Abstract
Purpose: Several retrospective studies have shown that radiotherapy (RT) can prevent progression of Dupuytren’s disease (DD), but so far no dose-response relationship has been established. This chapter presents long-term results of our previously published prospective randomized trial comparing two different RT doses with a control group without RT. Methods: From January 1997 to December 2009 over 600 patients with DD were referred to our clinic for RT to prevent further disease progression. As of January 2011, 489 pts (291 males; 198 females) with at least five (range 5–13; mean 8.5) years follow-up (FU) were included in the analysis. Due to bilateral affliction, a total of 718 hands (sites) were evaluated. Overall 73% of all hands were affected, 230 (47%) on both hands; according to Tubiana’s classification, 470 (65.5%) hands had stage N (nodules/cords, no extension deficit), 124 (17%) had stage N/I (≤ 10° deficit), 106 (15%) had stage I (11–45° deficit), and 18 (2.5%) had stage II (46–90° deficit) or more. After clinical assessment and informed consent, patients could choose between observation only (83 patients with 122 affected hands) and RT (406 patients with 596 affected hands); all patients in the RT group were randomized into two different RT concepts: One group (207 patients with 303 affected hands) received 10 × 3 Gy (total 30 Gy) in 2 series of each 5 × 3 Gy separated by a break of 12 weeks; the other group (199 patients with 297 affected hands) received 7 × 3 Gy (total 21 Gy) in one series within 2 weeks. Orthovoltage RT (120 kV) was applied using standard cones and individual shielding of uninvolved areas of the palm. The relevant patient and disease parameters were equally distributed between control and both RT groups. The clinical evaluation (side effects, efficacy) was performed at 3 and 12 months after RT and at last follow-up (FU) in December 2010. Subjective (patient’s satisfaction) and objective parameters (palpation, measurements, and comparative photographs) were applied to assess the response. The primary endpoints were objective clinical progression and necessity of salvage surgery. Secondary endpoints were treatment of side effects and specific objective disease parameters (number and size of nodules, cords) and patient’s subjective satisfaction. Results: The acute radiogenic toxicity was low with 26.5% CTC grade 1 and 2.5% CTC grade 2; late effects, such as dry skin, were acceptable low with 14% LENT grade 1; no secondary cancer was observed in the long-term follow-up. After a minimum FU of >5 and a mean FU of 8.5 years, a total of 119 (16.5%) sites showed remission of nodules, cords or stage; 383 (53%) remained stable and 206 (29%) progressed and of those 97 (13.5%) required surgery. The progression rate in the control group (any progression 62%, surgery 30%) as compared to RT groups (21 Gy: 24%/surgery 12%; 30 Gy: 19.5%/surgery 8%) was significantly higher (p < 0.0001). Similarly, the overall and mean number of nodules, cords, and other changes decreased in the RT groups as compared to the progression in the control group (p < 0.01). Tubiana’s classification at last FU revealed a stage progression in the control group in 63 (52%) sites as compared to 64 (22%) and 49 (16%) in the 21 and 30 Gy RT group. There were 50 (8%) relapses inside and 114 (19%) outside the RT field in the RT group as compared to 52% and 28% potential relapses in the control group. Salvage surgery was possible without healing problems. Symptomatic relief was achieved in 4 (8%) sites of the control group as compared to 24 (21%) and 32 (26%) sites in the 21 and 30 Gy group, respectively. Uni- and multivariate prognostic factors for disease progression were smoking habit (trend), symptom duration prior to RT over 24 months, Dupuytren stage, extension deficit, and digital involvement (all p < 0.05). The most important independent factor was the implementation of RT as compared to the control without RT. Conclusions: RT is effective to prevent progression of Dupuytren’s disease; it reduces the necessity of hand surgery which is required due to disease progression at a minimum FU of 5 years. In addition, RT can reduce disease-related symptoms or helps to avoid their progression. Both RT protocols have been found to be effective and well tolerated, with slight advantage for the 30 Gy group as compared to 21 Gy group. Both acute and chronic side effects were well accepted and tolerated by the patients; so far no secondary malignancy was observed. From the radiobiologic background and rationale of radiotherapy, it appears possible not only to implement radiotherapy in the beginning of the disease process but also during active disease periods, e.g., for early relapses after surgical procedures.
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Seegenschmiedt, M.H., Keilholz, L., Wielpütz, M., Schubert, C., Fehlauer, F. (2012). Long-Term Outcome of Radiotherapy for Early Stage Dupuytren’s Disease: A Phase III Clinical Study. In: Eaton, C., Seegenschmiedt, M., Bayat, A., Gabbiani, G., Werker, P., Wach, W. (eds) Dupuytren’s Disease and Related Hyperproliferative Disorders. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22697-7_44
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