Hans Blattmann - Academia.edu (original) (raw)
Papers by Hans Blattmann
Purpose: Microbeam radiation therapy (MRT), a novel experimental radiosurgery that largely spares... more Purpose: Microbeam radiation therapy (MRT), a novel experimental radiosurgery that largely spares the developing CNS and other normal tissues, is tolerated well by developing animals and palliates advanced 9LGS tumors.
This report, to our knowledge, is the first demonstration that gene-mediated immunotherapy (GMIMPR) enhances the efficacy of MRT for advanced 9LGS tumors.
Methods: Seventy-six male Fischer 344 rats were implanted ic with 104 9LGS cells on d0. By d14, the cells had generated 40 mm3 ic 9LGS tumours, experimental models for therapy of moderately aggressive human malignant astrocytomas. Each of the 14 untreated (control) rats died from a large (>100 mg) ic tumor before d29 (median, d21). On d14, the remaining 62 rats were given deliberately suboptimal microbeam radiation therapy (MRT) by a single lateral exposure of the tumor-bearing zone of the head to a 10.1 mm-wide, 11 mm-high array of 20–39 lm-wide, nearly parallel beams of synchrotron wiggler-generated radiation (mainly 50–150 keV X-rays) that delivered 625 Gy peak skin doses at 211 lm ctc intervals in 300 ms either without additional treatments (MRTonly, 25 rats), with post-MRT GMIMPR (MRT+GMIMPR, 23 rats: multiple sc injections of irradiated (clonogenically- disabled) GM-CSF gene-transfected 9LGS cells), or with post-MRT IMPR (MRT+IMPR, 14 rats:
multiple sc injections of irradiated (clonogenically-disabled) 9LGS cells.
Results: The median post-implantation survivals of rats in the MRT-only, MRT+GMIMPR and MRT+IMPR groups were over twice that of controls; further, 20% of rats in MRT-only and MRT+IMPR groups survived >1 yr with no obvious disabilities. Moreover, over 40% of MRT+GMIMPR rats survived >1 yr with no obvious disabilities, a significant (P<0.04) increase over the MRT-only and MRT+IMPR groups.
Significance: These data suggest that the combination of MRT+GMIMPR might be better than MRT only for unifocal CNS tumors, particularly in infants and young children.
Abstract. Microbeam radiosurgery (MBRS), also referred to as microbeam radiation therapy (MRT), w... more Abstract. Microbeam radiosurgery (MBRS), also referred to as microbeam radiation therapy (MRT), was tested at the European Synchrotron Radiation Facility (ESRF). The left tibiofibular thigh of a mouse bearing a subcutaneously (sc) implanted mouse model (SCCVII) of aggressive human squamous-cell carcinoma was irradiated in two orthogonal exposures with or without a 16 mm aluminium filter through a multislit collimator (MSC) by arrays of nearly parallel microbeams spaced 200 mm on centre (oc). The peak skin-entrance dose from each exposure was 442 Gy, 625 Gy, or 884 Gy from 35 mm wide beams or 442 Gy from 70 mm wide beams. The 442/35, 625/35, 884/35 and 442/70 MBRSs yielded 25 day, 29 day, 37 day and 35 day median survival times (MST) (post-irradiation), respectively, exceeding the 20 day MST from 35 Gy-irradiation of SCCVIIs with a seamless 100 kVp X-ray beam.
Background and purpose: To quantify the late dose-related responses of the rat cervical spinal co... more Background and purpose: To quantify the late dose-related responses of the rat cervical spinal cord to Xray irradiations by an array of microbeams or by a single millimeter beam.
Materials and methods: Necks of anesthetized rats were irradiated transversely by an 11 mm wide array of 52 parallel, 35 lm wide, vertical X-ray microbeams, separated by 210 lm intervals between centers. Comparison was made with rats irradiated with a 1.35 mm wide single beam of similar X-rays. Rats were killed when paresis developed, or up to 383 days post irradiation (dpi).
Results: Microbeam peak/valley doses of 357/12.7 Gy to 715/25.4 Gy to an 11 mm long segment of the spinal cord, or single beam doses of 146–454 Gy to a 1.35 mm long segment caused foreleg paresis and histopathologically verified spinal cord damage; rats exposed to peak/valley doses up to 253/9 Gy were paresis-free at 383 dpi.
Conclusions: Whereas microbeam radiation therapy [MRT] for malignant gliomas implanted in rat brains can be safe, palliative or curative, the high tolerance of normal rat spinal cords to similar microbeam exposures justifies testing MRT for autochthonous malignancies in the central nervous system of larger animals with a view to subsequent clinical applications.
Radiation and Environmental Biophysics, 2001
The tumour suppressor gene p53 and the intracellular signalling molecule ceramide have both been ... more The tumour suppressor gene p53 and the intracellular signalling molecule ceramide have both been shown to play crucial roles in the induction of apoptosis by ionising radiation. In this study we examined whether p53 and ceramide are involved in independent signal pathways, inducing different types of apoptosis. TK6 (p53wt/wt) and WTK1 (p53mut/mut) lymphoblastoid cells were treated with ionising radiation or N-acetyl-D-sphingosine (C2-ceramide). Flow cytometry and fluorescence microscopy studies were performed to characterise the time kinetics and morphological features of induced apoptosis. Ceramide- and radiation-induced apoptotic cells display characteristic differences in morphology and DNA staining and ceramide-induced apoptosis is expressed much faster than radiation-induced apoptosis. Radiation-induced apoptosis is p53-dependent and ceramide-induced apoptosis is p53-independent. The p53 pathway and the ceramide pathway are two independent signal pathways leading to distinct types of apoptosis. Since p53 is very often dysfunctional in tumour cells, modifying the ceramide pathway is a promising strategy to increase tumour sensitivity to radiation and other anticancer agents.
Boron Neutron Capture Therapy, 1992
Strahlentherapie Und Onkologie, Feb 1, 1990
Protons have a long tradition in precision treatment of lesions of limited size at limited depth.... more Protons have a long tradition in precision treatment of lesions of limited size at limited depth. Recently interest has developed in hospital based proton therapy accelerators, able to treat deep seated tumors. Heavy charged particles, and especially protons, are particularly suited to treat well localized tumors. Protons can be collimated as precisely as photons, but in addition have a well defined range. Protons are therefore predestinated for conformation radiotherapy also for larger target volumes. At the Swiss Institute for Nuclear Research a computer optimized treatment planning system has been developed for pion radiotherapy. The principle of this dynamic treatment technique can be adapted for proton therapy. It could prove to be a valid alternative to passive scattering for proton treatment especially of large irregularly shaped volumes. Dose calculations have been performed for specific cases using a 250 MeV pencil beam. The dose distributions and dose volume histograms have been compared with pion therapy. A horizontal experimental beam line, using a degraded 590 MeV proton beam of the PSI ring cyclotron, is set up to verify calculations in phantoms.
Int J Radiat Oncol Biol Phys, 1982
Nuclear Medicine and Biology, 2001
5-bromodeoxyuridine (BUdR) provides in vitro measures of tumor cell proliferation. We used positr... more 5-bromodeoxyuridine (BUdR) provides in vitro measures of tumor cell proliferation. We used positron emission tomography to study tissue and plasma kinetics of [76Br]BUdR in tumor-bearing animals. In order to account for the slow washout of the major plasma metabolite, [76Br]bromide, a mathematical correction for the distribution volume of [76Br]bromide was applied. However, following correction specific tumor tracer retention was low or even zero and did not correlate with independent measures of proliferation. The kinetic characteristics of [76Br]BUdR make this tracer unsuitable for proliferation imaging.
Radiat Environ Biophys, 1979
Monolayer cultures of the fibroblast-like Chinese hamster cell-line 19/1 were irradiated in the G... more Monolayer cultures of the fibroblast-like Chinese hamster cell-line 19/1 were irradiated in the G2-phase of the cell cycle by n--mesons (6 rad/min peak-pion dose rate). Frequencies of induced single-and isochromatid breaks, acentric fragments and interchanges were compared with data obtained from 140 kV X-rays.
International Journal of Radiation Biology
Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2005
Radiotherapy is among the most useful treatments of cancer. Penetrating radiation (ionizing parti... more Radiotherapy is among the most useful treatments of cancer. Penetrating radiation (ionizing particles or bremsstrahlung photons) is aimed toward the tumor-bearing target, gradually delivering as high radiation to it as is usefully suppressive of tumor growth, yet tolerated by normal vital tissues inevitably irradiated with the tumor. The high collimation and dose rate of synchrotron X-ray beams, even when monochromatized, favor radiotherapy. Photon activation therapy, tomotherapy, microbeam radiation therapy, and radiosurgery mediated by synchrotron wigglers are conceptually promising for difficult tumors. Radiotherapy of malignant brain tumors in rats has been encouraging, but suitable beam lines exist at only a few research facilities and much basic work must be done before the promise of synchrotron-based radiotherapy can be realized clinically. r
Radiation Oncology Investigations, 1993
In conformation radiotherapy a target is irradiated uniformly, whereas surrounding organs receive... more In conformation radiotherapy a target is irradiated uniformly, whereas surrounding organs receive non-unifonn radiation. Clinical data concerning complications with conventional radiation are not applicable there without appropriate compensation. A solution was proposed by Lyman b t J Radiat Oncol Biol Phys 13:103-109, 1987 and 17:433-436, 1989; Radiat Res Suppl 8:13-19, 19851 using dose-volume histograms. It reduces a given histogram to a single step which corresponds to the equivalent complication probability. It converts non-uniform radiation into a unique dose to the whole organ which has the equivalent complication probability. This method was applied to actual patients treated by pion conformation technique at Paul Schemer Institute (PSI). Of 90 pelvic tumors, 16 developed grade 111-IV bladder injury and 7 developed grade 111-IV rectal injury. The 90 cases were divided into roughly equal groups according to the equivalent doses to the entire bladder and rectum. Observed complication rates and the equivalent doses to the full organs in these groups could be represented by a sigmoid dose-effect relation. When the relative biological effectiveness (RBE) is assumed to be 2.1 for bladder injury, the observed complication rates of the bladder fit best to the theoretical curve. When the RBE value is 2.3, the rates of rectal injury fit best. These values are close to the conversion factor of 2.0 used in clinical practice. This agreement suggests the feasibility of the method.
Zeitschrift für medizinische Physik, 2004
A fast and accurate magnetic tracking system was developed for applications in real-time tumor tr... more A fast and accurate magnetic tracking system was developed for applications in real-time tumor tracking, computer-aided surgery, and endoscopy. The tracking is based on the application of miniaturized sensors. Once implanted in the patient, the sensors receive signals from an external field generator. The fast evaluation of the signals allows the online determination of position and orientation of each sensor. With the help of optical tracking, the sensor coordinates are transformed in the reference system used by the clinician. The effects of eddy currents in nearby electrically-conducting objects are taken into account using special computational methods. The present paper presents the results of a first experiment in a canine model.
Veterinary research communications, 1998
Spontaneous tumours in dogs and cats are an excellent model for clinical human research, such as ... more Spontaneous tumours in dogs and cats are an excellent model for clinical human research, such as in developing proton conformation radiotherapy for humans. The kinetics of tumour cells can be used effectively to predict prognosis and response to therapy in patients with tumours. Knowledge of the kinetic parameters in these tumours is therefore important. In the present study the kinetic parameters evaluated included the labelling index (LI), relative movement (RM), mitotic index (MI), and potential doubling time (Tpot). These parameters were determined using in vivo labelling with bromodeoxyuridine, flow cytometry and histological preparation. Samples were obtained and evaluated from 72 dogs and 20 cats, presenting as patients in our clinic. Within the groups of epithelial and mesenchymal tumours from dogs and cats, the kinetic parameters LI, RM and MI were compared with Tpot. Significant correlations were observed for the comparison Tpot and LI. No correlation was found between Tpo...
Cancer/Radiothérapie, 1998
Cellular and molecular biology (Noisy-le-Grand, France), 2000
The application of synchrotron radiation in medical research has become a mature field of researc... more The application of synchrotron radiation in medical research has become a mature field of research at synchrotron facilities worldwide. In the relatively short time that synchrotrons have been available to the scientific community, their characteristic beams of UV and X-ray radiation have been applied to virtually all areas of medical science which use ionizing radiation. The ability to tune intense monochromatic beams over wide energy ranges differentiates these sources from standard clinical and research tools. At the European Synchrotron Radiation Facility (Grenoble, France), a major research facility is operational on an advanced wiggler radiation beamport, ID17. The beamport is designed to carry out a broad range of research ranging from cell radiation biology to in vivo human studies. Medical imaging programs at ID17 include transvenous coronary angiography, computed tomography, mammography and bronchography. In addition, a major research program on microbeam radiation therapy...
Veterinary Radiology <html_ent glyph="@amp;" ascii="&"/> Ultrasound, 2003
Radiation treatment requires a precise procedure for interfraction repositioning of the patient. ... more Radiation treatment requires a precise procedure for interfraction repositioning of the patient. The purpose of this study was to determine the accuracy of our fixation device in treatment position and to evaluate the setup accuracy with two different methods. The positioning data of 19 canine patients with tumors in the head region (oral, nasal, cerebral) treated with photon or proton irradiation were included in this study. The patients were immobilized by means of an individualized fixation device. Focus was set upon interfraction displacement with systematic and random components. In one method, treatment position was evaluated using single plane port radiographs and megavoltage x-rays. In the other method, two orthogonal CT-topograms were acquired to evaluate the precision of positioning of the patient in the immobilization device. Systematic and random displacements were calculated and presented as mean values with corresponding 95% confidence intervals. In spite of a difference between both methods, the positioning seemed to he accurate within the expected range. It seems that a safety margin of 3.7 mm would be enough for both methods to take into account systematic and random position variability in the fixation device, thereby preventing geometric inaccuracies of treatment delivery. The reported immobilization protocol provides accurate patient immobilization for photon and conformal proton radiation therapy.
Veterinary Radiology & Ultrasound, 2009
Thirty dogs with spontaneous tumors were irradiated with proton therapy using a novel spot scanni... more Thirty dogs with spontaneous tumors were irradiated with proton therapy using a novel spot scanning technique to evaluate the safety and efficacy of the system, and to study the acute and late radiation reactions. Nasal tumors, soft tissue sarcomas, and miscellaneous tumors of the head were treated with a median total dose of 52.5 Gy given in 3.5 Gy fractions. Acute effects, late effects, tumor response, and outcome were analyzed. No unexpected radiation reactions were seen, however two dogs did develop in-field osteosarcoma, and one dog developed in-field bone necrosis. Complete response to therapy was seen in 40% (12/30), partial response in 47% (14/30), and no response in 13% (4/30). Median survival for all dogs was 385 days (range of 14-4583 days). Dogs with nasal cavity tumors had a median survival of 385 days (range of 131-1851 days) and dogs with soft tissue sarcomas had a median survival time of 612 days (range of 65-4588 days). Treatment outcome was similar to historical controls. This new proton spot scanning technique proved to be safe and reliable. Veterinary
Veterinary Radiology <html_ent glyph="@amp;" ascii="&"/> Ultrasound, 2004
Purpose: Microbeam radiation therapy (MRT), a novel experimental radiosurgery that largely spares... more Purpose: Microbeam radiation therapy (MRT), a novel experimental radiosurgery that largely spares the developing CNS and other normal tissues, is tolerated well by developing animals and palliates advanced 9LGS tumors.
This report, to our knowledge, is the first demonstration that gene-mediated immunotherapy (GMIMPR) enhances the efficacy of MRT for advanced 9LGS tumors.
Methods: Seventy-six male Fischer 344 rats were implanted ic with 104 9LGS cells on d0. By d14, the cells had generated 40 mm3 ic 9LGS tumours, experimental models for therapy of moderately aggressive human malignant astrocytomas. Each of the 14 untreated (control) rats died from a large (>100 mg) ic tumor before d29 (median, d21). On d14, the remaining 62 rats were given deliberately suboptimal microbeam radiation therapy (MRT) by a single lateral exposure of the tumor-bearing zone of the head to a 10.1 mm-wide, 11 mm-high array of 20–39 lm-wide, nearly parallel beams of synchrotron wiggler-generated radiation (mainly 50–150 keV X-rays) that delivered 625 Gy peak skin doses at 211 lm ctc intervals in 300 ms either without additional treatments (MRTonly, 25 rats), with post-MRT GMIMPR (MRT+GMIMPR, 23 rats: multiple sc injections of irradiated (clonogenically- disabled) GM-CSF gene-transfected 9LGS cells), or with post-MRT IMPR (MRT+IMPR, 14 rats:
multiple sc injections of irradiated (clonogenically-disabled) 9LGS cells.
Results: The median post-implantation survivals of rats in the MRT-only, MRT+GMIMPR and MRT+IMPR groups were over twice that of controls; further, 20% of rats in MRT-only and MRT+IMPR groups survived >1 yr with no obvious disabilities. Moreover, over 40% of MRT+GMIMPR rats survived >1 yr with no obvious disabilities, a significant (P<0.04) increase over the MRT-only and MRT+IMPR groups.
Significance: These data suggest that the combination of MRT+GMIMPR might be better than MRT only for unifocal CNS tumors, particularly in infants and young children.
Abstract. Microbeam radiosurgery (MBRS), also referred to as microbeam radiation therapy (MRT), w... more Abstract. Microbeam radiosurgery (MBRS), also referred to as microbeam radiation therapy (MRT), was tested at the European Synchrotron Radiation Facility (ESRF). The left tibiofibular thigh of a mouse bearing a subcutaneously (sc) implanted mouse model (SCCVII) of aggressive human squamous-cell carcinoma was irradiated in two orthogonal exposures with or without a 16 mm aluminium filter through a multislit collimator (MSC) by arrays of nearly parallel microbeams spaced 200 mm on centre (oc). The peak skin-entrance dose from each exposure was 442 Gy, 625 Gy, or 884 Gy from 35 mm wide beams or 442 Gy from 70 mm wide beams. The 442/35, 625/35, 884/35 and 442/70 MBRSs yielded 25 day, 29 day, 37 day and 35 day median survival times (MST) (post-irradiation), respectively, exceeding the 20 day MST from 35 Gy-irradiation of SCCVIIs with a seamless 100 kVp X-ray beam.
Background and purpose: To quantify the late dose-related responses of the rat cervical spinal co... more Background and purpose: To quantify the late dose-related responses of the rat cervical spinal cord to Xray irradiations by an array of microbeams or by a single millimeter beam.
Materials and methods: Necks of anesthetized rats were irradiated transversely by an 11 mm wide array of 52 parallel, 35 lm wide, vertical X-ray microbeams, separated by 210 lm intervals between centers. Comparison was made with rats irradiated with a 1.35 mm wide single beam of similar X-rays. Rats were killed when paresis developed, or up to 383 days post irradiation (dpi).
Results: Microbeam peak/valley doses of 357/12.7 Gy to 715/25.4 Gy to an 11 mm long segment of the spinal cord, or single beam doses of 146–454 Gy to a 1.35 mm long segment caused foreleg paresis and histopathologically verified spinal cord damage; rats exposed to peak/valley doses up to 253/9 Gy were paresis-free at 383 dpi.
Conclusions: Whereas microbeam radiation therapy [MRT] for malignant gliomas implanted in rat brains can be safe, palliative or curative, the high tolerance of normal rat spinal cords to similar microbeam exposures justifies testing MRT for autochthonous malignancies in the central nervous system of larger animals with a view to subsequent clinical applications.
Radiation and Environmental Biophysics, 2001
The tumour suppressor gene p53 and the intracellular signalling molecule ceramide have both been ... more The tumour suppressor gene p53 and the intracellular signalling molecule ceramide have both been shown to play crucial roles in the induction of apoptosis by ionising radiation. In this study we examined whether p53 and ceramide are involved in independent signal pathways, inducing different types of apoptosis. TK6 (p53wt/wt) and WTK1 (p53mut/mut) lymphoblastoid cells were treated with ionising radiation or N-acetyl-D-sphingosine (C2-ceramide). Flow cytometry and fluorescence microscopy studies were performed to characterise the time kinetics and morphological features of induced apoptosis. Ceramide- and radiation-induced apoptotic cells display characteristic differences in morphology and DNA staining and ceramide-induced apoptosis is expressed much faster than radiation-induced apoptosis. Radiation-induced apoptosis is p53-dependent and ceramide-induced apoptosis is p53-independent. The p53 pathway and the ceramide pathway are two independent signal pathways leading to distinct types of apoptosis. Since p53 is very often dysfunctional in tumour cells, modifying the ceramide pathway is a promising strategy to increase tumour sensitivity to radiation and other anticancer agents.
Boron Neutron Capture Therapy, 1992
Strahlentherapie Und Onkologie, Feb 1, 1990
Protons have a long tradition in precision treatment of lesions of limited size at limited depth.... more Protons have a long tradition in precision treatment of lesions of limited size at limited depth. Recently interest has developed in hospital based proton therapy accelerators, able to treat deep seated tumors. Heavy charged particles, and especially protons, are particularly suited to treat well localized tumors. Protons can be collimated as precisely as photons, but in addition have a well defined range. Protons are therefore predestinated for conformation radiotherapy also for larger target volumes. At the Swiss Institute for Nuclear Research a computer optimized treatment planning system has been developed for pion radiotherapy. The principle of this dynamic treatment technique can be adapted for proton therapy. It could prove to be a valid alternative to passive scattering for proton treatment especially of large irregularly shaped volumes. Dose calculations have been performed for specific cases using a 250 MeV pencil beam. The dose distributions and dose volume histograms have been compared with pion therapy. A horizontal experimental beam line, using a degraded 590 MeV proton beam of the PSI ring cyclotron, is set up to verify calculations in phantoms.
Int J Radiat Oncol Biol Phys, 1982
Nuclear Medicine and Biology, 2001
5-bromodeoxyuridine (BUdR) provides in vitro measures of tumor cell proliferation. We used positr... more 5-bromodeoxyuridine (BUdR) provides in vitro measures of tumor cell proliferation. We used positron emission tomography to study tissue and plasma kinetics of [76Br]BUdR in tumor-bearing animals. In order to account for the slow washout of the major plasma metabolite, [76Br]bromide, a mathematical correction for the distribution volume of [76Br]bromide was applied. However, following correction specific tumor tracer retention was low or even zero and did not correlate with independent measures of proliferation. The kinetic characteristics of [76Br]BUdR make this tracer unsuitable for proliferation imaging.
Radiat Environ Biophys, 1979
Monolayer cultures of the fibroblast-like Chinese hamster cell-line 19/1 were irradiated in the G... more Monolayer cultures of the fibroblast-like Chinese hamster cell-line 19/1 were irradiated in the G2-phase of the cell cycle by n--mesons (6 rad/min peak-pion dose rate). Frequencies of induced single-and isochromatid breaks, acentric fragments and interchanges were compared with data obtained from 140 kV X-rays.
International Journal of Radiation Biology
Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2005
Radiotherapy is among the most useful treatments of cancer. Penetrating radiation (ionizing parti... more Radiotherapy is among the most useful treatments of cancer. Penetrating radiation (ionizing particles or bremsstrahlung photons) is aimed toward the tumor-bearing target, gradually delivering as high radiation to it as is usefully suppressive of tumor growth, yet tolerated by normal vital tissues inevitably irradiated with the tumor. The high collimation and dose rate of synchrotron X-ray beams, even when monochromatized, favor radiotherapy. Photon activation therapy, tomotherapy, microbeam radiation therapy, and radiosurgery mediated by synchrotron wigglers are conceptually promising for difficult tumors. Radiotherapy of malignant brain tumors in rats has been encouraging, but suitable beam lines exist at only a few research facilities and much basic work must be done before the promise of synchrotron-based radiotherapy can be realized clinically. r
Radiation Oncology Investigations, 1993
In conformation radiotherapy a target is irradiated uniformly, whereas surrounding organs receive... more In conformation radiotherapy a target is irradiated uniformly, whereas surrounding organs receive non-unifonn radiation. Clinical data concerning complications with conventional radiation are not applicable there without appropriate compensation. A solution was proposed by Lyman b t J Radiat Oncol Biol Phys 13:103-109, 1987 and 17:433-436, 1989; Radiat Res Suppl 8:13-19, 19851 using dose-volume histograms. It reduces a given histogram to a single step which corresponds to the equivalent complication probability. It converts non-uniform radiation into a unique dose to the whole organ which has the equivalent complication probability. This method was applied to actual patients treated by pion conformation technique at Paul Schemer Institute (PSI). Of 90 pelvic tumors, 16 developed grade 111-IV bladder injury and 7 developed grade 111-IV rectal injury. The 90 cases were divided into roughly equal groups according to the equivalent doses to the entire bladder and rectum. Observed complication rates and the equivalent doses to the full organs in these groups could be represented by a sigmoid dose-effect relation. When the relative biological effectiveness (RBE) is assumed to be 2.1 for bladder injury, the observed complication rates of the bladder fit best to the theoretical curve. When the RBE value is 2.3, the rates of rectal injury fit best. These values are close to the conversion factor of 2.0 used in clinical practice. This agreement suggests the feasibility of the method.
Zeitschrift für medizinische Physik, 2004
A fast and accurate magnetic tracking system was developed for applications in real-time tumor tr... more A fast and accurate magnetic tracking system was developed for applications in real-time tumor tracking, computer-aided surgery, and endoscopy. The tracking is based on the application of miniaturized sensors. Once implanted in the patient, the sensors receive signals from an external field generator. The fast evaluation of the signals allows the online determination of position and orientation of each sensor. With the help of optical tracking, the sensor coordinates are transformed in the reference system used by the clinician. The effects of eddy currents in nearby electrically-conducting objects are taken into account using special computational methods. The present paper presents the results of a first experiment in a canine model.
Veterinary research communications, 1998
Spontaneous tumours in dogs and cats are an excellent model for clinical human research, such as ... more Spontaneous tumours in dogs and cats are an excellent model for clinical human research, such as in developing proton conformation radiotherapy for humans. The kinetics of tumour cells can be used effectively to predict prognosis and response to therapy in patients with tumours. Knowledge of the kinetic parameters in these tumours is therefore important. In the present study the kinetic parameters evaluated included the labelling index (LI), relative movement (RM), mitotic index (MI), and potential doubling time (Tpot). These parameters were determined using in vivo labelling with bromodeoxyuridine, flow cytometry and histological preparation. Samples were obtained and evaluated from 72 dogs and 20 cats, presenting as patients in our clinic. Within the groups of epithelial and mesenchymal tumours from dogs and cats, the kinetic parameters LI, RM and MI were compared with Tpot. Significant correlations were observed for the comparison Tpot and LI. No correlation was found between Tpo...
Cancer/Radiothérapie, 1998
Cellular and molecular biology (Noisy-le-Grand, France), 2000
The application of synchrotron radiation in medical research has become a mature field of researc... more The application of synchrotron radiation in medical research has become a mature field of research at synchrotron facilities worldwide. In the relatively short time that synchrotrons have been available to the scientific community, their characteristic beams of UV and X-ray radiation have been applied to virtually all areas of medical science which use ionizing radiation. The ability to tune intense monochromatic beams over wide energy ranges differentiates these sources from standard clinical and research tools. At the European Synchrotron Radiation Facility (Grenoble, France), a major research facility is operational on an advanced wiggler radiation beamport, ID17. The beamport is designed to carry out a broad range of research ranging from cell radiation biology to in vivo human studies. Medical imaging programs at ID17 include transvenous coronary angiography, computed tomography, mammography and bronchography. In addition, a major research program on microbeam radiation therapy...
Veterinary Radiology <html_ent glyph="@amp;" ascii="&"/> Ultrasound, 2003
Radiation treatment requires a precise procedure for interfraction repositioning of the patient. ... more Radiation treatment requires a precise procedure for interfraction repositioning of the patient. The purpose of this study was to determine the accuracy of our fixation device in treatment position and to evaluate the setup accuracy with two different methods. The positioning data of 19 canine patients with tumors in the head region (oral, nasal, cerebral) treated with photon or proton irradiation were included in this study. The patients were immobilized by means of an individualized fixation device. Focus was set upon interfraction displacement with systematic and random components. In one method, treatment position was evaluated using single plane port radiographs and megavoltage x-rays. In the other method, two orthogonal CT-topograms were acquired to evaluate the precision of positioning of the patient in the immobilization device. Systematic and random displacements were calculated and presented as mean values with corresponding 95% confidence intervals. In spite of a difference between both methods, the positioning seemed to he accurate within the expected range. It seems that a safety margin of 3.7 mm would be enough for both methods to take into account systematic and random position variability in the fixation device, thereby preventing geometric inaccuracies of treatment delivery. The reported immobilization protocol provides accurate patient immobilization for photon and conformal proton radiation therapy.
Veterinary Radiology & Ultrasound, 2009
Thirty dogs with spontaneous tumors were irradiated with proton therapy using a novel spot scanni... more Thirty dogs with spontaneous tumors were irradiated with proton therapy using a novel spot scanning technique to evaluate the safety and efficacy of the system, and to study the acute and late radiation reactions. Nasal tumors, soft tissue sarcomas, and miscellaneous tumors of the head were treated with a median total dose of 52.5 Gy given in 3.5 Gy fractions. Acute effects, late effects, tumor response, and outcome were analyzed. No unexpected radiation reactions were seen, however two dogs did develop in-field osteosarcoma, and one dog developed in-field bone necrosis. Complete response to therapy was seen in 40% (12/30), partial response in 47% (14/30), and no response in 13% (4/30). Median survival for all dogs was 385 days (range of 14-4583 days). Dogs with nasal cavity tumors had a median survival of 385 days (range of 131-1851 days) and dogs with soft tissue sarcomas had a median survival time of 612 days (range of 65-4588 days). Treatment outcome was similar to historical controls. This new proton spot scanning technique proved to be safe and reliable. Veterinary
Veterinary Radiology <html_ent glyph="@amp;" ascii="&"/> Ultrasound, 2004