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Radiotherapy for Early Stage M. Dupuytren - Long-Term Outcome - M.H. Seegenschmiedt, M. Wielpütz, C. Schubert, T. Olschewski, F. Guntrum Dep. of Radiation.

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Presentation on theme: "Radiotherapy for Early Stage M. Dupuytren - Long-Term Outcome - M.H. Seegenschmiedt, M. Wielpütz, C. Schubert, T. Olschewski, F. Guntrum Dep. of Radiation."— Presentation transcript:

1 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) Noninvasive Therapy of M. Dupuytren ASSH / IC10, Washington DC, September 7, 2006 ( final evaluation August 31, 2006 )

2 Why Radiotherapy ? – Rationale : Proliferating fibroblasts are sensitive target cells Therapeutic efficacy for keloids, M. Peyronie etc. Positive clinical studies Long-term progression: ~ 5 yrs require corrective hand surgery Noninvasive Therapy of M. Dupuytren 6 months 3 years 2 years

3 Proliferating Fibroblasts as Radiosensitive Target Tendon Cord Nodule Scar Noninvasive Therapy of M. Dupuytren

4 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. Dupuytren Rationale & Goals of Radiotherapy

5 Study Concept Noninvasive Therapy of M. Dupuytren

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

7 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) 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

8 Material & Methods Noninvasive Therapy of M. Dupuytren

9 Patient Referal Counselling & Decision RT 30Gy RT 21Gy R Stratification according to Disease Stage Control 0Gy Start: 07/1997 Study Population: 460 patients End: 06/2005 Observation Radiotherapy Observation Noninvasive Therapy of M. Dupuytren

10 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) Noninvasive Therapy of M. Dupuytren Individual portals : orthovoltage 150kV electrons 3 – 5 MeV

11 Patient Parameters ( N = 273 ) ControlRT 21Gy RT 30Gy No. Pats Age (yrs) 62.8 ± ± ± 8.6 M / F33 / 2360 / / 42 No. Hands22 / 3452 / / 54 (s / b =  ) 90 hds166 hds163 hds History +17 (31%)32 (30%)32 (29%) Med. Dx25 mos24 mos24 mos ControlRT 21Gy RT 30Gy No. Pats Age (yrs) 62.8 ± ± ± 8.6 M / F33 / 2360 / / 42 No. Hands22 / 3452 / / 54 (s / b =  ) 90 hds166 hds163 hds History +17 (31%)32 (30%)32 (29%) Med. Dx25 mos24 mos24 mos ( final evaluation August 31, 2006 ) Noninvasive Therapy of M. Dupuytren

12 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 System modified from Michon, Tubiana & Thomine, (1966) Classification System modified from Michon, Tubiana & Thomine, (1966) Total Extension Deficit of MP/ PIP/ DIP Joints Noninvasive Therapy of M. Dupuytren RT OP

13 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 Photons 150kV or electrons 3 - 6MeV Individual shielding (lead rubber plates) Portal with 1 – 2cm lateral margins Bolus if required Daily Control of Portal

14 Treatment Results Noninvasive Therapy of M. Dupuytren

15 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 (> 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. Dupuytren

16 Hand Parameters : # Nodules N = 419 Control RT 21Gy RT 30Gy n = 90 n = 166 n = 163 Prior to RT - mean ± SD4.2 ± ± ± median p = 0.013p 5 yrs) - mean ± SD5.2 ± ± ± median N = 419 Control RT 21Gy RT 30Gy n = 90 n = 166 n = 163 Prior to RT - mean ± SD4.2 ± ± ± median p = 0.013p 5 yrs) - mean ± SD5.2 ± ± ± median highly significant ( final evaluation August 31, 2006 ) Noninvasive Therapy of M. Dupuytren

17 Hand Parameters : Stage N = 419 Control RT 21Gy RT 30Gy n = 90 n = 166 n = 163 Prior to RT Stage N48 (53%) 107 (64%) 109 (67%) Stage N / I 18 (20%) 25 (15%) 30 (18%) Stage I - IV24 (27%) 34 (20%) 24 (14%) Last FU (> 5 yrs) n = 85 n = 163 n = 160 Stage N26 (31%) 92 (56%) 96 (60%) Stage N / I 15 (18%) 19 (12%) 22 (14%) Stage I - IV44 (52%) 52 (31%) 42 (26%) N = 419 Control RT 21Gy RT 30Gy n = 90 n = 166 n = 163 Prior to RT Stage N48 (53%) 107 (64%) 109 (67%) Stage N / I 18 (20%) 25 (15%) 30 (18%) Stage I - IV24 (27%) 34 (20%) 24 (14%) Last FU (> 5 yrs) n = 85 n = 163 n = 160 Stage N26 (31%) 92 (56%) 96 (60%) Stage N / I 15 (18%) 19 (12%) 22 (14%) Stage I - IV44 (52%) 52 (31%) 42 (26%) ( final evaluation August 31, 2006 ) Noninvasive Therapy of M. Dupuytren significant

18 Overall Disease last FU ( > 5 yrs ) Control RT 21Gy RT 30Gy (n = 87) (n = 165)(n = 163) Remission Stable Disease Progression54 (62%) 45 (27%) 36 (22%) p < n.s. Control RT 21Gy RT 30Gy (n = 87) (n = 165)(n = 163) Remission Stable Disease Progression54 (62%) 45 (27%) 36 (22%) p < n.s. 37 (47%) 120 (73%) 127 (78%) ( final evaluation August 31, 2006 ) Noninvasive Therapy of M. Dupuytren

19 Control RT 21Gy RT 30Gy (n = 87) (n = 165)(n = 163) Nodules24 (30%) 14 (10%)13 (10%) Cords (13%)14 (11%) Ext.Def. >10° 39 (48%) 26 (19%)23 (17%) Hands with P rogression 54 (62%) 45 (27%)36 (22%) Control RT 21Gy RT 30Gy (n = 87) (n = 165)(n = 163) Nodules24 (30%) 14 (10%)13 (10%) Cords (13%)14 (11%) Ext.Def. >10° 39 (48%) 26 (19%)23 (17%) Hands with P rogression 54 (62%) 45 (27%)36 (22%) ( final evaluation August 31, 2006 ) Noninvasive Therapy of M. Dupuytren Clinical last FU ( > 5 yrs )

20 Surgery at last FU ( > 5 yrs ) Control RT 21Gy RT 30Gy (n = 87) (n = 165)(n = 163) Remission Stable Disease Progression54 (62%) 45 (27%) 36 (22%) - clinical30 (34%) 19 (11%) 21 (13%) - surgery24 (28%) 26 (16%) 15 ( 9%) Control RT 21Gy RT 30Gy (n = 87) (n = 165)(n = 163) Remission Stable Disease Progression54 (62%) 45 (27%) 36 (22%) - clinical30 (34%) 19 (11%) 21 (13%) - surgery24 (28%) 26 (16%) 15 ( 9%) 37 (47%) 120 (73%) 127 (78%) ( final evaluation August 31, 2006 ) Noninvasive Therapy of M. Dupuytren

21 Summary & Conclusions RT reduces > 5years: control 62% vs. RT : 22% (A) or 27% (B) RT reduces hand > 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

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


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