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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 RadiologyAlfried Krupp
Krankenhaus, Essen (Germany)
ASSH / IC10, Washington DC, September 7, 2006
( final evaluation August 31, 2006 )
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Noninvasive Therapy of M. Dupuytren
Why Radiotherapy ? Rationale

• Proliferating fibroblasts are sensitive target
  cells
• Therapeutic efficacy for keloids, M. Peyronie
  etc.
• Positive clinical studies
• Long-term progression 50 _at_ 5 yrs require
  corrective hand surgery

3 years
6 months




2 years

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Noninvasive Therapy of M. Dupuytren
Proliferating Fibroblastsas Radiosensitive
Target
Cord
Tendon





Nodule
Scar
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Noninvasive Therapy of M. Dupuytren
Rationale Goals of Radiotherapy

• Inhibition of fibroblast proliferation
• Prevention or delay of progression
• Preservation of good hand function
• Relief or avoidance of symptoms, evtl.
  avoidance/ delay of hand OP

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Noninvasive Therapy of M. Dupuytren
Study Concept





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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Prospective Study Design
Study Goal Efficacy of Radiotherapy ?
Dose Reduction possible ? 1st Endpoint
Clinical Progression, evtl. ? Avoidance of
Hand Surgery Tx Concepts Observation ( Control)
versus 21Gy (7x 3Gy) or 30Gy (10x 3Gy)
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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Inclusion Criteria

• Progression of nodules/cords gt 6 months
• Beginning finger extension deficit (5 - 10)
• Contralateral hand poor surgical outcome
• Ipsilateral hand post-Op relapse lt 6 months
  (Exclusion stable disease, non-compliance)

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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Material Methods





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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Patient Referal
Counselling Decision
Observation Radiotherapy
R
Control0Gy
RT 30Gy
RT 21Gy
Stratification according to Disease Stage
Observation
Start 07/1997 Study Population
460 patients End 06/2005
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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Radiotherapy Concepts
A 30 Gy 5 x 3 Gy/ week 8 wks break 5
x 3 Gy / week (Monday - Friday)
(Monday - Friday)
B 21 Gy 7 x 3Gy within 2 weeks ( 3x /
week Mo / Wed / Fri)
Individual portals orthovoltage 150kVelectrons
3 5 MeV
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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Patient Parameters ( N 273 )
Control RT 21Gy RT 30Gy No. Pats.
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 22 / 34 52 / 57 55 / 54(s / b ?)
90 hds 166 hds 163 hds History 17 (31) 32
(30) 32 (29) Med. Dx 25 mos 24 mos 24
mos









( final evaluation August 31, 2006 )
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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 ? 10 I ? 45 II ? 90 I
II ? 135 IV ? 135
RT
Total Extension Deficitof MP/ PIP/ DIP Joints
OP
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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

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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Treatment Results





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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Radiation Side-Effects
RT 21Gy RT 30Gy (N 166) (N
163)Acute ( 90 days) CTC I 36 (22) 29
(18) CTC II 8 ( 5) 9 ( 6) n.s.
Chronic (gt 1 yr.) at 1 year 8 ( 5) 18
(11) at 3 years 19 (11) 22 (12) n.s.









( final evaluation August 31, 2006 )
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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Hand Parameters Nodules
N 419 Control RT 21Gy RT
30Gy n 90 n 166 n 163 Prior to
RT - mean SD 4.2 2.3 4.5 2.5 4.2
1.9 - median 4 4
4 p 0.013 p lt 0.0001 p lt 0.0001 Last FU
(gt 5 yrs) - mean SD 5.2 3.1 3.5 2.8
3.4 2.3 - median 5 3
3


highly significant







( final evaluation August 31, 2006 )
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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Hand Parameters Stage
N 419 Control RT 21Gy
RT 30Gy n 90 n 166 n 163
Prior to RT Stage N 48 (53) 107 (64)
109 (67) Stage N / I 18 (20) 25 (15)
30 (18) Stage I - IV 24 (27) 34
(20) 24 (14) Last FU (gt 5 yrs) n
85 n 163 n 160 Stage N 26
(31) 92 (56) 96 (60) Stage N / I
15 (18) 19 (12) 22 (14) Stage I
- IV 44 (52) 52 (31) 42 (26)




significant





( final evaluation August 31, 2006 )
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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Overall Disease Status _at_ last FU ( gt 5 yrs )
Control RT 21Gy RT 30Gy (n 87)
(n 165) (n 163) Remission Stabl
e Disease Progression 54 (62) 45
(27) 36 (22) p lt 0.001 n.s.
37 (47) 120 (73) 127 (78)









( final evaluation August 31, 2006 )
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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Clinical Progression _at_ last FU ( gt 5 yrs )
Control RT 21Gy RT 30Gy (n 87)
(n 165) (n 163)
Nodules 24 (30) 14 (10) 13 (10)
Cords -- 18 (13) 14 (11)
Ext.Def. gt10 39 (48) 26 (19) 23
(17) Hands withProgression 54 (62) 45
(27) 36 (22)









( final evaluation August 31, 2006 )
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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Surgery at last FU ( gt 5 yrs )
Control RT 21Gy RT 30Gy (n 87)
(n 165) (n 163) Remission Stabl
e Disease Progression 54 (62) 45
(27) 36 (22) - clinical 30 (34) 19
(11) 21 (13) - surgery 24 (28) 26
(16) 15 ( 9)
37 (47) 120 (73) 127 (78)









( final evaluation August 31, 2006 )
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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
Summary Conclusions

• RT reduces progression _at_ gt 5years control
  62 vs. RT 22 (A) or 27 (B)
• RT reduces hand surgery _at_ gt 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 lt 60, higher
  stage, and smoking habit worse (multivariate)
• Further indication early relapse after OP ?

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Noninvasive Therapy of M. Dupuytren
Noninvasive Therapy of M. Dupuytren
TREATMENTINDICATION
STAGE Functional Deficit
IV
Predisposing Risk Factors (?) or Specific Hand
Trauma (?)
135
III
Function Loss
Natural Course of Disease
HAND SURGERY
90
II
Progression Delay
Relapse
I
45
OP
OP
Stop of Progression
10
RADIOTHERAPY
N
0
Decades
Years
Months
TIME