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

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).

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

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  1. 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 )

  2. 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% @ 5 yrs require corrective hand surgery 3 years 6 months 2 years

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

  4. 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

  5. Noninvasive Therapy of M. Dupuytren Study Concept

  6. 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) versus21Gy(7x 3Gy) or30Gy(10x 3Gy)

  7. Noninvasive Therapy of M. Dupuytren 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)

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

  9. Noninvasive Therapy of M. Dupuytren Noninvasive Therapy of M. Dupuytren Patient Referal Counselling & Decision ObservationRadiotherapy R Control0Gy RT 21Gy RT 30Gy Stratification according to Disease Stage Observation Start: 07/1997 Study Population: 460 patients End: 06/2005

  10. 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

  11. Noninvasive Therapy of M. Dupuytren Noninvasive Therapy of M. Dupuytren Patient Parameters ( N = 273 ) Control RT 21GyRT 30Gy No. Pats.56107 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 )

  12. 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° III  135° IV  135° RT Total Extension Deficitof MP/ PIP/ DIP Joints 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

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

  15. Noninvasive Therapy of M. Dupuytren Noninvasive Therapy of M. Dupuytren Radiation Side-Effects RT 21GyRT 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 )

  16. 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 = 0.013p < 0.0001p < 0.0001Last FU (> 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 )

  17. 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 (> 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 )

  18. Noninvasive Therapy of M. Dupuytren Noninvasive Therapy of M. Dupuytren Overall Disease Status @ last FU ( > 5 yrs ) Control RT 21GyRT 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 )

  19. Noninvasive Therapy of M. Dupuytren Noninvasive Therapy of M. Dupuytren Clinical Progression @ last FU ( > 5 yrs ) Control RT 21GyRT 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 )

  20. Noninvasive Therapy of M. Dupuytren Noninvasive Therapy of M. Dupuytren Surgery at last FU ( > 5 yrs ) Control RT 21GyRT 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 )

  21. Noninvasive Therapy of M. Dupuytren 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 ?

  22. 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

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