Radiation Therapy For Benign Diseases Research Articles

Yes, it is time to redefine the role of low-dose radiation therapy for benign diseases! Response to Letter by Montero et al

We thank the authors, with affiliations of six departments of radiation oncology in Spain and Germany, for their interest in our randomised controlled trials (RCT) and their compliments on the...

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

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. 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. 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. 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.

Linear Accelerator Stereotactic Radiosurgery for Trigeminal Neuralgia

Background: Stereotactic radiosurgery is accepted as an alternative for patients with refractory trigeminal neuralgia, but existing evidence is fundamentally based on the Gamma Knife, which is a specific device for intracranial neurosurgery, available in few facilities. Over the last decade it has been shown that the use of linear accelerators can achieve similar diagnostic accuracy and equivalent dose distribution. Objectives: To assess the effectiveness and safety of linear-accelerator stereotactic radiosurgery for the treatment of patients with refractory trigeminal neuralgia. Methods: We carried out a systematic search of the literature in the main electronic databases (PubMed, Embase, ISI Web of Knowledge, Cochrane, Biomed Central, IBECS, IME, CRD) and reviewed grey literature. All original studies on the subject published in Spanish, French, English, and Portuguese were eligible for inclusion. The selection and critical assessment was carried out by 2 independent reviewers based on pre-defined criteria. In view of the impossibility of carrying out a pooled analysis, data were analyzed in a qualitative way. Results: Eleven case series were included. In these, satisfactory pain relief (BIN I-IIIb or reduction in pain ≥ 50) was achieved in 75% to 95.7% of the patients treated. The mean time to relief from pain ranged from 8.5 days to 3.8 months. The percentage of patients who presented with recurrences after one year of follow-up ranged from 5% to 28.8%. Facial swelling or hypoesthesia, mostly of a mild-moderate grade appeared in 7.5% – 51.9% of the patients. Complete anaesthesia dolorosa was registered in only study (5.3%). Cases of hearing loss (2.5%), brainstem edema (5.8%), and neurotrophic keratoplasty (3.5%) were also isolated. Conclusions: The results suggest that stereotactic radiosurgery with linear accelerators could constitute an effective and safe therapeutic alternative for drug-resistant trigeminal neuralgia. However, existing studies leave important doubts as to optimal treatment doses or the therapeutic target, long-term recurrence, and do not help identify which subgroups of patients could most benefit from this technique. Limitations: Paucity of literature and clear lack of clarification for clinical utilization of this technique. Key words: Radiosurgery, trigeminal neuralgia, functional radiosurgery, radiation therapy of benign diseases, stereotactic radiotherapy

DEGRO practical guidelines for the radiotherapy of non-malignant disorders - Part IV: Symptomatic functional disorders.

To summarize the updated DEGRO consensus S2e guideline recommendations for the treatment of benign symptomatic functional disorders with low-dose radiotherapy. This overview reports on the role of low-dose radiotherapy in the treatment of functional disorders in cases of heterotopic ossification (HO) and Graves orbitopathy (GO). 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. For both indications (HO, GO), retrospective and some prospective analyses have shown remarkable effects in terms of symptom relief. Nevertheless, the level of evidence (LoE) and the grade of recommendation (GR) vary: LoE 1-2 and GR A-B (HO), LoE 2 and GR B (GO). Low-dose radiotherapy for benign symptomatic functional disorders has proven to be effective, according to different authors, for 25-100 % of the patients studied and therefore it may be a reasonable prophylactic and therapeutic option if noninvasive or invasive methods have been used without persistent success. For HO, a single-fraction dose of 7-8Gy or fractionated radiation with five fractions of 3.5Gy is recommended. For GO, single-fraction doses of 0.3-2.0Gy, and total doses of 2.4-20Gy/series, applied in one daily fraction are recommended.

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

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. 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. 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. 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.

A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy(-1) of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

Der Stellenwert der Strahlentherapie bei symptomatischen Wirbelkörperhämangiomen (sWKH)*

To evaluate the efficacy of radiation therapy (RT) for symptomatic vertebral hemangioma (SVH). 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. 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. RT is a safe and effective for treatment of SVH. Total doses of at least 34 Gy are recommended to achieve optimal treatment response.

Treatment of Benign Diseases with Megavoltage X-ray Beams: Is there a Risk for Gonadal Damage?

Aims To measure the testicular and ovarian doses and to assess the risk for gonadal damage to patients treated with megavoltage X-ray beams for benign diseases. Materials and methods Radiation therapy of benign diseases was simulated on an anthropomorphic phantom with a 6 MV photon beam. The gonadal dose was calculated during the irradiation of heterotopic ossification, liver and vertebra haemangiomas, bone cysts, Graves' ophthalmopathy and gynaecomastia. Dose measurements were carried out using thermoluminescent dosimeters. For the radiotherapy of heterotopic ossification, the effect of using lead blocks to spare lymphatic drainage on the gonadal dose was determined. Results The ovarian and testicular total doses were found to be 2.00–680 and 2.0–39.0 mGy, respectively, depending on the gonadal location in respect to the treatment volume. The introduction of blocks into the primary beam resulted in an increase in gonadal dose up to a factor of 1.7. The radiation-induced risk of hereditary disorders in future generations was (1.0–40.8) × 10 −4 and (1.0–23.4) × 10 −4 for women and men, respectively. Conclusions Radiation therapy of benign diseases always resulted in gonadal doses below 1 Gy and therefore there was no risk for permanent gonadal failure. The excess risk of radiation-induced hereditary disorders in offspring was low in comparison with the natural frequency of these effects. However, there was a considerable excess in risk after irradiation in the hip bone.

116 poster Consensus guidelines for radiation therapy of benign diseases - a multi-center approach in Germany

116 poster Consensus guidelines for radiation therapy of benign diseases - a multi-center approach in Germany

Potential complications following radiotherapy for meningiomas

Background The rationale for radiotherapy of meningiomas is based on retrospective studies utilizing life-table statistics and historical controls. Most of these report minimal morbidity and high efficacy, while one study of radiation therapy for benign diseases reported a high complication rate during long-term follow-up. These reports were at variance with our personal experience in three patients. This study was therefore undertaken to corroborate the previous reports by retrospectively investigating possible adverse effects and efficacy. Methods The charts at Karolinska hospital were searched to identify all patients with meningiomas who were treated with conventional fractionated radiotherapy between 1975 and 1995. Surgical radicality was assessed according to Simpson. The patients were followed until recurrence, death, or a minimum of 5 years. Results Forty-five out of 1,820 patients were treated with fractionated radiotherapy. Fifty-six percent of these patients experienced serious complications from fractionated radiation treatment. The complications encompassed neuropsychological and neurologic motor and sensory deficits and were severe enough to cause hospitalization or a major change in lifestyle. Seventy-five percent of all subtotally resected and radiated meningiomas recurred during follow-up. Conclusion Our historical data from a heterogenous group of consecutive patients undergoing fractionated radiation therapy in meningioma management showed an unexpectedly high rate of complications and failed to corroborate previous historical reports of low morbidity and tumor control. Dose planning and radiation treatment has improved. Our data indicate a need for prospective investigations.

Consensus guidelines for radiation therapy of benign diseases: a multicenter approach in GERMANY

Purpose : To overcome the lack of written guidelines for radiation therapy (RT) of benign diseases, the German Working Group on Radiotherapy of Benign Diseases initiated a consensus process in 1999 to warrant continuous quality assurance and outcome research in this field. Methods : An expert panel was convened to define key issues and develop written guidelines for RT of benign diseases. Pertinent information and data from published literature were reviewed, and data of most importance were identified. In addition, a patterns of care study was conducted to obtain a nationwide survey on the current status and treatment standards. Results : From the data gathered, the expert panel prepared a first consensus statement that was open to propositions and comments from all participating institutions. After completion of the multicenter discussion, a final written consensus statement was compiled, discussed, and finally agreed on during a national conference of radiation therapists. For each individual nonmalignant disease, the accepted RT concepts were documented. Finally, specific evaluation tools and recommendations for follow-up examinations were defined. Conclusions : For the first time, written consensus guidelines for RT of nonmalignant diseases have been developed by the interaction of all institutions involved. These guidelines may serve as a starting point for quality assessment, prospective clinical trials, and outcome research.

Radiation therapy for benign diseases: patterns of care study in Germany

Background: Radiotherapy of benign diseases is controversial and rarely applied in Anglo-American countries, whereas in other parts of the world it is commonly practiced for several benign disorders. Similar to a European survey, a patterns of care study was conducted in Germany. Method: Using a mailed questionnaire, radiation equipment, treatment indication, number of patients, and treatment concepts were assessed in 1994, 1995, and 1996 in 134 of 152 German institutions (88%): 22 in East and 112 in West Germany; 30 in university hospitals and 104 in community hospitals. Average numbers of each institution and of all institutions were analyzed for frequencies and ratios between regions and among institutions. Radiation treatment concepts were analyzed. Results: A mean of 2 (range 1–7) megavoltage and 1.4 (range 0–4) orthovoltage units were available per institution; 32 institutions (24%) had no orthovoltage equipment. A mean of 20,082 patients were treated annually: 456 (2%) for inflammatory diseases (221 hidradenitis, 78 local infection, 23 parotitis; 134 not specified) 12,600 (63%) for degenerative diseases (2711 peritendinitis humeroscapularis, 1555 epicondylitis humeri; 1382 plantar/dorsal heel spur; 2434 degenerative osteoarthritis; 4518 not specified); 927 (5%) for hyperproliferative diseases (146 Dupuytren’s contracture, 382 keloids; 155 Peyronie’s disease; 244 not specified); 1210 (6%) for functional disorders (853 Graves’ orbitopathy; 357 not specified); and 4889 (24%) for other disorders (e.g., 3680 heterotopic ossification prophylaxis). In univariate analysis, there were geographic (West vs. East Germany) differences in using radiation therapy (RT) for inflammatory and degenerative disorders, and institutional differences (university versus community hospitals) in using RT for hyperproliferative and functional disorders ( p < 0.05). The prescribed dose concepts were mostly in the low dose range, <10 Gy but varied widely and inconsistently within geographic regions and institutions. Conclusion: Radiation therapy is a well-accepted and frequently practiced treatment for several benign diseases in Germany; however, there are significant geographic and institutional differences. As the number of orthovoltage units decreases, an increasing patient load will demand more megavoltage units, which may compromise the cost-effectiveness of this treatment. Only 4% of all clinical institutions have been involved in controlled clinical trials. To maintain a high level of RT service to other disciplines, RT treatment guidelines, quality control, and continuing medical education are required.

Consensus guidelines for radiation therapy of benign diseases - a multi-center approach

Consensus guidelines for radiation therapy of benign diseases - a multi-center approach

Strahlentherapie von gutartigen Erkrankungen: eine Bestandsaufnahme für Deutschland

Radiation therapy of benign diseases is controversially discussed and rarely applied in Anglo-American countries, while in other parts of the world, especially Central and East Europe, it is commonly practised for several benign disorders. Similar to the European Society of Therapeutic Radiology and Oncology survey, a patterns of care study was performed in Germany. A questionnaire was mailed in 3 years (1994, 1995, 1996) to all radiation facilities in Germany, which assessed equipment, indications, number of patients and treatment concepts. A total of 134 (88%) institutions returned all requested data: 22 in East and 112 in West Germany; 30 in university and 104 in community/private hospitals. The average data of each institution and of all institutions were analyzed for frequencies and ratios between different regions and institutions. A mean of 2 (range 1 to 7) megavoltage (Linac/Cobalt 60) and 1.4 (range 0 to 4) orthovoltage units were available per institution; 32 (24%) institutions had no orthovoltage equipment. A mean of 20,082 patients were treated per year: 456 (2%) for inflammatory diseases (221 hidradenitis, 78 nail bed infection, 23 parotitis, 134 not specified), 12,600 (63%) for degenerative diseases (2,711 peritendinitis humeroscapularis, 1,555 epicondylitis humeri, 1,382 heel spur, 2,434 degenerative osteoarthritis, 4,518 not specified), 927 (5%) for hypertrophic diseases (146 Dupuytren's contracture, 382 keloids, 155 Peyronie's disease, 244 not specified), 1,210 (6%) for functional disorders (853 Graves' orbitopathy, 357 not specified), and 4,889 (24%) for other disorders (e.g. 3,680 heterotopic ossification prophylaxis). In univariate analysis, there were significant geographical (West vs East Germany) differences in the use of radiotherapy for inflammatory and degenerative disorders and institutional differences (university vs community/private hospitals) in the use of radiotherapy for hypertrophic and functional disorders (p < 0.05). The prescribed dose concepts were mostly in the low dose range (< 10 Gy), but varied widely and inconsistently within geographic regions and institution types. Radiotherapy is a well accepted and frequently practised treatment for several benign diseases in Germany, however, there are significant geographical and institutional differences. As the number of orthovoltage units decreases, an increasing patient load is in demand of more megavoltage units, which may compromise the cost-effectiveness of this treatment. Only 4% of all clinical institutions are involved in controlled clinical trials. To maintain a high level of radiotherapy service to other disciplines, radiotherapy treatment guidelines, quality control and continuing medical education are required.

Radiation therapy for benign disease of the orbit

Benign diseases of the orbit can cause significant impairment of visual function through direct effects on the eye or supporting orbital tissues. Persistent moderate-to-severe inflammatory symptoms, diplopia, and visual loss may prompt therapeutic intervention. Low doses of external-beam irradiation (20 Gy in 2-Gy fractions) have an efficacy equivalent to corticosteroid medications in the treatment of both Graves' ophthalmopathy and orbital pseudotumor, with response rates of 50% to 80%. Appropriate patient selection, coordination with other medical subspecialties, and careful treatment planning are important in maximizing benefit from radiation therapy. In the case of Graves' ophthalmopathy, quantitative assessment of orbital disease severity and thyroid status as well as attainment of cross-sectional imaging should be performed before treatment. Patients whose thyroid disease is controlled but who have moderate-to-severe active orbital involvement can be offered orbital radiation therapy with a high likelihood of response. Stability of disease is generally obtained within 6 months; surgical correction of residual abnormalities may be required. For orbital pseudotumor, attainment of histological material before treatment is important in excluding benign or malignant systemic diseases, including malignant lymphoma. Genotypic abnormalities may exist in patients with reactive lymphoid hyperplasia, some of whom ultimately develop systemic lymphoma. Within the dose range recommended for treatment of Graves' ophthalmopathy and pseudotumor, late radiation effects on the retina or optic nerve should be nonexistent. Adequate lens shielding is required, however, to prevent cataract formation. This may require individualized treatment planning with computed tomography at the time of simulation. Pterygia recurrence after bare sclera excision occurs in at least 30% of cases, usually within 6 months of surgery. Radiation of the surgical bed using a strontium-90 source, beginning within 24 hours postoperatively, reduces the risk of recurrence substantially. Late scleral complications have been associated with large single-fraction treatments. To achieve maximal efficacy with minimal complications, fractionated treatment should be given by radiation oncologists experienced with the technique using sources calibrated by the National Bureau of Standards.

Radiation therapy for benign disease: an old area revisited

After expansion of the balloon causes mechanical injury to the intima, the internal elastic membrane, and the media, a mural thrombus develops because of platelet aggregation and fibrin deposition. A short time later (3–7 days) cells migrate into the intima and proliferate. Fibrosis and restenosis follow. Monocytes and macrophages may also be mediators in the process of retenosis. Radiation can inhibit postinjury neointimal proliferation, and preliminary data indicate that postangioplasty irradiation can reduce the restenosis rate to 17–25%. Rat and pig models of restenosis have been studied in this context. Delivery of about 15–20 Gy with iridium192 in high-dose-rate brachytherapy effectively inhibits intimal proliferation in pigs. Iridium-192 is a emitter, and so the cardiology team must leave the room during the actual procedure. -emitting isotopes, such as yttrium-90 and rhenium-188, have been used to deliver the radiation dose more rapidly and with lower radiation exposure risk to personnel. The endoluminal radiation can also be delivered at much lower dose rates with radioactive stents placed at the time of the angioplasty. All of the techniques described above for prophylaxis against restenosis result in heterogeneous radiation dose distributions across the abnormal vessel, especially for emitters and stents. External-beam radiotherapy provides more homogeneous dose delivery, although carefully tailored conformal fields, perhaps gated to the heart beat, would be needed to minimise the radiation dose to normal heart. Each of these approaches has its advantages and disadvantages, and it is too early to tell which will ultimately prove to be best in terms of medical outcome and cost-effectiveness. An experimental model has indicated that whether a 20 Gy dose can permanently prevent rather than merely postpone restenosis depends critically on the proliferative capacity of the injured normal tissue. Confirmation of this finding requires long-term follow-up beyond 2 years, which is missing in much of the animal work. Several clinical trials of the efficacy of radiation in preventing restenosis are in progress. The number of potential patients with wet-type macular degeneration and postangioplasty stenosis who might benefit from ionising radiation is greater than the number of cancer patients now receiving radiotherapy. The specialty treatment of human disease with ionising radiation was once called “radiation therapy”. Over the years it came to be called “radiation oncology”. It may be time to change it back.

Radiation therapy for benign diseases: A patterns of care study in 134 institutions in germany

Radiation therapy for benign diseases: A patterns of care study in 134 institutions in germany

Role of radiotherapy in benign diseases

Radiation therapy of benign diseases represent a wide panel of indications. Some indications are clearly identified as treatment of arteriovenous malformations (AVM), hyperthyroid ophtalmopathy, postoperative heterotopic bone formations or keloid scars. Some indications are under evaluation as complications induced by neo-vessels of age-related macular degeneration or coronary restenosis after angioplasty. Some indications remain controversial with poor evidence of efficiency as treatment of bursitis, tendinitis or Dupuytren's disease. Some indications are now obsolete such as warts, or contra-indicated as treatment of infant and children.

Calcium Status Following Neck Radiation Therapy in Hodgkin's Disease

Substantial evidence links the development of primary hyperparathyroidism with a medical history of neck radiation therapy for benign disease. This report concerns 220 patients with Hodgkin's disease seen at The University of Texas M. D. Anderson Hospital, Houston, treated with neck irradiation. Serum calcium levels had been analyzed two to 22 years after radiotherapy. Hyperparathyroidism was confirmed at surgery in one patient with hypercalcemia 15 years after radiotherapy. However, the maximum follow-up was 22 years and in a reported series the mean interval between irradiation and the development of hyperparathyroidism has ranged from 29 to 47 years. We conclude that patients who have received neck radiation therapy for malignant disease are not at an increased risk for the development of hyperparathyroidism in the first two decades following treatment but should continue to be screened for this development in subsequent decades.

Radiation-associated carcinoma of the salivary glands. A controlled study.

Five hundred fifty-four persons were evaluated who had received external radiation therapy for benign diseases of the head and neck in childhood and whose salivary glands were presumably included in the radiation field. A significant excess of salivary gland cancers were noted when they were compared to 958 nonirradiated control subjects.