Perspectives for Radiotherapy of Non-Malignant Diseases: Where History Encounters Future
Oliver Micke, Department of Radiotherapy and Radiation Oncology, Franziskus Hospital Bielefeld, Germany
15 September 2009
Dear Editor,
we like to thank Niewald et al. for their excellent and important contribution on radiotherapy for periarthritis of the shoulder [1]. Their retrospective evaluation showed that low dose irradiation is a very effective treatment method for painful periarthritis of the shoulder, exhibiting virtually no toxicity, and provides a good alternative to medication, injections, ESWT and surgery because of a high rate of long-lasting pain relief and improvement of mobility. Despite this excellent results and the fact that most patients were extensively pre-treated the criticism of a potential placebo effect could be never ruled out [1, 2, 3]. Therefore, even though treatment of degenerative and inflammatory diseases with low dose radiotherapy has a very long tradition in central Europe [4], there is deep scepticism about radiotherapy for benign diseases all over the rest of the world, in particular in the Anglo-American countries [2, 3, 5]. Another reason why colleagues from other specialities or other countries are reluctant to recommend radiotherapy are due to concerns about potential damage to gonads or tumour induction [3]. However, so far no increased tumour rate has been reported in the literature for the recommended dose range [5, 6]. In addition, the risks of pharmacological treatments such as NSAIDs, e.g. gastrointestinal, nephro- and hepatotoxicity, must be also taken into account [2, 6]. Radiotherapy for painful degenerative disorders, like osteoarthritis, plantar fasciitis, periarthritis of the shoulder or epicondylopathia humeri, is not well accepted on an international level, because its practice is based mostly on long-term experience rather than on well-defined clinical evidence. As most European literature on these topics is not written in English, it is rarely considered in reviews [2]. Conclusive controlled clinical trials are still missing, but there are three outdated randomized trials, performed more the 30 years ago, which are used to discredit radiotherapy for benign diseases and to demonstrate the ineffectiveness of the method [2, 3]: Goldie et al. [] treated in a double blinded study 399 patients with a large variety of different degenerative skeletal disorders (among which were nine heel spurs). Response rates for treated and untreated patients were 68% and 64%, respectively. Effectiveness of RT was considered questionable. However, the study was rightly criticised for its inadequate study design, the obvious flaws in outcome evaluation and the questionable results [2, 3]. Valtonen et al. [8] also performed a randomized double blinded study in 104 patients with 127 painful musculoskeletal disorders. They could not find any difference between the treatment arms, but they included many indications, which not suitable for low dose radiation (overall 49 patients!), e.g. intercostals neuralgia, spondylolisthesis, spinal spondyloses. The best effect of radiotherapy with some superiority versus placebo was observed in periarthropathia humeri, but with small patients’ number. Plenk [9] published already in 1952 a small study with just 38 patients with tendonitis calcarea of the shoulder. They found a moderate advantage for the radiation arm with 88 % versus 71 % placebo. This difference did not reach statistical significance because of the small sample size. All in all, these three studies have an absolutely insufficient methodical design in patient selection, statistical methods, endpoint definition, suitable follow-up as well as standardized documentation to answer the specific questions [2]. Nevertheless, in the Anglo-Saxon countries these studies were used again and again to discredit the radiation treatment of non-malignant disorders and as prove for the ineffectivity of this treatment [3]. However, even after extensive and numerous unsuccessful pretreatments of the patients a possible placebo effect of radiotherapy for pain treatment cannot be completely excluded so far [2, 5]. To overcome this scientific problem the German cooperative group on radiotherapy for benign diseases (GCGBD) initiated a randomized trial in painful heel spurs [10]. This is the first “modern” randomized trial using subjective as well as objective measures for outcome evaluation.
References 1. Niewald M, Fleckenstein J, Naumann S, Rübe C: Long-term results of radiotherapy for periarthritis of the shoulder: a retrospective evaluation. Radiation Oncology 2007, 2:34. 2. Micke O, Seegenschmiedt MH: Consensus guidelines for radiation therapy of benign diseases: a multicenter approach in Germany. Int J Radiat Oncol Biol Phys 2002, 52:496-513. 3. Muecke R, Micke O, Reichl B, Heyder R, Prott FJ, Seegenschmiedt MH, Glatzel M, Schneider O, Schäfer U, Kundt G: Demographic, clinical and treatment related predictors for event-free probability following low-dose radiotherapy for painful heel spurs - a retrospective multicenter study of 502 patients. Acta Oncol 2007; 46:239-246. 4. Sokoloff N: Röntgenstrahlen gegen Gelenkrheumatismus. Fortschr Röntgenstr 1898, 1: 209-213. 5. Schäfer U, Micke O, Glashörster M, Rübe C, Prott FJ, Willich N: [The radiotherapy treatment of painful calcaneal spurs]. Strahlenther Onkol 1995, 171:202-206. 6. Micke O, Seegenschmiedt MH: Radiotherapy in painful heel spurs (plantar fasciitis) - results of a national patterns of care study. Int J Radiat Oncol Biol Phys 2004; 58:828-843. 7. Goldie I, Rosengren B, Moberg E, Hedelin E: Evaluation of radiation treatment of painful conditions of the locomotor system. A double blind study. Acta Radiol Ther Phys Biol 1970; 9:311-322. 8. Valtonen EJ, Lilius HG, Malmio K. The value of roentgen irradiation in the treatment of painful degenerative and inflammatory musculoskeletal conditions. A double-blind study. Scand J Rheumatol 1975; 4:247-249. 9. Plenk HP. Calcifying tendinitis of the shoulder; a critical study of the value of x-ray therapy. Radiology 1952; 59: 384-389. 10. Niewald M, Seegenschmiedt MH, Micke O, Gräber S, the GCGBD (German cooperative group on the radiotherapy for benign diseases) of the DEGRO: Randomized multicenter trial on the effect of radiotherapy for plantar fasciitis (painful heel spur) using very low doses – a study protocol. Radiation Oncology 2008, 3:27.
Perspectives for Radiotherapy of Non-Malignant Diseases: Where History Encounters Future
15 September 2009
Dear Editor,
we like to thank Niewald et al. for their excellent and important contribution on radiotherapy for periarthritis of the shoulder [1]. Their retrospective evaluation showed that low dose irradiation is a very effective treatment method for painful periarthritis of the shoulder, exhibiting virtually no toxicity, and provides a good alternative to medication, injections, ESWT and surgery because of a high rate of long-lasting pain relief and improvement of mobility. Despite this excellent results and the fact that most patients were extensively pre-treated the criticism of a potential placebo effect could be never ruled out [1, 2, 3].
Therefore, even though treatment of degenerative and inflammatory diseases with low dose radiotherapy has a very long tradition in central Europe [4], there is deep scepticism about radiotherapy for benign diseases all over the rest of the world, in particular in the Anglo-American countries [2, 3, 5]. Another reason why colleagues from other specialities or other countries are reluctant to recommend radiotherapy are due to concerns about potential damage to gonads or tumour induction [3]. However, so far no increased tumour rate has been reported in the literature for the recommended dose range [5, 6]. In addition, the risks of pharmacological treatments such as NSAIDs, e.g. gastrointestinal, nephro- and hepatotoxicity, must be also taken into account [2, 6].
Radiotherapy for painful degenerative disorders, like osteoarthritis, plantar fasciitis, periarthritis of the shoulder or epicondylopathia humeri, is not well accepted on an international level, because its practice is based mostly on long-term experience rather than on well-defined clinical evidence. As most European literature on these topics is not written in English, it is rarely considered in reviews [2].
Conclusive controlled clinical trials are still missing, but there are three outdated randomized trials, performed more the 30 years ago, which are used to discredit radiotherapy for benign diseases and to demonstrate the ineffectiveness of the method [2, 3]: Goldie et al. [] treated in a double blinded study 399 patients with a large variety of different degenerative skeletal disorders (among which were nine heel spurs). Response rates for treated and untreated patients were 68% and 64%, respectively. Effectiveness of RT was considered questionable. However, the study was rightly criticised for its inadequate study design, the obvious flaws in outcome evaluation and the questionable results [2, 3].
Valtonen et al. [8] also performed a randomized double blinded study in 104 patients with 127 painful musculoskeletal disorders. They could not find any difference between the treatment arms, but they included many indications, which not suitable for low dose radiation (overall 49 patients!), e.g. intercostals neuralgia, spondylolisthesis, spinal spondyloses. The best effect of radiotherapy with some superiority versus placebo was observed in periarthropathia humeri, but with small patients’ number.
Plenk [9] published already in 1952 a small study with just 38 patients with tendonitis calcarea of the shoulder. They found a moderate advantage for the radiation arm with 88 % versus 71 % placebo. This difference did not reach statistical significance because of the small sample size.
All in all, these three studies have an absolutely insufficient methodical design in patient selection, statistical methods, endpoint definition, suitable follow-up as well as standardized documentation to answer the specific questions [2].
Nevertheless, in the Anglo-Saxon countries these studies were used again and again to discredit the radiation treatment of non-malignant disorders and as prove for the ineffectivity of this treatment [3].
However, even after extensive and numerous unsuccessful pretreatments of the patients a possible placebo effect of radiotherapy for pain treatment cannot be completely excluded so far [2, 5]. To overcome this scientific problem the German cooperative group on radiotherapy for benign diseases (GCGBD) initiated a randomized trial in painful heel spurs [10]. This is the first “modern” randomized trial using subjective as well as objective measures for outcome evaluation.
References
1. Niewald M, Fleckenstein J, Naumann S, Rübe C: Long-term results of radiotherapy for periarthritis of the shoulder: a retrospective evaluation. Radiation Oncology 2007, 2:34.
2. Micke O, Seegenschmiedt MH: Consensus guidelines for radiation therapy of benign diseases: a multicenter approach in Germany. Int J Radiat Oncol Biol Phys 2002, 52:496-513.
3. Muecke R, Micke O, Reichl B, Heyder R, Prott FJ, Seegenschmiedt MH, Glatzel M, Schneider O, Schäfer U, Kundt G: Demographic, clinical and treatment related predictors for event-free probability following low-dose radiotherapy for painful heel spurs - a retrospective multicenter study of 502 patients. Acta Oncol 2007; 46:239-246.
4. Sokoloff N: Röntgenstrahlen gegen Gelenkrheumatismus. Fortschr Röntgenstr 1898, 1: 209-213.
5. Schäfer U, Micke O, Glashörster M, Rübe C, Prott FJ, Willich N: [The radiotherapy treatment of painful calcaneal spurs]. Strahlenther Onkol 1995, 171:202-206.
6. Micke O, Seegenschmiedt MH: Radiotherapy in painful heel spurs (plantar fasciitis) - results of a national patterns of care study. Int J Radiat Oncol Biol Phys 2004; 58:828-843.
7. Goldie I, Rosengren B, Moberg E, Hedelin E: Evaluation of radiation treatment of painful conditions of the locomotor system. A double blind study. Acta Radiol Ther Phys Biol 1970; 9:311-322.
8. Valtonen EJ, Lilius HG, Malmio K. The value of roentgen irradiation in the treatment of painful degenerative and inflammatory musculoskeletal conditions. A double-blind study. Scand J Rheumatol 1975; 4:247-249.
9. Plenk HP. Calcifying tendinitis of the shoulder; a critical study of the value of x-ray therapy. Radiology 1952; 59: 384-389.
10. Niewald M, Seegenschmiedt MH, Micke O, Gräber S, the GCGBD (German cooperative group on the radiotherapy for benign diseases) of the DEGRO: Randomized multicenter trial on the effect of radiotherapy for plantar fasciitis (painful heel spur) using very low doses – a study protocol. Radiation Oncology 2008, 3:27.
Competing interests
None