Transcript Kein Folientitel - International Dupuytren Society

Noninvasive Therapy of M. Dupuytren
Radiotherapy for Early Stage M. Dupuytren
- Long-Term Outcome M.H. Seegenschmiedt, M. Wielpütz, C. Schubert,
T. Olschewski, F. Guntrum
Dep. of Radiation Oncology & Therapeutic Radiology
Alfried Krupp Krankenhaus, Essen (Germany)
ASSH / IC10, Washington DC, September 7, 2006
( final evaluation August 31, 2006 )
Noninvasive Therapy of M. Dupuytren
Why Radiotherapy ? – Rationale :
3 years
6 months
• Proliferating fibroblasts
are sensitive target cells
• Therapeutic efficacy for
keloids, M. Peyronie etc.
• Positive clinical studies
2 years
• Long-term progression:
~ 50% @ 5 yrs require
corrective hand surgery
Noninvasive Therapy of M. Dupuytren
Proliferating Fibroblasts
as Radiosensitive Target
Tendon
Nodule
Cord
Scar
Noninvasive Therapy of M. Dupuytren
Rationale & Goals of Radiotherapy
1. Inhibition of fibroblast proliferation
2. Prevention or delay of progression
3. Preservation of good hand function
4. Relief or avoidance of symptoms,
evtl. avoidance/ delay of hand OP
Noninvasive Therapy of M. Dupuytren
Study Concept
Noninvasive Therapy of M. Dupuytren
Prospective Study Design
Study Goal
1st Endpoint
Tx Concepts
Efficacy of Radiotherapy ?
Dose Reduction possible ?
Clinical Progression, evtl.
► Avoidance of Hand Surgery
Observation
21Gy
(= Control)
(7x 3Gy) or
30Gy
versus
(10x 3Gy)
Noninvasive Therapy of M. Dupuytren
Inclusion Criteria
• Progression of nodules/cords > 6 months
• Beginning finger extension deficit (5 - 10°)
• Contralateral hand: poor surgical outcome
• Ipsilateral hand: post-Op relapse < 6 months
(Exclusion: stable disease, non-compliance)
Noninvasive Therapy of M. Dupuytren
Material & Methods
Noninvasive Therapy of M. Dupuytren
Patient Referal
Counselling & Decision
Observation
Radiotherapy
R
Control
0Gy
Observation
Start: 07/1997
RT
21Gy
RT
30Gy
Stratification according to Disease Stage
Study Population: 460 patients
End: 06/2005
Noninvasive Therapy of M. Dupuytren
Radiotherapy Concepts
A
30 Gy
5 x 3 Gy/ week
8 wks break
(Monday - Friday)
B
21 Gy
7 x 3Gy within 2 weeks
( 3x / week : Mo / Wed / Fri)
5 x 3 Gy / week
(Monday - Friday)
Individual portals :
orthovoltage 150kV
electrons 3 – 5 MeV
Noninvasive Therapy of M. Dupuytren
Patient Parameters
( N = 273 )
Control
RT 21Gy
RT 30Gy
56
107
110
Age (yrs)
62.8 ± 10
61.8 ± 8.4
63.7 ± 8.6
M/F
33 / 23
60 / 47
68 / 42
No. Hands
(s / b = )
22 / 34
90 hds
52 / 57
166 hds
55 / 54
163 hds
History +
17 (31%)
32 (30%)
32 (29%)
Med. Dx
25 mos
24 mos
24 mos
No. Pats.
( final evaluation August 31, 2006 )
Noninvasive Therapy of M. Dupuytren
Classification System
modified from Michon, Tubiana & Thomine, (1966)
0
No Specific Signs & Symptoms
N
Nodules / Cords w/o Extension Deficit
N/I
Extension Deficit
I
II
III
IV
Total Extension Deficit
of MP/ PIP/ DIP Joints

10°

45°

90°

135°

135°
RT
OP
Noninvasive Therapy of M. Dupuytren
Radiation Technique
• Photons 150kV or
electrons 3 - 6MeV
• Individual shielding
(lead rubber plates)
• Portal with 1 – 2cm
lateral margins
• Bolus if required
• Daily Control of Portal
Noninvasive Therapy of M. Dupuytren
Treatment Results
Noninvasive Therapy of M. Dupuytren
Radiation Side-Effects
RT 21Gy
RT 30Gy
(N = 166)
(N = 163)
Acute ( 90 days)
CTC I°
CTC II°
36 (22%)
8 ( 5%)
29 (18%)
9 ( 6%)
Chronic (> 1 yr.)
at 1 year:
at 3 years:
8 ( 5%)
19 (11%)
18 (11%)
22 (12%)
( final evaluation August 31, 2006 )
n.s.
n.s.
Noninvasive Therapy of M. Dupuytren
Hand Parameters : # Nodules
N = 419
RT 21Gy
n = 166
RT 30Gy
n = 163
4.2 ± 2.3
4.5 ± 2.5
4.2 ± 1.9
4
4
4
p = 0.013
p < 0.0001
p < 0.0001
5.2 ± 3.1
3.5 ± 2.8
3.4 ± 2.3
5
3
3
Prior to RT
- mean ± SD
- median
Last FU (> 5 yrs)
- mean ± SD
- median
( final evaluation August 31, 2006 )
highly significant
Control
n = 90
Noninvasive Therapy of M. Dupuytren
Hand Parameters : Stage
N = 419
Control
n = 90
RT 21Gy
n = 166
RT 30Gy
n = 163
48 (53%)
18 (20%)
24 (27%)
107 (64%)
25 (15%)
34 (20%)
109 (67%)
30 (18%)
24 (14%)
n = 85
n = 163
n = 160
92 (56%)
19 (12%)
52 (31%)
96 (60%)
22 (14%)
42 (26%)
Prior to RT
Last FU (> 5 yrs)
Stage N
Stage N / I
Stage I - IV
26 (31%)
15 (18%)
44 (52%)
( final evaluation August 31, 2006 )
significant
Stage N
Stage N / I
Stage I - IV
Noninvasive Therapy of M. Dupuytren
Overall Disease Status @ last FU ( > 5 yrs )
Control
(n = 87)
Remission
Stable Disease
Progression
RT 21Gy
(n = 165)
RT 30Gy
(n = 163)
37 (47%)
120 (73%)
127 (78%)
54 (62%)
45 (27%)
36 (22%)
p < 0.001
( final evaluation August 31, 2006 )
n.s.
Noninvasive Therapy of M. Dupuytren
Clinical Progression @ last FU ( > 5 yrs )
Control
(n = 87)
Nodules
Cords
24 (30%)
--
RT 21Gy
(n = 165)
RT 30Gy
(n = 163)
14 (10%)
13 (10%)
18 (13%)
14 (11%)
Ext.Def. >10°
39 (48%)
26 (19%)
23 (17%)
Hands with
Progression
54 (62%)
45 (27%)
36 (22%)
( final evaluation August 31, 2006 )
Noninvasive Therapy of M. Dupuytren
Surgery at last FU ( > 5 yrs )
Control
(n = 87)
Remission
RT 21Gy
(n = 165)
RT 30Gy
(n = 163)
37 (47%)
120 (73%)
127 (78%)
54 (62%)
45 (27%)
36 (22%)
- clinical
30 (34%)
19 (11%)
21 (13%)
- surgery
24 (28%)
26 (16%)
15 ( 9%)
Stable Disease
Progression
( final evaluation August 31, 2006 )
Noninvasive Therapy of M. Dupuytren
Summary & Conclusions
• RT reduces progression @ > 5years:
control 62% vs. RT : 22% (A) or 27% (B)
• RT reduces hand surgery @ > 5years:
control 28% vs. RT : 13% (A) or 16% (B)
• Acute & late RT side-effects well acceptable:
salvage surgery is possible w/o problems (!)
• Prognosis for pts. with age < 60, higher stage,
and smoking habit worse (multivariate)
• Further indication : early relapse after OP ?
Noninvasive Therapy of M. Dupuytren
TREATMENT
INDICATION
STAGE = Functional Deficit
IV
III
II
I
Predisposing Risk Factors (?) or Specific Hand Trauma (?)
135°
90°
Function
Loss
Natural Course
of Disease
HAND SURGERY
Progression Delay
Relapse
45°
OP
OP
10°
Stop of Progression
RADIOTHERAPY
N 0
Months
Years
Decades
TIME