[Radiation-Induced Radiculopathy with Paresis of the Neck and Autochthonous Back Muscles with Additional Myopathy]. / Parese der Nacken- und autochthonen Rückenmuskulatur durch strahleninduzierte zervikale Radikulopathie mit Begleitmyopathie.

Radiation-induced tissue damage is caused by ionizing radiation mainly affecting the skin, vascular, neuronal or muscle tissue. Early damages occur within weeks and months while late damages may occur months or even decades after radiation.Radiation-induced paresis of the spine or the trunk muscles with camptocormia or dropped-head syndrome are rare but have already been described as long-term sequelae after treatment of Hodgkin's lymphoma. The differential diagnosis includes limb-girdle muscular dystrophy, fascioscapulohumeral muscular dystrophy (FSHD) or lysosomal storage diseases (e. g. Acid Maltase Deficiency). We present the case of a patient with long lasting diagnostics over many months due to different inconclusive results.

Phase I dose escalation study of telatinib (BAY 57-9352) in patients with advanced solid tumours.

Telatinib (BAY 57-9352) is an orally available, small-molecule inhibitor of vascular endothelial growth factor receptors 2 and 3 (VEGFR-2/-3) and platelet-derived growth factor receptor beta tyrosine kinases. In this multicentre phase I dose escalation study, 71 patients with refractory solid tumours were enroled into 14 days on/7 days off (noncontinuous dosing) or continuous dosing groups to receive telatinib two times daily (BID). Hypertension (23%) and diarrhoea (7%) were the most frequent study drug-related adverse events of CTC grade 3. The maximum-tolerated dose was not reached up to a dose of 1500 mg BID continuous dosing. Telatinib was rapidly absorbed with median t(max) of 3 hours or less. Geometric mean C(max) and AUC(0-12) increased in a less than dose-proportional manner and plateaued in the 900-1500 mg BID dose range. Two renal cell carcinoma patients reached a partial response. Tumour blood flow measured by contrast-enhanced magnetic resonance imaging and sVEGFR-2 plasma levels decreased with increasing AUC(0-12) of telatinib. Telatinib is safe and well tolerated up to a dose of 1500 mg BID continuous dosing. Based on pharmacokinetic and pharmacodynamic criteria, 900 mg telatinib BID continuously administered was selected as the recommended phase II dose.

[Current diagnostics and therapy recommendations for ocular basal cell carcinoma]. / Aktuelle Diagnostik und Therapieempfehlungen beim Basalzellkarzinom am Auge.

The treatment options for basal cell carcinoma (BCC) have recently been augmented with the introduction of novel chemotherapeutic drugs. New S2 guidelines on the disease have also been published. The aim of this article is to present a comprehensive state of the art description of the features of ocular BCC and an overview of the various therapeutic options. Particular emphasis is placed on the clinical signs, the diagnostic tools to identify periocular BCC and interpretation of the different histopathological subtypes. Tumor staging, TNM classification, interdisciplinary tumor conference reviews as well as psycho-oncological services play an important role in patients with pronounced periocular BCC. Surgical removal with a histological R0 resection is an important component of therapy options in this disease and includes the microsurgical excision into healthy tissue and the subsequent covering of the defect. A special focus of this article is the treatment of locally extensive and metastasized BCC.

[Lymphoma of the ocular adnexa]. / Lymphome der okulären Adnexe.

BACKGROUND: Lymphomas of the ocular adnexa are heterogeneous and demonstrate a wide range of clinical, histological, immunohistochemical and molecular genetic characteristics. AIM: The aim of this article is to give an overview of the interdisciplinary diagnostics and individually adapted lymphoma subtype-based therapy. DIAGNOSTICS: Depending on the lymphoma localisation, i.e. whether in the eyelid, the conjunctiva or in the orbit, a photograph or a radiological scan is required to record the tumor extent. Visual function is more likely to be impacted when the lymphoma arises in the posterior orbit, close to the optic nerve and imaging diagnostics are therefore necessary. Histological investigations are essential for confirming the lymphoma diagnosis and give information about the particular subtype, which in turn will determine subsequent patient management, Clinical staging investigations for determining the systemic extent of the lymphoma manifestation (e.g. imaging, blood analyses as well as bone marrow biopsy) are mandatory. THERAPY: External beam radiation, local and systemic chemotherapy or in some cases antibiotics are treatment options after surgical excision in isolated ocular adnexal lymphoma. The TNM classification of the American Joint Committee on Cancer or the Ann Arbor staging system, as well as the guidelines of the German Society of Hematology and Medical Oncology are all tools to aid the choice of the appropriate individually adapted therapy for systemic disease, which includes psycho-oncological care.

Endovascular irradiation--a new method to avoid recurrent stenosis after stent implantation in peripheral arteries: technique and preliminary results.

PURPOSE: A high dose rate (HDR) afterloading technique for prevention of vascular stenosis or occlusion after percutaneous transluminal arteriography and subsequent stent implantation caused by intimal hyperplasia is presented. METHODS AND MATERIALS: The frequency of recurrent stenosis or occlusion following implantation of stents into peripheral arteries is relatively high. The cause of relapse is rapid intimal hyperplasia. To prevent proliferation of the intimal layer, intravascular brachytherapy was performed in cases of recurrent vascular occlusion or severe stenosis. After recanalization by percutaneous transluminal angioplasty and stent implantation, a 9-French-ReKa catheter was placed within the lumen of the stent. This catheter served as a guide for a 5-French flexible applicator. Then after individual calculation of the isodose, 12 Gy were applied to the vessel wall. This procedure was followed by 72 h of heparinization. Follow-up by Doppler digital subtraction angiography and magnetic resonance imaging was done 3, 6, and 12 months after the procedure and later on once a year. RESULTS: Intraluminal irradiation was performed in 13 patients (nine male and four female). All patients had a clinically relevant restenosis or reocclusion in the superficial femoral artery (clinical stage according to Fontaine IIb-III). Follow-up time ranged from 3-27 months. After irradiation the stented area remained patent in all cases and there were no signs of recurrent stenosis in the treated arterial segment. CONCLUSION: With high dose rate 192Ir afterloading after percutaneous transluminal angioplasty and subsequent stent implantation restenosis or reocclusion caused by intimal hyperplasia can be prevented.

Comparison of two strategies for the treatment of radiogenic leukopenia using granulocyte colony stimulating factor.

PURPOSE: Radiation-induced leukopenia can cause a delay or discontinuation of radiotherapy. This complication can be overcome with the use of granulocyte colony-stimulating factor (G-CSF). However, an uncertainty exists regarding the mode of application of G-CSF in patients treated with radiotherapy. For this reason, the efficacy of two strategies for the administration of G-CSF in irradiated patients was compared in a prospective randomized clinical study. METHODS AND MATERIALS: Forty-one patients who developed leukopenia (< 2.5 x 10(9) per liter) while undergoing radiotherapy were treated with G-CSF at a daily dose of 5 microg/kg. The first group received single injections of G-CSF as required (n = 21). The second group received G-CSF on at least 3 consecutive days (n = 20). An analysis was made of the changes in leukocyte counts, the number of days on which radiotherapy had to be interrupted, and the side effects of growth-factor treatment. RESULTS: An increase in leukocyte values in the peripheral blood was observed in all patients treated with G-CSF. In the group which received G-CSF when required, two injections (range: 1-8) were administered in most cases. In the second group, most of the patients received three injections (range: 3-9). The average duration of therapy interruptions due to leukopenia was 4.8 days (0-28) in the first therapy arm and 2.5 (0-20) in the second arm. The variance in the duration of therapy interruptions between the two groups was not significant (p = 0.2). Radiotherapy had to be terminated in two patients due to thrombocytopenia but the application of G-CSF did not seem to be a reason of decreasing platelet counts. CONCLUSIONS: Our results reveal that G-CSF is safe and effective in the treatment of radiation-induced leukopenia regardless of the mode of application. Because the calculated difference related to radiation treatment interruptions has no clinical relevance, both approaches examined in our study appear reasonable.

The use of a standardized positioning support cushion during daily routine of breast irradiation.

PURPOSE: The use of positioning and immobilization techniques during external beam irradiation of the female breast is time consuming and expensive. The currently available standardized positioning devices are insufficient. For this reason, we designed a new and generally useable hard foam positioning support cushion for the use during breast irradiation, and tested its clinical usefulness in a prospective study. METHODS AND MATERIALS: Fifty-five female breast cancer patients receiving adjuvant radiotherapy following breast-conservative surgery were irradiated either without immobilization (n = 27) or with the positioning support cushion (n = 28). The time necessary for patient setup, the lying subjective comfort and--comparing portal images with simulator images--the reproducibility of the set up were determined. RESULTS: Irradiation reproducibility was significantly improved (average deviation without positioning support cushion: 8.4 mm, with positioning support cushion: 6.1 mm, p < 0.001). The time required for the positioning of the patient with positioning support cushion was in average 73 s, without cushion it was 55 s. A significantly higher proportion of patients (72%) found the position with the positioning support cushion as pleasant, whereas only 46% of patients were pleased with the position without cushion. CONCLUSION: The positioning support cushion designed in our department makes a substantial contribution to quality assurance in breast irradiation. It significantly increases the patients' comfort in a supine position. In contrast to conventional positioning and fixation aids it may be quickly and easily applied at low costs. Therefore, its use can be recommended.

Survival of very young children with medulloblastoma (primitive neuroectodermal tumor of the posterior fossa) treated with craniospinal irradiation.

PURPOSE: Very young children with medulloblastoma are considered to have a worse prognosis than older children. As radiotherapy remains an important part of the treatment, the adverse prognosis could be due to inadequate radiation treatment rather than biological factors. We analyzed the published literature to examine the impact of radiotherapy on survival in this group. METHODS AND MATERIALS: A Medline search was performed and we reviewed studies of treatment of medulloblastoma where radiotherapy was delivered using megavoltage equipment and the minimum follow-up allowed the calculation of 5-year survival rates. RESULTS: Thirty-nine studies were published between 1979 and 1996 with a treatment including craniospinal irradiation and boost to the posterior fossa. Eleven studies comprising 1366 patients analyzed survival by age at diagnosis. Eight of 11 studies showed a worse 5-year survival for the younger patient group which reached statistical significance in two. There is also a suggestion of a higher proportion of children with metastatic disease at presentation in the very young age group. The usual policy in younger children was to give a lower dose of radiotherapy to the craniospinal axis (CSA) and posterior fossa (PF) with reduction of dose in the range of 15 to 25% compared to standard treatment. As dose reduction to the posterior fossa is associated with worse survival and local recurrence is the predominant site of failure, the major determinant of worse survival in very young children with medulloblastoma may be suboptimal radiotherapy. Protocols including postoperative chemotherapy with delayed, omitted, or only local tumor irradiation do not reach survival rates of protocols with standard radiotherapy, also suggesting a continued importance for irradiation. CONCLUSION: Very young children with medulloblastoma have a worse prognosis than older children. Inadequate radiation dose and technique to the primary tumor region may be a major contributing factor. Current chemotherapeutic regimes alone are not sufficient to compensate for reduced radiation doses and volumes.

Improvement of radiation treatment planning in squamous-cell head and neck cancer by immuno-SPECT.

UNLABELLED: Previous studies have shown high accuracy for immunoscintigraphy with 99mTc-MAb-174 in patients with squamous-cell carcinoma of the head and neck region compared to CT and MRI. We conducted a prospective study to determine if immunoscintigraphy provides additional diagnostic information for radiation treatment planning. METHODS: Radioimmunoscintigraphy (RIS) was performed on 40 patients (planar, whole-body, SPECT) with histologically confirmed squamous-cell carcinoma (30 primary tumors, 10 recurrences) after injection of the 99mTc (1.1 GBq) labeled monoclonal anti-squamous-cell cancer antibody 174H0.64 (murine IgG1). Results were combined with information obtained by clinical examination, sonography, panendoscopy and x-ray CT. The strategy for radiation treatment and the required treatment volumes were defined with and without immunoscintigraphical findings. RESULTS: Additional diagnostically relevant information from RIS was obtained from 10 patients (25%) with advanced tumors or recurrences. In three patients (7.5%), the treatment volume had to be extended. The therapeutic strategy for seven patients (17.5%) had to be changed due to the detection of metastatic disease beyond the head and neck region. RIS of patients with squamous-cell cancers of the head and neck region with 99mTcMAb-174H0.64 enabled the detection of tumors that were not depicted by other conventional diagnostic imaging procedures. CONCLUSION: The use of RIS in radiation treatment planning of advanced tumors of the head and neck region appears to yield important diagnostic information that may alter patient management.

Palliative radiotherapy in plasma cell myeloma.

Pain symptoms caused by bone lesions of multiple myeloma can be relieved by a local irradiation treatment. To estimate the influence of systemic treatment on the palliative effect of local radiotherapy the records of 70 myeloma patients treated with chemotherapy combined with or followed by local irradiation were reviewed. The local response rate, defined as complete pain relief at the irradiated site, was 80% in patients receiving irradiation during chemotherapy (melphalan and prednisone) and this palliative effect endured 31.8 +/- 3.6 months. If irradiation was started in the period without systemic treatment the local response rate was 39.6% and lasted 24.8 +/- 17.9 months. In sites treated with more than one radiotherapy course 94% response rate after the first treatment, 56% after the second treatment and no response after the third course was achieved. The duration of local pain control was positively related to the applied radiation dose. It is concluded that irradiation during concomitant chemotherapy is superior to radiotherapy performed in a period without systemic treatment. Local long-term palliation can only be achieved by a sufficient high radiation dose.

Increase of surface dose using wound dressings during percutaneous radiotherapy with photons and electrons.

Different wound dressings are used for the supportive treatment of patients with radiation-induced skin lesions. Depending on beam quality and energy, an increase of the dose administered to the skin and thus an aggravated skin reaction is to be expected during percutaneous irradiation. The increase of the skin dose during irradiation with photons (Co60, 6 MV, 42 MV) and electrons (7 MeV, 20 MeV, 42 MeV) was determined using thermoluminescence dosimetry. The use of wound dressings during electron irradiation and during soft irradiation therapy does not significantly increase the dose administered to the skin and does not therefore cause any problems. During irradiation with high energy photons only extremely thin dressings should be used; if there is an aggravated skin reaction, the dressing should be taken off before irradiation commences.

Changes of the surface proteolytic activity in synchronized Ehrlich ascites tumor cells grown in vivo.

Changes of the cell surface proteolytic activity during the cell cycle in vitro were reported. Using an easy assay, with casein as a substrate, the proteolytic activity on the surface of Ehrlich ascites tumor (EAT) cells grown in vivo was determined. The cleavage of casein incubated with EAT cells increased linearly for 20 min and permitted reproducible enzyme activity determinations. If the proliferation of exponentially growing EAT cells was partially synchronized by an intraperitoneal bleomycin injection, a significant increase of the surface enzymatic activity was observed in cells with an increased DNA content. This finding supports the results obtained with transformed cells in vitro, indicating that elevated proteolytic surface activity occurs in the late synthesis phase and prior to mitosis. However, the observed effect may also be due to changes of gene expression caused by bleomycin.

Influence of radiotherapy on psychological health in breast cancer patients after breast conserving surgery.

BACKGROUND: The purpose of this study was the evaluation of the radiotherapy-induced psychological distress of patients and changes in psychological health during radiotherapy (RT). PATIENTS AND METHODS: 53 breast cancer patients undergoing irradiation after breast conserving surgery participated in this study. In the beginning and at the end of radiotherapy they answered a questionnaire asking for coping strategies, psychological distress with regard to irradiation and influence of surroundings. RESULTS: 92% stated to be well informed about radiotherapy. Coping strategies in order of importance: Talking to physician (94%) or partner (84%), 81% try to distract themselves, 56% repress thoughts about radiotherapy. 40% were anxious about RT and expected side effects (54%). At the end of therapy anxiety was reduced: 77% were anxious only initially or never. CONCLUSIONS: Patients are very interested in information about RT. Their experience of radiotherapy was more positive than initially expected. The relation to medical staff plays an important part in the reduction of irradiation-related psychological distress.

Can prophylactic application of immunoglobulin decrease radiotherapy-induced oral mucositis?

Therapeutic application of immunoglobulin is reported to be successful in radiation-induced oral and oropharyngeal mucositis. In this study the efficacy of prophylactic application of immunoglobulin was investigated. In 42 patients with head and neck cancer, postoperative radiation treatment or radiation combined with chemotherapy was performed. In 20 consecutive patients, prophylactic mucositis treatment consisted of panthenol (4 x 10 ml/day) and nystatin (4 x 1 ml/day). The 22 following patients received, supplementary to panthenol and nystatin, 800 mg (5 ml) human immunoglobulin intramuscularly once weekly. During the treatment time, the degree of mucositis was examined 3 times a week. The distribution of maximal mucositis degree revealed slightly more severe mucous membrane reaction in the control group compared with the immunoglobulin group (n.s.). The analysis of mean mucositis degrees in both groups demonstrated statistically significant differences (t test, p = 0.031) related to the entire group (n = 42) and to those 16 patients receiving radiation combined with chemotherapy. There was no significant immunoglobulin-induced effect on mucositis in patients treated by radiation alone. The time from the beginning of therapy to the first interruption could be prolonged 5 days in the immunoglobulin group (n.s.). In conclusion, it is demonstrated that the prophylactic application of immunoglobulin seems to lower the degree of radiation-induced mucositis. In comparison to the published data about therapeutically given immunoglobulin, the clinical efficacy of the prophylactic application of immunoglobulin as it is performed in this study is less evident.

Bilateral breast carcinoma versus unilateral disease. Review of 498 patients.

In literature data, an uncertainty exists whether occurrence of bilateral breast cancer decreases the survival probability of affected patients. Therefore, we analyzed the medical records of 498 postoperatively irradiated (1977-1982) female breast cancer patients (T1-4,N0-3,M0). In the follow-up time, in 36 patients a bilateral breast carcinoma treated by surgery with or without radiotherapy was found. The 10-year overall survival rates were 54% in patients who had unilateral disease, compared with 56% in bilateral carcinoma patients, respectively. The incidence of metastasis did not differ between both groups: 24.2% versus 38.8%. Eleven percent of unilateral cancers recurred; in the other group, local failure of the first and second tumor was observed in 19.4% and 11.1%, respectively. We conclude that the occurrence of bilateral breast cancer has no significant impact on survival, although the development of local failures and metastases seems to be more frequent. The therapeutic strategy in bilateral carcinoma should resemble the treatment procedure in unilaterally affected patients.

Value of a multileaf prescription preparation system for palliative external beam irradiation.

In palliative treatment, irregularly shaped fields are used to reduce side-effects and can improve, or avoid, field matching. We investigated the effectiveness of a multileaf collimator (MLC) supported by a digitizing data entry system in the palliative radiotherapy treatment of 66 patients and compared it with conventional shielding with geometrically shaped blocks. After conventional simulation of rectangular fields, irregular field shapes were marked on the simulator film in 17 patients (27%) to reduce radiotherapy related side-effects. Individual leading was performed with an MLC. Digitizing and fitting of the optimum leaf position were carried out using a multileaf preparation system (MLP, Elekta, Crawley, UK). Target volumes included bone metastases in the pelvis, spine and extremities, mediastinal soft tissues, lymph nodes and central nervous system. In 10 patients, treated with a parallel pair for pelvic metastases, MLC and conventional shielding were prospectively compared with regard to time requirements and area shielded. Compared with conventional blocking, the mean simulation, preparation and treatment time required for MLP fields was shorter (9.55 +/- 1.44 min vs 16.90 +/- 2.64 min, and 5.50 +/- 1.14 min vs 8.97 +/- 1.75 min). The mean shielded area was 31 cm2 larger for MLC fields compared with geometrically shaped blocks (p < 0.05). Compared with cerrobend blocking, the use of an MLC, supported by preparation data entry software, is more flexible and reduces radiotherapy resources. Therefore, a preparation data entry system as a separate device, or integrated into the treatment planning system, is a useful tool in palliative treatment.

In vivo dose increase in the presence of dental alloys during 60Co-gamma-ray therapy of the oral cavity.

During irradiation of the mouth cavity, dental metallic materials emit secondary electrons and thus increase the applied radiation dose in their vicinity. Therefore, local destruction of the mucous membrane contacting metallic dental crowns and fillings may be observed. Available data on this dose increase are based on measurements with beam arrangements perpendicular to the metallic surface. Since the dose modification depends on the beam direction in relation to specimen surface, a reliable prediction of dose modification in the close vicinity of dental caps on fillings under complex beam arrangements, as applied in the irradiation of head and neck region from the published data is not possible. Therefore, we measured dose increase in the immediate surrounding of metallic dental material using thermoluminescence dosimetry on the phantom and during routinely applied 60Co gamma ray therapy. Phantom measurements were carried out using several oblique irradiation angles and rotational therapy. In vivo measurements were carried out at alloy specimens containing gold, palladium, and amalgam in six patients and at permanently fixed golden teeth in five patients. In vivo, the following relative dose increase values according to a simultaneously measured reference value were obtained at the surface of different dental materials: 61% for fixed golden caps. 68% for the specimen containing gold, 33% for the specimen of palladium and 61% for the specimen of amalgam. The measured dose increases due to metallic dental material during routinely applied external 60Co beam irradiation are lower compared with those of perpendicular beam arrangements. Although, the extent of dose modification is less than expected, we still advocate protection of the oral mucosa to prevent painful lesion spots.

[Postoperative, conventional fractionated radiotherapy for prevention of heterotopic ossification after total endoprosthesis of the hip joint]. / Die postoperative, konventionell fraktionierte Strahlentherapie zur Prävention heterotoper Ossifikationen nach TEP des Hüftgelenkes.

Radiotherapy is the only local means of treatment in the prevention of heterotopic bone formation. It is possible to reduce the incidence of HO following total hip arthroplasty from an average of 50% without further treatment to an average of 8% using different doses and fractionation schemes. In this retrospective clinical study 22 hips of 20 patients were treated with a conventional fractionated radiotherapy. Total doses of 12.0-20.0 Gy in daily fractionation of 200 cGy single doses were applied 18 hips were postoperatively irradiated as secondary prophylaxis against recurrence of HO. 4 hips were high-risk cases with contralateral HO after previous hip surgery. After 6-30 months observation periods the roentgenogramms were analyzed with a modified Brooker-Score. Patients with a score > II were classified as nonresponders. 95.5% of the treated hips showed satisfactory results, only one hip (4.5%) achieved a score IIIA. In this case radiotherapy was interrupted after 3 x 200 cGy. The high therapeutic efficiency of local irradiation in the prevention of heterotopic bone formation following total hip replacement could be proved. No considerable side effects were observed. Further prospective clinical investigations are necessary to optimize the doses and fractionation schemes.