radiotherapy for early stage m. dupuytren - long-term outcome -
DESCRIPTION
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). - PowerPoint PPT PresentationTRANSCRIPT
Radiotherapy for Early Stage M. Dupuytren
- Long-Term Outcome -
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)
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
ASSH / IC10, Washington DC, September 7, 2006
( final evaluation August 31, 2006 )
Why Radiotherapy ? – Rationale :
Why Radiotherapy ? – Rationale :
• Proliferating fibroblasts are sensitive target cells
• Therapeutic efficacy for keloids, M. Peyronie etc.
• Positive clinical studies
• Long-term progression: ~ 50% @ 5 yrs require corrective hand surgery
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
6 months6 months3 years3 years
2 years2 years
Proliferating Fibroblastsas Radiosensitive Target Proliferating Fibroblastsas Radiosensitive Target
Tendon
Tendon
CordCord
NoduleNodule ScarScar
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
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
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. DupuytrenNoninvasive Therapy of M. Dupuytren
Rationale & Goals of RadiotherapyRationale & Goals of Radiotherapy
Prospective Study Design Prospective Study Design
Study Goal Efficacy of Radiotherapy ? Dose Reduction possible ?
1st Endpoint Clinical Progression, evtl. ► Avoidance of Hand Surgery
Tx Concepts Observation (= Control)
versus21Gy (7x 3Gy) or 30Gy (10x 3Gy)
Study Goal Efficacy of Radiotherapy ? Dose Reduction possible ?
1st Endpoint Clinical Progression, evtl. ► Avoidance of Hand Surgery
Tx Concepts Observation (= Control)
versus21Gy (7x 3Gy) or 30Gy (10x 3Gy)
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Inclusion CriteriaInclusion 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)
• 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. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Material & Methods
Material & Methods
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Patient ReferalPatient Referal Counselling & Decision Counselling & Decision
RT 30Gy
RT 21Gy
R
Stratification according to Disease Stage
Stratification according to Disease Stage
Control0Gy
Start: 07/1997 Study Population: 460 patients End: 06/2005
Start: 07/1997 Study Population: 460 patients End: 06/2005
Observation Radiotherapy Observation Radiotherapy
Observation
Observation
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Radiotherapy Concepts Radiotherapy Concepts
AA
30 Gy30 Gy 5 x 3 Gy/ week 8 wks break 5 x 3 Gy/ week 8 wks break 5 x 3 Gy / 5 x 3 Gy / weekweek
(Monday - Friday)(Monday - Friday) (Monday - Friday) (Monday - Friday)
BB
21 Gy21 Gy 7 x 3Gy within 2 7 x 3Gy within 2 weeksweeks
( 3x / week : Mo / Wed / ( 3x / week : Mo / Wed / Fri)Fri)
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Individual portals : orthovoltage
150kVelectrons 3 – 5 MeV
Patient Parameters ( N = 273 )
Patient Parameters ( N = 273 )
Control RT 21Gy RT 30Gy
No. Pats. 56 107 110Age (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 mos24 mos
Control RT 21Gy RT 30Gy
No. Pats. 56 107 110Age (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 mos24 mos
( final evaluation August 31, 2006 )
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
0 No Specific Signs & Symptoms
N Nodules / Cords w/o Extension Deficit
N/I Extension Deficit 10°
I 45°
II 90°
III 135°
IV 135°
Classification Systemmodified from Michon, Tubiana & Thomine, (1966)
Classification Systemmodified from Michon, Tubiana & Thomine, (1966)
Total Extension Deficitof MP/ PIP/ DIP Joints
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
RT
OP
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Radiation Technique 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
• Photons 150kV or electrons 3 - 6MeV
• Individual shielding (lead rubber plates)
• Portal with 1 – 2cm lateral margins
• Bolus if required
• Daily Control of Portal
Treatment Results Treatment Results
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Radiation Side-EffectsRadiation 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 (> 1 yr.)at 1 year: 8 ( 5%) 18 (11%) at 3 years: 19 (11%) 22 (12%)
n.s.
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 (> 1 yr.)at 1 year: 8 ( 5%) 18 (11%) at 3 years: 19 (11%) 22 (12%)
n.s.( final evaluation August 31, 2006 )
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Hand Parameters : # NodulesHand Parameters : # Nodules
N = 419 Control RT 21Gy RT 30Gyn = 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 < 0.0001 p < 0.0001 Last FU (> 5 yrs)
- mean ± SD 5.2 ± 3.1 3.5 ± 2.8 3.4 ± 2.3
- median 5 3 3
N = 419 Control RT 21Gy RT 30Gyn = 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 < 0.0001 p < 0.0001 Last FU (> 5 yrs)
- mean ± SD 5.2 ± 3.1 3.5 ± 2.8 3.4 ± 2.3
- median 5 3 3
hig
hly
sig
nifi
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igh
ly s
ign
ifican
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( final evaluation August 31, 2006 )
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Hand Parameters : Stage 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 (> 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%)
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 (> 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%)
( final evaluation August 31, 2006 )
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren s
ign
ifican
t s
ign
ifican
t
Overall Disease Status @ last FU ( > 5 yrs )
Overall Disease Status @ last FU ( > 5 yrs )
Control RT 21Gy RT 30Gy (n = 87) (n = 165) (n = 163)
Remission
Stable Disease
Progression 54 (62%) 45 (27%) 36 (22%)
p < 0.001 n.s.
Control RT 21Gy RT 30Gy (n = 87) (n = 165) (n = 163)
Remission
Stable Disease
Progression 54 (62%) 45 (27%) 36 (22%)
p < 0.001 n.s.
37 (47%) 120 (73%) 127 (78%)
( final evaluation August 31, 2006 )
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
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. >10° 39 (48%) 26 (19%) 23 (17%)
Hands withProgression 54 (62%) 45 (27%) 36 (22%)
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. >10° 39 (48%) 26 (19%) 23 (17%)
Hands withProgression 54 (62%) 45 (27%) 36 (22%)
( final evaluation August 31, 2006 )
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Clinical Progression @ last FU ( > 5 yrs )
Clinical Progression @ last FU ( > 5 yrs )
Surgery at last FU ( > 5 yrs )
Surgery at last FU ( > 5 yrs )
Control RT 21Gy RT 30Gy (n = 87) (n = 165) (n = 163)
Remission
Stable Disease
Progression 54 (62%) 45 (27%) 36 (22%)
- clinical 30 (34%) 19 (11%) 21 (13%)
- surgery 24 (28%) 26 (16%) 15 ( 9%)
Control RT 21Gy RT 30Gy (n = 87) (n = 165) (n = 163)
Remission
Stable 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 )
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
Summary & ConclusionsSummary & 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. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
I
N 0Month
sDecade
sTIME
STAGE = Functional Deficit
Years
45°45°
90°90°
135°135°
10°10°
HAND SURGERYHAND SURGERY
RADIOTHERAPYRADIOTHERAPY
III
II
IV
Function Loss
Function Loss
Stop of Progression
Stop of Progression
Predisposing Risk Factors (?) or Specific Hand Trauma (?)Predisposing Risk Factors (?) or Specific Hand Trauma (?)
Natural Course of Disease
Natural Course of Disease
Progression DelayProgression Delay
TREATMENTINDICATIONTREATMENTINDICATION
OPOP
RelapseRelapse
Noninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. DupuytrenNoninvasive Therapy of M. Dupuytren
OPOP