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.

Variation in "supraclavicular" lymph node depth is partly determined by treatment position.

BACKGROUND: The so-called "supraclavicular" region bears the confluence of deep jugular, upper mediastinal and axillary lymph node groups and therefore it is often part of the target volume in common malignancies like lung cancer, breast cancer and head and neck cancer. For treating this area, several authors recommend an anterior portal with the dose prescribed to a tissue depth of 3 cm, which does not fit our institution's experience. PATIENTS AND METHODS: In 119 consecutive patients a computed tomography for planning purposes was performed. We used the subclavian blood vessels between clavicula and first rib as an estimate of the confluence of the mentioned lymph node regions and determined their tissue depth (which does not describe the deepest part of the lymph vessels). RESULTS: Mean and median of the tissue depth were 5 cm in a range from 2 to 9 cm. Only in less than 20% of the measurements we found the vessels located 3 cm or less under the surface which would correspond to a depth of the lymph node target volume 4 to 5 cm. Increasing body mass resulted in deeper location of the vessels. The position of the patient's arms influenced the tissue depth even more. Arms risen above the head resulted in 55% of the measurements in tissue depths of 6 cm or deeper compared to 6% in patients treated with arms beside the body. CONCLUSION: Standardized treatment prescriptions do not cope adequately with individual anatomy. Treatment position especially of the arms influences location of the "supraclavicular" lymph node region in thoracic treatment. Target volume delineation by computed tomography seems the most accurate solution, although it is the most expensive one. Patient immobilization is crucial for accuracy of treatment delivery.

[Radiotherapy of non-malignant diseases: principles and recommendations]. / Strahlenbehandlung von nicht-malignen Erkrankungen: Grundsätze und Empfehlungen.

The plenty options and high quality of radiation therapy for non-malignant disorders is not well known outside the field of radiology. It is necessary to transfer this information to cooperating general practitioners, surgeons, orthopedics and other specialists. To warrant quality assurance and quality control and to allow a uniform performance of radiotherapy of non-malignant conditions, general guidelines and recommendations according to the German Working Group of Scientific Medical Societies are useful. This paper summarizes the essential aspects of radiotherapy for non-malignant diseases: indication of, informed consent for, documentation and conduct of radiation therapy for non-malignant diseases using orthovoltage equipment and specific recommendations for follow up examinations. Radiotherapy concepts for non-malignant diseases are summarized.

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.

[Radiotherapy of benign diseases: a pattern of care study in Germany]. / Strahlentherapie von gutartigen Erkrankungen: eine Bestandsaufnahme für Deutschland.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

[Radiotherapy of follicle center lymphoma. Results of a German multicenter and prospective study. Members of the Study Group "NHL-early stages"]. / Strahlenbehandlung von follikulären Keimzentrumslymphomen. Ergebnisse einer deutschen multizentrischen und prospektiven Studie. Mitglieder der Studiengruppe "NHL--frühe Stadien".

PURPOSE: Follicle centre lymphoma grade I, II (REAL) or centroblastic-centrocytic lymphoma (Kiel classification) present a well defined clinical entity from a clinical point of view. These lymphomas are not curable by chemotherapy in early or advanced stages. They are treated by radiation therapy in early stages, but up to now the curative potency of radiotherapy has not been confirmed by prospective clinical trials. PATIENTS AND METHODS: Between January 1986 and August 1993 117 adults with follicle centre lymphoma were recruited from 24 institutions to enter the multicentric prospective, not randomised clinical trial. Patients with histologically proven nodal follicle centre lymphoma of stages I, II and limited III were included. They were treated by a standardised radiotherapy regimen, in stage I by extended field and in stages II and III by total nodal irradiation. Dose per fraction was 1.8 to 2.0 Gy, in the abdominal bath 1.5 Gy up to a total dose of 26 Gy in adjuvant situation and 36 Gy to enlarged lymphoma. RESULTS: All patients developed a complete remission at the end of radiotherapy. Median follow-up is 68 months. Overall survival of all patients in 86 +/- 3% at 5 and 8 years. Stage adjusted survival at 5 and 8 years was 89% for stage I, 86% for stage II and 81% for III. Patients in stages I and II < 60 years had survival rates of 94% at 5 and 8 years, patients > 60 years 63% (p < 0.0001). Recurrence free survival of all patients is 70% at 5 and 60 +/- 5% at 8 years. The number of recurrences is high with 29% at 5 and 41% at 8 years. All recurrences were seen within 7 years. The probability of localised nodal in-field recurrences is 11% and 22% at 5 and 8 years, respectively. Adverse prognostic factors were identified by multivariate analysis: age > 60 years, treatment breaks > or = 7 days and dose deviations > 20% from prescribed doses. Acute side effects of extended field irradiation were moderate. CONCLUSIONS: On the basis of these results radiotherapy is a potentially curative therapeutic approach in stages I, II and limited III of follicle centre lymphoma. The optimal technique is total lymphoid irradiation with doses of 30 Gy in the adjuvant situation and 40 to 44 Gy in enlarged lymphomas. The number of local recurrences leads to the assumption, that the extension of radiotherapy to the total lymphoid system might reduce their frequency.

Extended field and total central lymphatic radiotherapy in the treatment of early stage lymph node centroblastic-centrocytic lymphomas: results of a prospective multicenter study. Study Group NHL-frühe Stadien.

BACKGROUND: A prospective multicenter trial was performed to evaluate survival, patterns of relapse, and toxicity for clinically staged patients with lymph node centroblastic-centrocytic (cb/cc) lymphomas in Stages I-IIIA after large extended field irradiation (EFI) or total central lymphatic irradiation (TCLI). METHODS: Between January 1986 and August 1993, 117 adults with clinical Stage I-IIIA lymph node cb/cc lymphoma (Kiel classification) were recruited. Patients in Stages I or II with mediastinal, hilar, periaortic, iliac, or mesenteric involvement and in Stage IIIA received TCLI, whereas patients with more peripherally located cb/cc lymphomas were treated with EFI. TCLI and EFI were administered to a total dose of 26 gray (Gy) with 2 Gy per daily fraction, with the exception of the whole abdomen, which was irradiated to a total dose of 25.5 Gy with 1.5 Gy per fraction. A boost of 10 Gy with 2 Gy per fraction was administered to enlarged and involved lymph nodes at the start of radiotherapy. RESULTS: Sixty, 40, and 17 patients had Stage I, II, and limited IIIA disease (no bulk and less than 6 involved lymph node regions), respectively. Overall survival was 86% at 5 and 7 years; median follow-up was 68 months. The probabilities of relapse at any site, recurrences in lymph nodes, and in-field lymph node recurrences after TCLI were 17% in Stage I; 56%, 43%, and 40% in Stage II, respectively; and 44%, 35%, and 35% in Stage IIIA, respectively. The risk of disseminated extralymphatic relapses was 9% at 7 years. The most important adverse prognostic factor for in-field lymph node recurrences was a deviation of >20% from the assigned total radiation dose. After EFI, patients in Stage I had a significantly lower risk of recurrences in adjuvant irradiated lymph node regions than in unirradiated lymph node regions. Acute toxicity of EFI and TCLI was moderate. CONCLUSIONS: In-field lymph node recurrences remained the main risk after TCLI, and a deviation of >20% from the assigned radiation dose was the major risk factor for in-field recurrences. From these data, a total dose of 40-44 Gy in conventional fractionation for the treatment of macroscopic cb/cc lymphomas and 30 Gy for the treatment of subclinical disease is recommended. A randomized study comparing TCLI with EFI is now being organized by this group.

Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.

PURPOSE: The prognosis of patients with locally advanced esophageal cancer (LAEC) remains poor when treated with local modalities. An intensive preoperative program with chemoradiotherapy was used to evaluate the curative resection rate, pathologic response, and survival of patients with LAEC. PATIENTS AND METHODS: Ninety patients with LAEC were treated preoperatively with chemotherapy (three courses of fluorouracil, leucovorin, etoposide, and cisplatin [FLEP]) followed by concurrent chemoradiotherapy (one course of cisplatin plus etoposide in combination with 40 Gy of radiation). Transthoracic esophagectomy was performed 4 weeks after the end of radiation. RESULTS: Seventy-two patients were included in this evaluation. Forty-four (61%) underwent a complete tumor resection, and 16 (22%) had no tumor in the resected specimen (pathologic complete response [PCR]). The operative mortality rate was 15%. At a median follow-up time of 22 months (range, 12 to 41), the median survival duration of all 72 patients was 17 months (range, 1 to 41+). The calculated survival rates at 3 years were 33%, 42%, and 68% for all patients, patients after complete resection, and patients with PCR, respectively. CONCLUSION: This combined treatment modality is active in LAEC, with a PCR in 33% of the patients undergoing surgery. The results appear improved compared with those reported with surgery alone, by approximately doubling the 3-year survival rate. The high efficacy of preoperative chemoradiation warrants evaluation of the role of surgery in LAEC.

Feasibility study of postoperative adjuvant chemotherapy and radiotherapy for soft-tissue sarcoma.

In a nonrandomized trial, postoperative, adjuvant, combined chemotherapy and radiotherapy were given to 17 patients with high-grade soft-tissue sarcomas. All patients had undergone conservative limb-sparing surgery. Soft-tissue sarcomas were localized in the extremities (13 patients), superficial trunk (3), and neck (1). In all, 13 patients received 50 mg/m2 doxorubicin and 5 g/m2 ifosfamide with mesna uroprotection for a total of 6 cycles and 4 patients received CYVADIC (cyclophosphamide/vincristine/doxorubicin/dacarbazine). Chemotherapy was started immediately after wound healing. Irradiation using the shrinking-field technique was commenced 3-7 days following chemotherapy; a total dose of 65 Gy was applied. The major side effects of chemotherapy were nausea and vomiting [17 of 17 patients, 5 experiencing World Health Organization (WHO) grade 3 toxicity and 1, WHO grade 4], leukopenia of <3.0 x 10(9)/l (17 patients), and leukopenia of <1.0 x 10(9)/l (7 patients). The median leukocyte nadir was reached on day 11 (range, days 7-16). The duration of critical leukopenia did not exceed 1 week. Reversible alopecia occurred in all patients. Temporary cardiomyopathy was recorded in 1 patient. Following radiotherapy, 11 episodes of epitheliolysis and 1 case of moderate lymphedema were documented. There was no life-threatening condition. After a follow-up of 58 months, the outcome was as follows: disease-free survival, 9 patients; distant metastases, 7; local recurrence, 1. Excluding 3 patients who entered the study after undergoing surgery for local relapse, the rate of distant metastases was 36%. In summary, the postoperative use of chemotherapy/radiotherapy is feasible, producing relevant but manageable toxicity. This combination results in effective local tumor control with good functional results following limb-sparing surgery. The incidence of distant metastases, however, is high.

[Normal pressure hydrocephalus in geriatric patients--a treatable form of dementia]. / Normaldruckhydrozephalus bei geriatrischen Patienten--eine behandelbare Form der Demenz.

Six geriatric patients are presented who were treated because of normal pressure hydrocephalus. A tentative diagnosis was made if dementia, gait disturbance, and incontinence together with a typical CAT-scan were present. In these cases an operation was carried out. After ventriculo-peritoneal shunting clinical improvements were seen in four patients. Postoperative complications were hygromas in three patients and a shunt-dislocation in another patient. A chronic subdural bleeding was recorded also in one of these patients with only a temporary success in this case. Two patients showed no clinical improvement at any time. However, in these cases additional neurologic symptoms together with typical CAT-scan changes were present. Before making a decision for an operation vascular processes and Alzheimer's disease should be ruled out.

[Radiation treatment of intracranial arteriovenous malformations--experiences with a semi-stereotactic technic]. / Die Strahlenbehandlung intrakranieller arteriovaskulärer Malformationen--Erfahrungen mit semi-stereotaktischer Technik.

Since 1982 79 patients with intracranial AVM's were irradiated at linear accelerator with 10 MV photons. Diagnosis, localization and therapy were done immobilizing the head for identical positioning. In a controlled study the therapy was done with fractionated irradiation up to 50 Gy in 25 fractions within 5 weeks or with 20 Gy in 4 fractions within 7 days. Complications, due to therapy, did not occur. Suffering from convulsion was not affected. Five patients have died, one patient got a hemorrhage 36 months later. The angiographical analysis of the first 25 patients until 30 months after radiotherapy gave complete obliterations and reduction of volume in more than 50% with minor AVM's. The result are not detrimental compared with a group after photon irradiation.

[Esophageal carcinoma: the final results of a multicenter and controlled German study with misonidazole and radiation]. / Osophaguskarzinom: Endergebnis einer multizentrischen und kontrollierten deutschen Studie mit Misonidazol und Bestrahlung.

A prospective, randomized clinical study on 91 patients with squamous cell carcinoma of the oesophagus was undertaken in order to investigate the radiosensitizing effect of misonidazole. After histologic verification and extensive diagnosis, the greater tumor region was at first irradiated during 2.5 weeks with ten fractions of 3 Gy each up to a target volume dose of 30 Gy. Prior to each fraction, patients received randomly misonidazole or a placebo in a dose of 1 g/m2 body surface. Then they were presented to the oncologic surgeon in order to decide whether a surgical resection should be performed or not. Following to this operation no further radiotherapy was performed. However, if a surgical intervention did not take place, radiotherapy was continued without administration of misonidazole or placebo up to a target volume dose of 60 to 70 Gy. There was no evidence of neurotoxic side effects or modifications of the blood count and some laboratory parameters caused by misonidazole. As to recurrence-free interval and survival time, no significant differences were found between the different therapy groups, so that a radiosensitizing effect of misonidazole was not demonstrated in this study. Regarding several positive phase II studies with misonidazole, some hopes had been placed in this study because at present the therapeutic situation in oesophagus carcinoma is extremely unsatisfactory. Even the combination of a most sophisticated operation technique prior or following to irradiation could not essentially improve the poor healing rates.

[Somatic radiation risk in large-field irradiation]. / Somatisches Strahlenrisiko bei Grossfeldbestrahlungen.

The somatic dose index was determined for large-field irradiations with the 10 MeV bremsstrahlung of a linear accelerator. Among the possible field shapes, the authors investigated the mantle field, the inverted Y field, the boomerang field, as well as total body irradiation and upper and lower partial body irradiation. The measured data are discussed with respect to clinical aspects.

[Radiotherapy of arteriovenous malformations of the brain]. / Die Radiotherapie arteriovenöser Malformationen des Hirnes.

Arterio-venous malformations of the brain are accompanied by a risk of hemorrhages which increases in the course of time. Thus a therapy is indicated as soon as the arterio-venous malformation is discovered. If surgical treatment is contra-indicated, radiotherapy can be applied with a high rate of success (obliteration of the arterio-venous malformation after two years in up to 88% of cases). Percutaneous radiotherapy has to be performed with a stereotaxic technique under controlled conditions. The stipulations for this treatment are described on the basis of our own method. Between August 1982 and July 1983, twenty patients have been treated without any complications due to therapy or to the disease. This form of radiotherapy using the bremsstrahlung of a linear accelerator can be considered as an alternative method with respect to proton irradiation.