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J Debus

Publications and source records attributed to J Debus.

At least 19 recordsLinked to original sources

Diagnostic performance of spectroscopic and perfusion MRI for distinction of brain tumors.

OBJECTIVE: To assess the value of spectroscopic and perfusion MRI for glioma grading and for distinguishing glioblastomas from metastases and from CNS lymphomas. METHODS: The authors examined 79 consecutive patients with first detection of a brain neoplasm on nonenhanced CT scans and no therapy prior to evaluation. Spectroscopic MRI; arterial spin-labeling MRI for measuring cerebral blood flow (CBF); first-pass dynamic, susceptibility-weighted, contrast-enhanced MRI for measuring cerebral blood volume; and T1-weighted dynamic contrast-enhanced MRI were performed. Receiver operating characteristic analysis was performed, and optimum thresholds for tumor classification and glioma grading were determined. RESULTS: Perfusion MRI had a higher diagnostic performance than spectroscopic MRI. Because of a significantly higher tumor blood flow in glioblastomas compared with CNS lymphomas, a threshold value of 1.2 for CBF provided sensitivity of 97%, specificity of 80%, positive predictive value (PPV) of 94%, and negative predictive value (NPV) of 89%. Because CBF was significantly higher in peritumoral nonenhancing T2-hyperintense regions of glioblastomas compared with metastases, a threshold value of 0.5 for CBF provided sensitivity, specificity, PPV, and NPV of 100%, 71%, 94%, and 100%. Glioblastomas had the highest tumor blood flow values among all other glioma grades. For discrimination of glioblastomas from grade 3 gliomas, sensitivity was 97%, specificity was 50%, PPV was 84%, and NPV was 86% (CBF threshold value of 1.4), and for discrimination of glioblastomas from grade 2 gliomas, sensitivity was 94%, specificity was 78%, PPV was 94%, and NPV was 78% (CBF threshold value of 1.6). CONCLUSION: Perfusion MRI is predictive in distinguishing glioblastomas from metastases, CNS lymphomas and other gliomas vs MRI and magnetic resonance spectroscopy.

Brain Neoplasms↗

Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment.

BACKGROUND: Presenting the initial clinical results in the treatment of complex shaped adenoid cystic carcinomas (ACC) of the head and neck region by inverse planned stereotactic IMRT. MATERIALS: 25 patients with huge ACC in different areas of the head and neck were treated. At the time of radiotherapy two patients already suffered from distant metastases. A complete resection of the tumor was possible in only 4 patients. The remaining patients were incompletely resected (R2: 20; R1: 1). 21 patients received an integrated boost IMRT (IBRT), which allow the use of different single doses for different target volumes in one fraction. All patients were treated after inverse treatment planning and stereotactic target point localization. RESULTS: The mean follow-up was 22.8 months (91-1490 days). According to Kaplan Meier the three year overall survival rate was 72%. 4 patients died caused by a systemic progression of the disease. The three-year recurrence free survival was according to Kaplan Meier in this group of patients 38%. 3 patients developed an in-field recurrence and 3 patient showed a metastasis in an adjacent lymph node of the head and neck region. One patient with an in-field recurrence and a patient with the lymph node recurrence could be re-treated by radiotherapy. Both patients are now controlled. Acute side effects >Grade II did only appear so far in a small number of patients. CONCLUSION: The inverse planned stereotactic IMRT is feasible in the treatment of ACC. By using IMRT, high control rates and low side effects could by achieved. Further evaluation concerning the long term follow-up is needed. Due to the technical advantage of IMRT this treatment modality should be used if a particle therapy is not available.

Adult↗

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer.

This trial aimed to assess the feasibility and tumour control of concurrent chemoradiotherapy or radiotherapy alone after docetaxel-based induction chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy with docetaxel (85 mg m(-2), day 1) plus cisplatin (40 mg m(-2), days 1 and 2). Patients without disease progression on day 43 were randomised to radiotherapy (2 Gy for 5 days week(-1); total 60 Gy) alone or with docetaxel 20 mg m(-2) once weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104 were evaluable for response. After induction chemotherapy, the overall response rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were subsequently randomised to local treatment. After randomised therapy, the ORR was 53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and 14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities during induction chemotherapy and randomised therapy were grades 3-4 neutropenia and grade 3 lymphocytopenia, respectively. Docetaxel-cisplatin induction therapy followed by concurrent docetaxel and thoracic radiotherapy is a feasible treatment option, showing good clinical activity and tolerability, for locally advanced NSCLC.

Adolescent↗

[Application of (1)H MR spectroscopic imaging in radiation oncology: choline as a marker for determining the relative probability of tumor progression after radiation of glial brain tumors].

PURPOSE: To determine the relative signal intensity ratios of choline (Cho), phosphocreatine (CR) and N-acetyl-aspartate (NAA) in MR spectroscopic imaging (proton-MRSI) for differentiating progressive tumors (PT) from non-progressive tumors (nPT) in follow-up and treatment planning of gliomas. Threshold values to indicate the probability of a progressive tumor were also calculated. MATERIAL AND METHODS: Thirty-four patients with histologically proven gliomas showing a suspicious brain lesion in MRI after stereotactic radiotherapy were evaluated on a 1.5 Tesla unit (Magnetom Vision, Siemens, Erlangen, Germany) using 2D proton MRSI (repetition time/echo time = 1500/135 msec, PRESS; voxel size 9 x 9 x 15 mm (3)). A total of 274 spectra were analyzed (92 voxel were localized within the suspicious brain lesion). Relative signal intensities Cho, Cr and NAA were measured and their ability to discern between PT and nPT was assessed using the linear discrimination method, logistic regression, and the cross-validation method. PT and nPT were differentiated between on the basis of clinical course and follow-up by MRI, CT and positron emission tomography. RESULTS: The Cho parameter and the relative signal intensity ratios of Cr and NAA were most effective in differentiating between PT and nPT. The logistic regression method using the parameter ln(Cho/Cr) and ln(Cho/NAA) had the best predictive results in cross-validation. A sensitivity of 93.8 % and specificity of 85.7 % were achieved in the differentiation of PT from nPT by proton-MRSI. CONCLUSION: (1)H-MRSI has a high sensitivity and specificity for differentiating between therapy-related effects and the relapse of irradiated gliomas. This method allows for assessment of the probability of radiotherapy response or failure.

Adult↗

Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518).

BACKGROUND: Even today, treatment of Stage III NSCLC still poses a serious challenge. So far, surgical resection is the treatment of choice. Patients whose tumour is not resectable or who are unfit to undergo surgery are usually referred to a combined radio-chemotherapy. However, combined radio-chemotherapeutic treatment is also associated with sometimes marked side effects but has been shown to be more efficient than radiation therapy alone. Nevertheless, there is a significant subset of patients whose overall condition does not permit administration of chemotherapy in a combined-modality treatment. It could be demonstrated though, that NSCLCs often exhibit over-expression of EGF-receptors hence providing an excellent target for the monoclonal EGFR-antagonist cetuximab (Erbitux) which has already been shown to be effective in colorectal as well as head-and-neck tumours with comparatively mild side-effects. METHODS/DESIGN: The NEAR trial is a prospective phase II feasibility study combining a monoclonal EGF-receptor antibody with loco-regional irradiation in patients with stage III NSCLC. This trial aims at testing the combination's efficacy and rate of development of distant metastases with an accrual of 30 patients. Patients receive weekly infusions of cetuximab (Erbitux) plus loco-regional radiation therapy as intensity-modulated radiation therapy. After conclusion of radiation treatment patients continue to receive weekly cetuximab for 13 more cycles. DISCUSSION: The primary objective of the NEAR trial is to evaluate toxicities and feasibility of the combined treatment with cetuximab (Erbitux) and IMRT loco-regional irradiation. Secondary objectives are remission rates, 3-year-survival and local/systemic progression-free survival.

Adult↗

[Advances in radio-oncology. From precision radiotherapy with photons to ion therapy with protons and carbon ions].

Modern techniques in radiation oncology, such as fractionated stereotactic radiotherapy (FSRT), stereotactic radiosurgery (SRS) or intensity modulated radiotherapy (IMRT) allow the application of high local doses to defined treatment volumes, while normal structures in close vicinity can be spared; high local control rates can be achieved, while treatment-related toxicity can be minimized. Innovative Hi-Art tomotherapy systems offer an alternative, combining a 6 MV photon accelerator with a CT scanner. Ion beams, such as protons and carbon ions, have been shown to be beneficial for distinct tumor entities. Both offer a characteristic physical dose distribution with an inverse dose profile contributing to beneficial dose conformality. Carbon ions also offer the advantage of increased relative biological effectiveness. For certain tumor types, a significant increase in local control and survival rates could be obtained with carbon ions.

Carbon↗

[Solitary iris metastasis from breast cancer. Effective local therapy with electron beam irradiation].

BACKGROUND: The prevalence of intraocular metastases from breast cancer is approximately 4-5%. Solitary metastases of the iris are rare. We report on successful treatment of a solitary iris metastasis using electron beam irradiation. CASE REPORT: A 30-year-old patient presented with an amelanotic tumor of the iris and the anterior chamber angle of her right amblyopic eye. The patient had undergone left-sided breast-conserving surgery and lymph node dissection 3 years before followed by chemotherapy and radiotherapy. The iris tumor was considered a metastasis. Fractionated electron beam irradiation was performed applying a total dose of 50 Gy in fractions of 5 x 2 Gy/week, electrons (9 MeV). The iris metastasis was completely resolved 13 months after radiotherapy. Until now no signs of cataract have been detected and visual acuity has remained stable. CONCLUSION: Electron beam irradiation of this iris metastasis was an effective treatment for preserving visual acuity and ocular function with tolerable acute toxicity and so far no adverse side effects.

Adult↗

Kilovoltage CT using a linac-CT scanner combination.

Modern radiotherapy techniques such as intensity modulation are capable of generating complex dose distributions whose high dose areas tightly conform to the tumour target volume, sparing critical organs even when they are located in close proximity. This potential can only be exploited to its full extent when the accumulated dose actually delivered over the complete treatment course is sufficiently close to the dose computed on the initial CT scan used for treatment planning. Exact patient repositioning is mandatory, but also other sources of error, e.g. changes of the patient's anatomy under therapy, should be taken into account. At the German Cancer Research Center, we use a combination of a linear accelerator and a CT scanner installed in one room and sharing the same couch. It allows the quantification and correction of interfractional variations between planning and treatment delivery. In this paper, we describe treatments of prostate, paraspinal and head and neck tumours. All patients were immobilized by customized fixation devices and treated in a stereotactic setup. For each patient, frequent CT scans were taken during the treatment course. Each scan was compared with the original planning CT using manual checks and automatic rigid matching algorithms. Depending on the individual case, the adaptation to variations was carried out offline after several fractions or in real-time between the CT scan and linac irradiation. We discuss the techniques for detecting and correcting interfractional errors and outline the procedural steps of a linac-CT scanner-supported radiation treatment course.

Humans↗

[Comparison of diagnostic accuracy of (18)F-FDG PET, (123)I-IMT- and (99m)Tc-MIBI SPECT: evaluation of tumour progression in irradiated low grade astrocytomas].

AIM: To evaluates the diagnostic accuracy of the SPECT-tracers 3-(123)I-alpha-methyl-L-tyrosine (IMT) and (99m)Tc(I)- hexakis(2-methoxyisobutylisonitrile) (MIBI) as well as the PET-tracer 2-(18)F-2-deoxyglucose (FDG) for detecting tumour progression in irradiated low grade astrocytomas (LGA). PATIENTS, METHODS: We examined 91 patients (56 males; 35 females; 44.7 +/- 11.5 years), initially suffering from histologically proven LGAs (mean WHO grade II) and treated by stereotactic radiotherapy (59.0 +/- 4.6 Gy). On average 21.9 +/- 11.2 months after radiotherapy, patients presented new Gd-DTPA enhancing lesions on MRI, which did not allow a differentiation between progressive tumour (PT) and non-PT (nPT) at this point of time. PET scans (n = 82) were acquired 45 min after injection of 208 +/- 32 MBq FDG. SPECT scans started 10 min after injection of 269 +/- 73 MBq IMT (n = 68) and 15 min after injection of 706 +/- 63 MBq MIBI (n = 34). Lesions were classified as PT and nPT based on prospective follow-up (clinically, MRI) for 17.2 +/- 9.9 months after PET/SPECT. Lesion-to-normal ratios (L/N) were calculated using contra lateraly mirrored reference regions for the SPECT examinations and reference regions in the contra lateral grey (GM) and white matter (WM) for FDG PET. Ratios were evaluated by Receiver Operating Characteristic (ROC) analysis. RESULTS: In the patient groups nPT and PT, L/N ratios for FDG (GS) were 0.6 +/- 0.3 vs. 1.2 +/- 0.5 (p = 0.003), for FDG (WS) 1.2 +/- 0.4 vs. 2.6 +/- 0.4 (p < 0.001), for IMT 1.1 +/- 0.1 vs. 1.8 +/- 0.4 (p < 0.001) and for MIBI 1.6 +/- 0.7 vs. 2.6 +/- 2.2 (p = 0.554). Areas under the non-parametric ROC-curves were: 0.738 +/- 0.059 for FDG (GS), 0.790 +/- 0.057 for FDG (WS), 0.937 +/- 0.037 for IMT and 0.564 +/- 0.105 for MIBI. CONCLUSION: MIBI-SPECT examinations resulted in a low accuracy and especially in a poor sensitivity even at modest specificity values. A satisfying diagnostic accuracy was reached with FDG PET. Using WM as reference region for FDG PET, a slightly higher AUC as compared to GM was calculated. IMT yielded the best ROC characteristics and the highest diagnostic accuracy for differentiating between PT and nPT in irradiated LGA.

Adult↗

Randomized phase II--study evaluating EGFR targeting therapy with cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer--PARC: study protocol [ISRCTN56652283].

BACKGROUND: Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR. METHODS/DESIGN: The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrollment. DISCUSSION: The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment). Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life.

Antibodies, Monoclonal↗

Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma -- CapRI: study protocol [ISRCTN62866759].

UNLABELLED: After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. DESIGN: The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrollment. DISCUSSION: The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

Adenocarcinoma↗

Monitoring of liver metastases after stereotactic radiotherapy using low-MI contrast-enhanced ultrasound--initial results.

The purpose of this study was to monitor liver metastases after radiotherapy using contrast-enhanced ultrasound (CEUS). In 15 patients, follow-up examinations after stereotactic, single-dose radiotherapy were performed using CEUS (low mechanical index (MI), 2.4-ml SonoVue) and computed tomography (CT). Besides tumor size, the enhancement of the liver and the metastases was assessed at the arterial, portal venous, and delayed phases. The sizes of the tumor and of a perifocal liver reaction after radiotherapy measured with CEUS significantly correlated with those measured at CT (r=0.93, p<0.001). CEUS found a significant reduction of the arterial vascularization in treated tumors (p<0.05). In the arterial phase, the perifocal liver tissue was hypervascularized compared to the treated tumor (p<0.001); in the late phase, it was less enhanced than the liver (p<0.001) and more than the tumor (p<0.01). The perifocal liver reaction was also seen in CT, but with a variable enhancement at the arterial (50% hyperdense compared to normal liver tissue), venous, or delayed phase (each with 70% hyperdense reactions). CEUS allows for the assessment of tumor and liver perfusion, in addition to morphological tumor examination, which was comparable with CT. Thus, changes of tumor perfusion, which may indicate tumor response, as well as the perifocal liver reaction after radiotherapy, which must be differentiated from perifocal tumor growth, can be sensitively visualized using CEUS.

Contrast Media↗

[Treatment of metastases--the place of radiotherapy].

Radiotherapy has a permanent place in the treatment of metastases. Irradiation--both in palliative and curative intent--is applied mainly to treat brainand bone metastases. In the case of the latter, an appreciable reduction in pain, but also recalcification of osteolytic lesions posing a threat to bone stability can be induced. The neurological symptoms of cerebral metastases, as well as overall survival, are also improved. Here, local tumor control is largely equal to that achieved with surgical treatment of metastases. Through the use of very precise stereotactic irradiation techniques sparing normal tissue, side effects can also be kept low. Similar techniques of precision irradiation are now also being applied to visceral metastases. Impressive remission rates have been achieved in the lungs and liver.

Aged↗

[Stereotactic radiation therapy for liver metastases].

Advances in radiation oncology made possible the locally curative treatment approach of stereotactically guided radiation therapy of liver tumours. Results of this highly focussed therapy were published by only a few centres. The radiation dose is delivered in one or a few fractions with high single doses. All published results show high local tumour control with low treatment morbidity. The treatment results of this noninvasive technique are similar to those of minimally invasive ablative therapies. Our own and other published data are summarized and discussed. The long-term results of this technique are currently being evaluated in a prospective multicentre trial.

Colorectal Neoplasms↗

[Imaging of sacral chordoma: comparison between MRI and CT].

AIM: Sacral chordoma is a primarily benign tumor with a high tendency to recur. A correct definition of tumor volume is a significant prognostic factor. We compared the value of CT and MRI in diagnosing a sacral chordoma. METHODS: 31 patients with a histologically proven sacral chordoma were included in this study. Following parameters were analyzed by two independent radiologists: septation, signs of blood and ossification in the tumor tissue, contrast enhancement, maximal tumor diameter, infiltration of the soft tissue, the dural salc and the cauda equina and multifocality. RESULTS: In CT all chordomas showed a hypodensity to the normal tissue and in MRI a hyperintensity on T2w images with a low level of contrast enhancement. On the basis of the more precise soft tissue contrast of MRI compared with CT, MRI was significantly more accurate in all tested parameters (p <0.05) besides in detecting tumor ossification. In CT tumor volume was frequently underestimated. CONCLUSION: MRI in sacral chordoma is an essential tool in the pretherapeutic diagnostic regimen and in a state of relapse.

Adult↗

Recurrent low-grade gliomas: the role of fractionated stereotactic re-irradiation.

PURPOSE: To assess the effectiveness of re-irradiation in recurrent low-grade gliomas (LGG). PATIENTS AND METHODS: Sixty-three patients were treated with fractionated stereotactic re-irradiation in the case of recurrent gliomas. At primary diagnosis of the tumor, the histology was grade II astrocytoma, oligodendroglioma or oligoastrocytoma. Fifty-two (82.5%) recurrences were in-field, three (4.8%) were localized at the field border, and eight (12.7%) tumors were localized completely out-field of the former RT field, respectively. Using three to four irregular non-coplanar fields formed with a multi-leaf-collimator, we applied a median total dose of 36 Gy (range 15-62 Gy)with a weekly fractionation of 5 x 2 Gy/week depending on the size and the location of the lesion. No concomitant chemotherapy was applied. RESULTS: Radiation was well tolerated by all patients. No severe side effects occurred. Median overall survival was 111 months (range 12-240 months). Extent of neurosurgical resection significantly influenced overall survival (P = 0.02). Median interval between the first radiation therapy and re-irradiation was 50 months (range 5-204 months). From the time point of re-irradiation, median survival was 23 months. Median progression-free survival from the time point of re-irradiation was 12 months (range 2-63 months). No prognosticators could be identified for survival from re-irradiation and progression free survival. CONCLUSION: Our retrospective data suggest that stereotactically guided fractionated re-irradiation in recurrent glioma represents an effective treatment option with good results and few complications. However, further investigation is warranted to consolidate these results and to combine radiation with chemotherapy in the case of recurrent LGG.

Adult↗