Collateral damage has been the bane of radiation therapy from the beginning: Radiation-induced morbidity can significantly reduce a patient's quality of life.

Initially, radiation therapy was delivered to a few generally rectangular fields. Conformal therapy shaped the radiation fields more closely to the outline of the tumor, and for three-dimensional conformal therapy, beams from multiple directions were shaped independently. Today, it is possible to manipulate the fluence as well as the shape of the beams. A target can be divided into hundreds of tiny volumes, each of which receives an individualized radiation dose. With this methodintensity-modulated radiation therapy (IMRT)it is possible to create concave isodose shapes that spare nearby organs at risk (OARs). Community hospitals1 as well as academic centers are now offering IMRT in the hope of killing the cancer without causing serious long-term morbidity.

TECHNIQUES FOR IMRT

Numerous methods have been devised for IMRT (for a review, see Webb²) In static-field therapy, radiation quanta are delivered in sequence, with the shape of the field being altered between quanta by a multileaf collimator (MLC) ("step and shoot"). An alternativedynamic MLC therapyfeatures a constantly changing field shape during radiation delivery. A variant of this method is intensity-modulated arc therapy, in which numerous customized fields are shaped every 5 to 10 degrees around the patient.³ Another popular option is tomotherapy, in which the tissue is treated one slice at a time as the patient table moves past the radiation source and the radiation field is continuously shaped by an MLC.⁴

Conventional methods of radiation planning are too time-consuming when applied to IMRT. Instead, inverse planning is used.⁵ The tumor is imaged in three dimensions, ideally by more than one modality, and the data are registered with a coordinate system. The tumor and the OARs are marked, and the desired radiation doses for each volume are indicated. The delivery plan is then optimized by iterative simulations to come as close as possible to the ideal dose to the tumor while minimizing the cost (eg, OAR dose). Finally, the plan is reviewed and approved.

SOME CLINICAL USES OF IMRT

One of the earliest reported successes of IMRT was for the treatment of head and neck tumors in dogs. Use against human head and neck tumors has since become popular because of the ability to reduce the radiation dose to the visual apparatus, spinal cord, and salivary glands.^6-9 Other reported applications taking advantage of the precise accuracy of IMRT have been treatment of a tumor on one vocal cord while sparing the other; ablation of meningioma¹⁰; treatment of cancers in the ethmoid sinus⁹, brain,¹¹,¹² spine,¹³ cervix,^14,15 and breast¹⁵; as well as palliation for recurrences in previously irradiated sites.¹¹,¹³ Perhaps the most popular application of IMRT has been for prostate cancer. At Memorial Sloan-Kettering, 772 men received a total dose of 81.0 or 86.4 Gy. The 3-year actuarial likelihood of late Grade 2 or higher rectal toxicity was 4%, and the 3-year actuarial risk of late urinary toxicity was 15%, significantly better than the toxicity of 3D conformal radiotherapy at the same institution. The 3-year relapse-free survival rates were 92%, 86%, and 81%, respectively, for patients with favorable, intermediate-risk, and unfavorable cancers. This institution now uses IMRT routinely for the treatment of localized prostate cancer.¹⁶ Comparable cancer-control and toxicity results have been reported from other institutions, including the University of California,¹⁷ the Cleveland Clinic,¹⁸ and Baylor College of Medicine, where IMRT also is used for postprostatectomy irradiation.¹¹

ISSUES IN IMRT

Certainly, IMRT is not needed for all tumors. According to one estimate, only about 30% of cancers have features that warrant IMRT.¹⁹ Studies in which various forms of radiation are planned for the same lesion and the doses and normal tissue exposure are compared can help identify classes of cancers in which IMRT is most likely to be beneficial.¹⁹

Even if it is not applied to all cancers, enthusiasm for IMRT is not universal. There is concern that the close tailoring of the radiation field to the tumor will leave parts untreated, and it is clear that IMRT is more sensitive than is traditional radiation to geometric uncertainty in defining the lesion.²⁰ Intensity-modulated radiation therapy also has been criticized for its complexity and time intensiveness, features that might increase the chances of dose delivery errors.²¹ Webb has provided a summary of these and other objections to IMRT, as well as the counterarguments.²

Intensity-modulated therapy imposes significant demands for patient immobilization, quality assurance,²² and verification, which often is required for each fraction.¹⁹ Greater leakage from the linear accelerator head may make greater shielding of the room necessary,²³ and concerns have been expressed about the potential for greater radiation exposure of health care personnel because of the high-energy accelerator.²⁴ Other concerns are the greater whole-body dose secondary to greater leakage and longer beam-on time and thus the higher risk of second cancers.²⁵ By one estimate (reviewed by Webb²), the lifetime risk of such cancers by treatment at 6 MV is 0.4% with conventional radiation therapy, 1.0% with conformal therapy, and 2.8% with IMRT by tomotherapy. This feature is a particular concern if the advantages of IMRT are to be sought for children.²⁶

THE FUTURE

Despite its drawbacks, the benefits of IMRT seem certain to win it a permanent place in the clinic, and it has satisfied the criteria for reimbursement.²⁷ Although the equipment, software, and staff training required increase the costs, the better patient outcomes and reduced morbidity suggest that IMRT will prove cost-effective.^28,29 One of the pioneers of the modality recently wrote that as progress is made in predicting the responsiveness of an individual tumor to radiation, "radiation therapy will become an exact science, allowing truly individual optimization..."³⁰

Margery Tallman is a contributing writer for Decisions in Imaging Economics.

References:

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