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We’ve Got a Treatment, but What’s the Disease?

or A Brief History of Hypofractionation and its Relationship to Stereotactic Radiosurgery

Department of Radiation Oncology, Harold C. Simmons Comprehensive Cancer Center, University of Texas, Southwestern Medical Center at Dallas, Dallas, Texas, USA

Correspondence: David I. Rosenthal, M.D., Department of Radiation Oncology, Harold C. Simmons Comprehensive Cancer Center, University of Texas, Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75235-9122, USA. Telephone: 214-648-2824; Fax: 214-648-7613.

Hypofractionation has been a recurring issue during the near century-long history of radiation oncology. Coutard first introduced protracted dose-fraction regimens that uniquely allowed for the control of "deep" tumors. Subsequent studies have consistently shown that hypofractionation leads to an increase in complication rates and a paradoxical decrease in cure rates. There have, nonetheless, been several resurgences of interest in hypofractionation, based on titration of treatment for acute isoeffects and for the accommodation of an adjuvant treatment relating to presumed hypoxia-induced resistance, and more recently, stereotactic radiosurgery. In final analysis of the earlier studies, the same effects on cure and complication were noted and there was a return to multi-fractionation. Stereotactic radiosurgery is now being evaluated.

Stereotactic radiosurgery takes hypofractionation to an extreme by use of a single, large fraction of radiation therapy. In doing so, the late effects radiation oncologists ordinarily strive to avoid are brought about intentionally, minimizing or even eliminating any therapeutic index within the treatment volume. Stereotactic radiosurgery has been used successfully for treatment of benign lesions such as arteriovenous malformations in which total volume necrosis of small dimensions appears to be efficacious therapy. Stereotactic radiosurgery has also recently been extrapolated to malignant tumors in the brain which require larger treatment volumes, but the data on outcome following such treatment remain sparse. Therapeutic index must be preserved to obviate an intolerable volume of necrosis and other late effects. The single fraction approach to stereotactic radiosurgery for cancer is vulnerable to the same radiobiological criticisms that have been a recurrent theme with hypofractionation. Fractionated stereotactic radiosurgery is far more consistent with the principles of conventional radiobiology and oncology and represents the quintessential application of three-dimensional treatment planning. Stereotactic radiosurgery is really stereotactic radiotherapy, and when applied in single fraction to the treatment of cancer, it is suboptimal radiation oncology. Its utilization is virtually predicated on the ability to perform another craniotomy to remove focal necrosis.

Key Words. Stereotactic radiosurgery • Fractionation • Brain tumors • Malignancy • Gamma knife • Linear accelerator

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