Radiation therapy for benign disease: an old area revisited

Abstract

After expansion of the balloon causes mechanical injury to the intima, the internal elastic membrane, and the media, a mural thrombus develops because of platelet aggregation and fibrin deposition. A short time later (3–7 days) cells migrate into the intima and proliferate. Fibrosis and restenosis follow. Monocytes and macrophages may also be mediators in the process of retenosis. Radiation can inhibit postinjury neointimal proliferation, and preliminary data indicate that postangioplasty irradiation can reduce the restenosis rate to 17–25%. Rat and pig models of restenosis have been studied in this context. Delivery of about 15–20 Gy with iridium192 in high-dose-rate brachytherapy effectively inhibits intimal proliferation in pigs. Iridium-192 is a emitter, and so the cardiology team must leave the room during the actual procedure. -emitting isotopes, such as yttrium-90 and rhenium-188, have been used to deliver the radiation dose more rapidly and with lower radiation exposure risk to personnel. The endoluminal radiation can also be delivered at much lower dose rates with radioactive stents placed at the time of the angioplasty. All of the techniques described above for prophylaxis against restenosis result in heterogeneous radiation dose distributions across the abnormal vessel, especially for emitters and stents. External-beam radiotherapy provides more homogeneous dose delivery, although carefully tailored conformal fields, perhaps gated to the heart beat, would be needed to minimise the radiation dose to normal heart. Each of these approaches has its advantages and disadvantages, and it is too early to tell which will ultimately prove to be best in terms of medical outcome and cost-effectiveness. An experimental model has indicated that whether a 20 Gy dose can permanently prevent rather than merely postpone restenosis depends critically on the proliferative capacity of the injured normal tissue. Confirmation of this finding requires long-term follow-up beyond 2 years, which is missing in much of the animal work. Several clinical trials of the efficacy of radiation in preventing restenosis are in progress. The number of potential patients with wet-type macular degeneration and postangioplasty stenosis who might benefit from ionising radiation is greater than the number of cancer patients now receiving radiotherapy. The specialty treatment of human disease with ionising radiation was once called “radiation therapy”. Over the years it came to be called “radiation oncology”. It may be time to change it back.