ArthroRad trial: randomized multicenter single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis-final results after 12-month follow-up.

OBJECTIVE: Updated report about the randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard dose vs. a very low dose regime after a follow-up of 1 year. PATIENTS AND METHODS: Patients presenting with OA of the hand/finger and knee joints were included. After randomization (every joint region was randomized separately) the following protocols were applied: (a) standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice a week; (b) experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice a week. The dosage was blinded for the patients. For evaluation the scores after 1­year visual analog scale (VAS), Knee Injury and Osteoarthritis Outcome Score-Short Form (KOOS-PS), Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH) and 12-item Short-Form Health Survey (SF-12) were used (for further details: see [1]). RESULTS: The standard dose was applied to 77 hands and 33 knees, the experimental dose was given to 81 hands and 30 knees. After 12 months, the data of 128 hands and 45 knees were available for evaluation. Even after this long time, we observed a favorable response of pain to radiotherapy in both trial arms; however, there were no reasonable statistically significant differences between both arms concerning pain, functional, and quality of life scores. Side effects did not occur. The only prognostic factor was the pain level before radiotherapy. CONCLUSIONS: We found a favorable pain relief and a limited response in the functional and quality of life scores in both treatment arms. The possible effect of low doses such as 0.3 Gy on pain is widely unknown.

ArthroRad trial: multicentric prospective and randomized single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis depending on the dose-results after 3 months' follow-up.

PURPOSE: Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime PATIENTS AND METHODS: Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used. RESULTS: A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment. CONCLUSION: We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer.

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial.

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer. DESIGN: Prospective, open label, randomised controlled clinical trial. SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada. PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT). INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients). MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes. RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005). CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned. TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.

Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival: Long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer.

Importance: Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed. Objective: To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control. Design, Setting, and Participants: In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019. Interventions: The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound. Main Outcomes and Measures: A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes. Results: Overall, 581 women (mean [SD] age, 63 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P = .052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P = .38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P = .98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P = .80). Conclusions and Relevance: These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival. Trial Registration: ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684.

Should I Stay or Should I Go? A Prospective, Blinded Study Comparing the Diagnostic Capability of Dynamic and Stationary Pedobarography in Plantar Fasciitis.

The aim of this study was to determine the diagnostic capability of a dynamic gait analysis insole and compare its ability to detect clinical correlations to a common stationary analysis tool. Twenty-five patients with chronic plantar fasciitis were included in this prospective, blinded, diagnostic study. Conventional, stationary gait analysis on a force plate on an even surface and continuous dynamic pedobarography on a standardized course consisting of different gait tasks were performed and correlated to the disease severity. Mean patient age was 53.6 (range 41 to 68) years, with a mean pain level of 6.1 (range 4 to 10) on the Visual Analogue Scale and a calcaneodynia score of 48.7 (range 33 to 66). Significant correlations were seen between several dynamic gait values and clinical scoring: cadence (rs = 0.56, p = .004), stance time (rs = -0.6, p = .002), center-of-pressure velocity (rs = 0.44, p = .046), and double support time (rs = 0.42, p = .042). No significant correlations were seen between any force plate gait analysis values and clinical scoring. In this study setting, dynamic gait analysis was able to identify clinically relevant correlations to plantar fasciitis disease severity that standard force plate measurements could not.

Radiotherapy of painful heel spur with two fractionation regimens : Results of a randomized multicenter trial after 48 weeks' follow-up.

BACKGROUND: In this randomized multicenter trial, we compared the effect of a lower single dose of 0.5 Gy vs. a standard single dose of 1 Gy concerning pain relief and quality of life, while maintaining a uniform total dose of 6 Gy. On the basis of laboratory observations, the lower single dose would be expected to be more effective. PATIENTS AND METHODS: A total of 127 patients suffering from painful heel spur were randomized: Patients in the standard group were treated with single fractions of 6 × 1 Gy twice a week, while the experimental group was treated with single fractions of 12 × 0.5 Gy three times a week. Patients who did not show satisfactory pain relief after 12 weeks were offered re-irradiation with the standard dose. The study's primary endpoints were pain relief and quality of life. Therapy results were evaluated and compared based on follow-up examinations after 12 and 48 weeks. RESULTS: The data of 117 patients could be evaluated. There was no significant difference between the groups concerning the results of a visual analogue scale (VAS), Calcaneodynia Score (CS), and the somatic scale of the 12-Item Short-Form Health Survey(SF-12). Patients undergoing re-irradiation showed a significant benefit concerning pain relief. Their total outcome was comparable to patients showing a good response from the beginning. No relevant acute or chronic side effects were recorded. CONCLUSION: Both patient groups showed good results concerning pain relief. A fractionation schedule of 12 × 0.5 Gy was not superior to the current standard dose of 6 × 1 Gy. Further trials are necessary to explore the best fractionation schedule.

Cancer of unknown primary (CUP) of the head and neck: retrospective analysis of 81 patients.

The treatment of patients with cervical lymph node metastases without detectable primary tumor remains an important challenge, until today, no standard therapy is available. The present study investigated the multimodal treatment of patients with head and neck CUP syndrome (HNCUP) and their follow-up retrospectively. 81 patients with cervical lymph node metastases without a primary tumor were treated at the Departments of Otorhinolaryngology as well as Radiotherapy and Radiation Oncology at the University of Saarland in Homburg, Germany in the period between 1991 and 2013. All patients received routine work-up consisting of CUP panendoscopy and imaging. Neck dissection was then performed in 77% of the patients. The most common histology was squamous cell carcinoma (80%). Ten percent of the patients had distant metastases. All patients underwent primary or adjuvant radiation therapy, or simultaneous radiochemotherapy. After a median follow-up of 3.5 years, the 5-year survival rate was 30%. There was a local recurrence that was known in 20/63 patients (31%) and distant metastases were documented in 19/61 M0 patients (31%). Higher grade late toxicity (grade 3-4) was observed in 12% of patients. Neck dissection and radiation therapy remains an integral part of HNCUP therapy, while the use of chemotherapy could be considered in selected cases. Prospective multicenter randomized trials would be necessary to identify the best target volume and to clarify the role of chemotherapy.

Initial evidence for Sec62 as a prognostic marker in advanced head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy with an increasing incidence. To aid with the selection of the most appropriate therapy, biomarkers have become a specific research focus. Sec62 is involved in endoplasmic reticulum stress tolerance and cell migration, and has been identified as a novel prognostic marker for non-small cell lung cancer. In addition, Sec62 may be a promising candidate in HNSCC. Pretreatment biopsies of 35 patients with locally advanced HNSCC, who were treated with definitive chemoradiation therapy without prior surgery, were examined for the expression of Sec62 protein, as well as the expression of epidermal growth factor receptor (EGFR), p16 and survivin proteins. Immunohistological results were correlated with patient overall survival (OS) and progression-free survival (PFS) times. In the present patient cohort, 12/35 cases (34%) demonstrated strong and 8/35 cases (23%) moderate Sec62 staining intensity. Additionally, in 11/35 cases (31%), weak staining was observed, and only 4/35 cases (11%) were Sec62-negative. Notably, a high Sec62 protein level was associated with a significantly poorer OS and PFS (P=0.020 and P=0.028, respectively). Furthermore, higher nuclear survivin expression showed a weak trend for poorer OS rate (P=0.079), whilst neither cytoplasmic survivin, EGFR nor p16 influenced OS or PFS significantly. The present study indicated that Sec62 is a promising prognostic marker for HNSCC. Increased Sec62 protein expression may indicate a poorer prognosis in advanced HNSCC. As the present study was focused on patients treated by chemoradiation therapy, further studies with larger patient cohorts and alternative treatment approaches are required in order to define the prognostic value of Sec62 in HNSCC.

Customized individual applicators for endocavitary brachytherapy in patients with cancers of the nasal cavity, sinonasal region and nasopharynx.

Brachytherapy has become an established therapeutic regimen for primary, persistent, recurrent and metastatic tumour disease in the head and neck region. This study presents the authors' preliminary experience with intracavitary brachytherapy by means of an individual silicone applicator in the treatment of patients with nasal, sinonasal, orbital and nasopharyngeal cancer. Between January 2001 and January 2013, twenty patients with cancer of the nasal cavity, the paranasal sinuses and nasopharynx underwent surgery and intracavitary brachytherapy with the aid of an individually manufactured silicone applicator in the Department of Otolaryngology, Head and Neck Surgery and in the Department of Radiotherapy and Radiooncology at the Saarland University Medical Center of Homburg, Germany. The tumour was localized in the nasal cavity/paranasal sinuses (15) affecting the orbit twice and the nasopharynx (5). There were 14 patients with squamous cell carcinoma, 2 patients with mixed tumours and one patient with adenocarcinoma, adenoid cystic carcinoma, mucosal melanoma or plasmocytoma. The majority of the patients presented with advanced disease (T3 or T4 tumours). In 18/20 patients, brachytherapy was performed as a boost technique, in the remaining two solely because of a previous radiation series. All surgical interventions were performed endonasally. Three to six weeks after surgery, a cast of the nasal cavity was created under general anaesthesia. Subsequently, an individual brachytherapy silicon applicator with two to four plastic tubes was manufactured. The radiation therapy was applied using the Ir-192 high-dose-rate-afterloading method (total dose 10-20 Gy) in two to five sessions, additionally in 18/20 patients a percutaneous radiotherapy with a total dose of 30-60 Gy was applied. After a mean duration of follow-up of 2 years, 7/20 patients experienced a local progression, 5/19 a regional recurrence in the neck nodes and 4/19 distant metastases. The 2-year survival was 57.3 %. No serious complications were reported. The silicone applicator was well tolerated by all patients. Because of the complexity of the sinonasal anatomy with the finding of mainly advanced tumours, the presented individual silicone brachytherapy applicator has proven to be useful and meaningful for endocavitary brachytherapy of malignancies of the nasal cavities, paranasal sinuses and nasopharynx.

Set-up errors and planning margins in planar and CBCT image-guided radiotherapy using three different imaging systems: A clinical study for prostate and head-and-neck cancer.

PURPOSE: The purpose of this work is to compare the positioning accuracy achieved by three different imaging techniques and planar vs. CBCT imaging for two common IGRT indications. METHODS: A collective of prostate cancer and head-and-neck cancer patients treated at our institution during the year 2013 was retrospectively analyzed. For all treatment fractions (3078 in total), the kind of acquired set-up image and the performed couch shift before treatment were assessed. The distribution of couch corrections was compared for three different imaging systems available at our institution: the treatment beam line operating at 6 MV, a dedicated imaging beam line of nominally 1 MV, and the kVision system at 70-121 kV. Shifts were analyzed for planar and cone-beam CT images. Based on the set-up corrections, CTV to PTV expansion margins were calculated. RESULTS: The difference in set-up corrections performed for the three energies and both techniques (planar vs. CBCT) was not significant for head-and-neck cancer patients. For prostate cancer all shifts had equal variance. Averages ranged from -0.7 to +0.7 mm. The set-up margins calculated on the basis of the observed shifts are 4.0 mm (AP) and 3.8 mm (SI, LR) for the head-and-neck PTV and 6.6 mm (SI), 6.7 mm (AP) and 7.9 mm (LR) for the prostate cancer patients. CONCLUSIONS: For three different linac-based imaging energies and planar/CBCT imaging, no relevant differences in set-up shifts were observed. The suggested set-up margins for these indications are of the order of 4 mm for head-and-neck and 6-8 mm for prostate treatment.

Randomized multicenter follow-up trial on the effect of radiotherapy on painful heel spur (plantar fasciitis) comparing two fractionation schedules with uniform total dose: first results after three months' follow-up.

BACKGROUND: Our first trial on radiotherapy for painful heel spur published in 2012 comparing the analgesic effect of a standard dose (6 × 1.0 Gy within three weeks) to that of a very low one (6 × 0.1 Gy within three weeks) resulted in a highly significant superiority of the standard dose arm. In the meantime, experimental data have shown that lower single doses in the range of 0.5 - 0.7 Gy might be even more effective than the current standard dose of 1.0 Gy. Therefore, we conducted a second trial comparing the analgesic effect of standard single doses of 1.0 Gy to that of low single doses of 0.5 Gy using uniform total doses of 6 Gy. PATIENTS AND METHODS: One hundred twenty-seven 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 the same total dose applied in 12 fractions of 0.5 Gy three times weekly (experimental dose). In all patients lateral opposing 6MV photon beams were used. The results were measured using Visual analogue scale (VAS), Calcaneodynia score (CS) and SF-12 health survey. The first phase of this trial ended after a three months' follow-up; it will be continued up to 48 weeks. RESULTS: Nine patients had to be excluded after randomization either due to the withdrawal of informed consent to radiotherapy by the patients or radiotherapy with an incorrect dosage. The groups were comparable concerning biographical and disease data. The mean calcaneodynia score (CS) was higher in the experimental group (p = 0.002). After three months' follow-up, we saw a very favorable pain relief in both arms (decline of VAS score: standard arm 42 points, experimental arm 44 points (n.s.), but we did not notice any statistically significant difference between the arms neither concerning the pain parameters nor the quality of life parameters. No relevant acute side effects were recorded. CONCLUSIONS: Favorable laboratory results could not be translated into an enhanced pain relief in our patients. This trial was terminated after the interim analysis (127 patients randomized). Further trials will be necessary to explore the best fractionation schedule. This trial has been approved by the expert panel of the DEGRO as well as by the Ethics committee of the Saarland Physicians' chamber. TRIAL REGISTRATION: Current trial registration at German Clinical Trials Register with the number DRKS00004458.

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.

Randomized multicenter follow-up trial on the effect of radiotherapy for plantar fasciitis (painful heels spur) depending on dose and fractionation - a study protocol.

BACKGROUND: An actual clinical trial showed the effect of low dose radiotherapy in painful heel spur (plantar fasciitis) with single doses of 1.0 Gy and total doses of 6.0 Gy applied twice weekly. Furthermore, a lot of animal experimental and in vitro data reveals the effect of lower single doses of 0.5 Gy which may be superior in order to ease pain and reduce inflammation in patients with painful heel spur. Our goal is therefore to transfer this experimentally found effect into a randomized multicenter trial. STUDY DESIGN/METHODS: This was a controlled, prospective, two-arm phase III-multicenter trial. The standard arm consisted of single fractions of 1.0 Gy applied two times a week, for a total dose of 6.0 Gy (total therapy time: 3 weeks). The experimental arm consisted of single fractions of 0.5 Gy applied 3 times a week, for a total dose of 6.0 Gy (total therapy time: 4 weeks). Following a statistical power calculation, there were 120 patients for each investigation arm. The main inclusion criteria were: age > = 40 years, clinical and radiologically diagnosed painful heel spur (plantar fasciitis), and current symptoms for at least 6 months. The main exclusion criteria were: former local trauma, surgery or radiotherapy of the heel; pregnant or breastfeeding women; and a pre-existing severe psychiatric or psychosomatic disorder. METHODS: After approving a written informed consent the patients are randomized by a statistician into one of the trial arms. After radiotherapy, the patients are seen after six weeks, after twelve weeks and then every twelve weeks up to 48 weeks. Additionally, they receive a questionnaire every six weeks after the follow-up examinations up to 48 weeks. The effect is measured using the visual analogue scale of pain (VAS), the calcaneodynia score according to Rowe and the SF-12 score. The primary endpoint is the pain relief three months after therapy. Patients of both therapy arms with an insufficient 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. TRIAL REGISTRATION: Current trial registration at German Clinical Trials Register with the number DRKS00004458.

DEGRO guidelines for the radiotherapy of non-malignant disorders. Part II: Painful degenerative skeletal disorders.

BACKGROUND AND PURPOSE: The purpose of this article is to summarize the updated DEGRO consensus S2e guideline recommendations for the treatment of benign painful degenerative skeletal disorders with low-dose radiotherapy. MATERIALS AND METHODS: This overview reports on the role of low-dose radiotherapy in the treatment of enthesiopathies (shoulder syndrome, trochanteric bursitis, plantar fasciitis, and elbow syndrome) and painful arthrosis (knee, hip, hand, and finger joints). The most relevant aspects of the DEGRO S2e Consensus Guideline Radiation Therapy of Benign Diseases 2014 regarding diagnostics, treatment decision, dose prescription as well as performance of radiotherapy and results are summarized. RESULTS: For all indications mentioned above, retrospective and some prospective analyses have shown remarkable effects in terms of pain relief. Nevertheless, the Level of Evidence (LoE) and the Grade of Recommendation (GR) vary: LoE 1b-4 and GR A-C. CONCLUSION: Low-dose radiotherapy for painful degenerative skeletal disorders is effective in the majority of the patients and therefore it may be a reasonable therapeutic alternative when simple and non-invasive methods have been used without persistent success. For all discussed entities, single fraction doses of 0.5-1.0 Gy and total doses of 3.0-6.0 Gy/series applied with 2-3 fractions per week are recommended.

Dental status, dental treatment procedures and radiotherapy as risk factors for infected osteoradionecrosis (IORN) in patients with oral cancer - a comparison of two 10 years' observation periods.

OBJECTIVES: Dental status, dental treatment procedures and radiotherapy dosage as potential risk factors for an infected osteoradionecrosis (IORN) in patients with oral cancers: Retrospective evaluation of 204 patients treated in two observation periods of approximately ten years each. PATIENTS AND METHODS: In group A, 90 patients were treated in the years 1993-2003, in group B 114 patients in the years 1983-1992 (data in brackets). All patients had histopathologically proven squamous cell cancers, mainly UICC stages III and IV. 70% (85%, n.s.) had undergone surgery before radiotherapy. All patients were referred to the oral and maxillofacial surgeon for dental rehabilitation before further treatment. Radiotherapy was performed using a 3D-conformal technique with 4-6MV photons of a linear accelerator (Co-60 device up to 1987). The majority of patients were treated using conventional fractionation with total doses of 60-70 Gy in daily fractions of 2 Gy. Additionally, in group A, hyperfractionation was used applying a total dose of 72 Gy in fractions of 1.2 Gy twice daily (time interval > 6 hours). In group B, a similar schedule was used up to a total dose of 82.8 Gy (time interval 4-6 hours). 14 (0) patients had radiochemotherapy simultaneously. After therapy, the patients were seen regularly by the radiooncologist and - if necessary - by the oral and maxillofacial surgeon. The duration of follow-up was 3.64 years (5 years, p = 0.004). RESULTS: Before radiotherapy, the dental health status was very poor. On average, 21.5 (21.2, n.s.) teeth were missing. Further 2.04 teeth (2.33, n.s.) were carious, 1.4 (0.3, p = 0.002) destroyed. Extractions were necessary in 3.6 teeth (5.8, p = 0.008), conserving treatment in 0.4 (0.1, p = 0.008) teeth. After dental treatment, 6.30 (4.8, n.s.) teeth remained. IORN was diagnosed after conventionally fractionated radiotherapy in 15% (11%, n.s.), after hyperfractionation in 0% (34%, p = 0.01). CONCLUSION: Within more than 20 years there was no improvement in dental status of oral cancer patients. Extensive dental treatment procedures remained necessary. There was an impressive reduction of the IORN frequency in patients treated in a hyperfractionated manner probably resulting from a dose reduction and an extension of the interfraction time.

Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation.

PURPOSE: Retrospective evaluation of the dental status of patients with oral cancer before radiotherapy, the extent of dental rehabilitation procedures, demographic and radiotherapy data as potential risk factors for development of infected osteoradionecrosis of the lower jaw. METHODS: A total of 90 patients who had undergone radiotherapy for oral cancer were included into this retrospective evaluation. None of them had distant metastases. After tumour surgery the patients were referred to an oral and maxillofacial surgeon for dental examination and the necessary dental rehabilitation procedures inclusive potential tooth extraction combined with primary soft tissue closure. Adjuvant radiotherapy was started after complete healing of the gingiva (> 7 days after potential extraction). The majority of patients (n = 74) was treated with conventionally fractionated radiotherapy with total doses ranging from 50-70Gy whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy. The records of the clinical data were reviewed. Furthermore, questionnaires were mailed to the patients' general practitioners and dentists in order to get more data concerning tumour status and osteoradionecrosis during follow-up. RESULTS: The patients' dental status before radiotherapy was generally poor. On average 10 teeth were present, six of them were regarded to remain conservable. Extensive dental rehabilitation procedures included a mean of 3.7 tooth extractions. Chronic periodontitis with severe attachment loss was found in 40%, dental biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90 patients (12%), mostly within the first 4 years after radiotherapy. We could not find significant prognostic factors for the occurrence of IORN, but a trendwise correlation with impaired dental status, rehabilitation procedures, fraction size and tumour outcome. CONCLUSION: The occurrence of IORN is an important long-term side effect of radiotherapy for oral cancers. From this data we only can conclude that a poor dental status, conventional fractionation and local tumour progression may enhance the risk of IORN which is in concordance with the literature.