Whether intraoperative radiation for advanced cancer is ready for wider use drew some mixed but hopeful responses at a recent annual meeting of the Society of Surgical Oncology in Orlando, Fla.
William Sindelar, M.D., of Good Samaritan Hospital in Baltimore, Md., called intraoperative radiation "a technique for maximizing the radiation dose where it is needed most, while attempting to minimize toxicity to normal structures."
It is also clearly a local modality, although in only a few cases for breast and some locally advanced rectal tumors "does this appear to translate into improved survival," according to Sindelar. However, what it does do, in many cases, he said, is improve a patient's quality of life. In pancreatic cancer, for example, Sindelar and others reported intraoperative radiotherapy can relieve pain, and it offers some quality of life improvement for other especially hard-to-treat cancers such as retroperitoneal sarcomas and mesotheliomas, where complete resection is usually impossible.
The idea of irradiating the tumor or tumor bed, without the skin or other tissues getting in the way so that higher radiation doses can be given, is not exactly a new idea. The first use of this approach, within a decade of Roentgen's discovery of the x-ray, was in l905, in a woman who had had a total abdominal hysterectomy, node dissection, and partial cystectomy. Subsequently, occasional patients have also had intraoperative radiotherapy often having to lie for hours under the low voltage machines of the day.
The modern era, using electron beam radiation, did not start until the l960s, explained Christopher Willett, M.D., Massachusetts General Hospital, Boston, who chaired the special session. He said single-institution experience along with some phase III studies have given those involved, "a pretty clear understanding of the indications, results, and toxicity as well as the limitations of this particular technology."
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One problem, historically, has been that patients were usually operated on in one room and then sent over to the radiation suite, which involved juggling transportation between suites and other logistical problems. Only a few institutions had the expensive intraoperative suites needed to solve this problem.
More recently, a portable, shielded, linear accelerator, the Mobetron, has been developed, which can be stuck in the corner of the operating room, or moved by hospital elevator to an operating room.
"This makes possible the unanticipated [use of] intraoperative radiotherapy, when someone is explored and found to have a clinical situation that would benefit," Sindelar said. "So intraoperative radiotherapy can be delivered almost on the spur of the moment. I think machines such as this affect the practicality of the technique, so it can be much more widely disseminated."
But what are the clinical results, so far? Sindelar said that in a small study of 41 gastric cancer patients, none had an increase in complications, and all had a significant improvement in both local and regional complications when intraoperative radiation was added. He says that the same was true for 35 patients with retroperitoneal sarcomas.
Hollis Merrick, M.D., of the Medical College of Ohio found that local regional control also improved in patients with pancreatic and early breast cancer, at a radition dose two to three times the normal dose given with external beam radiotherapy.
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In a joint study with investigators in Montpelier, France, patients with early breast cancer have been given an intraoperative radiation boost after incisional biopsy. The median follow-up in 72 patients is 84 months, with follow-ups as long as 14 years.
"We believe this is an alternative to irridium implants or an electron boost after lumpectomy," he said. "We believe it [intraoperative radiotherapy] shortens the time of treatment by giving a boost at the time of surgery, and saves the patient an additional 2 to 3 weeks of treatment.
"But the key thing is it avoids the possibility of missing the treatment area. The breast is a highly mobile structure and it moves all over the place. With external beam you may easily miss the crucial area and heighten the incidence of recurrence."
David Jablons, M.D., of the University of California, San Francisco, said several studies show local control of lung cancer with intraoperative radiation and that 5-year survival in these patients is slightly better than that in historical controls. In one study, 110 patients with bulky tumors showed a 25% incidence of local control, although overall survival was not improved. An international prospective study is badly needed, he said, using multimodality therapy, including intraoperative radiotherapy, in carefully staged lung cancer patients.
Jablons said 15 mesothelioma patients showed a survival approaching 20 months, compared to the 9 to 10 months expected for this disease, when intraoperative radiation was added to multimodality therapy. About a third recurred locally, and half distally.
Mark Ott, M.D., of Massachusetts General Hospital, Boston, reported that, for the treatment of colorectal or other cancers, the hospital has a dedicated intraoperative radiotherapy suite, so that this treatment only adds about another 45 minutes to the time of conventional surgery. He, Willett, and others are also involved in several studies of multimodality therapy, which include intraoperative radiation, and also a hypoxic radiosensitizer, to try to improve results.
Brachytherapy
Willett also reported that an "attractive alternative" to intraoperative radiotherapy now being used at Massachusetts General is high-dose-rate brachytherapy, a technique developed by Louis Harrison, M.D., and Albert Cohen, M.D., when both were at Memorial Sloan-Kettering Cancer Center, New York. (Cohen is now at Beth Israel Hospital in New York). In this procedure, a superflap applicator is placed on the tumor bed, where a series of cable connections are connected to a high-dose-rate machine, which houses an irridium source.
Willett said that it appears that in many ways these two techniques intraoperative radiotherapy and brachytherapy appear to be complementary, "and it would be ideal to have access to both." Ohio State University, Columbus, is one place that does use both technologies, he said.
"I think in the future we will have not only the use of the Mobetron and other portable units, but also this rather interesting technique of high-dose brachytherapy."
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