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IMRT could be safe for brain tumours in young children
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Our ability to detect cancer before it can spread has taken another step forward, as scientists at two leading US laboratories have detected large numbers of cancer cells in the blood vessels feeding microtumours (Chang et al. Proc Natl Acad Sci USA 2000; 97: 14608–13). Colon carcinoma tissue, where the cells had been labelled with green fluorescence, were xenografted into mice, and was allowed to develop new blood vessels. Chang and colleagues (Harvard Medical School, Massachussetts, and University of California, San Francisco, USA) found that some of the new vessels had a ‘mosaic’ of endothelial cells and malignant cells (4%) on their luminal surface. Their results help explain previous reports that cancer cells enter the blood at the rate of one million cells per gram of tumour per day. “This phenomenon has been ignored for years because of a lack of quantitative data”, said senior investigator Lance Munn (Harvard Medical School); “Sensitive technology means we can now show its importance.” The group also observed that mosaics make up 15% of tumour blood vessels in human cancer biopsy samples. “Because killing these exposed cells will impair blood flow in
Courtesy of L Munn
Mosaic vessels shed cancer clues by the million
Confocal microscopy showing mosaic vessel (arrow), where tumour cells (green) are not covered by endothelium (red)
mosaic vessels, our results may explain why agents, such as cyclophosphamide, are effective at low ‘antiangiogenic’ doses,” says Munn, “doses that are lower and less toxic, than those used in conventional therapy”. From the observation that resection of a large tumour can sometimes be followed by the rapid development of multiple metastases, Judah Folkman, also at Harvard Medical School, originated the idea that tumours not only actively develop their own blood supply but also secrete angiogenesis inhibitors into the circulation. Commenting on the findings of Chang and colleagues (Proc Natl Acad Sci USA 2001; 98: 398–400),
Folkman points out that they may also influence cancer diagnosis. “Genetic analysis of cancer cells in the blood may be added to conventional tumour imaging techniques in the foreseeable future”, he said. There are now more than 20 angiogenesis inhibitors in development and they may be about to come into their own. Paul Workman, Director of the Cancer Research Campaign Centre for Cancer Therapeutics (Sutton, UK) commented, “A range of new mechanismbased angiogenesis inhibitors with enormous potential are entering clinical trials, of which the vascular endothelial growth factor receptor tyrosine kinase inhibitors look exceptionally promising”. “It is not that surgery will become outmoded”, said Folkman, “but that if and when molecular methods are used to diagnose cancer at the microtumour stage, newer methods of therapy may be needed to supplement surgery, radiotherapy, or conventional cytotoxic chemotherapy. These therapies will include angiogenesis inhibitors, vaccine therapies and gene therapy, guided by the appropriate molecular markers.” Janet Stephenson
IMRT could be safe for brain tumours in young children Australian researchers believe a new radiotherapy technique that sculpts radiation beams to match tumour shape could result in safer treatment of brain tumours in very young children. Robert Smee (Prince of Wales Hospital, Sydney) has pioneered the use of a new form of stereotactic intensity modulated radiation therapy (IMRT), involving two variations on current clinical practice. The first is a head fixation device which can set a coordinate point as a target for the radiotherapy, rather than on the basis of volume, as other techniques have done. This allows the radiotherapy to be more precise. The second difference is that the multileaf collimator uses 4 mm leaves, rather than the usual 1 cm width.“This allows us to conform more precisely 130
around a structure”, he explains. “Existing radiotherapy software was modified so that the computer automatically determines the best configuration of radiation beams to match the tumour, reducing both treatment times and harmful radiation to surrounding healthy tissues.” Smee, who presented a paper on his research to the International Congress on Radiation Oncology in Melbourne (January 2001), believes the new technique will be particularly useful for treating tumours of the brain and head, where high doses of radiation could damage the brain, optic nerve or pituitary gland. It is also expected to be beneficial for treating brain tumours in children under the age of 4 years, who are at increased risk of cognitive damage
from traditional radiotherapy because their brains are still growing. “Until now, we’ve treated children with these sorts of tumours and know they can be long-time survivors, but often with adverse affects,” he said. It is estimated that, in Australia, 100 children a year could benefit from this type of treatment. Over the past 7 years, Smee has used $ 1 million (Australian) of his own funds to pay for the new equipment, which is located in a public hospital. IMRT was recently trialled successfully on two adult patients with benign but aggressive meningiomas and will be used to treat the first two paediatric patients soon. One child will be treated for a primary brain tumour and another for an ependymoma. Megan Howe THE LANCET Oncology Vol 2 March 2001
For personal use only. Reproduce with permission from The Lancet Publishing Group.
Our ability to detect cancer before it can spread has taken another step forward, as scientists at two leading US laboratories have detected large numbers of cancer cells in the blood vessels feeding microtumours (Chang et al. Proc Natl Acad Sci USA 2000; 97: 14608–13). Colon carcinoma tissue, where the cells had been labelled with green fluorescence, were xenografted into mice, and was allowed to develop new blood vessels. Chang and colleagues (Harvard Medical School, Massachussetts, and University of California, San Francisco, USA) found that some of the new vessels had a ‘mosaic’ of endothelial cells and malignant cells (4%) on their luminal surface. Their results help explain previous reports that cancer cells enter the blood at the rate of one million cells per gram of tumour per day. “This phenomenon has been ignored for years because of a lack of quantitative data”, said senior investigator Lance Munn (Harvard Medical School); “Sensitive technology means we can now show its importance.” The group also observed that mosaics make up 15% of tumour blood vessels in human cancer biopsy samples. “Because killing these exposed cells will impair blood flow in
Courtesy of L Munn
Mosaic vessels shed cancer clues by the million
Confocal microscopy showing mosaic vessel (arrow), where tumour cells (green) are not covered by endothelium (red)
mosaic vessels, our results may explain why agents, such as cyclophosphamide, are effective at low ‘antiangiogenic’ doses,” says Munn, “doses that are lower and less toxic, than those used in conventional therapy”. From the observation that resection of a large tumour can sometimes be followed by the rapid development of multiple metastases, Judah Folkman, also at Harvard Medical School, originated the idea that tumours not only actively develop their own blood supply but also secrete angiogenesis inhibitors into the circulation. Commenting on the findings of Chang and colleagues (Proc Natl Acad Sci USA 2001; 98: 398–400),
Folkman points out that they may also influence cancer diagnosis. “Genetic analysis of cancer cells in the blood may be added to conventional tumour imaging techniques in the foreseeable future”, he said. There are now more than 20 angiogenesis inhibitors in development and they may be about to come into their own. Paul Workman, Director of the Cancer Research Campaign Centre for Cancer Therapeutics (Sutton, UK) commented, “A range of new mechanismbased angiogenesis inhibitors with enormous potential are entering clinical trials, of which the vascular endothelial growth factor receptor tyrosine kinase inhibitors look exceptionally promising”. “It is not that surgery will become outmoded”, said Folkman, “but that if and when molecular methods are used to diagnose cancer at the microtumour stage, newer methods of therapy may be needed to supplement surgery, radiotherapy, or conventional cytotoxic chemotherapy. These therapies will include angiogenesis inhibitors, vaccine therapies and gene therapy, guided by the appropriate molecular markers.” Janet Stephenson
IMRT could be safe for brain tumours in young children Australian researchers believe a new radiotherapy technique that sculpts radiation beams to match tumour shape could result in safer treatment of brain tumours in very young children. Robert Smee (Prince of Wales Hospital, Sydney) has pioneered the use of a new form of stereotactic intensity modulated radiation therapy (IMRT), involving two variations on current clinical practice. The first is a head fixation device which can set a coordinate point as a target for the radiotherapy, rather than on the basis of volume, as other techniques have done. This allows the radiotherapy to be more precise. The second difference is that the multileaf collimator uses 4 mm leaves, rather than the usual 1 cm width.“This allows us to conform more precisely 130
around a structure”, he explains. “Existing radiotherapy software was modified so that the computer automatically determines the best configuration of radiation beams to match the tumour, reducing both treatment times and harmful radiation to surrounding healthy tissues.” Smee, who presented a paper on his research to the International Congress on Radiation Oncology in Melbourne (January 2001), believes the new technique will be particularly useful for treating tumours of the brain and head, where high doses of radiation could damage the brain, optic nerve or pituitary gland. It is also expected to be beneficial for treating brain tumours in children under the age of 4 years, who are at increased risk of cognitive damage
from traditional radiotherapy because their brains are still growing. “Until now, we’ve treated children with these sorts of tumours and know they can be long-time survivors, but often with adverse affects,” he said. It is estimated that, in Australia, 100 children a year could benefit from this type of treatment. Over the past 7 years, Smee has used $ 1 million (Australian) of his own funds to pay for the new equipment, which is located in a public hospital. IMRT was recently trialled successfully on two adult patients with benign but aggressive meningiomas and will be used to treat the first two paediatric patients soon. One child will be treated for a primary brain tumour and another for an ependymoma. Megan Howe THE LANCET Oncology Vol 2 March 2001
For personal use only. Reproduce with permission from The Lancet Publishing Group.