Updated strategies in the treatment of benign diseases-a patterns of care study of the german cooperative group on benign diseases.

PURPOSE: Radiation therapy (RT) is a common treatment for benign diseases in Germany. Because the treatment concepts are inconsistent, we conducted this pattern-of-care study on behalf of the German Cooperative Group on Benign Diseases to evaluate treatment standards in Germany. METHODS AND MATERIALS: Questionnaires were mailed to all radiation therapy facilities in Germany. We assessed the treatment equipment, annual number of patients, treatment indications, and, in particular, treatment strategies in patients with benign diseases in 2014. RESULTS: We evaluated questionnaires returned by 116 participating institutions, of which 41 were ambulatory health care centers, 28 were private institutions, 27 were community hospitals, and 20 were university hospitals. On average, 2 linac accelerators and 2 megavoltage units were available in each institution. In 2014, a total of 36,830 patients were treated for benign diseases: 16,989 for degenerative diseases (peritendinitis humeroscapularis n = 2691; epicondylitis humeri n = 3788; heel spur n = 10,510); 14,936 for osteoarthritis (coxarthrosis n = 2230; gonarthrosis n = 2623; omarthrosis n = 2691; rhizarthrosis n = 2440; polyarthrosis n = 2297; others n = 2655); 1563 for hyperproliferative diseases (morbus Dupuytren n = 960; morbus Ledderhose n = 441; keloids n = 139; pterygium of the conjunctiva n = 3; other hyperproliferative diseases n = 20); 2440 for functional disorders (gynecomastia n = 843; Graves' disease n = 205; lymphatic fistula n = 178; heterotopic ossification prophylaxis n = 1214); 859 for stereotactic RT in the central nervous system (arteriovenous malformation n = 53; meningioma n = 425; acoustic neuroma n = 201; pituitary adenoma n = 131; others n = 49), and 43 for rare indications (pigmented villonodular synovitis n = 20 or vertebral hemangioma n = 23). The mean whole dose was <10 Gy in the treatment of degenerative disorders, 25 Gy for hyperproliferative diseases, 15 Gy for functional disorders, and <50 Gy for stereotactic RT. CONCLUSIONS: In 2014, RT had an important role in the treatment of benign diseases. Because treatment concepts are inherent, we recommend treatment based on the guidelines written by the German Cooperative Group on Benign Diseases.

Planning benchmark study for SBRT of early stage NSCLC : Results of the DEGRO Working Group Stereotactic Radiotherapy.

PURPOSE: The aim was to evaluate stereotactic body radiation therapy (SBRT) treatment planning variability for early stage nonsmall cell lung cancer (NSCLC) with respect to the published guidelines of the Stereotactic Radiotherapy Working Group of the German Society for Radiation Oncology (DEGRO). MATERIALS AND METHODS: Planning computed tomography (CT) scan and the structure sets (planning target volume, PTV; organs at risk, OARs) of 3 patients with early stage NSCLC were sent to 22 radiotherapy departments with SBRT experience: each department was asked to prepare a treatment plan according to the DEGRO guidelines. The prescription dose was 3 fractions of 15 Gy to the 65% isodose. RESULTS: In all, 87 plans were generated: 36 used intensity-modulated arc therapy (IMAT), 21 used three-dimensional conformal radiation therapy (3DCRT), 6 used static field intensity-modulated radiation therapy (SF-IMRT), 9 used helical radiotherapy and 15 used robotic radiosurgery. PTV dose coverage and simultaneously kept OARs doses were within the clinical limits published in the DEGRO guidelines. However, mean PTV dose (mean 58.0 Gy, range 52.8-66.4 Gy) and dose conformity indices (mean 0.75, range 0.60-1.00) varied between institutions and techniques (p ≤ 0.02). OARs doses varied substantially between institutions, but appeared to be technique independent (p = 0.21). CONCLUSION: All studied treatment techniques are well suited for SBRT of early stage NSCLC according to the DEGRO guidelines. Homogenization of SBRT practice in Germany is possible through the guidelines; however, detailed treatment plan characteristics varied between techniques and institutions and further homogenization is warranted in future studies and recommendations. Optimized treatment planning should always follow the ALARA (as low as reasonably achievable) principle.

Radiotherapy for aneurysmal bone cysts : A rare indication.

BACKGROUND: Aneurysmal bone cysts (ABC) are rapidly growing benign osseous lesions composed of blood-filled channels separated by fibrous septa. Since the value of external beam radiotherapy (EBRT) for ABC has not been well defined, the German Cooperative Group on Radiotherapy for Benign Diseases performed the national register study described herein. PATIENTS AND METHODS: Five German institutions collected data regarding clinical features, treatment concepts, and outcome for patients with ABC who had been referred for local EBRT over the past 30 years. RESULTS: Between 1990 and 2015, 10 patients with ABC were irradiated (5 female/5 male). Median age was 23 years (range 14-40 years). Involved sites were: spine (n = 3), sacrum/pelvis (n = 2), shoulder/scapula (n = 2), humerus (n = 1), femur (n = 1), and radius (n = 1). The median EBRT total and fractional doses were 28 Gy (range 5-40 Gy) and 2 Gy (range 1-2 Gy), respectively. Median follow-up was 65 months (range 12-358 months). Persistent pain relief was achieved for all patients. However, long-term follow-up response data were only available for 7/10 patients. All 7 patients exhibited a radiological response and experienced no recurrent disease activity or pain during follow-up. Acute and late radiogenic toxicities ≥ grade 3 and secondary malignancies were also not observed. CONCLUSION: Primary or adjuvant EBRT seems to be an effective and safe treatment option for persistent or recurrent ABC. Fractionated doses below 30 Gy may be recommended.

Stereotactic radiosurgery for treatment of brain metastases. A report of the DEGRO Working Group on Stereotactic Radiotherapy.

BACKGROUND: This report from the Working Group on Stereotaktische Radiotherapie of the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) provides recommendations for the use of stereotactic radiosurgery (SRS) on patients with brain metastases. It considers existing international guidelines and details them where appropriate. RESULTS AND DISCUSSION: The main recommendations are: Patients with solid tumors except germ cell tumors and small-cell lung cancer with a life expectancy of more than 3 months suffering from a single brain metastasis of less than 3 cm in diameter should be considered for SRS. Especially when metastases are not amenable to surgery, are located in the brain stem, and have no mass effect, SRS should be offered to the patient. For multiple (two to four) metastases--all less than 2.5 cm in diameter--in patients with a life expectancy of more than 3 months, SRS should be used rather than whole-brain radiotherapy (WBRT). Adjuvant WBRT after SRS for both single and multiple (two to four) metastases increases local control and reduces the frequency of distant brain metastases, but does not prolong survival when compared with SRS and salvage treatment. As WBRT carries the risk of inducing neurocognitive damage, it seems reasonable to withhold WBRT for as long as possible. CONCLUSION: A single (marginal) dose of 20 Gy is a reasonable choice that balances the effect on the treated lesion (local control, partial remission) against the risk of late side effects (radionecrosis). Higher doses (22-25 Gy) may be used for smaller (< 1 cm) lesions, while a dose reduction to 18 Gy may be necessary for lesions greater than 2.5-3 cm. As the infiltration zone of the brain metastases is usually small, the GTV-CTV (gross tumor volume-clinical target volume) margin should be in the range of 0-1 mm. The CTV-PTV (planning target volume) margin depends on the treatment technique and should lie in the range of 0-2 mm. Distant brain recurrences fulfilling the aforementioned criteria can be treated with SRS irrespective of previous WBRT.

Radiotherapy in langerhans cell histiocytosis - a rare indication in a rare disease.

INTRODUCTION: Langerhans Cell Histiocytosis (LCH) represents a rare benign disorder, previously designated as "Histiocytosis X", "Type II Histiocytosis" or "Langerhans Cell Granulomatosis". Clinical presentation includes osteolysis, ulcerations of skin and soft tissues but also involvement of the CNS is described.Because treatment concepts are not well defined the German Cooperative Group on Radiotherapy for Benign Diseases performed a retrospective analysis. METHODS AND MATERIAL: Eight closely cooperating centres collected patients' data of the past 45 years. As study endpoints disease free survival, recurrent disease, death and therapy related side effects were defined. RESULTS: A total of 80 patients with histologically proven LCH were irradiated within the past 45 years. According to the LCH classification of Greenberger et al. 37 patients had stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb and the median age was 29 years. The median Follow up was 54 months (range 9-134 months). A total of 39 patients had a surgical intervention and 23 patients a chemotherapy regimen.Radiation treatment was carried out with a median total dose of 15 Gy (range 3-50.4 Gy). The median single fraction was 2 Gy (range 1.8-3 Gy).Overall, 77% patients achieved a complete remission and 12.5% achieved a partial remission. The long-term control rate reached 80%. Within an actuarial overall 5-year survival of 90% no radiogenic side and late effects ≥EORTC/RTOG II° were observed. CONCLUSION: In the present study a large collective of irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe treatment option and even low RT doses show sufficient local control.

Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net.

Langerhans Cell Histiocytosis (LCH) is an orphan disease of clonal dendritic cells which may affect any organ of the body. Most of the knowledge about the diagnosis and therapy is based on pedriatic studies. Adult LCH patients are often evaluated by physicians who focus on only the most obviously affected organ without sufficient evaluation of other systems, resulting in patients being underdiagnosed and/or incompletely staged. Furthermore they may be treated with pediatric-based therapies which are less effective and sometimes more toxic for adults. The published literature on adult LCH cases lacks a comprehensive discussion on the differences between pediatric and adult patients and there are no recommendations for evaluation and comparative therapies. In order to fill this void, a number of experts in this field cooperated to develop the first recommendations for management of adult patients with LCH. Key questions were selected according to the clinical relevance focusing on diagnostic work up, therapy, and follow up. Based on the available literature up to December 2012, recommendations were established, drafts were commented by the entire group, and redrafted by the executive editor. The quality of evidence of the recommendations is predominantly attributed to the level of expert opinion. Final agreement was by consensus.

Radiotherapy for prevention and therapy of gynecomastia due to antiandrogen treatment in prostate cancer patients: a patterns-of-care study.

BACKGROUND: Gynecomastia is a frequent side effect of antiandrogen therapy for prostate cancer and may compromise quality of life. Although it has been successfully treated with radiotherapy (RT) for decades, the priority of RT as a preferred treatment option has recently been disputed as tamoxifen was also demonstrated to be effective. The aim of the present paper is to provide an overview of indications, frequency, and technique of RT in daily practice in Germany, Switzerland, and Austria. PATIENTS AND METHODS: On behalf of the DEGRO-AG GCG-BD (German Cooperative Group on Radiotherapy of Benign Diseases) a standardized questionnaire was sent to 294 RT institutions. The questionnaires inquired about patient numbers, indications, RT technique, dose, and - if available - treatment results. Moreover, the participants were asked whether they were interested in participating in a prospective study. RESULTS: From a total of 294 institutions, 146 replies were received, of which 141 offered RT for gynecomastia. Seven of those reported prophylactic RT only, whereas 129 perform both preventive and symptomatic RT. In 110 of 137 departments, a maximum of 20 patients were treated per year. Electron beams (76%) were used most often, while 24% of patients received photon beams or orthovolt x-rays. Total doses were up to 20 Gy for prophylactic and up to 40 Gy for therapeutic RT. Results were reported by 19 departments: prevention of gynecomastia was observed in 60-100% of patients. Only 13 institutions observed side effects. CONCLUSION: Prophylactic and symptomatic RT is widely used in the German-speaking countries, but patient numbers are small. The clinical results indicate that RT is a highly effective and well-tolerated treatment.

Radiotherapy of splenomegaly : a palliative treatment option for a benign phenomenon in malignant diseases.

PURPOSE: Since the 20(th) century, radiotherapy (RT) has been used for treatment of symptomatic splenomegaly (SM). SM occurs in association with hematologic disorders. The purpose of this analysis was to determine the indication, treatment concepts, and efficiency of RT. MATERIAL AND METHODS: Clinical features, treatment concepts, and outcome data during the past 20 years were analyzed. Endpoints were pain relief, symptomatic and hematological response, and treatment-related side effects. RESULTS: From 1989-2009, a total of 122 patients received 246 RT courses because of symptomatic SM. Overall 31 patients had chronic myelogenous leukemia (CML), 37 had chronic lymphocytic leukemia (CLL), 23 had osteomyelofibrosis (OMF), 17 had polycythemia vera (PV), 5 had acute myelogenous leukemia, 4 had idiopathic thrombocytopenic purpura (ITP), 3 had non-Hodgkin lymphoma (NHL), and 2 had multiple myeloma (MM). Patients were treated with (60)Co gamma rays or 5-15MV photons. The fraction size ranged from 10-200 cGy and the total dose per treatment course from 30-1600 cGy. Significant pain relief was achieved for 74.8% of the RT courses given for splenic pain. At least 50% regression was attained for 77% of the RT courses given for SM. 36 patients died within 2 months due to the terminal nature of their disease. Of the RT courses applied for cytopenia, 73.6% achieved a significant improvement of hematological parameters and reduction of transfusion need. Notable hematologic toxicities were reported < EORTC/RTOG II°. CONCLUSION: The present analysis documents the efficacy of RT. In addition, RT as a palliative treatment option for symptomatic SM should not be forgotten.

[Training in radiation oncology in Germany. Current status and necessary developments]. / Weiterbildung zum Facharzt für Strahlentherapie in Deutschland : Aktueller Status und notwendige Entwicklungen.

BACKGROUND AND PURPOSE: A sufficient number of well-trained specialists in radiation oncology is needed for an adequate supply in radiation oncology. Therefore, the training in radiation oncology is of utmost importance. This requirement is faced with a growing lack of physicians in Germany. The aim of this study was to characterize the current situation of radiation oncology training in Germany and to work out proposals to avoid a lack of radiotherapists. MATERIAL AND METHODS: In summer 2008, 233 questionnaires were sent out to potential trainers in radiation oncology in Germany. The questions included, among others, the individual training situation and problems in finding physicians. A second questionnaire was addressed to trainees in radiation oncology and contained, e.g., questions regarding satisfaction, motivation for the choice of radiation oncology, a previous work in another discipline, and future perspectives. RESULTS: Answers were obtained from 107 supervisor physicians of whom 84.1% had the permission to employ trainees in radiation oncology. The finding of new trainees provided large problems in 47.1%; 35.3% had few and 17.6% no problems. For specialists in radiation oncology, 47.2% reported large, 26.4% few and 26.4% no problems in finding candidates. 113 trainees answered the questionnaires. Almost half of them (46.9%) had previously worked in another discipline. The majority was quite (44.2%) or fully (46.0%) satisfied with their job, 84.1% stated good up to excellent future perspectives. The vast majority (88.5%) would decide for a training in radiation oncology again. CONCLUSION: Trainees in radiation oncology in Germany are satisfied with their training, see good future perspectives and would again decide to do their training in radiation oncology. However, there are large problems in finding candidates for open jobs. A positive promotion is recommended to face these problems.

Radiotherapy for Peyronie's Disease: a European survey.

BACKGROUND AND PURPOSE: Peyronie's Disease (PD) is a benign condition characterized by penile nodules, pain and curvature. Radiotherapy has been used for many years with positive outcomes, however all studies published were non-randomized or non-controlled. The purpose of this survey was to understand which treatment policy is followed in Europe before setting up a randomized trial. MATERIALS AND METHODS: A questionnaire was sent out to 908 European radiotherapy institutions, 402 questionnaires were sent back and filled out correctly (44.5%). The questionnaire consisted of different items, regarding number of patients referred, fraction dose, total dose and technique used, and eventually treatment outcome of clinical trials. RESULTS: Seventy-three institutions irradiate PD (19%), 304 do not (81%). Reasons for not treating were insufficient referrals from urologists or no interest in treating benign diseases. The most common fraction dose is 2 (range 0.5-8) Gy and the total radiation dose 20 (range 3-30) Gy. Most of the institutions use electrons (n = 44) or orthovoltage (n = 32). Decreased pain is reported in about 80% of the cases, and side effects by eight institutions. CONCLUSIONS: So far, a large variation of treatment schedules for radiotherapy of PD has been detected in European countries. Although the results are good and side effects minimal, there is still a need to set up a European randomized trial to prospectively evaluate the efficacy of radiotherapy for PD.

Quality control of involved field radiotherapy in patients with early-favorable (HD10) and early-unfavorable (HD11) Hodgkin's lymphoma: an analysis of the German Hodgkin Study Group.

PURPOSE: The German Hodgkin Study Group (GHSG) set up a radiotherapy (RT) reference center within the Department of Radiation Oncology at the University of Cologne to undertake quality assurance of the group's clinical studies. In the HD10 trial (early-favorable stages) and HD11 trial (early-unfavorable stages) all patients received involved field (IF)-RT (30 Gy vs. 20 Gy) within a combined-modality approach. For these patients a central prospective review of all diagnostic imaging was performed by expert radiation oncologists to control disease extension and to define IF treatment volume. METHODS AND MATERIALS: On the basis of simulation films, verification films, and radiotherapy case report form (CRF) an expert panel evaluated retrospectively the adequacy of irradiated IF treatment portals according to the RT prescription, applied radiation doses, treatment time, and technical parameters. RESULTS: Between 1999 and 2006 a total of 825 of 1370 randomized patients of the HD10 trial (60%) and 954 of 1422 patients of the HD11 trial (67%) were evaluated by the panel. Radiotherapy was rated as suboptimal in 47% of all reviewed cases. Although the participating RT centers received a precise RT prescription, most difficulties occurred in the adequate coverage of the IF (40%), followed by technical faults (12%). Deviations from the prescribed single daily dose (1.8-2 Gy), weekly dose, and total reference dose were rare (1%). CONCLUSIONS: As a consequence of these findings, radiation oncologists were trained on the definition of IF-RT at GHSG meetings and at the annual meetings of the German Society for Therapeutic Radiation Oncology. Possible correlations between RT quality and relapse rate will be investigated.

Radiotherapy of non-malignant disorders: where do we stand?

During a consensus meeting in Nice the role of radiotherapy in benign disorders was discussed. Based on this meeting we categorized the indication into three categories: (A) accepted indication; (B) only accepted in clinical trial; (C) not accepted. The results of this consensus meeting are presented for disorders of the eye, joints and bones, brain and soft tissue.

Estimation of the carcinogenic risk of radiotherapy of benign diseases from shoulder to heel.

BACKGROUND AND PURPOSE: To estimate risk on fatal tumour induction in patients by radiotherapy of benign diseases at various body sites, including heterotopic ossification, omarthritis, gonarthrosis, heel spurs and hidradenitis suppurativa. MATERIAL AND METHODS: The carcinogenic risk is estimated by applying the effective dose concept from the ICRP with the average risk factor of 10% per Sv for high dose and high dose rate. Although, the concept of effective dose for the present study has limitations, its use is considered acceptable for a fairly rough risk estimate. The organ doses are calculated using a Monte Carlo radiation transport code and anthropomorphic mathematical phantoms. Special risk modifying factors like patient's age at exposure and gender are taken into account. RESULTS: For the treatment of heterotopic ossification, omarthritis, gonarthrosis, heel spurs and hidradenitis suppurativa the effective dose is in the range of 5-400 mSv. For an average-aged population, the estimated number of radiation-induced fatal tumours due to these treatments is assessed to be between 0.5 and 40 persons per 1000 patients treated. At higher ages the risks are reduced. CONCLUSIONS: The range of effective doses found for the various types of treatment at various body sites is large. There are several possibilities to optimise the treatment protocols resulting in reduced effective doses and related radiation risks.

Multimodality therapy including radiotherapy and chemotherapy improves event-free survival in stage C esthesioneuroblastoma.

BACKGROUND: To evaluate the efficacy of multimodality therapy in patients with esthesioneuroblastoma (ENB). PATIENTS AND METHODS: From 01/1979 through 08/2001, 47 patients with ENB (20 men, 27 women, age 5-81 years), were registered from 18 oncologic centers. There were 14 tumors stage B and 33 stage C according to the Kadish classification. Initial treatment included surgery alone in seven patients, radiotherapy (RT) with or without chemotherapy (CTX) in twelve, surgery plus postoperative RT in 15, and multimodality therapy (surgery plus pre- or postoperative CTX plus postoperative RT) in 13. RESULTS: The 5-year overall survival (OS) for the whole group was 64 +/- 8% and the 5-year event-free survival (EFS) 50 +/- 8%. Patients with multimodality treatment had a significantly better 5-year EFS (74 +/- 13%) compared to the other patients (41 +/- 9%; p = 0.05), while the 5-year OS was not significantly different between the treatment groups (p = 0.39). For patients with Kadish stage C, multimodality therapy (n = 11) resulted in superior 5-year EFS (72 +/- 14% vs 17 +/- 9%; p = 0.01). These patients tended to have an improved OS (69 +/- 15% vs 47 +/- 12%; p = 0.19) compared to the other treatment groups. None of the patients with multimodality treatment had a metastatic relapse. CONCLUSION: Multimodality treatment (surgery plus pre- or postoperative CTX plus postoperative RT) appears to be highly efficient in preventing local and systemic relapse in patients with advanced ENB. Timing and optimal agents of CTX need to be further evaluated.

[Ovarian suppression in the adjuvant treatment of breast cancer: GnRh analogs, ovariectomy or radio-castration--"the philosopher's stone" instead of "chamber of horrors"]. / Ovarielle Suppression in der adjuvanten Therapie des Mammakarzinoms: GnRH-Analoga, Ovarektomie oder Radiomenolyse--"Stein der Weisen" statt "Kammer des Schreckens"?

BACKGROUND: Ovarian suppression in the adjuvant treatment of perimenopausal women with breast cancer is an important option. The therapeutic goal can be accomplished by administration of GnRH-analogues, ovarectomy or radiocastration. PATIENTS AND METHODS: We describe the advantages and the therapy related side effects and compare the different treatment modalities with each other. RESULTS: Because of its reversibility and patient's compliance GnRH-analogues seem to be advantageous especially in younger premenopausal women. When longer term side effects of artificially induced menopause are less important, therapeutic alternatives such as radiocastration or ovarectomy are effective without obvious superiority between these options. CONCLUSION: Even in the background of the increasing use of GnRH-analogues radiocastration remains still a therapeutic alternative because of its cost-effectiveness and feasibility. This accounts especially for peri- or premenopausal women above the age of 45.