Radiotherapy for ostheoarticular degenerative disorders: When nothing else works

Journal Pre-proof Radiotherapy for ostheoarticular degenerative disorders: when nothing else works Beatriz Álvarez, MD, Ángel Montero, MD PhD, Francisco Aranburu, MD PhD, Enrique Calvo, MD PhD, Miguel Ángel de la Casa, MD PhD, Jeannette Valero, MD PhD, Ovidio Hernando, MD PhD, Mercedes López, MD, Raquel Ciérvide, MD PhD, Mariola García-Aranda, MD, Silvia Rodríguez, MD, Emilio Sánchez, MD, Xin Chen, MD, Rosa Alonso, MD, Paloma García de la Peña, MD PhD, Carmen Rubio, MD PhD

PII:

S2665-9131(19)30019-6

DOI:

https://doi.org/10.1016/j.ocarto.2019.100016

Reference:

OCARTO 100016

To appear in:

Osteoarthritis and Cartilage Open

Received Date: 13 November 2019 Accepted Date: 27 November 2019

Please cite this article as: B. Álvarez, Á. Montero, F. Aranburu, E. Calvo, M. Ángel de la Casa, J. Valero, O. Hernando, M. López, R. Ciérvide, M. García-Aranda, S. Rodríguez, E. Sánchez, X. Chen, R. Alonso, P. García de la Peña, C. Rubio, Radiotherapy for ostheoarticular degenerative disorders: when nothing else works, Osteoarthritis and Cartilage Open, https://doi.org/10.1016/j.ocarto.2019.100016. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Osteoarthritis Research Society International (OARSI). Published by Elsevier Ltd.

Title: RADIOTHERAPY FOR OSTHEOARTICULAR DEGENERATIVE DISORDERS: WHEN NOTHING ELSE WORKS. Running Title: DISORDERS.

RADIOTHERAPY

OSTEOARTICULAR

DEGENERATIVE

+

Beatriz Álvarez1, MD; *+Ángel Montero1, MD PhD; Francisco Aranburu3, MD PhD; Enrique Calvo3, MD PhD; Miguel Ángel de la Casa2, MD PhD; Jeannette Valero1, MD PhD; Ovidio Hernando1, MD PhD ; Mercedes López1, MD Raquel Ciérvide1, MD PhD ; Mariola GarcíaAranda1, MD Silvia Rodríguez3, MD; Emilio Sánchez1, MD; Xin Chen1, MD; Rosa Alonso1,MD; Paloma García de la Peña3, MD PhD; Carmen Rubio1, MD PhD. 1

Radiation Oncology, Hospital Universitario HM Sanchinarro, Madrid. Radiophysics, Hospital Universitario HM Sanchinarro, Madrid. 3 Rheumatology, Hospital Universitario HM Sanchinarro, Madrid. 2

CONFLITS OF INTEREST: NONE.

NO FINANCIAL SUPPORT. * Corresponding author. Ángel Montero Luis. Radiation Oncology, Hospital Universitario HM Sanchinarro, Madrid. C/Oña, 10. Madrid 28050, Spain. +34 91 7567800. [email protected] +

These two authors have contributed equally to the work and development of the manuscript. Both are responsible for statistical analyses.

OBJECTIVES: Expose results in terms of pain and functionality, using low-dose radiotherapy in osteOarticular degenerative disorders (OADD). Review of the evidence. MATERIAL AND METHODS: Patients with OADD refractory to other treatments, receive 6Gy in 6 fractions of 1 Gy, each other day, repeating the scheme if necessary. Evaluation based on Visual Analogic Scale, analgesia intake and VonPannewitz score. RESULTS Results observed in our series of patients treated with low doses of radiotherapy are similar to those previously published and reinforce the consideration of radiotherapy as a useful option for degenerative musculoskeletal disorders. CONCLUSION Low dose radiotherapy seems to be a good alternative for aged patients suffering from OADD.

Keywords: low-dose radiotherapy, benign diseases, anti-inflammatory effect.

1

INTRODUCTION

2

Musculoskeletal disorders represent one of the greatest challenges in medicine. Not

3

only the individuals who suffer them are affected, also national health systems are

4

exposed due to the enormous impact the cause in medical, social and economic terms.

5

Globally, it is estimated that 24% of the general adult population suffers from

6

osteoarthritis, affecting 10% of men and 18% of women above 60 years old in high-

7

income countries. This means pain, stiffness and functional impotence for many

8

activities of daily living. Age, obesity and history of previous joint trauma are the

9

principal risk factors associated with degenerative OA. A WHO report recognized that

10

OA can become the fourth leading cause of disability by 2020 [1]. In Spain, prevalence

11

of OA is 17%, being osteoarthritis of knees and hands the most frequent, affecting 10%

12

and 6% of the population, respectively. We find a higher prevalence in women over

13

men and the economic impact of its treatment reaches 0.5% of GDP, making OA a real

14

sociosanitary problem. [2, 3].

15 16

Degenerative OA can affect any joint, being hands, knees, feet and hips most commonly

17

involved. The pathophysiology of degenerative OA consists of a progressive destruction

18

of the articular cartilage which results in chronic inflammation and other changes that

19

affect the synovial membrane of the periarticular joint, bone and muscle. When

20

osteoarthritis evolves, radiological changes such as loss of joint space, subchondral

21

bone sclerosis and the presence of osteophytes (bone spurs in the margins of the joints)

22

are observed. [4] There is no specific and definitive treatment for degenerative OA.

23

Weight loss, maintaining moderate exercise and physical rehabilitation approaches are

24

some of the conservative measures taken. Analgesics and NSAIDs, Symptomatic slow

25

acting drugs for osteoarthritis (SYSADOAs), corticosteroids, anesthetics and other local

26

injections, have also been proposed for the relief of the symptoms. In the end, a

27

prosthetic replacement of the damaged joint is done. However, none of these options

28

have demonstrated high efficacy, but ight have serious side effects (i.e.: gastrointestinal

29

bleeding, kidney disorders, cardiac disorders, etc.) that can even compromise the

30

patient's life.

31

Low-dose radiotherapy has been used for the treatment of different benign conditions,

32

including osteoarticular affections. Nowadays, as we know more about radiotherapy

33

mechanisms of action, and after the publication of guidelines and recommendations

34

about safety and efficacy, there has been a relaunch of low-dose radiation therapy use.

35

Thus, radiotherapy currently represents 10-30% of the daily activity of most

36

departments of Radiation Oncology in Germany, with painful osteoarticular

37

degenerative disorders being the most frequently treated benign pathology. [5]

38 39

In this paper we present the experience of our center using low doses of radiotherapy as

40

an alternative treatment for symptomatic degenerative OA relief.

41 42

METHODS AND MATERIALS

43

Adult patients with osteoarticular degenerative diseases refractory to other conventional

44

treatment were offered to enrol our prospective non-randomized study using low-dose

45

radiotherapy delivered to the affected joint. Local Ethics and Clinical Committee

46

approved the study and all the patients signed an informed consent document prior to

47

their inclusion.

48

Study endpoints

49

The primary study endpoint was subjective pain relief according to the 10-point Visual

50

Analogic Scale (VAS) (0, no pain; 10, strongest pain), upon the von Pannewitz score

51

(VPS) (painless, markedly improved, slightly improved, or stable). and daily

52

requirements of analgesics (more, equal, less or null). [6]

53

All patients were evaluated before radiotherapy, immediately after, 8 to 10 weeks after

54

radiotherapy and at least 3, 6, 9 and 12 months later on.

55

Radiation procedures

56

All patients were treated up to a total dose of 6 Gy delivered in single fractions of 1 Gy

57

every other day, three fractions per week. Radiotherapy was performed maintaining

58

identical quality standards to those used in oncological treatments. A CT-simulation

59

was performed to all patients, using the correct immobilization systems for each

60

location. CTV (Clinical Target Volume) included painful join and surrounding soft

61

tissue; PTV (Planning Target Volume) included CTV and 5mm isotropic margin. This

62

volumes, nearby organs at risk (guided by ALARA protocol (keep the dose as low as

63

reasonably achievable) and clinical dosimetry were achieved using RayStation®

64

(RaySearch Laboratories AB, Stockholm, Sweden) planning system. Treatments were

65

delivered in an Oncor linear accelerator (Siemens, Erlangen, Germany) using 6MV

66

photons. Those patients who did not reach a complete response after the treatment, or

67

were subjectively dissatisfied with the relief obtained, received a second course of

68

radiotherapy with identical dose and fractionation 8-12 weeks after first irradiation.

69

Statistical analysis

70

The differences between the parameters studied before and after radiation therapy were

71

calculated for each patient and compared using the Wilcoxon test for non-parametric

72

paired samples [7]. A p value <0.05 was considered significant for all statistical tests.

73

Statistical analysis was performed using the SPSS 19.0 program for Windows (SPSS

74

Inc., Chicago, IL, USA).

75

76

RESULTS

77

Between April 2015 and February 2018, 184 treatments of degenerative osteoarticular

78

disorders were performed in 108 patients in our department. Some patients received

79

treatment in more than one different location and so they have been accounted for

80

differently.

81

We included 88 (81.5%) women and 20 (18.5%) men with a median age of 64 years

82

(range 30-89 years). The degenerative osteoarticular disorders included in this study

83

were: trochanteric syndrome (20%) gonarthrosis (18%), finger joints osteoarthritis

84

(14%), periarthropathia humeroescapularis (9%), rhizarthrosis (14%), spondyloarthrosis

85

(9%),

86

epicondylopathia humeri (2%) and painful calcinosis (1%). Three percent of treated

87

cases corresponded to disorders of other locations including coxarthrosis and

88

tarsometatarsal joint arthritis.

89

Characteristics of included patients are detailed in Table 1.

tibialis

tenosynovitis

(posterior/anterior)

(5%),

plantar

fasciitis

(4%),

90 91

In 96 cases (52.17%), a second additional course of radiotherapy was given (total

92

accumulated dose 12 Gy) due to persistence of the symptoms in the first evaluation 8

93

weeks after first treatment.

94 95

According to the VAS scale, 82.5% of the patients presented with 7-10 score, 17% of

96

patients between 4-6 and 0.5% of patients reported pain around 3 or less. . Overall, and

97

with a follow-up of 8 months (range 1-31 months), 91% of patients experienced pain

98

relief. The pain reported according to the VAS scale was 0-3 in 32.6% of the patients, 4-

99

6 in 36.7% and greater or equal to 7 in 20.1% of treated patients. (Table 2). In the

100

comparative analysis, including all the patients, the mean VAS before treatment was

101

7.43±47 versus mean VAS of 3.3±2.47 after treatment, being this difference statistically

102

significant (p < 0.0001). (Figure 1). Except EH, all the categories showed significant

103

differences before and after treatment when analysed individually. (Table 3)

104 105

Eighty-nine cases with long follow-up (> 6 months) have been analysed to assess late

106

response and persistence of response when reached quickly according to the scale

107

proposed by von Pannewitz, and needs of daily analgesia intake. More than two thirds

108

of patients (66.3%) reported improvement of their symptomatology compared to before

109

treatment, being 7.9% of them painfree. Similarly, 46% report that they needed less

110

analgesia intake and 15% did not need to take analgesics of any kind. (Table 4)

111 112

Both in the immediate and long-term follow-up, no acute or late side effects have been

113

assessed resulting from treatment.

114 115

CONCLUSIONS

116

Degenerative osteoarticular diseases represent one of the most prevalent problems in

117

developed countries. They mean high sanitary costs and important social difficulties.

118

The efficacy of available treatments is limited and their potential adverse effects can be

119

occasionally life threatening [4] and so alternative solutions are necessary, especially in

120

the elderly multipathologic and polymedicated population. [8]

121 122

Anti-inflammatory efficacy of low-dose radiotherapy has been confirmed in several

123

experimental models, both in vitro and in vivo. In contrast to high-dose radiotherapy

124

that induces the production of proinflammatory cytokines in the immune system and the

125

endothelial cells, low doses of radiotherapy (0.5-1.5 Gy) act on the cells that participate

126

in the inflammatory response, producing anti-inflammatory effects, including inhibition

127

of the interactions between leukocytes and endothelial cells, a decrease in the

128

production of adhesion molecules to the endothelium, a decrease of mediators of

129

inflammation and less expression of pro-inflammatory cytokines as well as induction of

130

apoptosis of macrophages and polymorphonuclear. Low-dose irradiation also results in

131

a decrease in levels of NO synthetase (iNOS), L- and E- selectins, reactive oxygen

132

species (ROS), tumor necrosis factor alpha (TNF-α) or the secretion of IL-beta 1 in

133

conjunction to an increase in the production and expression of anti-inflammatory

134

cytokines such as the transforming growth factor of anti-inflammatory cytokine β1

135

(TGF-β1) and apoptosis mediator such as nuclear factor kappa- beta (NF-κB). [15-18].

136

All these changes result in a local anti-inflammatory environment that would explain

137

the clinical effects of low-dose radiation therapy.

138 139

Since 1898 [9,10] low dose radiotherapy is known to be effective for pain relief and

140

functionality recovery of the joints [11-14], however there is wide fear related to its

141

possible side effects, in particular, developing a radio-induced tumor. The evidence

142

supporting the risk of radioinduced tumors comes from historical data based on old

143

planning techniques treatments, obsolete equipments and little controlled dosimetry.

144

Radio-induced tumors require a prolonged latency time before their manifestation,

145

something that must be confronted against the usually advanced age of treated OA

146

patients. It has been estimated that the probability of a fatal cancer for a 25 year old

147

individual is about one magnitude, i.e. nine times, higher than that for a 75 year old

148

person, and the group of OA candidates for treatment are usually the oldest. [20-23].

149

More precisely, the lifetime risk of developing a radioinduced basal cell carcinoma

150

(BCC) has been estimated at approximately 0.006% based on 100 cm2 of skin treated

151

with an average dose of 3Gy, below the risk of spontaneous onset of cancer skin

152

throughout life, estimated at 0.2%. Risk of sarcoma development after radiotherapy is

153

well known, although at a very low frequency (0.05%), and extremely rare with doses

154

below 10 Gy. [24]

155 156

There are marked regional differences regarding its recommendations (Germany and

157

Eastern Europe, 85% vs. North America and Western Europe, 23%), however, from the

158

end of the 20th century and the beginning of the 21st, increasing knowledge about

159

underlying radiobiology and potential risks of the treatment, has awakened a renewed

160

interest in this old modality. In fact, guidelines and recommendations on radiotherapy

161

have been published in benign pathology both from DEGRO in Germany and from the

162

RCR in the United Kingdom that justify and support the use of radiotherapy in these

163

diseases. [11-14, 25]

164 165

During the last two decades, German groups have published results of surveys about

166

patterns-of-care using radiotherapy for the treatment of different degenerative

167

osteoarticular pathologies. In 2000, Seegenschmiedt et al. analyzed the patients affected

168

by different non-tumor pathologies treated in Germany between 1994-1996. Eighty-

169

eight per cent of German institutions with radiotherapy facilities treated non-tumor

170

diseases. The authors collected data from a total of 20,082 patients of which 63%

171

(12,600)

172

periarthropathia humeroscapularis [n = 2,711 (22%)], epicondylopathia humeri [n =

173

1,555 (12%)], plantar / dorsal heel spur [n = 1,382 (11%)], osteoarthrosis of various

174

joints [n = 2,434 (19%)], and other unspecified disorders [n = 4,518 (36%)]. The mean

175

total dose administered was less than 12 Gy (range 3-12 Gy), in 2/3 fractions per week

corresponded

to

degenerative

osteoarticular

pathology

including

176

and daily doses of 0.3-1 Gy. [26] Recently, the authors have published the results of the

177

repetition of the survey analyzing on this occasion the patients treated in the year 2014

178

in 116 institutions. A total of 36,830 patients were treated for benign diseases: 31,925

179

(87%) for degenerative osteoarticular diseases including peritendinitis humeroscapularis

180

(8%, n = 2,691, epicondylitis humeri (12%, n = 3,788), plantar / dorsal heel spur (33%,

181

n = 10,510), coxarthrosis (7%, n = 2,230), gonarthrosis (8%, n = 2,623),

182

periarthropathia humeroscapularis (8%, n = 2,691), rhizarthrosis (8%, n = 2,440),

183

polyarthrosis (7%, n = 2297), or other unspecificed arthrosis (8%, n = 2,655). [27]. By

184

locations, Micke et al. have published patterns of care data for painful heel spurs from

185

76 different institutions including a total of 7,947 patients at a dose of 2.5 Gy- 8.75 Gy

186

(median 6 Gy to 1 Gy per fraction). With a median follow-up 28 months (range 3-335),

187

59% of patients reported total or partial improvement of pain and motility [28].

188

Likewise, Mucke et al. collected data from 238 institutions in Germany, of which 188

189

(79%) used low-dose radiation therapy for the treatment of knee osteoarthritis. The

190

authors analyzed data from 4,544 patients treated in 2008 with a median dose of 6 Gy

191

(range 3-12 Gy) by 2 or 3 weekly fractions of 1 Gy of median dose (range 0.25-3 Gy).

192

Thirty per cent of patients received a second series of radiotherapy 6-12 weeks after

193

completion of the first. The authors observed symptomatic response in the form of pain

194

relief in 79.5% of patients. No acute complications or late adverse effects of treatment

195

were observed during follow-up [29]. One of the main limitations of most of these

196

studies are the absence of a control group with standard treatment, although almost all

197

of them included patients refractory to other therapies. Only Canylmaz et al. study,

198

randomized 124 patients with plantar fasciitis to receive radiotherapy (6 Gy in 1 Gy

199

fractions) vs. local corticosteroid and anesthetic injections. With a median follow-up of

200

12.5 months, pain relief was significantly higher in those receiving radiotherapy over

201

local injections, 68% vs. 28%, p <0.001. [30]

202 203

Table 5 shows the results of studies published since year 2000 using low doses of

204

radiotherapy for the treatment of different OA conditions [30-59]. Most studies analyze

205

the response to treatment according to the gain in pain relief measured according to the

206

visual analog scale (VAS) after radiotherapy and during follow-up period. In many

207

cases, pain relief was also measured according to the von Pannewitz four-degree scale

208

(VPS). Globally, response rates, including partial and complete response, in terms of

209

pain relief varies between 59% -98%. In our experience, 91% of the patients

210

experienced some degree of relief in their symptoms being greater in the cases of

211

plantar fasciitis (100%) and trochanteric syndrome (97.3%) and lower in finger joint

212

OA (80, 8%) and spondyloarthrosis (81%). Recently, Micke et al have published the

213

results observed in 703 patients treated with radiotherapy at low doses for

214

calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and

215

painful shoulder syndrome. With a median follow-up of 33 months, there was a better

216

effect of treatment for enthesiopathies in comparison with gonathrosis [59].

217 218

As in our practice, most authors deliver doses between 0.5-1.0 Gy per fraction in 2-3

219

weekly fractions up to a total doses of 3-6 Gy. Although it is true that laboratory studies

220

[15, 17] demonstrated the maximum anti-inflammatory effect of radiotherapy in the

221

environment of 0.3-0.7 Gy per fraction, the observed clinical results in the randomized

222

trials comparing 6 fractions of 1 Gy versus 6 fractions of 0.1-0.5 Gy favors 1 Gy,

223

although the difference is not statistically significant except when compared against the

224

use of 0.1 Gy fractions [48, 49, 51, 52]. Similarly, in vitro experiments demonstrated

225

that the anti-inflammatory effect of low doses of radiotherapy was maximum at 48 h

226

after irradiation and it was lost after 72 h. This explains why it is recommended to

227

administer the dose in separate fractions every 48-72 h [17]. As in many other studies,

228

those patients in our series who did not reach a complete response or who were

229

subjectively dissatisfied with the relief obtained, received a second course of

230

radiotherapy with identical dose and fractionation 8-12 weeks after first irradiation. The

231

median age in our series is 64 years old (range 30-89). As shown in Table 4, the median

232

age in the vast majority of studies exceeds 50 years, and it is exceptional to include

233

patients under the age of 40 years. Even with the renewed interest in the use of low-dose

234

radiation therapy for OA and the availability of advanced planning and treatment

235

techniques, caution should be taken in young patients, especially in the case of children

236

who should only be treated in emergency situations if no other viable therapeutic

237

alternatives are available. [Read 2007] In a recent review of the state of the art and

238

update of the evidence of radiotherapy in benign osteoarticular processes,

239

Seegenschmiedt et al conclude that irradiation at low doses in patients resistant to other

240

standard treatments should be performed with a total dose of 3-6 Gy and a fractionation

241

0.5-1 Gy two / three times a week and otherwise restricted to patients older than 40

242

years. [5]

243 244

Delayed onset of analgesic effects low dose radiotherapy has been previously

245

established by different authors and results in a significantly improved long-term

246

efficacy in comparison to the results immediately after radiotherapy [45, 55, and 59]. It

247

has been suggested that this delayed response to radiotherapy would be related to the

248

previously mentioned radiobiological mechanisms that justify its efficacy. In our series,

249

in those patients with more than 6 months of follow-up after treatment, the percentage

250

of patients reporting absence or only mild pain (VAS 0-3) increased from 33% at the

251

end of radiotherapy to the 59.5%, and the percentage of patients with severe pain (VAS

252

7-10) was reduced from 20% to 11%. In addition, the percentage of patients who

253

reported having improved with treatment according to VPS increased from 53% to 66%

254

with more than 6 months of follow-up with respect to the moment immediately

255

following the end of treatment.

256 257

Neither in our series nor in any other paper published since 2000 have shown late

258

complications attributable to treatment, and only Niewald et al reported the appearance

259

of grade 1 epithelitis in one patient treated of PHE. However, it is advisable to maintain

260

a long follow-up of patients to rule out the appearance of late complications.

261 262

All in all, the use of low doses of radiotherapy achieves significant pain relief in

263

patients with different degenerative OA disorders. In addition to the improvement of

264

pain, patients report subjective functional improvement and require less daily analgesia.

265

The relief achieved at the end of the treatment was maintained or even improved during

266

follow-up. All in all, it appears to improve quality of life with no acute or long-term

267

side effects.

268 269 270 271 272 273 274

275

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FIGURE LEGENDS Table 1: Patients and treatment characteristics. Table 2: Response rates and results after radiotherapy. Table 3: Comparative analysis of mean VAS before and after LDRT for different locations. Table 4: Characteristics and results of patients with longer follow-up. Table 5: Results of studies since year 2000. Figure 1: VAS before and after treatment.

TABLE 1: PATIENTS AND TREATMENT CHARACTERISTICS N 64 (30-89) Median age: Gender Male 29 Female 155 Treated location: Finger joint osteoarhritis 26 Bursitis trochanterica 37 Gonarthrosis 33 Periarthropathia humeroescapularis 16 Plantar fasciitis 8 Rhizarthrosis 25 Spondyloarthrosis 16 Epycondilopathia humeri 4 Painful calcinosis 3 Tibial Tenosynovitis 10 Other 6 Visual Analogic Scale (VAS) of Pain Before Treatment: 0-3 1 4-6 32 7-10 151 Total dose: 6 Gy (1 Gy x 6) 88 12 Gy [(1 Gy x 6) + (1 Gy x 6)] 96

%

15,76 84,24 14,13 20,12 17,93 8,7 4,35 13,58 8,7 2,17 1,63 5,43 3,26 0,54 17,39 82,07 48 52

1

TABLE 2: RESPONSE RATES AND RESULTS AFTER RADIOTHERAPY (N=184) N Rate Positive response by location: Finger Joint osteoarthritis 26 80,8% Gonarthrosis 33 87,9% Rizarthrosis 25 90,1% Periarthropathia humeroscapularis 16 90,9% Spondyloarthrosis 16 75% Epycondilopathia humeri 4 75% Trochanteric Bursitis 37 97,3% Tibialis Tenosynovitis 10 100% Plantar Fasciitis 8 100% Others 7 87,5 Visual Analogic Scale (VAS) of pain after treatment: 0-3 60 32,61 4-6 73 36,67 7-10 37 20,11 Von Pannewitz’s functional score after treatment: Unknown 38 20,66 Stable 46 25 Slightly Improved 10 5,43 Markedly improved 68 36,96 Painless 22 11,96 Analgesic intake after treatment: Unknown 69 37,5 No intake 19 26,63 Less 40 21,74 More 5 2,72 Equal 51 27,72

2

TABLE 3: COMPARATIVE ANALYSIS OF MEAN VAS VALUE BEFORE AND AFTER LDRT FOR DIFFERENT LOCATIONS Mean pre-RT-VAS

Mean post-RT-VAS

PHE

7.75±1.18

3.75±2.67

p =0.001

EH

5.5±1.29

3.25±3.77

p =0.18

FJ

6.62±1.74

3.69±2.25

p <0.0001

RA

7.59±1.6

3.48±2.70

p <0.0001

BT

7.75±1.42

3.26±2.73

p <0.0001

GA

7.59±1.30

3.21±2.21

p <0.0001

TT

8.5±0.70

3.10±2.84

p =0.007

PF

7.5±0.75

2.75±2.49

p =0.011

SA

7.25±1.23

2.81±1.90

p =0.001

PHE: periarthropathia humeroescapularis; EH: epicondylopathia; FJ: finger joints OA; RA: rhizarthrosis; humeri; BT: bursitis trochanterica; GA: gonarthrosis; TT: tibialis tendinopathy; PF: plantar fasciitis;

3

TABLE 4: CHARACTERISTICS & RESULTS OF PATIENTES WITH LONGER FOLLOW-UP (N=89) N (%) Response rates (%) 62 (30-89) Median age: Gender: Male 13 (14.6) 91,3 Female 76 (85.4) 73,7 Treated localization: Finger joint osteoarthritis 16 (18) 85,7 81,8 Bursitis trochanterica 22 (24.7)) 90 Gonarthrosis 10 (11.2) 100 Periarthropathia humeroescapularis 10 (11.2) Plantar fasciitis Rhizarthrosis Spondyloarthrosis Epycondilopathia humeri Painful calcinosis Tibialis Tenosynovitis Other

5 (5.6) 11 (12.4) 3 (3.4) 4 (4.5) 2 (2.2) 3 (3.4) 3 (3.4)

100 88,89 100 66,67 100 100 93,8

Visual Analogic Scale (VAS) of pain before treatment: 0-3 4-6 7-10

0 16 73

0 17,98 81,94

0-3 4-6 7-10 Von Pannewitz’s functional score after treatment: Unknown Stable Slightly Improved

52 27 10

59,48 30,34 11,24

6 24 2

6,74 26,97 2,25

Markedly improved

50

56,18

Painless

7

7,87

18 13 28 4 26

20,22 14,61 31,46 4,49 29,21

Visual Analogic Scale (VAS) of pain after treatment:

Analgesic intake after treatment: Unknown No intake Less More Equal

4

5

TABLE 5: Results of studies since year 2000.

CONTRIBUTIONS • Conception and design: Ángel Montero, Beatriz Álvarez. • Analysis and interpretation of the data: Ángel Montero. • Critical revision of the article for important intellectual content: Carmen Rubio. • Final approval of the article: Carmen Rubio, Paloma García de la Peña • Provision of study materials or patients: Francisco Aramburu, Enrique Calvo, Silvia Rodríguez, Rosa Alonso, Jeannette Valero, Ovidio Hernando, Mariola García-Aranda, Mercedes López, Raquel Ciérvide. • Statistical expertise: Ángel Montero. • Administrative, technical, or logistic support: Miguel Ángel de la Casa. • Collection and assembly of data: Beatriz Álvarez.

Ángel Montero ([email protected]) and Beatriz Álvarez ([email protected]) take responsibility for the integrity of the work as a whole, from inception to finished article.

No conflints of interest to declare.