Radiotherapy for Early Stage M. Dupuytren - Long-Term Outcome -

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


6 months6 months3 years3 years

2 years2 years

Proliferating Fibroblastsas Radiosensitive Target Proliferating Fibroblastsas Radiosensitive Target

Tendon

Tendon

CordCord

NoduleNodule ScarScar


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


Rationale & Goals of RadiotherapyRationale & Goals of Radiotherapy

Study Concept Study Concept


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)


Material & Methods

Material & Methods


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


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)


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



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


RT

OP


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


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 )


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

can

t h

igh

ly s

ign

ifican

t



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


N = 419 Control RT 21Gy RT 30Gy n = 90 n = 166 n = 163

Prior to RT


Last FU (> 5 yrs) n = 85 n = 163 n = 160



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.


Remission

Stable Disease

Progression 54 (62%) 45 (27%) 36 (22%)

p < 0.001 n.s.

37 (47%) 120 (73%) 127 (78%)




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%)


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%)



Clinical Progression @ last FU ( > 5 yrs )

Clinical Progression @ last FU ( > 5 yrs )

Surgery at last FU ( > 5 yrs )

Surgery at last FU ( > 5 yrs )


Remission

Stable Disease

Progression 54 (62%) 45 (27%) 36 (22%)

- clinical 30 (34%) 19 (11%) 21 (13%)

- surgery 24 (28%) 26 (16%) 15 ( 9%)


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%)



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 ?


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


OPOP

Radiotherapy for Early Stage M. Dupuytren - Long-Term Outcome -

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