Kiel, A. Le Duc, F. Desgranchamps, J. de la Rosette, A. Gelet
HIFU for the Treatment of Localized Prostate Cancer: Efficacy Results of the European Multicentric Study
The Journal Of Urology, May 2001, Vol. 165, 5:388
 Device
 Treatment
CLINICAL
Large cohort of patients: European Multicentric Study

Long term follow-up: Results from Lyon

Optimal Efficacy: Results from Munich

Minimal Morbidity: Results from Munich
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
Large Cohort: European Multicentric
Study
EM Study
HIFU
Long Term
Efficacy
Adverse
Events
Conclusio
n
 Technology
Patients included from 1995 to 1999, in 6 European sites:
 History
ABLATHERM
 Device
 A. Gelet, Lyon - France
 Treatment
 C. Chaussy, S. Thüroff, Münich - Germany
CLINICAL
 W. Wieland, H.J. Kiel, Regensburg - Germany
 Effects
 G. Vallancien, Paris - France
 Results
HIGHLIGHTS
 Indications
 Benefits
 A. Le Duc, F. Desgranchamps, Paris - France
 J. de la Rosette, Nijmegen - The Netherlands
 Positioning
n = 559 patients
up to 51 months follow-up
1/5
The Journal Of Urology, May 2001
Large Cohort: European Multicentric
Study
EM Study
Long Term
Efficacy
HIFU
Adverse
Events
Conclusio
n
STUDY POPULATION
 Technology
 History
n=8
ABLATHERM
n=35
n=104
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
n=10
n=402
 Indications
 Benefits
 Positioning
T1-T2
Orch./Hormonotherapy
RX Failure
T3-T4
Prostatectomy
Mean age: 69 years (range 45 - 88)
2/5
The Journal Of Urology, May 2001
Large Cohort: European Multicentric
Study
EM Study
HIFU
 Technology
 Device
Efficacy
Adverse
Events
Conclusio
n
T1-T2 Population
 History
ABLATHERM
Long Term
Patients baseline characteristics
 Treatment
# Positive
biopsy samples
0
CLINICAL
PSA (ng/ml)
Gleason score
1
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
< 10
50.9%
2 - 4/G1
10.5%
10 - 20
33.0%
5 - 7/G2
73.2%
> 20
 Positioning
Total
16.1%
100%
8 - 10/G3
Total
16.3%
100%
2
3
4
5
6
Total
0.7%
(TURP)
28.4%
29.5%
19.6%
6.5%
4.6%
10.7%
100%
3/5
The Journal Of Urology, May 2001
Large Cohort: European Multicentric
Study
EM Study
HIFU
 Technology
Long Term
Efficacy
Adverse
Events
Conclusio
n
Overall results observed in the T1 - T2 population
 History
ABLATHERM
 Device
Negative biopsy rate
 Treatment
87.2%
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
after
complete treatment
0.0
after
partial treatment
median
0.1
0.6
75th percentile
0.4
2.2
Nadir PSA
ng/ml
25th percentile
 Positioning
4/5
The Journal Of Urology, May 2001
0.1
Large Cohort: European Multicentric
Study
EM Study
Long Term
HIFU
 Technology
 History
ABLATHERM
Efficacy
Adverse
Events
Conclusio
n
Stratification of the results according to the initial
disease-related risk level
 Device
Negative biopsy rate
 Treatment
CLINICAL
 Effects
Low risk patients
92.1%
Intermediate risk
patients
86.4%
High risk patients
82.1%
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
Low-risk patients: T1-T2a and PSA 10 ng/ml and Gleason score 6
Intermediate-risk patients: T2b or 10 < PSA 20 ng/ml or Gleason sc. = 7
High-risk patients: T2c or PSA > 20 ng/ml or Gleason score  8
5/5
The Journal Of Urology, May 2001
Evidence-based Efficacy
EM Study
HIFU
Long Term
Efficacy
Adverse
Events
Conclusio
n
 Technology
 History

Large cohort of patients: European Multicentric Study

Long term follow-up: Results from Lyon
ABLATHERM
 Device
 Treatment
CLINICAL
Ref: L. Poissonnier, A. Gelet et al. - Résultats du traitement par ultrasons focalisés transrectaux du cancer localisé de la prostate
(120 Patients avec PSA  à 10 ng/ml) - Progrès en Urologie, 2003, vol. 13, p. 60-72
 Effects
 Results
HIGHLIGHTS

Optimal Efficacy: Results from Munich

Minimal Morbidity: Results from Munich
 Indications
 Benefits
 Positioning
Long-term Follow-up: Results from Lyon
EM Study
HIFU
 Technology
Long Term
Efficacy
Inclusion criteria:
 History
Adverse
Events
Conclusio
n
Localized prostate cancer (T1-T2)
HIFU: primary care for PCa treatment
Initial PSA  10 Ng/mL
ABLATHERM
 Device
Total population: n=120
 Treatment
CLINICAL
Age (years)
T1: n = 61
T2: n = 59
2 - 6: n = 77
7 - 10: n = 43
71.2  5.3
PSA Value (ng/ml)
5.67  2.47
Prostate Volume (cc)
33.6  15.5
Clinical Stage
 Effects
 Results
Gleason Score
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/3
Progrès en Urologie, 2001
Long-term Follow-up: Results from
Lyon
EM Study
Long Term
Efficacy
HIFU
 Technology
 History
ABLATHERM
 Device
Adverse
Events
Conclusio
n
Overall Disease Free
Rate (DFR)
FAILURE CRITERION
 Positive random sextant biopsy
 Treatment
CLINICAL
(whatever the PSA level )
 Effects

 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning




2/3
OR (even if negative control
biopsies)
– biochemical evidence of 3
consecutive rising in PSA
level
– PSA velocity > 0.75 ng/ year
Follow up:
Negative Biopsies:
Nadir PSA < 0.5:
Mean prostate volume:
Progrès en Urologie, 2003
Months
Up to 96 months
85.8% (103/120)
75% (90/120)
14.6  14.1 cc
Long-term Follow-up: Results from
Lyon
EM Study
HIFU
 Technology
 History
Long Term
Efficacy
Adverse
Events
Conclusio
n
DFR according to the baseline Gleason Score
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
DFR %
p<0.05
 Indications
 Benefits
 Positioning
Months
3/3
Progrès en Urologie, 2001
Evidence-based Efficacy
EM Study
HIFU
Long Term
Efficacy
Adverse
Events
Conclusio
n
 Technology
 History

Large cohort of patients: European Multicentric Study

Long term follow-up: Results from Lyon

Optimal Efficacy: Results from Munich

Minimal Morbidity: Results from Munich
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
Optimal Efficacy: Results from
Munich
EM Study
HIFU
Long Term
Efficacy
Adverse
Events
Conclusio
n
 Technology
 History
Inclusion criteria:
ABLATHERM
 Device
 Treatment
Localized prostate cancer (T1-T2)
HIFU : primary care for PCa treatment
First treatment session : 3 MHz - 5 sec
CLINICAL
 Effects
 Results
HIGHLIGHTS
• Patients evaluable for PSA nadir and/or stability: n = 104
• Mean follow-up: 1 year
 Indications
 Benefits
 Positioning
1/2
Stability: ASTRO definition
 Non stable PSA:
Biochemical evidence of 3 consecutive rising in PSA level
from nadir, measured at least 3 months apart
Optimal Efficacy: Results from
Munich
EM Study
HIFU
 Technology
Long Term
Efficacy
Adverse
Events
Conclusio
n
Results observed on the overall population:
 History
ABLATHERM
 Device
Negative Biopsy
Rate
88.9 %
 Treatment
Nadir PSA (ng/ml)
CLINICAL
 Effects
 Results
10th percentile
0.00
HIGHLIGHTS
30th percentile
0.00
 Indications
 Benefits
 Positioning
Median
70th percentile
0.28
90th percentile
2.10
PSA Stability Rate
2/2
0.00
84.1 %
Evidence-based Efficacy
EM Study
HIFU
Long Term
Efficacy
Adverse
Events
Conclusio
n
 Technology
 History

Large cohort of patients : European Multicentric Study

Long term follow-up : Results from Lyon

Optimal Efficacy : Results from Munich

Minimal Morbidity : Results from Munich
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
Ref: C. Chaussy, S. Thüroff - High Intensity Focused Ultrasound: Complications and Adverse Events
Molecular Urology, 2000, Vol. 4, 3:183-7
Minimal Morbidity: Results from Munich
EM Study
HIFU
 Technology
 History
ABLATHERM
 Device
 Treatment
CLINICAL
Long Term
Efficacy
Adverse
Events
Adverse Events
Death (Intra and post-op)
Fistula
Rectal wall burn
Hemorrhoïdal pain
Stress incontinence
 Effects
Grade I (average 27 days)
 Results
Grade II (average 32 days)
HIGHLIGHTS
Grade III (TURP)
 Indications
 Benefits
 Positioning
1/1
Conclusio
n
Urge
incontinence
Urg
ency
UTIs
Significant hematuria
Immediate post-treatment retention
Total erectile dysfunction Ejaculation
problems
Molecular Urology, 2000
Last 100 patients
EM Study
0
0
0
1
9
2
1
0
7
13
0
100
22
100
Evidence-based Efficacy
EM Study
Long Term
HIFU
Efficacy
Adverse
Events
Conclusio
n
 Technology
 History

Large cohort of patients studied

Long term follow-up available
ABLATHERM
 Device
 Treatment
CLINICAL

Optimal efficacy proven

Minimal morbidity observed
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/2
Ablatherm is now an evidence-based
valuable treatment option
Situation
EM Study
Long Term
Efficacy
HIFU
Adverse
Events
Conclusio
n
 Technology
 History
ABLATHERM
Where are we today?
 Device
 Treatment
ABLATHERM is a treatment option with a proven efficacy and
CLINICAL
 Effects
a low morbidity
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
24 sites using an ABLATHERM in routine daily practice in
Europe
More than 3500 patients treated as of April 31, 2003
2/2
Indications
HIFU
 Technology
LOCALIZED PROSTATE CANCER
 History
ABLATHERM
 Device
 Treatment
• As a first choice therapy
CLINICAL
 Effects
 Results
HIGHLIGHTS
• As a salvage therapy
 Indications
 Benefits
 Positioning
1/1
In case of local recurrence
Benefits
HIFU
 Technology
 History
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/1
• Non-Invasive:
no port, no seeds, no radiation
• Effective:
precise and definitive necrosis of the targeted area
• Early Feedback:
nadir PSA after only 3 months
• Quality of Life:
minimal side effects
• Repeatable:
if needed at any time during follow up
• Adaptable:
to the physician and the patient’s therapeutic goals
• No Therapeutic
Impasse:
alternative options still open post Ablatherm
Positioning
HIFU
 Technology
 History
ABLATHERM
The HIFU Treatment
for Localized Prostate Cancer, that
 Device
1. Offers unique therapeutic advantages versus other existing therapies
 Treatment
CLINICAL
2. Can be used as first choice therapy as well as salvage therapy
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
1/1
3. Offers economic benefits versus other existing therapies
4. Allows the urologists to remain the sole therapist during the overall
patient management
Ablatherm®
HIFU
 Technology
 History
ABLATHERM
 Device
 Treatment
CLINICAL
 Effects
 Results
HIGHLIGHTS
 Indications
 Benefits
 Positioning
The HIFU Treatment
for Localized Prostate Cancer