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ABSTRACT: Mit der Einführung der computerunterstützten, dreidimensionalen Bestrahlungsplanung auf schnittbildtomographischer Basis sowie
präziser Strahlformung durch individuelle Blöcke und Multi-leaf-Kollimatoren in den 90er Jahren wurde es möglich, hohe Dosisgradienten
zwischen dem Zielvolumen einerseits und strahlenempfindlichem Normalgewebe andererseits zu erzeugen. Für das Prostatakarzinom
existiert eine deutliche Abhängigkeit zwischen applizierter Dosis und therapeutischem Erfolg, insbesondere für mittlere und
ungünstige Prognosekriterien. In konventioneller Technik ist die Bestrahlungsdosis jedoch durch die Toleranz von Rektum und
Harnblase limitiert. Neue technische Methoden ermöglichen eine sichere und toxizitätsarme Eskalation der therapeutischen Dosis.
Die lokale Kontrollrate und das PSA-freie Überleben konnten deutlich verbessert werden. Die vorliegende Übersicht beschreibt
die verschiedenen etablierten Verfahren perkutaner sowie interstitieller Bestrahlungstechniken sowie die erzielten klinischen
Ergebnisse.
The implementation of computer-assisted three-dimensional radiotherapy treatment planning methods based on computed tomography
together with sophisticated beam modeling with individual blocks and multi-leaf-collimators in the 90's enabled the creation
of steep dose gradients between the target volume and surrounding radiosensitive normal tissue. For prostate cancer, a clear
dose dependence between the treated radiation dose and the treatment success is proven, especially for patients with intermediate
and unfavorable prognostic criteria. However, with conventional radiotherapy, rectum and urinary bladder are limiting the
applicable dose. New technical methods allow a safe dose escalation without increasing of treatment-related toxicity. An improvement
in terms of PSA remission and local control was yielded. This article presents the different established external beam and
interstitial treatment techniques and their clinical results.
Der Radiologe 04/2012; 43(6):448-454. · 0.61 Impact Factor
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ABSTRACT: This paper presents the BioShuttle platform as a delivery vehicle for transfer of contrast agents and genetic material into target cells, which can be followed by activation of the BioShuttle inside the target cell. Here, we present a transporter system and summarize the findings on transporter use in vivo and in vitro. The results here are limited to examples where cargoes (drugs, genetically active materials or contrast agents) are covalently associated with the transporter module. A further example, in which the cargo is non-covalently attached to the BioShuttle, is also discussed. Finally, attempts have been made to solve some of the issues surrounding the efficiency of transfer of therapeutic or diagnostic agents and their later activity in the cell.
Biochemical Society Transactions 09/2007; 35(Pt 4):829-32. · 3.71 Impact Factor
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R Krempien,
M W Muenter,
P E Huber,
S Nill,
H Friess,
C Timke, B Didinger,
P Buechler,
S Heeger,
K K Herfarth,
A Abdollahi,
M W Buchler,
J Debus
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
BMC Cancer 02/2005; 5:131. · 3.01 Impact Factor
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ABSTRACT: The GSI carbon ion radiotherapy facility established the first completely active beam shaping system for heavy ions, using energy variation on the synchrotron and pencil beam scanning. The introduction of an active beam shaping system for carbon ions has considerable impact on the design of the treatment planning system (TPS). The TPS has to account for the capability of the beam delivery and the biological modelling, which is needed to calculate the RBE for the resulting varying depth dose modulation. The TPS used in clinical routine with carbon ions is described and its use in treatment planning studies are outlined. A clinical trial with carbon ion therapy as primary therapy for chordoma and chondrosarcoma of the base of skull has been completed in 2001. Currently, carbon ion therapy as a boost treatment together with conventional conformal photon therapy or IMRT is under investigation in clinical trials for adenoid cystic carcinoma, chordoma and chondrosarcoma of the cervical spine and sacrococcygeal chordoma. Treatment planning studies comparing carbon ion therapy with IMRT, using optimization of combination therapy, and optimization of beam-line design have already been completed. Analysis of uncertainties in treatment planning has been started with the investigation of range uncertainties stemming from CT imaging. Uncertainties coming from the beam delivery play only a minor role. An attempt to asses the uncertainties introduced in treatment plans by the biological modelling, was done, using phantom verification of calculated cell survival levels. The clinical trials and planning studies are of special importance for the upcoming new clinical ion facility of the Heidelberg university hospital.
Radiotherapy and Oncology 01/2005; 73 Suppl 2:S86-91. · 5.58 Impact Factor
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R Krempien,
MW Muenter,
PE Huber,
S Nill,
H Friess,
C Timke, B Didinger,
P Buechler,
S Heeger,
KK Herfarth,
A Abdollahi,
MW Buchler,
J Debus
[show abstract]
[hide abstract]
ABSTRACT: Abstract
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 enrolment.
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.
BMC Cancer. 01/2005;
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ABSTRACT: Spinal chordomas cannot be treated with an effective dose using conventional radiation therapy (RT) without exceeding the tolerance dose of the spinal cord while ensuring sufficient target coverage at the same time. In this study we investigate the potential physical advantages of combined photon intensity-modulated radiation therapy (IMRT) and raster-scanned carbon ion RT over photon IMRT alone. For a representative patient we generated a carbon ion RT plan and a photon IMRT plan. Additionally, combined plans consisting of both carbon ions and photon IMRT were calculated using ratios of 20:40 GyE, 30:30 GyE and 40:20 GyE. The best target coverage was obtained using carbon ions alone. Using a combination of photon IMRT and carbon ions, the target coverage was better than with photon IMRT alone. Due to the applied dose constraints, the sparing of the spinal cord was comparable for all plans. Using carbon ions alone, the non-target tissue volume irradiated to at least 30 GyE/50.4 GyE was reduced by 72%/84% compared to photon IMRT alone. These advantages were evident even with combined techniques. The actually delivered dose distribution is expected to be more dependent on patient misalignment with carbon ions compared with photon IMRT. A combination of carbon ions and photon IMRT might be preferable in order to profit by the physical advantages of carbon ions while ensuring a safe treatment.
Physics in Medicine and Biology 09/2003; 48(16):2617-31. · 2.83 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The implementation of computer-assisted three-dimensional radiotherapy treatment planning methods based on computed tomography together with sophisticated beam modeling with individual blocks and multi-leaf-collimators in the 90's enabled the creation of steep dose gradients between the target volume and surrounding radiosensitive normal tissue. For prostate cancer, a clear dose dependence between the treated radiation dose and the treatment success is proven, especially for patients with intermediate and unfavorable prognostic criteria. However, with conventional radiotherapy, rectum and urinary bladder are limiting the applicable dose. New technical methods allow a safe dose escalation without increasing of treatment-related toxicity. An improvement in terms of PSA remission and local control was yielded. This article presents the different established external beam and interstitial treatment techniques and their clinical results.
Der Radiologe 07/2003; 43(6):448-54. · 0.61 Impact Factor
