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
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Papers by Hans Blattmann
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.
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.
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.
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.