DEGRO practical guidelines for radiotherapy of non-malignant disorders: Part I: physical principles, radiobiological mechanisms, and radiogenic risk.

PURPOSE: Synopsis of the introductory paragraph of the DEGRO consensus S2e-guideline recommendations for the radiotherapy of benign disorders, including physical principles, radiobiological mechanisms, and radiogenic risk. MATERIALS AND METHODS: This work is based on the S2e-guideline recommendations published November 14, 2013. The basic principles of radiation physics and treatment delivery, evaluation of putative underlying radiobiological mechanisms, and the assessment of genetic and cancer risk following low-dose irradiation will be presented. RESULTS: Radiation therapy of benign diseases is performed according to similar physical principles as those governing treatment of malignant diseases in radiation oncology, using the same techniques and workflows. These methods comprise usage of orthovoltage X-ray units, gamma irradiation facilities, linear accelerators (LINACs), and brachytherapy. Experimental in vitro and in vivo models recently confirmed the clinically observed anti-inflammatory effect of low-dose X-irradiation, and implicated a multitude of radiobiological mechanisms. These include modulation of different immunological pathways, as well as the activities of endothelial cells, mono- and polymorphonuclear leukocytes, and macrophages. The use of effective dose for radiogenic risk assessment and the corresponding tumor incidence rate of 5.5%/Sv are currently controversially discussed. Some authors argue that the risk of radiation-induced cancers should be estimated on the basis of epidemiological data. However, such data are rarely available at present and associated with high variability. CONCLUSION: Current radiobiological studies clearly demonstrate a therapeutic effectiveness of radiation therapy used to treat benign diseases and implicate various molecular mechanisms. Radiogenic risks should be taken into account when applying radiation treatment for benign diseases.

Multicenter, phase III trial comparing selenium supplementation with observation in gynecologic radiation oncology: follow-up analysis of the survival data 6 years after cessation of randomization.

PURPOSE: In 2010, we reported that selenium (Se) supplementation during radiation therapy (RT) is effective for increasing blood Se levels in Se-deficient cervical and uterine cancer patients, and reduced the number of episodes and severity of RT-induced diarrhea. In the current study, we examine whether of Se supplementation during adjuvant RT affects long-term survival of these patients. PATIENTS AND METHODS: Former patients were identified and questioned with respect to their health and well-being. RESULTS: A total of 81 patients were randomized in the initial supplementation study, 39 of whom received Se (selenium group, SeG) and 42 of whom served as controls (control group, CG). When former patients were reidentified after a median follow-up of 70 months (range = 0-136), the actuarial 10-year disease-free survival rate in the SeG was 80.1% compared to 83.2% in the CG (P = .65), and the actuarial 10-year overall survival rate of patients in the SeG was 55.3% compared to 42.7% in the CG (P = .09). CONCLUSIONS: Our extended follow-up analysis demonstrates that Se supplementation had no influence on the effectiveness of the anticancer irradiation therapy and did not negatively affect patients' long-term survival. In view of its positive effects on RT-induced diarrhea, we consider Se supplementation to be a meaningful and beneficial adjuvant treatment in Se-deficient cervical and uterine cancer patients while undergoing pelvic radiation therapy.

Impact of treatment planning target volumen (PTV) size on radiation induced diarrhoea following selenium supplementation in gynecologic radiation oncology--a subgroup analysis of a multicenter, phase III trial.

BACKGROUND: In a previous analysis (Int J Radiat Oncol Biol Phys 70:828-835,2010), we assessed whether an adjuvant supplementation with selenium (Se) improves Se status and reduces the radiation-induced side-effects of patients treated by adjuvant radiotherapy (RT) for cervical and uterine cancer. Now, a potential relation between the planning target volume (PTV) of the RT and the Se effect concerning radiation induced diarrhoea was evaluated in detail. METHODS: Whole blood Se concentrations had been measured in patients with cervical (n=11) and uterine cancer (n=70) after surgical treatment, during, and at the end of RT. Patients with initial Se concentrations of less than 84 µg/l were categorized as Se-deficient and randomized before RT to receive Se (as sodium selenite) per os on the days of RT, or to receive no supplement during RT. Diarrhoea was graded according to the Common Toxicity Criteria system (CTC, Version 2a). The evaluation of the PTV of the RT was ascertained with the help of a specialised computer-assisted treatment planning software used for radiation planning procedure. RESULTS: A total of 81 patients had been randomized for the initial supplementation study, 39 of which received Se [selenium group, SeG] and 42 serving as controls [control group, CG]. Mean Se levels did not differ between SeG and CG upon study initiation, but were significantly higher in the SeG compared to the CG at the end of RT. The actuarial incidence of at least CTC 2 radiation induced diarrhoea in the SeG was 20.5% compared to 44.5% in the CG (p=0.04). The median PTV in both groups was 1302 ml (916-4608). With a PTV of <= 1302 ml (n=41) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 22.3% (4 of 18 patients) compared to 34.8% (8 of 23 patients) in the CG (p=0.50). In patients with a PTV of > 1302 ml (n=40) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 19.1% (4 of 21 patients) versus 52.6% (10 of 19 patients) in the CG (p=0.046). CONCLUSIONS: Se supplementation during RT was effective to improve blood Se status in Se-deficient cervical and uterine cancer patients, and reduces episodes and severity of RT-induced diarrhoea. This effect was most pronounced and significant in patients with large PTV (> 1302 ml).

Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology.

PURPOSE: We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. METHODS AND MATERIALS: Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84µg/L were randomized before RT either to receive 500 µg of selenium (in the form of sodium selenite [selenase, biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouth on the days of RT and 300 µg of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. RESULTS: A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. CONCLUSIONS: Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.

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.