Radioablation of adrenal gland malignomas with interstitial high-dose-rate brachytherapy : Efficacy and outcome.

PURPOSE: To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM). MATERIALS AND METHODS: From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5-82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified. RESULTS: The median biological equivalent dose (BED) was 37.4 Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both. CONCLUSION: Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment.

Diagnosis and Treatment of Nasopharyngeal Carcinoma in Children and Adolescents - Recommendations of the GPOH-NPC Study Group.

Nasopharyngeal carcinoma (NPC) is a rare malignant tumor arising from epithelial cells of the nasopharynx. Its incidence is highest in Southeast Asia. Age distribution of NPC is bimodal, with one peak in young adolescents and another in patients 55-59 years of age. EBV appears to be the primary etiologic agent in the pathogenesis, environmental factors such as nitrosamines and genetic factors are contributory. NPC is most commonly diagnosed in locally advanced stages, with lymph node metastases occurring in up to 90% of patients. About 5-10% of patients present with distant metastases. Diagnosis of NPC is made histologically, supported by an abnormal anti-EBV-VCA IgA titer and elevated plasma EBV-DNA load. Superior results in children and adolescents with advanced locoregional NPC, with overall and event-free survival rates>90%, have been achieved by neoadjuvant chemotherapy with 5-fluoruracil and cisplatin, followed by synchronous radiochemotherapy and subsequent maintenance therapy with interferon-ß as demonstrated by the 2 prospective studies GPOH-NPC-91 and -2003. Response to therapy can be assessed by PET-imaging and in patients with complete remission after neoadjuvant chemotherapy, the radiation dose to the primary tumor can be safely reduced from 59.4 to 54.4 Gy. Since the majority of long term sequalae such as xerostomia, skin and tissue fibrosis are caused by high radiation dosages, radiotherapy modalities such as intensity-modulated radiotherapy should be used to efficiently spare non-tumorous tissue. For patients with metastatic disease and relapse, survival chances are low. New treatment strategies, such as the application of EBV-specific T-lymphocytes should be considered for these patients.

Attosecond control in photoionization of hydrogen molecules.

We report experiments where hydrogen molecules were dissociatively ionized by an attosecond pulse train in the presence of a near-infrared field. Fragment ion yields from distinguishable ionization channels oscillate with a period that is half the optical cycle of the IR field. For molecules aligned parallel to the laser polarization axis, the oscillations are reproduced in two-electron quantum simulations, and can be explained in terms of an interference between ionization pathways that involve different harmonic orders and a laser-induced coupling between the 1sσ(g) and 2pσ(u) states of the molecular ion. This leads to a situation where the ionization probability is sensitive to the instantaneous polarization of the molecule by the IR electric field and demonstrates that we have probed the IR-induced electron dynamics with attosecond pulses.

[Requirements and performance profile of the Paediatric Radiation Oncology Working Group (APRO): evaluation of the present situation and description of future developments]. / Anforderungen und Leistungsprofile der Arbeitsgemeinschaft Pädiatrische Radioonkologie (APRO): Eine Bestandsaufnahme und Darstellung zukünftiger Entwicklungen.

BACKGROUND: Radiation therapy is an integral component in the management of childhood malignancies and undergoes a continuous process of optimization within the prospective trials of the GPOH. At present there are approximately 20 active protocols, some specifying radio-oncological study questions, in which about 500 to 600 children annually are given radiotherapy. MATERIALS/METHODS: The Pediatric Radiation Oncology Working Group (APRO) of the German Society for Radiation Oncology (DEGRO) represents the organizational link between GPOH and DEGRO. Their activities range from phrasing guidelines of radio-oncological therapy, through writing a protocol for a prospective study on radiation-induced late effects (RISK--in co-operation with GPOH, 695 patients registered so far) and organizing meetings for information transfer, to implementing radio-oncology within the prospective studies of the GPOH by establishing study chairs for radio-oncology when radio-oncological questions are a primary focus and/or to function as a reference institution for quality assurance. These activities also include individual case consultations outside the study proper. Twice annually the members of the APRO meet for an update on current knowledge and future directions where a representative of the GPOH is invited to contribute special aspects of pediatric oncology. CONCLUSIONS: In the future, modern technology (intensity modulated radiotherapy, proton therapy, inclusion of imaging in treatment planning) will be part of disease management in pediatric oncology. A working group for modern radiotherapy technology was established to enhance this development. Prospective studies of the GPOH with primary or secondary radio-oncological questions require the implementation of corresponding tasks (documentation, monitoring, etc.) in order to meet future demands on clinical trials and to achieve the aims of the protocol. Consequently adequate financial support is indispensable.

Modulation of prion protein structural integrity by geldanamycin.

The cellular prion protein PrPc is of crucial importance for the development of neurodegenerative diseases called transmissible spongiform encephalopathies. We investigated if the function of members of the HSP90 family is required for the integrity of the normal, nonpathogenic prion protein called PrPc. Eukaryotic cells were treated with the structurally unrelated HSP90-inhibitors geldanamycin (GA) or radicicol (RC). In either case the cellular prion protein was induced and exhibited faster migrating bands on western blot analysis, whereas geldampicin (GE), an analog of GA known not to bind to HSP90, had no effect. Ongoing protein and messenger RNA synthesis during treatment were found to be necessary for the appearance of these bands. Cotreatment with tunicamycin abrogated any effect of HSP90 inhibitors on the cellular prion protein. Finally, enzymatic deglycosylation with peptide:N-glycosidase F of the normal prion protein as well as the variant induced by benzoquinone ansamycins resulted in very similar band patterns. These experiments indicate that either altered glycosylation, or a change in conformation, or both are involved in the induction of faster migrating bands by HSP90 inhibitors. Thus the inhibition of the function of members of the HSP90 family of molecular chaperones results in profound changes in the physicochemical properties of PrPc.

Heat-shock protein 90: potential involvement in the pathogenesis of malignancy and pharmacological intervention.

Heat-shock protein 90 (Hsp90) is an essential, cytosolic protein. Its overexpression in a wide variety of malignant tumors makes it a candidate target for pharmacological intervention. The association with Hsp90 stabilizes key regulatory proteins like Fak, Bcr-Abl, ErbB2, mutant p53 and Raf-1. The disruption of these heterocomplexes by Hsp90 inhibitors causes the rapid degradation of Hsp90-client proteins by the proteasome. Benzoquinone ansamycins were the first group of compounds for which interference with Hsp90 function was shown to be the major mechanism of action. They are in the early phase of clinical development. Radicicol and its derivatives are functional analogues of benzoquinone ansamycins without structural similarity. Flavonoids and stresgenin B share the ability to suppress heat-shock protein synthesis. Recently, it became apparent that coumarin antibiotics, cisplatin and paclitaxel also bind to Hsp90. The clinical value of the newly characterized agents with activity towards Hsp90 remains to be determined.

[Preoperative chemotherapy in primary operable breast cancer with a dose-dense combination of doxorubicin and docetaxel (ADoc) - Experience of the GEPARDO-GABG study group]. / Präoperative Chemotherapie operabler primärer Mammakarzinome mit einer dosisdichten Kombination von Adriamycin und Docetaxel (ADoc) - Die Erfahrungen der GEPARDO-GABG-Studiengruppe -

OBJECTIVE: The German Adjuvant Breast Cancer Study Group (GABG) conducts trials of preoperative chemotherapy in patients with primary breast cancer using a combination of doxorubicin and docetaxel (ADoc). - PATIENTS AND METHODS: We conducted a parallel-grouped phase IIa-study with 42 patients with a conventionally dosed and a dose-dense ADoc-schedule (4 cycles of Doxorubicin 50 mg/m(2), Docetaxel 75 mg/m(2) i. v. day 1, q day 15 or 22; G-CSF day 3-15 only for the dose-dense schedule) and a randomized phase IIb-study (GEPARDO-Study) with 250 patients with ADoc +/- Tamoxifen. Biological factors were determined immunohistochemically on 197 core biopsies before treatment. A comparison to a sequential AC-Doc regimen including 913 patients has been completed recently. - RESULTS: ADoc can be applicated on schedule in 93 % of all patients. The dose-dense regimen shows a tendency to more toxicity but also to more efficacy. The rate of complete pathological remissions (pCR) was 9.7 %. No difference was found between chemo- and chemoendocrine treatment. Clinically negative lymphnodes and a negative estrogen receptor status is predictive for a higher pCR-rate. To date no differences in toxicity could be found between ADoc and AC-Doc. - CONCLUSIONS: The dose-dense ADoc regimen is well tolerated and highly effective as preoperative therapy of breast cancer.

Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study.

PURPOSE: To investigate the effect of adding tamoxifen to a preoperative dose-dense doxorubicin and docetaxel regimen on the pathologic response of primary operable breast cancer. PATIENTS AND METHODS: Patients (tumor size > or = 3 cm, N0 to 2, M0) were prospectively randomized to receive every 14 days a total of four cycles of doxorubicin 50 mg/m2 and docetaxel 75 mg/m(2), either with (ADocT) or without (ADoc) simultaneous tamoxifen. Granulocyte colony-stimulating factor (G-CSF) was routinely given on days 5 to 10. Surgery followed 8 to 10 weeks after the start of treatment. RESULTS: Within 14 months, 250 patients were included in the study at 56 centers. Of 992 planned cycles, 97.9% were administered. Pathologically complete remission (pCR) with no detectable viable tumor cells was achieved in 9.7%. There was a nonsignificant difference of -1.2% in favor of ADoc, with a 95% confidence interval of -8.6% to 6.2%. A further 2.4% had only noninvasive tumor residues, and 13.8% had focal invasive residues. Complete and partial responses detected by palpation were observed in 28.9% and 52.4%, respectively. The response rates (complete and partial) by best appropriate imaging methods were 77.5% and 67.5% for ADocT and ADoc, respectively. Breast conservation was possible in 68.8% of the patients. A tendency toward more frequent toxic events was observed with ADocT treatment. Significant predictors of pCR to chemotherapy were negative lymph node and negative estrogen receptor status. CONCLUSION: A dose-dense regimen of ADoc with G-CSF offers high compliance, moderate toxicity, and rapid efficacy as a form of preoperative chemotherapy in operable breast cancer. Concurrent treatment with tamoxifen for 8 weeks could not improve the pathologic response rate.

[Coping in patients with malignant glioma in the course of radiation therapy]. / Krankheitsverarbeitung bei Hirntumorpatienten. Eine Untersuchung im Verlauf der Bestrahlung.

UNLABELLED: Twenty-one patients with malignant glioma were interviewed in the course of radiation therapy (before start, in the middle and at the end of treatment and six weeks later). We used the "Freiburger Fragebogen zur Krankheitsverarbeitung (FKV)", an assessment of coping strategies, the "State-Trait-Anxiety-Inventory (STAI)", the "Beck-Depression-Scale (BDI)", and the QLQ-C 30 questionnaire of the EORTC. RESULTS: The coping strategies of our patients are comparable with other cancer patients. They are mainly characterized by "self-encouragement", "compliance" and "trust in the treating physician". Anxiety was low and showed no significant changes. Depressivity was higher than in the normal population, however, it also showed no significant changes in the course of therapy. Quality of life scores remained constant, despite an increase of fatigue. In our patients with malignant glioma, the influence of radiation on coping, anxiety, depression and quality of life seems insignificant in comparison to that of the diagnosis of cancer.

[Metastatic epidural spinal compression: prognostic factors and results of radiotherapy]. / Metastatische epidurale Spinalkanalkompression: Prognostische Faktoren und Ergebnisse der Strahlentherapie.

BACKGROUND: The metastatic epidural spinal cord compression is an oncologic emergency. Presently, there is no agreement on a standard diagnostic or therapeutic algorithm. In spite of improvement in diagnostic imaging, a great proportion of patients are plegic at the time of the first presentation. PATIENTS AND METHODS: Therapy charts of 53 consecutive patients--31 male and 22 female--with metastatic epidural spinal cord compression treated with radiation therapy only have been analyzed. Median age was 60 years. The most frequent primary tumors were bronchogenic carcinoma (13 patients), breast cancer (ten patients) and prostate cancer (ten patients). RESULTS: MRI was the most sensitive diagnostic tool in detecting spinal cord compression. Plain X-ray films were not useful. Pain symptoms were improved in 66% of the patients. The most important prognostic factor was the pretreatment mobility status. 94% of the ambulatory patients kept their walking ability, but only one plegic patient could walk again after radiation therapy (p < 0.001). Patients whose back pain was presented to an oncologist were more likely to keep their walking ability by the end of the therapy. Patients with bronchogenic cancer and plegic patients had a significantly worse survival. CONCLUSION: Patients with a known malignant tumor and progressive or axial back pain should undergo MRI scan to rule out spinal cord compression. For patients without severe neurologic deficit and MRI proven epidural compression, radiation therapy is able to preserve walking ability and reduce pain. For patients with neurologic symptoms radiation therapy should start within 24 hours.

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.

Management of cerebral metastases from malignant melanoma: results of a combined, simultaneous treatment with fotemustine and irradiation.

We report results of a conservative treatment for brain metastases from malignant melanoma with a combination of irradiation and chemotherapy (fotemustine and/or DTIC). To date, 12 patients have been treated. There was a complete remission of the brain metastases in four patients. In two patients a partial remission was observed. The mean survival of the responder was 8.2 months (95% confidence interval 3.8-12.6 months). The most common side effects were thrombocytopenia, leukopenia, and alopecia. Altogether, the treatment was well tolerated. As the outcome of patients with brain metastases from malignant melanoma is generally poor, this combined chemo- and radiation therapy may provide improved care for such patients.

The role of docetaxel (Taxotere) in neoadjuvant chemotherapy of breast cancer.

Neoadjuvant chemotherapy has become standard therapy in the management of breast cancer patients with locally advanced disease with inoperable tumors and inflammatory breast cancer. Patients with earlier stage breast cancer and operable tumors may also benefit from treatment with neoadjuvant chemotherapy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) is thought to be one of the most potent agents in the treatment of metastatic breast cancer and is therefore being investigated for its likely benefit in preoperative, neoadjuvant regimens. Several large phase II and randomized phase III trials are evaluating docetaxel as a single agent, in combination, and/or sequentially in the preoperative setting. Preliminary findings demonstrate high complete and partial response rates and a tolerable toxicity profile. These results are consistent with the view that incorporation of docetaxel in neoadjuvant chemotherapy regimens will contribute to improved patient outcome. Ongoing studies will provide important information regarding the most appropriate regimens and schedules of docetaxel to use in the preoperative, neoadjuvant setting.

[Use of G-CSF (Neupogen) in multimodal treatment in radiotherapy]. / Einsatz von G-CSF (Neupogen) bei multimodalen Therapiekonzepten in der Strahlentherapie.

BACKGROUND: Therapy-induced leukopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen). PATIENTS AND METHODS: In this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neuropogen) was already given at leukocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It administered subcutaneously every other day, based on body weight until reaching normal leucocyte levels. RESULTS: In 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treated with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light "flu like" symptoms in 14% of the patients, no side effects were observed. CONCLUSIONS: When a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.

Nasopharyngeal carcinoma in childhood and adolescence: concept and preliminary results of the cooperative GPOH study NPC-91. Gesellschaft für Pädiatrische Onkologie und Hämatologie.

BACKGROUND: The increasing use of chemotherapy has improved the prognosis of patients with nasopharyngeal carcinoma (NPC), and the authors demonstrated the beneficial effect of adjuvant interferon (IFN)-beta in a previous pilot study of children with advanced stage NPC. The current multi-institutional, cooperative GPOH (Gesellschaft für Pädiatrische Onkologie und Hämatologie) study NPC-91 was begun in 1992 to determine the efficacy of preradiation chemotherapy, radiotherapy, and adjuvant IFN-beta, in the treatment of advanced stage NPC. METHODS: Of a total of 22 patients, 21 had American Joint Committee on Cancer Stage III or IV disease, and 1 had Stage II disease. The median age was 12 years (range, 8-16 years). Twenty of 22 received 3 courses of preradiation chemotherapy consisting of methotrexate 120 mg/m2 on Day 1, cisplatin 100 mg/m2 on Day 1, and 5-fluorouracil 1000 mg/m2 for five days as well as 6 doses of leucovorin 25 mg/m2 every six hours beginning on Day 2. The Stage II patient received no chemotherapy, and chemotherapy was terminated for another during the first course. All patients had radiation therapy, stratified by stage. The cumulative dose to the primary sites was 59.4 gray (Gy), with single doses of 1.8 Gy. A total of 45 Gy was delivered to the neck area. Finally, all patients were treated with recombinant IFN-beta (10(5) U per kg of body weight) 3 times a week for 6 months. RESULTS: The response rate was 91%. These patients stayed in first remission during a median follow-up of 32 months. With the exception of one reversible cardiotoxicity, moderate chemotherapy-related toxicity was observed. CONCLUSIONS: In this study, patients with advanced stage NPC had a good prognosis with treatment consisting of neoadjuvant cisplatin and 5-fluorouracil, radiotherapy, and adjuvant IFN-beta. It is particularly noteworthy that distant metastases did not develop.

[Spectrographic studies on the radioresistance of Miltex and miltefosine]. / Spektrographische Untersuchungen zur Strahlenresistenz von Miltex und Miltefosin.

AIM: With simultaneous application of Miltex and radiation therapy in the combined treatment of topical relapses and skin metastases in breast carcinoma patients the question arises, how radioresistant is the new cytotoxic agent. Because of the long penetration times of the active agent miltefosine the answer is important with particular regard to the time of the external application of Miltex. MATERIAL AND METHOD: After the application of a single dose of 10 Gy we studied the stability of the commercial preparation and its active agent miltefosine by means of absorption spectroscopy. RESULTS: Immediately following the irradiation no alterations in absorption spectra of Miltex and miltefosine were found. However, 2 and 8 h post radiation the absorption curves of Miltex and miltefosine solutions were distinctly changed. The radiation induced changes of Miltex dilutions were smaller than those of the miltefosine solutions. For the commercial preparation the amount of the radiation-induced destruction is 0.10. CONCLUSIONS: Consequently Miltex has shown a sufficient radioresistance or its decrease in the effectiveness is small. With daily single doses of 2 Gy in the radiotherapy of the topical relapses and skin metastases the destruction degree should be reduced to 0.02 assuming linear changes. Because of the distinct changes in the spectra and relative slow penetration of miltefosine in various cell lines [10, 11, 14] we will propose an application of the commercial cytotoxic agent 5 h before the radiation fractions. The smaller effect on Miltex is discussed in relation to the solution mediators of the active agent.

Using an artificial neural network to define the planning target volume in radiotherapy.

A neural network for predicting the planning target volume in radiotherapy from the shape of the detected tumor is designed and tested in this research project. The proposed neural network is able to generalize expert medical knowledge and predict the planning target volume from a three-dimensional image of the detected tumor. Initial results for simple shaped brain tumors are presented in this paper.