Radiation-induced DNA double-strand breaks in peripheral leukocytes and therapeutic response of heel spur patients treated by orthovoltage X-rays or a linear accelerator.

PURPOSE: Biodosimetric assessment and comparison of radiation-induced deoxyribonucleic acid (DNA) double-strand breaks (DSBs) by γH2AX immunostaining in peripheral leukocytes of patients with painful heel spur after radiation therapy (RT) with orthovoltage X­rays or a 6-MV linear accelerator (linac). The treatment response for each RT technique was monitored as a secondary endpoint. PATIENTS AND METHODS: 22 patients were treated either with 140-kV orthovoltage X­rays (n = 11) or a 6-MV linac (n = 11) with two weekly fractions of 0.5 Gy for 3 weeks. In both scenarios, the dose was prescribed to the International Commission on Radiation Units and Measurements (ICRU) dose reference point. Blood samples were obtained before and 30 min after the first RT session. γH2AX foci were quantified by immunofluorescence microscopy to assess the yield of DSBs at the basal level and after radiation exposure ex vivo or in vivo. The treatment response was assessed before and 3 months after RT using a five-level functional calcaneodynia score. RESULTS: RT for painful heel spurs induced a very mild but significant increase of γH2AX foci in patients' leukocytes. No difference between the RT techniques was observed. High and comparable therapeutic responses were documented for both treatment modalities. This trial was terminated preliminarily after an interim analysis (22 patients randomized). CONCLUSION: Low-dose RT for painful heel spurs with orthovoltage X­rays or a 6-MV linac is an effective treatment option associated with a very low and comparable radiation burden to the patient, as confirmed by biodosimetric measurements.

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.

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.

[Retrobulbar irradiation for Graves' ophthalmopathy -- long-term results]. / Retrobulbäre Bestrahlung bei endokriner Orbitopathie -- Erfahrungen im Langzeitverlauf.

BACKGROUND: Significance of retrobulbar irradiation in patients suffering form Graves' ophthalmopathy, though established since almost one century, is subject of scientific debate. The present study investigated the effect of retrobulbar irradiation using a standardized protocol focussing on long term results. PATIENTS AND METHODS: Between 1981 and 1997, 104 patients treated by retrobulbar irradiation (10 to 20 Gray) due to Graves' disease. Twenty-nine of these underwent irradiation as sole treatment (mean follow-up 57 months), while in the remaining 75, it was combined with a systemic steroid treatment (mean follow-up 40 months). Patients were evaluated regarding proptosis, intraocular pressure, lid signs, motility as well as subjective assessment of double vision and retrobulbar pain. RESULTS: While proptosis remained unchanged, lid signs, chemosis and intraocular pressure showed slight and statistically significant improvement. However, these findings were considered to be clinically insignificant. Retrobulbar pain was improved in 75 % of patients. 25 % of patients showed improved motility, 75 % remained stable, and in none of them was there a deterioration of ductions. Results proved stable even in long-term follow-up. 25 % per cent of patients underwent a surgical procedure one year after radiotherapy. CONCLUSIONS: In our series, we could not demonstrate an additional benefit of systemic steroids when combined with retrobulbar irradiation. Up to sixteen years after treatment, no treatment-related adverse reaction was seen. We found a remarkable improvement in ocular motility. This holds even more true in comparison to the natural course of the condition. Retrobulbar irradiation seems to shorten the duration of the disease, thus allowing earlier performance of eventual rehabilitative surgery.