Radiotherapy for painful benign skeletal disorders : Results of a retrospective clinical quality assessment.

PURPOSE: The aim of this retrospective clinical quality assessment was to evaluate the efficacy of low-dose radiotherapy (RT) for painful benign skeletal disorders. METHODS: Patients with different painful benign skeletal disorders (arthrosis and enthesopathies) were recruited for this retrospective clinical quality assessment between January 2014 and December 2015. RT was applied with a linear accelerator. Single doses of 0.5 Gy (total dose 3.0-5.0 Gy) were used. Pain was measured before and immediately after RT (early response) by a 10-point visual analogue scale (VAS). We defined a VAS score of 0-2 as a good response. Pain relief was measured during follow-up. RESULTS: A total of 598 evaluable patients (394 females, 204 males) with a mean age of 61.4 years (range 33-81 years) were recruited. The median VAS score was 7.0 (interquartile range [IQR] 2) before treatment and 5.0 (IQR 4) upon completion of RT (p < 0.001). A good response was achieved upon completion of RT in 83 patients (13.9%), with a median follow-up of 38 months (range 29-47 months) in 373 patients (62.4%; p < 0.001). In general, RT had a better effect on enthesopathies than on arthrosis. CONCLUSION: Low-dose RT is a very effective treatment for the management of painful benign skeletal disorders. Due to the delayed onset of analgesic effects, low-dose RT results in significantly improved long-term efficacy compared to the results immediately after RT. These findings confirm the results of other retrospective, prospective, and randomized trials.

Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases.

For decades, low- and moderate-dose radiation therapy (RT) has been shown to exert a beneficial therapeutic effect in a multitude of non-malignant conditions including painful degenerative muscoloskeletal and hyperproliferative disorders. Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the hand/foot with fibrotic nodules and fascial cords, which determine debilitating contractures and deformities of fingers/toes, while keloids are exuberant scar formations following burn damage, surgery, and trauma. Although RT has become an established and effective option in the management of these diseases, experimental studies to illustrate cellular composites and factors involved remain to be elucidated. More recent findings, however, indicate the involvement of radiation-sensitive targets like mitotic fibroblasts/myofibroblasts as well as inflammatory cells. Radiation-related molecular mechanisms affecting these target cells include the production of free radicals to hamper proliferative activity and interference with growth factors and cytokines. Moreover, an impairment of activated immune cells involved in both myofibroblast proliferative and inflammatory processes may further contribute to the clinical effects. We here aim at briefly describing mechanisms contributing to a modulation of proliferative and inflammatory processes and to summarize current concepts of treating hyperproliferative diseases by low and moderate doses of ionizing radiation.

Low-Dose Radiation Therapy for Benign Painful Skeletal Disorders: The Typical Treatment for the Elderly Patient?

PURPOSE: To prospectively evaluate the short-term and long-term efficacy of low-dose radiation therapy (RT) for calcaneodynia, achillodynia, painful gonarthrosis, and painful bursitis trochanterica in elderly patients aged ≥70 years. METHODS AND MATERIALS: Between October 2011 and October 2013, patients aged ≥70 years with painful degenerative disorders of joints were recruited for a prospective trial. Single doses of 0.5 to 1.0 Gy and a total dose of 6.0 Gy per series were used. Pain was measured before and right after RT (early response) with a 10-point visual analogue scale. Additionally, pain relief was measured with the 4-point pain scale according to "von Pannewitz" immediately on completion of RT and during follow-up. We defined a good response as complete pain relief and markedly improved. RESULTS: A total of 166 evaluable patients with a mean age of 76.6 years (range, 70-90 years) with calcaneodynia (n=51), achillodynia (n=8), painful gonarthrosis (n=80), and painful bursitis trochanterica (n=27) were recruited. The mean visual analogue scale value before treatment was 6.38 and immediately upon completion of RT was 4.49 (P<.001). Concerning the von Pannewitz status immediately on completion of RT, 6 patients were free of pain, 56 were much improved, 47 reported slight improvement, and 57 experienced no change. After a median follow-up of 29 months, 109 patients could be reached for evaluation of follow-up results. Thirty-three patients were free of pain, 21 had marked improvement, 18 had some improvement, and 37 experienced no change. Therefore, a good response immediately on completion of RT could be achieved in 62 of 166 patients, and with the follow-up in 54 of 109 patients (P=.001). CONCLUSIONS: Low-dose RT is a very effective treatment for the management of painful degenerative disorders of joints in the elderly. Low-dose RT offers a low-risk, genuinely conservative, noninvasive therapeutic alternative for elderly patients.

DEGRO guidelines for the radiotherapy of non-malignant disorders : part III: hyperproliferative disorders.

BACKGROUND AND PURPOSE: Radiation therapy (RT) is an established and effective treatment modality in the management of a large variety of hyperproliferative disorders and benign neoplasms. Objective of this article is to summarize the updated DEGRO consensus S2e guideline recommendations. MATERIALS AND METHODS: This report comprises an overview of the relevant aspects of the updated guidelines with regard to treatment decision, dose prescription, and RT technique for a selected group of disorders including Morbus Dupuytren (MD)/Morbus Ledderhose (ML), keloids, Peyronie's disease (induratio penis plastica, IPP), desmoid tumors, pigmented villonodular synovitis (PVNS), symptomatic vertebral hemangiomas (sVH), and Gorham-Stout syndrome (GSS). On the basis of results in the literature, we attempted to classify the level of evidence (LoE) and the grade of recommendation (GR) according to the Oxford criteria. RESULTS: There is comprehensive evidence in the literature that RT is a reasonable and effective treatment modality for the treatment of all the above-mentioned disorders. The LoE varies from 2c to 4, and GR varies from A to C. CONCLUSIONS: The use of RT can be recommended for the interdisciplinary management of most of the reported disorders. It can be used in the primary treatment approach and as an effective adjunct to other treatment modalities or in some indications as a valuable alternative treatment option. We hope that the updated DEGRO S2e consensus guideline recommendations are a helpful tool for radiation oncologists in the clinical decision-making process.

Radiotherapy is effective for desmoid tumors (aggressive fibromatosis) - long-term results of a German multicenter study.

BACKGROUND: Desmoids (aggressive fibromatosis) are defined as benign neoplasms of the connective tissue that arise from the deep muscle fascia, aponeurosis, tendons, and scar tissue. Recurrence rates between 40 and 80% were reported after surgery alone. We addressed the impact of radiation therapy (RT) in the management of aggressive fibromatosis. PATIENTS AND METHODS: A large literature review was performed, and the data was compared with the results of a multicenter study of the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD). RESULTS: This analysis included 52 patients treated with RT. 37 patients received postoperative RT (20 patients after R2 resection and 17 patients after R1 resection). 15 patients received RT alone (6 patients with inoperable primary tumor and 9 patients with inoperable recurrent tumor). In the case of postoperative RT, a median dose of 50 Gy (range 50-60 Gy) was used; for definitive RT, a median dose of 55 Gy (range 55-65 Gy) was used. The local control rate was 79% for the whole group. The median follow-up was 44 month (range 8-62 months). CONCLUSION: Given the large number of patients, these data show that RT is highly effective in the treatment of desmoid tumors. RT is an attractive alternative to mutilating surgery.

Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose x-irradiation.

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

Randomized, multicenter trial on the effect of radiation therapy on plantar fasciitis (painful heel spur) comparing a standard dose with a very low dose: mature results after 12 months' follow-up.

PURPOSE: To conduct a randomized trial of radiation therapy for painful heel spur, comparing a standard dose with a very low dose. METHODS AND MATERIALS: Sixty-six patients were randomized to receive radiation therapy either with a total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy twice weekly (standard dose) or with a total dose of 0.6 Gy applied in 6 fractions of 0.1 Gy twice weekly (low dose). In all patients lateral opposing 4- to 6-MV photon beams were used. The results were measured using a visual analogue scale, the Calcaneodynia score, and the SF12 health survey. The fundamental phase of the study ended after 3 months, and the follow-up was continued up to 1 year. Patients with insufficient pain relief after 3 months were offered reirradiation with the standard dosage at any time afterward. RESULTS: Of 66 patients, 4 were excluded because of withdrawal of consent or screening failures. After 3 months the results in the standard arm were highly significantly superior compared with those in the low-dose arm (visual analogue scale, P=.001; Calcaneodynia score, P=.027; SF12, P=.045). The accrual of patients was stopped at this point. Further evaluation after 12 months' follow-up showed the following results: (1) highly significant fewer patients were reirradiated in the standard arm compared with the low-dose arm (P<.001); (2) the results of patients in the low-dose arm who were reirradiated were identical to those in the standard arm not reirradiated (reirradiation as a salvage therapy if the lower dose was ineffective); (3) patients experiencing a favorable result after 3 months showed this even after 12 months, and some results even improved further between 3 and 12 months. CONCLUSIONS: This study confirms the superior analgesic effect of radiation therapy with 6-Gy doses on painful heel spur even for a longer time period of at least 1 year.

Radiotherapy for giant cell tumors of the bone: a safe and effective treatment modality.

BACKGROUND: Giant cell tumor of the bone (GCTB) is a benign or sometimes semi-malignant neoplasm accounting for 5% of all primary bone tumors. This type of tumor has been historically considered as radioresistant, but nowadays radiotherapy (RT) is used in unresectable, recurrent or incompletely resected cases. Since the value of RT is not well defined, a national cohort study was conducted. PATIENTS AND METHODS: Six German institutions collected data from 35 patients treated during the last 35 years and analyzed them. RESULTS: From 1975-2010 16 male and 19 female patients with 39 lesions were irradiated for GCTB. The median age was 30 years and the median follow-up 65 months. Nineteen patients had undergone RT for recurrent or unresectable disease and 16 patients for non-in-sano resection. The actuarial 5-year overall and disease-free survival rates were 90% and 59%, respectively. CONCLUSION: RT is an easy, safe and effective method for the treatment of GCTB. It may provide an attractive alternative to mutilating surgery.

Radiation therapy for Gorham-Stout syndrome: results of a national patterns-of-care study and literature review.

PURPOSE: The German Cooperative Group on Radiotherapy for Benign Diseases conducted a national patterns-of-care study to investigate the value of radiation therapy (RT) in the management of Gorham-Stout syndrome. METHODS AND MATERIALS: In 2009 a structured questionnaire was circulated to 230 German RT institutions to assess information about the number of patients, the RT indication and technique, and the target volume definition, as well as accompanying treatments, outcome data, and early or late radiation toxicity. RESULTS: In November 2009 responses were available from 197 departments (85.6%): 29 university hospitals (14.7%), 89 community hospitals (45.2%), and 79 private RT offices (40.1%). Of these institutions, 8 (4.0%) had experience using RT, for a total of 10 cases in various anatomic sites. Four patients underwent irradiation postoperatively, and six patients received primary RT. The total doses applied after computed tomography-based treatment planning ranged from 30 to 45 Gy. After a median follow-up period of 42 months, local disease progression was avoided in 8 cases (80.0%). In 2 of these cases a progression occurred beyond the target volume. Acute and late toxicity was mild; in 4 patients RT was associated with Grade I side effects according to Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. The literature analysis of 38 previously published articles providing results after the use of RT in 44 patients showed stable or regressive disease in 77.3%. CONCLUSIONS: RT may prevent disease progression effectively in Gorham-Stout syndrome in 77% to 80% of cases. Total doses ranging from 30 to 45 Gy applied after computed tomography-based treatment planning are recommended.

[The significance of radiation therapy for symptomatic vertebral hemangiomas (SVH)]. / Der Stellenwert der Strahlentherapie bei symptomatischen Wirbelkörperhämangiomen (sWKH).

PURPOSE: To evaluate the efficacy of radiation therapy (RT) for symptomatic vertebral hemangioma (SVH). MATERIAL AND METHODS: Based on the Registry for Rare Benign Disorders (RRBD) of the German Cooperative Group on Radiation Therapy for Benign Diseases (GCG-BD), the clinical information, treatment plans and outcome data from seven cooperating German RT institutions were analyzed retrospectively. RESULTS: Over a period of 39 years (1969-2008), a total of 84 patients with 96 symptomatic lesions underwent RT. The predominant indication was pain in 97.6%, and, in addition, 28.6% of patients had neurological deficits. The median total dose was 34 Gy (4.5-45 Gy), and the median single dose 2.0 Gy (0.5-3.0 Gy). After a median follow-up of 68 months (6-422 months), complete symptom relief (CR) occurred in 61.9% of patients, 28.6% had partial relief, and 9.5% had no relief (NR). The overall response rate (CR + PR) was 90.5%. In 26.2% of patients, radiologic signs of remineralization were noted. After a median follow-up of 70 months (8-124 months), symptom progression occurred in eight patients (9.5%). Therefore, the long-term rate of local control was 80.9%. Multivariate statistical analysis revealed a significantly higher rate of symptom relief and local control for total doses > or = 34 Gy. Side effects > RTOG/EORTC grade 2 were not observed. CONCLUSION: RT is a safe and effective for treatment of SVH. Total doses of at least 34 Gy are recommended to achieve optimal treatment response.

Radiation therapy for treatment of pigmented villonodular synovitis: results of a national patterns of care study.

PURPOSE: The German Cooperative Group on Radiotherapy in Benign Diseases (GCG-BD) conducted a pattern-of-care study (PCS) to analyze the radiation therapy (RT) practice for pigmented villonodular synovitis (PVNS). METHODS AND MATERIALS: In 2007, a structured questionnaire to assess the number of patients, the pretreatments, the RT indication, technique, target volume concepts, outcome data, and possible early or late toxicity was circulated to 227 institutions. RESULTS: Until August 2008, a response was available from 189 institutions (83.2 %), of whom 19 (10.0 %) experienced RT for PVNS. Complete clinical information was available for 41 patients from 14 RT departments. Thirty patients (73.2 %) received postsurgical RT because of primary incomplete resection, 11 patients (26.8 %) as an adjunct after complete resections of recurrences or unclear resection status. The total doses ranged from 30 to 50 Gy (median, 36 Gy), the median single dose was 2.0 Gy. Local control was achieved 95.1%, and 82.9% had no or only slight functional impairment. The early and late toxicity was mild (

[Radiotherapy in painful gonarthrosis. Results of a national patterns-of-care study]. / Strahlentherapie bei schmerzhafter Kniegelenkarthrose (Gonarthrose): Ergebnisse einer deutschen Patterns-of-Care-Studie

BACKGROUND AND PURPOSE: After a patterns-of-care study (PCS) in 2003/2004 addressing benign disorders in general, the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) conducted several multicenter cohort studies including the use of radiotherapy (RT) in painful gonarthrosis (GNA). MATERIAL AND METHODS: From 2006 to 2008, a PCS for GNA was conducted in all German RT institutions using a standardized structured questionnaire. Patient accrual, patient number, pretreatment, pain record, treatment indications, RT technique, and target volume concepts for painful GNA were assessed. In addition, the long-term functional and subjective outcomes were evaluated. RESULTS: 238/248 institutions (95.9%) returned the questionnaire: 50 (21%) reported no clinical experience with RT in GNA, while 188 (79%) institutions treated 4,544 patients annually (median 15; range one to 846 cases per institution). Indications for treatment were acute pain symptoms in 18.9%, chronic pain in 95.3%, and treatment-refractory pain in 81.1%. The median total dose was 6 Gy (range 3-12 Gy), with a median single dose of 1 Gy (0.25-3 Gy). 40.4% of the institutions applied two fractions and 51.4% three fractions weekly. RT was delivered with orthovoltage units (25%), linear accelerators (79.6%), and cobalt-60 units (8.3%). 42 institutions evaluated the long-term clinical outcome in a total of 5,069 cases. Median pain reduction for at least 3 months was reported in 60% (5-100%), median pain reduction for at least 12 months in 40% (10-100%), and median persistent pain reduction in 27.8% (10-85%) of the treated patients. In 30% of patients (7-100%), a second RT series was applied for inadequate pain response or early pain recurrence. No radiogenic acute or chronic side effects were observed. CONCLUSION: This PCS comprises the largest number of cases reported for RT in painful and refractory GNA. Despite variations in daily RT practice, high response and low toxicity for this treatment in a very large number of painful and refractory GNA cases renders low-dose RT an effective conservative therapy which can be applied prior to surgical procedures.

Radiotherapy for symptomatic vertebral hemangiomas: results of a multicenter study and literature review.

PURPOSE: The current study analyzes the potential role of radiotherapy (RT) in symptomatic vertebral hemangioma (SVH). METHODS AND MATERIALS: Seven cooperating German institutions collected clinical information, treatment plans, and outcome data for all patients with SVH referred for local RT. RESULTS: From 1969 to 2008, a total of 84 patients with 96 symptomatic lesions were irradiated for SVH. The primary indication for radiotherapy was pain (97.6%), and 28.6% of patients had additional neurological symptoms. RT was performed at a median total dose of 34 Gy, with a median single dose of 2.0 Gy. After receiving a median follow-up of 68 months, the overall patient response rate was 90.5%. Complete symptom remission occurred in 61.9% of patients, 28.6% of patients had partial pain relief, and 9.5% of patients had no pain relief. In 26.2% of patients, radiological signs of reossification were observed in long-term follow-up but not significantly correlated with pain relief. Most importantly, total doses of >/=34 Gy resulted in significantly greater symptomatic relief and control rate than total doses of <34 Gy. CONCLUSIONS: This study consists of the largest database of cases reported so far using RT for SVH. RT is easy, safe, and effective for pain relief treatment for SVH. Total doses of at least 34 Gy give the best symptomatic response.

Randomized multicenter trial on the effect of radiotherapy for plantar Fasciitis (painful heel spur) using very low doses--a study protocol.

BACKGROUND: A lot of retrospective data concerning the effect of radiotherapy on the painful heel spur (plantar fasciitis) is available in the literature. Nevertheless, a randomized proof of this effect is still missing. Thus, the GCGBD (German cooperative group on radiotherapy for benign diseases) of the DEGRO (German Society for Radiation Oncology) decided to start a randomized multicenter trial in order to find out if the effect of a conventional total dose is superior compared to that of a very low dose. METHODS/DESIGN: In a prospective, controlled and randomized phase III trial two radiotherapy schedules are to be compared:standard arm: total dose 6.0 Gy in single fractions of 1.0 Gy applied twice a weekexperimental arm: total dose 0.6 Gy in single fractions of 0.1 Gy applied twice a week (acting as a placebo)Patients aged over 40 years who have been diagnosed clinically and radiologically to be suffering from a painful heel spur for at least six months can be included. Former trauma, surgery or radiotherapy to the heel are not allowed nor are patients with a severe psychiatric disease or women during pregnancy and breastfeeding. According to the statistical power calculation 100 patients have to be enrolled into each arm. After having obtaining a written informed consent a patient is randomized by the statistician to one of the arms mentioned above. After radiotherapy, the patients are seen first every six weeks, then regularly up to 48 months after therapy, they additionally receive a questionnaire every six weeks after the follow-up examinations. The effect is measured using several target variables (scores): Calcaneodynia-score according to Rowe et al., SF-12 score, and visual analogue scale of pain. The most important endpoint is the pain relief three months after therapy. Patients with an inadequate result are offered a second radiotherapy series applying the standard dose (equally in both arms). This trial protocol has been approved by the expert panel of the DEGRO as well as by the Ethics committee of the Saarland Physicians' Chamber. The trial is supported by a HOMFOR grant (Saarland University Research Grant). TRIAL REGISTRATION: Current controlled trials ISRCTN94220918.

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.

A total of 502 patients treated between 1990 and 2002 with low-dose radiotherapy (RT) for painful heel spurs were analysed for prognostic factors for long-term treatment success. The median follow-up was 26 months, ranging from 1 to 103 months. Events were defined as (1) slightly improved or unchanged pain after therapy, or (2) recurrent pain sensations during the follow-up period. Overall 8-year event-free probability was 60.9%. Event-free probabilities of patients with one/two series (414/88) were 69.7%/32.2% (p<0.001); >58/ < or = 58 years (236/266), 81.3%/47.9% (p=0.001); high voltage/orthovoltage (341/161), 67.9%/60.6% (p=0.019); pain anamnesis < or = 6 months/ >6 months (308/194), 76.3%/43.9% (p=0.001); single dose 0.5/1.0 Gy (100/401), 86.2%/55.1% (p=0.009); without/with prior treatment (121/381), 83.1%/54.9% (p=0.023); men/women (165/337), 61.2%/61.5% (p=0.059). The multivariate Cox regression analysis with inclusion of the number of treatment series, age, photon energy, pain history, single-dose and prior treatments revealed patients with only one treatment series (p<0.001), an age >58 years (p=0.011) and therapy with high voltage photons (p=0.050) to be significant prognostic factors for pain relief. Overall low-dose RT is a very effective treatment in painful heel spurs.

[Radiotherapy of Graves' ophthalmopathy--state of the art and review of the literature]. / Radiotherapie der endokrinen Orbitopathie--State of the Art und Literaturübersicht.

Graves' ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves' disease, is a disorder of autoimmune origin, the pathogenic mechanisms of which are still incompletely understood. Although GO is severe in only 3-5% of affected individuals, quality of life is severely impaired even in patients with mild GO. The role of radiotherapy in the management of GO is discussed controversially. However, recent randomized clinical trials have, with one exception, confirmed that orbital radiotherapy is an effective and safe therapeutic procedure for GO. This article describes the sequences, dosages and fractionation schemes as well as the risks and side effects of the radiotherapy.

Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies.

Radiotherapy-induced nausea and vomiting (RINV) can be one of the most distressing symptoms of radiotherapy treatment, which if incompletely controlled may last for several weeks with fractionated radiotherapy and prevent completion of the planned treatment course. Current treatment guidelines recommend the use of 5-HT(3) receptor antagonists with or without corticosteroids for highly and moderately emetogenic radiotherapy, though only granisetron and ondansetron are currently indicated for RINV in most countries. Granisetron is a potent and highly selective 5-HT(3) receptor antagonist, with demonstrated efficacy in RINV in both placebo-controlled and comparative studies. In this paper the clinical experience with granisetron in RINV is reviewed, and its efficacy and safety compared with other antiemetic therapies.