Radiotherapy for non-malignant disorders: state of the art and update of the evidence-based practice guidelines.

Every year in Germany about 50,000 patients are referred and treated by radiotherapy (RT) for "non-malignant disorders". This highly successful treatment is applied only for specific indications such as preservation or recovery of the quality of life by means of pain reduction or resolution and/or an improvement of formerly impaired physical body function owing to specific disease-related symptoms. Since 1995, German radiation oncologists have treated non-malignant disorders according to national consensus guidelines; these guidelines were updated and further developed over 3 years by implementation of a systematic consensus process to achieve national upgraded and accepted S2e clinical practice guidelines. Throughout this process, international standards of evaluation were implemented. This review summarizes most of the generally accepted indications for the application of RT for non-malignant diseases and presents the special treatment concepts. The following disease groups are addressed: painful degenerative skeletal disorders, hyperproliferative disorders and symptomatic functional disorders. These state of the art guidelines may serve as a platform for daily clinical work; they provide a new starting point for quality assessment, future clinical research, including the design of prospective clinical trials, and outcome research in the underrepresented and less appreciated field of RT for non-malignant disorders.

[Possibilities and perspectives of quality management in radiation oncology]. / Möglichkeiten und Perspektiven des Qualitätsmanagements in der Radioonkologie.

The medical discipline radiation oncology and radiation therapy (treatment with ionizing radiation) has developed rapidly in the last decade due to new technologies (imaging, computer technology, software, organization) and is one of the most important pillars of tumor therapy. Structure and process quality play a decisive role in the quality of outcome results (therapy success, tumor response, avoidance of side effects) in this field. Since 2007 all institutions in the health and social system are committed to introduce and continuously develop a quality management (QM) system. The complex terms of reference, the complicated technical instruments, the highly specialized personnel and the time-consuming processes for planning, implementation and assessment of radiation therapy made it logical to introduce a QM system in radiation oncology, independent of the legal requirements. The Radiation Center Hamburg (SZHH) has functioned as a medical care center under medical leadership and management since 2009. The total QM and organization system implemented for the Radiation Center Hamburg was prepared in 2008 and 2009 and certified in June 2010 by the accreditation body (TÜV-Süd) for DIN EN ISO 9001:2008. The main function of the QM system of the SZHH is to make the basic principles understandable for insiders and outsiders, to have clear structures, to integrate management principles into the routine and therefore to organize the learning processes more effectively both for interior and exterior aspects.

[The role of external beam radiation therapy in the adjuvant treatment of pigmented villonodular synovitis]. / Stellenwert der externen Radiotherapie bei der adjuvanten Behandlung der pigmentierten villonodulären Synovitis.

AIM: Pigmented villonodular synovitis (PVNS) is a rare proliferative disorder arising from synovial cells of the tendon sheets and joint capsules. The potential value of external beam radiation therapy in the interdisciplinary management of PVNS is demonstrated by a comprehensive literature review on the clinical use of radiotherapy and the results of national patterns of care study (PCS) which was conducted by the German Cooperative Group on Radiotherapy in Benign Diseases (GCG-BD) in 2008-2009. MATERIAL AND METHOD: A structured questionnaire was mailed to all 227 RT institutions in Germany to assess all previous treatments, the RT indication and techniques, the rate of local control, the functional outcome and the possible adverse effects related to the use of external beam radiation therapy (RT). For comparison of the clinical outcome data, a systematic literature research in several international electronic databases and a conventional library search were performed to identify publications addressing the use of RT for PVNS. RESULTS: Based on an overall response rate of 83.2%, the PCS was nationally representative. Ten percent of institutions presented clinical experience with the use of RT for PVNS; from this database a total of 41 treated sites from 14 institutions were evaluable for long-term analysis. The primary therapeutic approach was cytoreductive surgery in all cases. In cases of residual tissue or complete resection of extensive local recurrences, RT was applied in 39 cases (95.1%). An excellent or good functional outcome was noted in 34 cases (82.9%). The use of RT was not associated with early or late toxicity larger than RTOG grade II. The literature review identified 19 published studies (1940-2009) which represented a total of 140 cases or patients, respectively. After follow-up periods ranging from 1-250 months and administration of total doses in the range of 16-50 Gy the overall rate of local control was 84.5%. CONCLUSION: Both the results of the national PCS and the literature review demonstrate that RT is a very safe and effective treatment option for the prevention of disease progression or recurrence in PVNS after primary surgical interventions. The planned treatment volume should include the whole synovial space and eventually all invasive components of the disease. Currently, total doses in the range of 30-36 Gy are recommended.

[Acute and chronic side effects of local radiotherapy]. / Strahlenreaktionen bei der Behandlung von Tumorpatienten. Die kritischen Punkte der Radiotherapie.

Local radiotherapy of a tumor is frequently applied in combination with chemotherapy or surgical measures. Possibly occurring toxicity must therefore be considered within the overall context. The radiosensitivity of the various organs is dependent on the sensitivity of the respective stem or mature end cells, and shows considerable differences within the individual cell systems. Apart from the application of prophylactic procedures, some radiation sequelae can be ameliorated by initiating specific measures (e.g. cosmetic products, drug treatment).

[Endourethral brachytherapy for the prevention of recurrent strictures following internal urethrotomy]. / Endoluminale Brachytherapie zur Vorbeugung von rezidivierenden Strikturen nach Urethrotomia interna.

METHODS AND MATERIALS: Between November 2000 and December 2002 endoscopic incision or transurethral scar resection was followed by endourethral brachytherapy (BT) which was performed in patients with recurrent bulbar strictures ( n=9), bladder neck stenosis after transurethral prostatectomy (TUR-P) ( n=3), anastomotic stricture after radical prostatectomy ( n=2) or penile urethral stricture ( n=1). High dose rate (HDR) iridium-192 BT started on the day of the endoscopic incision or resection and continued for the following 3 days. The BT fractionation scheme was 4x3 Gy in the first three patients (until first relapse) and 4x4 Gy in all following patients. The dose was calculated at 3 mm tissue depth using 3-dimensional CT-planning. As of February 2004, the median follow-up of all patients reached 22 months. RESULTS: Seven of 15 patients (46%) are recurrence free. In two patients (13.3%), recurrent strictures developed 12 month later, outside of the region of initial treatment. In six patients (40%) the treatment was considered to be unsuccessful as recurrent strictures were found between 2 and 12 months after the initial or second course of treatment. CONCLUSION: Endourethral brachytherapy after endoscopic incision or resection is a promising treatment for the prevention of recurrent strictures of the urethra, bladder neck or vesicourethral anastomosis. The initial results have been very good, but with longer follow-up recurrence occurred in the irradiated area in 40% of patients. Prospective randomized studies in patients with a strictly defined type of recurrent stricture, or even after the first internal urethrotomy, should be done in the future.

[Radiotherapy of osteoarthritis. Indication, technique and clinical results]. / Radiotherapie von Arthrosen. Indikation, Technik, klinische Ergebnisse.

Regarding orthopedic topics, radiotherapy of degenerative joint disorders is actually not well researched. So far, adequate long-term observations and reliable assessment of symptoms according to objective orthopedic criteria are still missing. From 1984 to 1994, 85 patients with symptomatic knee joint and hip joint osteoarthritis as well as omarthritis and rhizarthritis were treated. A total of 73 patients or 103 joints (due to bilateral symptoms) were documented in a long-term follow-up using orthopedic scores including objective criteria. Of the patients previously resistant to therapy, 63% responded to RT. Endoprosthetic surgery was necessary for only three patients. With regard to the endpoints "complete pain relief" or "major pain relief," only the parameter "symptom exists 2 years or more" indicated a significantly negative prognosis in multivariate analysis ( p<0.05). Radiotherapy of degenerative joint disorders is an effective alternative treatment for refractory osteoarthritis compared to conventional conservative treatment options.

[Value of radiotherapy in breast cancer. Breast preservation rises to 80%]. / Stellenwert der Strahlentherapie beim Mammakarzinom. Brusterhaltung in bis zu 80%!

The indication for radiotherapy for mamma carcinoma is determined in particular by the macroscopic and microscopic tumor findings, the number of lymph nodes identified, receptor status, the surgical report and (neo)adjuvant chemotherapy. Irradiation is applied in particular in conjunction with breast-preserving first-line treatment in the case of ductal in situ carcinomas, and postoperatively following breast conservation in the case of invasive mamma carcinoma. The indication for irradiation following mastectomy is controversial and is determined by tumor size and location, together with further factors (see the Guidelines of the German Society of Senology). The indications applying to the irradiation of regional lymph nodes are determined by the sites of the respective metastases. The combination of radio- and chemotherapy is carried out in close cooperation between oncologists and radiologists.

[Adjuvant therapy concepts in advanced stomach carcinoma. Future treatment not without irradiation?]. / Adjuvante Therapiekonzepte beim fortgeschrittenen Magenkarzinom. Künftig nicht ohne Bestrahlung?

Perforation of the wall of the stomach, or positive lymph nodes appreciably worsens the prognosis of resected gastric carcinoma. In such a situation, neither adjuvant chemotherapy [12] nor optimal lymph node resection achieves a significant improvement in overall survival [5-8]. In contrast, a significant benefit of adjuvant radiochemotherapy after curative resection of advanced gastric carcinoma has been demonstrated. Thus, standardized postoperative radiochemotherapy should be applied after standardized surgery with a D1 resection. Optimal supportive treatment, that is, at least 1500 kcal/day, appropriate treatment of reflux or dumping symptoms, and supplementation for iron, vitamin B12 and calcium deficiency, is mandatory, if therapeutic success is not to be compromised [13,14].

Radiation prophylaxis for heterotopic ossification about the hip joint--a multicenter study.

PURPOSE: Prophylactic radiotherapy (RT) can prevent ectopic bone formation about the hip after total hip arthroplasty. The German Cooperative Group on Radiotherapy for Benign Diseases conducted a patterns of care study about this indication addressing the involved institutions, RT dose concepts, clinical handling, and treatment outcome of prophylactic RT about the hip joint. METHODS AND MATERIALS: In 1999, a patterns of care study was conducted in all German institutions to analyze the accrual pattern, number of patients, and different indications for the use and performance of prophylactic RT about the hip. The applied RT concepts of prophylactic RT were evaluated with regard to the RT technique, timing of RT (pre- or postoperative), RT dose prescription (median, range of single and total doses), and treatment outcome. All institutions were asked about the radiologic and functional failure rates at least 1 year after the completion of RT using the established radiologic (Brooker) and functional (Harris) scores with objective and subjective evaluation components. RESULTS: One hundred fourteen institutions reported their clinical experience with prophylactic RT for the prevention of heterotopic ossification about the hip joint: 70 community hospitals, 23 university hospitals, and 21 private RT practices. In 1999, 5677 patients (5989 hips) had received prophylactic RT. The median number per institution was 36 patients (range 8-240). The interdisciplinary referral included orthopedic surgery (89 institutions; 3763 patients), trauma surgery (82 institutions; 1611 patients), or other disciplines (8 institutions; 298 patients). Preoperative RT was applied in 53 institutions 0.5-24 h before surgery, and postoperative RT was applied in 54 institutions 1-120 h after surgery. Most patients received 1 x 7 Gy either pre- or postoperatively. The total dose range was 5-10 Gy (preoperative RT) or 5-16 Gy (postoperative RT); the median total RT dose of both RT concepts was 7 Gy. Cobalt-60 (n = 15), linear accelerators (n = 95), and a few lower energy units (n = 4) were used. Bony structures or prostheses were shielded with standard blocks in 31 and with individual blocks in 27 institutions. Long-term clinical evaluation was available in 30 institutions from 4377 hips. Of those, 475 (11%) developed radiologic failures according to Brooker's criteria. Functional hip evaluation was available in 5 institutions from 685 hips. Of those, 34 (5%) had functional failures according to the criteria of Harris. No difference in outcome was found between pre- and postoperative RT, but was with regard to the patient's referral and the timing of RT. The patients who were treated >8 h before surgery or >72 h after surgery experienced a higher radiologic failure rate; radiologic failures were an important precondition for functional failures (p <0.05). CONCLUSION: This patterns of care study comprises the largest number of cases reported for prophylactic hip RT to date. The results reveal that both preoperative (within 24 h) and postoperative RT (within 72 h) are effective in preventing heterotopic ossification after hip surgery. Both RT concepts achieved a similar low radiologic and functional failure rate. Single-dose RT concepts, especially, can be recommended as an excellent treatment alternative for patients with contraindications to long-term steroid or nonsteroidal anti-inflammatory agents, and this approach has become standard in most German RT institutions.

[Radiotherapy and bisphosphonate therapy in bone metastases of prostate carcinoma]. / Strahlen- und Bisphosphonat-therapie des ossär metastasierenden Prostatakarzinoms.

Prostate carcinoma patients with bone metastases do not have a dismal prognosis or short life expectancy by itself. Thus, often palliative therapeutic measures are required with respect of a life span beyond one year, especially if no lyphogenic or visceral metastases have developed. Similarly to patients with breast carcinoma the metastatic bone lesions in prostate carcinoma patients have mixed osteolytic and osteoblastic features with increased metabolic bone turn-over. This is the mechanism, in which bisphosphonates interfere and can prevent the pathologic bone resorption by blocking osteoclast activity. This improves not only painful clinical conditions but also reduces the rate of skeletal related events (SRE = hypercalcemia, bone fracture, myelon compression, surgery or radiotherapy to bone etc.). Generally, clinical studies suggest the benefit of bisphosphonates for patients with bone metastases and good life expectancy. For patients with prostate carcinoma large controlled studies have to consolidate this potential benefit.

[Radiotherapy for basal cell carcinoma. Local control and cosmetic outcome]. / Strahlentherapie des Basalzellkarzinoms. Lokale Kontrolle und kosmetisches Ergebnis.

BACKGROUND: The basal cell carcinoma which is often occurring in the elderly can be well treated by surgery. For large and recurrent lesions and in cosmetically difficult locations external beam radiotherapy provides an equally effective treatment alternative. PATIENTS AND METHODS: From 1986 to 1999, 60 females and 39 males received primary radiotherapy for a total of 127 histologically verified basal cell carcinoma lesions. Tumors were mostly localized in the face at the temple, nose and forehead. Radiotherapy was applied with orthovoltage equipment and energies of up to 100 kV. Single doses ranged from 2 to 5 Gy related to the 80%-isodose depth. Weekly doses ranged from 8 to 25 Gy and total doses from 25 to 60 Gy. The mean follow-up period was 36 +/- 21 months. The acute sequelae were scored according to CTC criteria. Radiogenic late effects as single events were related to the radiation portal. RESULTS: 3 months after treatment all besides one patient (99%) experienced complete tumor remission (CR). In all cases, acute radiation reaction occurred within the radiation portal: CTC Grade 1 in 100%, CTC Grade 2 in 54% and CTC Grade 3 in 30% of the cases. All side effects regressed under simple local measures without further complications. Late sequelae were observed in three cases. Overall cosmetic outcome was good to excellent in almost all patients (98%). In two cases (2%) a local recurrence was observed 6 and 20 months after radiotherapy. CONCLUSION: External beam (orthovoltage) radiotherapy is very effective and yields high tumor control rates and good cosmetic results in long-term follow-up. Former dermatological treatment concepts should be replaced by an ICRU-based radiophysical dose prescription and should respect the newer radiobiological fractionation principles.

[Optimization of radiotherapy in Dupuytren's disease. Initial results of a controlled trial]. / Optimierung der Radiotherapie bei Morbus Dupuytren. Erste Ergebnisse einer kontrollierten Studie.

PURPOSE: Radiotherapy prevents progression of Dupuytren's contracture. Herein, 1-year results of a prospective randomized trial comparing 2 different dose concepts are presented. PATIENTS AND METHODS: 129 patients (67 males, 62 females) were included in the study with a minimum 1-year follow-up: 69 had bilateral and 60 unilateral involvement of Dupyutren's disease accounting for 198 irradiated hands. According to Tubiana, 73 hands had Stage N, 61 Stage N/I (< or = 10 degrees flexion deformity), 59 Stage I (11 to 45 degrees) and 5 Stage II disease (46 to 90 degrees). Radiotherapy was randomly delivered: group A (63 patients/95 hands) received 10 times 3 Gy (total: 30 Gy) in 2 series (each 5 times 3 Gy) separated by 8 weeks; group B (66 patients/103 hands) received 7 times 3 Gy (total: 21 Gy) within 2 weeks. Orthovoltage radiotherapy (120 kV) with 40 cm standard cones and individual shielding was applied. Patient and disease parameters were equally distributed in both groups. Evaluation (toxicity, efficacy) was performed at 3 and 12 months with regard to subjective (patient's opinion) and objective parameters (palpation, measurements, comparative photographs--physician). RESULTS: Acute toxicity was minimal: 76 (38%) hands had skin reactions CTC Grade 1, 12 (6%) CTC Grade 2. Chronic side effects (dryness, skin atrophy, change of sensation, LENT Grade 1) occurred in 9 (5%) hands without differences between treatment groups. At 3 and 12 months follow-up, subjective symptoms and objective signs, nodules and cords, were reduced in both groups (p < 0.01) with no differences between groups: a total of 110 (55%) hands (group A: 55, group B: 55) regressed, 74 (37%) hands (group A: 35; group B: 39) were stable. Overall and mean number of nodules, cords and skin changes decreased at 3 and 12 months. 16 of 198 (8%) hands (group A: 7; group B: 9) progressed at 12 months follow-up ("treatment failure"); at 1 year, 7 of 60 patients with unilateral Dupyutren's disease required prophylactic radiotherapy for the contralateral hand due to disease progression. CONCLUSIONS: Prophylactic radiotherapy reduces symptoms and prevents disease progression in early-stage Dupyutren's disease. Both treatment concepts are well-tolerated and equally effective. Acute toxicity is slightly increased with treatment concept B (7 times 3 Gy), while chronic sequelae are low in both treatment groups. Long-term evaluation with follow-up of more than 5 years has to be awaited to recommend one or the other dose concept.

[Chronic radiation effects on dental hard tissue (radiation caries). Classification and therapeutic strategies]. / Chronische Strahlenfolgen an den Zahnhartgeweben ("Strahlenkaries"). Klassifikation und Behandlungsansätze.

OBJECTIVES: Since the first description of rapid destruction of dental hard tissues following head and neck radiotherapy 80 years ago, "radiation caries" is an established clinical finding. The internationally accepted clinical evaluation score RTOG/EORTC however is lacking a classification of this frequent radiogenic alteration. MATERIAL AND METHODS: Medical records, data and images of radiation effects on the teeth of more than 1,500 patients, who underwent periradiotherapeutic care, were analyzed. Macroscopic alterations regarding the grade of late lesions of tooth crowns were used for a classification into 4 grades according to the RTOG/EORTC guidelines. RESULTS: No early radiation effects were found by macroscopic inspection. In the first 90 days following radiotherapy 1/3 of the patients complained of reversible hypersensitivity, which may be related to a temporary hyperemia of the pulp. It was possible to classify radiation caries as a late radiation effect on a graded scale as known from RTOG/EORTC for other organ systems. This is a prerequisite for the integration of radiation caries into the international nomenclature of the RTOG/EORTC classification. CONCLUSIONS: The documentation of early radiation effects on dental hard tissues seems to be neglectable. On the other hand the documentation of Late radiation effects has a high clinical impact. The identification of an initial lesion at the high-risk areas of the neck and incisal part of the tooth can lead to a successful therapy as a major prerequisite for orofacial rehabilitation. An internationally standardized documentation is a basis for the evaluation of the side effects of radiooncotic therapy as well as the effectiveness of protective and supportive procedures.