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J Debus

Publications and source records attributed to J Debus.

At least 55 records · Page 3Linked to original sources
PubMed2003

Particle beams for cancer therapy.

Particle beams from protons to carbon ions have a number of important advantages for radiation therapy. Besides the physical selectivity that makes ions especially efficient for deep-seated tumours and tumours close to critical organs, carbon ions with their enhanced relative biological effectiveness offer an additional biological advantage for slow-growing radioresistant tumours, with an additional gain for tumours with hypoxic sections. These advantages can only be fully exploited by active beam-shaping and biology-based treatment planning.

Animals↗
PubMed2003

Assessment of brain metastases with dynamic susceptibility-weighted contrast-enhanced MR imaging: initial results.

PURPOSE: To assess if preradiation and early follow-up regional cerebral blood volume (CBV) measurements can help predict treatment outcome in patients with cerebral metastases and to evaluate regional CBV changes in tumor and normal tissue after radiosurgery. MATERIALS AND METHODS: In 18 patients, dynamic susceptibility-weighted contrast material-enhanced magnetic resonance (MR) imaging was performed with a 1.5-T unit, which allowed an absolute quantification of the regional CBV. Measurements were performed prior to and at 6 weeks and 3 months after therapy. Treatment outcome was classified according to tumor volume changes at 6 months. The regional CBV of the metastases and the normal adjacent brain tissue were determined with a region-of-interest analysis. Regional CBV values were correlated with the patient outcome to assess the sensitivity and specificity of dynamic susceptibility-weighted contrast-enhanced MR imaging. RESULTS: The pretherapeutic regional CBV was not able to help predict a treatment outcome; however, the method proved to be highly sensitive and specific for treatment outcome prediction at the 6-week follow-up. A decrease of the regional CBV value helped predict the treatment outcome with a sensitivity of more than 90%. The tumor volume change alone had a sensitivity of only 64%. The measured regional CBV values of normal brain tissue and their ratio were comparable to physiologic data and remained unchanged with therapy. CONCLUSION: The results suggest that dynamic susceptibility-weighted contrast-enhanced MR imaging is a useful method for the assessment of radiosurgically treated brain metastases. The implemented technique with determination of the arterial input function enables an absolute quantification of the regional CBV and prediction of tumor response.

Adult↗
PubMed2003

Heavy ion therapy: status and perspectives.

Starting with the pioneering work at the University of California in Berkeley in 1977, heavy ion radiotherapy has been of increasing interest especially in Japan and Europe in the last decade. There are currently 3 facilities treating patients with carbon ions, two of them in Japan within a clinical setting. In Germany, a research therapy facility is in operation and the construction of a new hospital based facility at the Heidelberg university will be started soon. An outline of the current status of heavy ion radiotherapy is given with emphasis to the technical aspects of the respective facilities. This includes a description of passive and active beam shaping systems, as well as their implications for treatment planning and dosimetry. The clinical trials and routine treatments performed at the German heavy ion facility are summarized. An overview over the upcoming new facilities and their technical possibilities is given. It is discussed what the necessary improvements are to fully exploit the potential of these facilities. Especially the new Heidelberg facility with the possibility of active beam scanning in combination with the first isocentric gantry for ions and offering beams of protons, helium, oxygen and carbon ions has implications on treatment planning, dosimetry and quality assurance. The necessary and ongoing developments in these areas are summarized. The new facilities also offer the possibilities to perform more extensive clinical studies and to explore future indications for radiotherapy with heavy ions. An overview over the indications and treatment schemes is also given.

Carbon↗
PubMed2003

Calcification in coronary arteries as quantified by CT scans correlated with tobacco consumption in patients with inoperable non-small cell lung cancer treated with three-dimensional radiotherapy.

It has been shown that radiological manifestations of coronary artery sclerosis are an indirect measure of co-morbidity and predictive of survival. The aim of the present study is to evaluate the outcome and side effects after three-dimensional (3D) radiotherapy in patients with unresectable non-small cell lung cancer (NSCLC) stage I, II and IIIA, depending on coronary artery calcification, Karnofsky performance index (KI) and co-morbidity. Between 1993 and 1999, 89 patients with unresectable NSCLC were treated with 3D-radiotherapy. The median age was 66.6 years and median KI 80%. All patients had 3D-treatment planning, based on CT scans. The median total dose was 60 Gy in 2 Gy fractions five times a week. The mean follow-up period was 13.2 months and mean survival time 12.2 months. Significant prognostic factors for improved survival were KI and tumour stage. Patients with a KI<90% had a median survival of 6.5 months compared with 14 months, in patients with KI>/==" BORDER="0">90% (p<0.001). NSCLC stage I+II showed a significantly longer median survival than patients with NSCLC stage IIIA (16.5 months versus 7 months, p<0.004). A significant correlation was seen between pack-years and coronary artery calcification (p<0.05) and between age and marked coronary artery calcification. The incidence of calcification was 67% in smokers (>/==" BORDER="0">20 pack-years) and 43/58 in patients >60 years (p<0.007). Side effects, e.g. pneumonitis, did not correlate with coronary artery calcification but correlated with chronic obstructive lung disease in 19/89 patients. Conventional CT scans for 3D-treatment planning are able to detect coronary artery calcification. There is a significant correlation between age, KI, tobacco consumption and vascular calcification. Although there was a trend to worse overall survival, coronary artery calcification was not a significant predictor of progression-free and overall survival.

Adult↗
PubMed2002

[Successful long-term treatment of multiple metastases from renal cell carcinoma: combination of stereotactically guided percutaneous single-dose convergent beam irradiation and surgery].

The case of a patient suffering from renal cell carcinoma and recurrent brain metastases shows how the survival period can be significantly prolonged by a combination of stereotactically guided percutaneous single-dose convergent beam irradiation and surgery. This 58-year-old man's left kidney was completely excised because of a renal cell carcinoma. After 18 months and 25 months, respectively, a right frontal brain metastasis was operated on. In the next 7 years, biannual MRI checks were carried out which successively showed five different brain metastases, each of which was immediately subjected to single-dose stereotactic irradiation (median dosage: 20 Gy prescribed to the 80% isodose). In the following 2 years, operations were carried out on two metastases which could not be treated by radiation because of their considerable size and partial compression of the ventricle. In the next 3 years, four more brain metastases were subjected to single-dose stereotactic irradiation. There were no metastases in the other organs. At present, the patient is in good clinical condition and mobile. A negative prognosis is usually delivered for patients suffering from renal cell carcinoma and brain metastasis. However, in individual cases, the survival period can be significantly prolonged by regular MRI examinations and a combination of neurosurgery and single-dose stereotactic irradiation.

Brain Neoplasms↗
PubMed2002

Differentiation of radiation necrosis from tumor progression using proton magnetic resonance spectroscopy.

We report on a young woman who was treated by stereotactic radiotherapy for recurrence of an initially resected low-grade astrocytoma. MRI follow-up examination 7 months after radiotherapy showed a gadolinium-DTPA-enhancing mass lesion indicative of high-grade tumor progression. This assumption was also supported by positron emission tomography with [2-18F]fluoro-2-deoxy-D-glucose (FDG-PET). In contrast, proton MR spectroscopy (1H-MRS) indicated radiation necrosis, which was confirmed histopathologically in surgical specimens. Subsequent follow-up examinations up to 19 months after surgery showed no evidence of tumor recurrence.

Adult↗
PubMed2002

Detection and quantification of the soluble form of the human erythropoietin receptor (sEpoR) in the growth medium of tumor cell lines and in the plasma of blood samples.

The erythropoietin receptor (EpoR) belongs to the cytokine superfamily and is a type I transmembrane protein. Like other members of this family, EpoR is also synthesized as a soluble form, and is subsequently secreted by the cell. To investigate whether soluble EpoR (sEpoR) is expressed in human tumor cell lines, we developed a sensitive quantitative ELISA, using an anti-human EpoR antibody and recombinant sEpoR as standard control. With this ELISA, sEpoR could be detected in the supernatant of human tumor cell lines. Analysis of blood samples showed that sEpoR was coprecipitated during coagulation. Therefore only plasma was suitable for analysis and first measurements of plasma samples were investigated. In conclusion, an ELISA to quantify the sEpoR was established and the expression of sEpoR in human tumor cell lines was demonstrated for the first time.

Adult↗
PubMed2002

Cytosine deaminase and thymidine kinase gene therapy in a Dunning rat prostate tumour model: absence of bystander effects and characterisation of 5-fluorocytosine metabolism with 19F-NMR spectroscopy.

The rat prostate tumour cell line R3327 AT-1 was transfected with a gene coding for a fusion protein comprised of cytosine deaminase (CD from E. coli) and thymidine kinase (TK from Herpes simplex virus, HSV-1). The resulting AT-1/CDglyTK cell line was sensitive to the prodrug 5-fluorocytosine (IC(50) = 78 microM, 96-h incubation) via CD and to ganciclovir (GCV, IC(50) = 1 microM, 96 h) via TK. Subcutaneous tumours generated from 100% CDglyTK(+) cells responded well to 5-FC therapy (500 mg/kg, i.p., 14 daily treatments, four out of seven animals in remission) and to GCV therapy (30 mg/kg, i.p., 14 daily treatments, five of six animals in remission). However, experiments with mixtures of CDglyTK(+) and CDglyTK(-) cells showed low levels of connexins (intercellular gap junctions) and no bystander effect for nontransfected cells using either 5-FC or GCV therapy. Furthermore, (19)F-NMR spectroscopy showed that incubation of cultured CDglyTK(+) cells with 774 microM 5-FC for 16 h resulted in the following intracellular concentrations: 5-FC = 314 microM, 5-FU = 52 microM, cytotoxic fluoronucleotides = 163 microM; extracellular 5-FU reached only 6.4 microM. Thus, in this model system intracellular trapping of 5-FU (slow export) contributes to the failure of the CD/5-FC bystander effect via an extracellular route.

Animals↗
PubMed2002

Dose-dependent differential effects of low and pulsed dose-rate brachytherapy in a radioresistant syngenic rat prostate tumour model.

PURPOSE: To study the response of the Dunning prostate carcinoma (R3327-AT1 subline) to continuous low dose-rate (CLDR) and pulsed dose-rate (PDR) brachytherapy. MATERIALS AND METHODS: After subcutaneous tumour transplantation into the thigh of the Copenhagen rat, doses of 0, 20, 30, 40 and 50 Gy were applied to the tumour surface (tumour diameter 9+/-1mm). Eight animals were irradiated per dose group and exposure condition. Interstitial PDR ((192)Ir source, 37 GBq) and CLDR ((192)Ir seed, 150 MBq) brachytherapy were carried out with 0.75 Gy/pulse h(-1) and a dose-rate of 0.75Gyh(-1), respectively. Treatment response was assessed in terms of growth delay expressed as the time (T(5)) required for each tumour to reach five times the initial tumour volume. RESULTS: The median T(5) times for the CLDR groups (in the order: control, 20, 30, 40, 50 Gy) were 12 (12), 54.5 (21), 64.5 (31), 85.5 (51), and 65 (47.5) days. Values after PDR brachytherapy are given in parentheses and resulted in a significantly impaired tumour growth delay (log-rank test) in the 20Gy (p =0.006) and 30 Gy (p =0.036) groups. No significant difference was found in the 40-50 Gy dose range. CONCLUSIONS: In contrast to previous results and predictions of biological models we observed dose-dependent differential effects of PDR and CLDR brachytherapy with reduced efficacy of PDR in the lower dose range.

Animals↗
PubMed2002

Preferential radiosensitization in p53-mutated human tumour cell lines by pentoxifylline-mediated disruption of the G2/M checkpoint control.

PURPOSE: There is evidence that the duration of the G2/M delay following irradiation is correlated with cell survival. We studied the radiosensitizing potential of pentoxifylline (PTX) and the PTX-mediated modulation of cell-cycle progression dependent on the p53 status of various human tumour cell lines. MATERIALS AND METHODS: The cellular radiosensitivity of human MCF-7 (wild-type p53) and HT-29 (p53-defective) tumour cells, which were exposed to PTX (2 mM) immediately after gamma-irradiation was determined by colony forming assay. The influence on cell cycle progression after irradiation (6 Gy) was assessed by flow cytometric analysis using p53 wild-type MCF-7 and HPR600 cells, and p53-defective HT-29 and WiDr cells. RESULTS: Clonogenic survival assays up to 8 Gy demonstrated that p53-defective HT-29 cells (sensitizer enhancement ratio [SER]=1.54) were sensitized by PTX (2 mM) to a significantly higher degree than p53 wild-type MCF-7 (SER=1.14) cells. Exposure of irradiated (6 Gy) cells to PTX (2 mM) resulted in abrogation of the radiation-induced G2/M arrest in the p53-defective HT-29 and WiDr cells, whereas the p53 wild-type-expressing MCF-7 and HPR600 cells showed less significant impairment of the G2/M checkpoint. In HT-29 cells, the rate of transition into mitosis was even higher than in the sham-treated control cells. G2/M abrogation was accompanied by an increase of apoptosis only in HPR600 cells. CONCLUSIONS: Since PTX was less effective in cells expressing intact p53, the application of PTX suggests a promising strategy of pharmacological disruption of the G2/M checkpoint control by which preferentially radiation-resistant tumours with defective p53 function might be rendered more sensitive to ionizing radiation.

Cell Cycle↗
PubMed2002

Intensity-modulated radiotherapy - technology and clinical applications.

Intensity-modulated radiotherapy (IMRT) is one of the most important developments in radiooncology of the last years. As an extension of 3D conformal radiotherapy, it provides the possibility of delivering a high radiation dose to the tumor tissue, protecting radiosensible critical organs nearby or even surrounded by the target. This is realized by the overlaying of beams from different directions, which are not homogeneous like in conventional radiotherapy, but inhomogeneous themselves. The sum of the beams from all directions forms finally the desired complex-shaped dose distribution. Because choosing the right intensity modulation of each beam is a nontrivial problem, the best treatment plan could only hardly be found in a trial-and-error process, but has to be computer- optimized. Therefore, IMRT has always to be spoken together with the term of 'inverse planning'. This describes the approach of telling the computerized planning system the desired radiation doses to the target and the allowed maximum doses to organs at risk (OAR), then letting the system compute the optimal modulated beams, called 'fluence profiles', by an iterative algorithm. Because the ideal dose distribution, giving 100% dose to the tumor and 0% dose to the healthy tissue, is never realizable, inverse planning has to be understood as an optimization problem. The present article shows the technical bases of IMRT and inverse planning and then describes important clinical applications.

Algorithms↗
PubMed2002

Comparison of forward planned conformal radiation therapy and inverse planned intensity modulated radiation therapy for esthesioneuroblastoma.

The purpose of this study was to compare dose distribution of inverse planned intensity modulated radiation therapy (IMRT) with that of conformal radiation therapy (SCRT) in the treatment of esthesioneuroblastoma, and to report initial clinical results. 13 patients with esthesioneuroblastoma were planned both with IMRT and SCRT using complete three-dimensional data sets. A target dose of 60 Gy was prescribed. We performed a detailed dose volume histogram analysis. Dose coverage was equal in both plans while dose distribution was more conformal to the target volume with IMRT. Mean and maximum dose of the brain stem, chiasm, optic nerves and orbits were lower using IMRT than SCRT. The reduction was significant regarding orbit and optic nerve (p<0.05). IMRT was superior in sparing of organs at risk compared with SCRT. The additional sparing by IMRT was positively correlated to the size of the target volume, which was evident with target volumes above 200 cm3. Treatment time was approximately 20 minutes per fraction using IMRT compared with 15 minutes per fraction using SCRT. We conclude that IMRT is both feasible and a valuable tool for more conformal dose distribution in the treatment of esthesioneuroblastoma and to spare organs at risk that are in critical relationship to the tumour. This advantage could be seen especially well in complex shaped target volumes above 200 cm3. Thus, using IMRT, risk of complications may be minimized and local tumour control may be increased.

Esthesioneuroblastoma, Olfactory↗
PubMed2002

Detection of NGF-receptors TrkA and p75NTR in human tumor cell lines and effect of NGF on the growth characteristic of the UT-7/EPO cell line.

The receptors for nerve growth factor (NGF)--TrkA and p75NTR--were detected at the mRNA and the protein level in various human tumor cell lines. The NGF receptor TrkA was found on all examined tumor cell lines and is not restricted to cells belonging to the nervous system. NGF did not influence the proliferation rate of TrkA-positive cells NMB, K562, UT-7/EPO and PC-12. After NGF induction, the production level of the differentiation marker c-fos was increased in UT-7/EPO and PC- 12 cells. NGF-treatment of the UT-7/EPO cells and deprivation of erythropoietin (EPO) led to the new adherent cell line UT-7/NGF. Although UT-7/NGF showed a similar growth curve as UT-7/EPO, there were differences in the pattern of adhesion molecules and of the cytoskeleton. The effect of NGF on the cytoskeleton could not be induced in other human cell lines like NMB or KTCTL-30. TrkA inhibition with K252a--a blocker of Trk-induced receptor kinase--suggests, that the NGF signal may be transduced by the TrkA receptor in UT-7/NGF cells. This indicates that NGF is a decisive mediator of cellular adhesion.

Blotting, Western↗
PubMed2002

Daily patient set-up control in radiation therapy by coded light projection.

Advances in conformal radiation therapy to control disease via dose escalation are challenged by set-up uncertainties. Recently, techniques have been developed to use surface features to evaluate the patient's position and correct it where necessary. The aim of this study was to use the patient's surface as a tool for daily set-up control and monitoring. We use a surface scanner based on the projection of coded light to receive--in a daily routine--a large amount of surface points which enables us to register the CT-based planning data with the patients current position. By superimposing current and planned volumes, a volume of congruency was obtained. An error below 1 mm was considered acceptable. In cases where set-up was not satisfactory a map of the surface comparison was evaluated showing the areas of missing alignment. According to this information a manual repositioning was performed. This procedure was repeated until the error was acceptable. No more then 3 repetitions where necessary to obtain an acceptable result. The whole procedure including registration, calculation and visualization took about 20 sec for one repetition. The use of structured light projection in the daily set-up control and monitoring proved to be a noninvasive, easy, quick, inexpensive and reliable solution.

Data Collection↗
PubMed2001

Management of benign cranial nonacoustic schwannomas by fractionated stereotactic radiotherapy.

Schwannomas are the most common tumors of cranial nerves. Nonacoustic schwannomas are very rare tumors, accounting for approximately 10% of intracranial schwannomas. Standard treatment is complete surgical resection if possible. The role of fractionated stereotactic radiotherapy remains to be defined. Thirteen patients with cranial nonacoustic schwannomas underwent fractionated stereotactic radiotherapy. Seven patients had trigeminal schwannomas, three schwannomas of the lower cranial nerves, and three located in the cerebellopontine angle without involvement of the acoustic nerve. Treatment included primary or adjuvant radiotherapy in progressive disease. Tumor volume ranged from 4.5 to 76.0 cc (median 19.8 cc). Median dose was 57.6 Gy with 1.8 Gy/fraction. Median follow-up was 33 months (range 13-70 months). Local tumor control rate was 100% (13/13). Tumor size remained stable in nine patients and decreased in four. Improvement of preexisting neurological deficits was seen in four cases. No patient developed new cranial nerve or brain stem deficits. No patient showed clinically significant complications of irradiation. Fractionated stereotactic radiotherapy is an effective and well-tolerated noninvasive treatment for cranial nonacoustic schwannomas with excellent tumor control rates. It is an option for patients at higher risk for microsurgical resection or in residual and recurrent tumors.

Adult↗
PubMed2001

Intensity-modulated radiotherapy with an integrated boost to the macroscopic tumor volume in the treatment of high-grade gliomas.

Integrated boost radiotherapy (IBRT) delivers a higher fraction size to the gross tumor volume and a conventional fraction size to the surrounding tissue of microscopic spread. We compared stereotactic conformal radiotherapy (SCRT) and intensity-modulated radiotherapy (IMRT) with regard to their suitability for IBRT in the treatment of high-grade gliomas. In 20 patients treated with conventional radiotherapy, an additional treatment plan for IBRT [planning target volume (PTV1) defined as contrast-enhancing lesion plus margin due to setup errors 75 Gy, PTV2 defined as edema plus margin due to microscopic spread and setup error 60 Gy] with 7 non-coplanar beams for IMRT and for SCRT was carried out and compared. The part of the PTV2 irradiated with more than 107% of the prescribed dose was 13.9% for IMRT and 30.9% for SCRT (P < 0.001). Dose coverage of PTV2 (volume above 95% of the prescribed dose) was improved with IMRT (88.4% vs. 75.3% with SCRT, P < 0.001). Dose coverage of PTV1 was slightly higher with SCRT (93.7% vs. 87.5% with IMRT), but the conformity to the boost shape was improved by IMRT [conformity index (COIN95) = 0.85 vs. 0.69 with SCRT]. Simultaneously the brain volume irradiated with > 50 Gy was reduced from 60 to 33 cc (P < 0.001). We conclude that IMRT is suitable for local dose escalation in the enhancing lesion and for delivering a homogeneous dose to the PTV2 outside the PTV1 at the same time. Our encouraging results justify application of IMRT for IBRT in the treatment of high-grade gliomas. For clinical evaluation a phase III study has been initiated.

Brain Neoplasms↗
PubMed2001

A new noninvasive approach in breast cancer therapy using magnetic resonance imaging-guided focused ultrasound surgery.

An ideal vision of modern medicine includes tumor surgery with the human body remaining completely intact. A noninvasive therapy could avoid infections and scar formation; it would require less anesthesia, reduce recovery time, and possibly also reduce costs. This study investigated whether human breast cancer can be effectively treated with a novel combination of image guidance and energy delivery, noninvasive magnetic resonance imaging (MRI)-guided focused ultrasound (FUS). We have developed a FUS therapy unit guided by MRI for the treatment of human breast tumors in a clinical 1.5 T MR scanner. With interactive target segmentation on MRI, defined volumes could be noninvasively treated in a single session with on-line MR temperature control. The ultrasound waves were focused through the intact skin and resulted in the localized thermal tissue ablation at a maximum temperature of 70 degrees C. The therapy principle was first demonstrated in sheep breast in vivo and was then applied in a patient with core biopsy-proven invasive breast cancer 5 days before breast-conserving surgery. MRI proved suitable to delineate the breast cancer, served as stereotactic treatment planning platform, and delineated the FUS-related tissue changes such as interruption of tumor blood flow. Furthermore, MRI localized the hot spot in the tumor and measured temperature elevation during the treatment. This allowed us to monitor the efficacy and safety of FUS therapy. Immunohistochemistry of the resected specimen demonstrated that FUS homogeneously induced lethal and sublethal tumor damage with consecutive up-regulation of p53 and loss of proliferative activity. This effect was realized without anesthesia and damage to the surrounding healthy tissue or systemic effects. Overall, our results show that noninvasive MRI-guided therapy of breast cancer is feasible and effective. Thus, MRI-guided FUS may represent a new strategy for the neoadjuvant, adjuvant, or palliative treatment in selected breast cancer patients and in patients with other soft-tissue tumors.

Animals↗