Since its inception in the early 20th century, brachytherapy and its evolution have had a close association with medical physics. The 50  year history of the American Association of Physicists in Medicine (AAPM) has coincided not only with the emergence of medical physics as a mature profession, but with truly revolutionary innovations in radiological physics, including nuclear reactors, new particle accelerators, three-dimensional (3D) imaging, and computer-assisted treatment planning. Along with conceptual advances in radiation transport and modulation of clinical response, these developments have dramatically altered the practice of brachytherapy. Through fortunate intersections of technological opportunity and clinical need, brachytherapy has continued to serve an important, if rapidly changing, role in cancer management despite challenges to its survival from surgery and other treatment modalities. A recently published review and a 50th anniversary article have thoroughly covered the history of brachytherapy technology¹ and dosimetry,^1,2 an area in which the AAPM has had a major impact as an organization. Rather than duplicate or summarize these excellent reviews, we propose to focus this article on current trends and challenges in brachytherapy, particularly those that fall within the scope of medical physics practice or research activities.

Probably the highest impact technological advances in the last half century were the introduction of artificial radionuclides and afterloading into clinical brachytherapy.¹ These advances significantly lowered cost, reduced personnel exposure, and increased technical flexibility. They also set the stage for the renaissance of low dose-rate (LDR) temporary brachytherapy techniques beginning in the early 1960s in spite of the rapid penetration and development of megavoltage beam therapy, which made curative external-beam therapy feasible. Other important advances, reviewed elsewhere,^2,3 were computer-assisted treatment planning/dose evaluation and advances in dosimetry. Together, these advances set the stage for dramatic shifts in both clinical indications and technical practice that have occurred in the last 15  years.

One remarkable trend has been the nearly exponential growth of transrectal ultrasound (TRUS)-guided brachytherapy for treatment of low and intermediate risk prostate cancer using low-activity ¹⁰³Pd or ¹²⁵I. Perhaps due to the attraction of a 1  day procedure along with a favorable profile of normal tissue complications, the number of procedures has grown from less than 5000 in 1995 to between 40 000 and 60 000 in 2002.⁴ This is approximately 30% to 40% of all eligible patients diagnosed annually in the United States, challenging radical prostatectomy as the standard of treatment. A second major growth area is breast conservation therapy, in which lumpectomy is followed by fractionated high dose-rate (HDR) brachytherapy (34  Gy in ten fractions administered over 5  days) using either interstitial brachytherapy^5,6 or a balloon applicator⁷ in place of 6  weeks of external-beam therapy. A third clinical indication for a new brachytherapy application is intravascular brachytherapy (IVBT), which was introduced in the late 1990s with much excitement in the radiation oncology community. Randomized clinical trials soon showed that IVBT dramatically lowered the incidence of restenosis following percutaneous coronary angioplasty relative to unirradiated controls.⁸ As many as 40 000 intravascular brachytherapy procedures were performed annually as its utilization peaked in 2002. Perhaps due to unequivocally positive results only for in-stent restenosis, late stent thrombosis, and recurrent restenosis at the edge of the treated field,⁹ IVBT was abandoned as rapidly as it was developed in favor of rapamycin- and paclitaxel-eluting stents.^10,11 This remarkable phenomenon illustrates how vulnerable specialized surgical procedures practiced by nonsurgeons, e.g., brachytherapists, are to competing surgical technologies.

Growth in the areas of permanent prostate brachytherapy and HDR ¹⁹²Ir accelerated partial breast irradiation has been accompanied by a reduction in the use of temporary LDR brachytherapy at other sites. This reduction is due, in part, to migration of traditional LDR brachytherapy procedures, e.g., intracavitary brachytherapy for gynecological malignancies, to fractionated HDR. At least in the United State, use of definitive brachytherapy for sites such as early stage head and neck has failed to compete effectively with other therapeutic options, including intensity-modulated radiation therapy (IMRT) and surgery.

Throughout most of its long life, brachytherapy has evolved as a surgical art, in which seed or applicator positioning was guided by palpation or visualization of the target tissue. Treatment planning consisted of calculating dose relative to the source positions derived from orthogonal radiographs, not the underlying anatomy. While a number of pioneering publications investigated the registration of dose distributions to 3D medical images throughout the 1980s and 1990s, only with the rise of prostate seed brachytherapy did image-guided source placement or image-based planning achieve widespread use in brachytherapy. TRUS-guided seed placement and post-implant x-ray and computer-aided tomography (CT) imaging, used to evaluate the final dose distribution, are now standards of practice.¹² CT-based catheter guidance and dose evaluation is commonplace for partial breast brachytherapy,¹³ and magnetic resonance imaging is emerging as the planning image modality of choice for gynecological tumors.¹⁴ These exciting developments offer many potential advantages, including a planning process conceptually similar to that of teletherapy, less dependence on surgical skill, and most importantly, enhanced targeting accuracy, target conformality, and normal tissue avoidance. Associated developments include intraoperative planning (planning and delivery integrated into a single procedure)¹⁵ and intraoperative adaptive planning (intraoperative dose replanning used to correct source position).^16,17 On the horizon, positron emission tomography and other biological imaging modalities should work its way into brachytherapy treatment planning as it has in external-beam radiotherapy.¹⁸

The rapidly growing utilization of low-energy interstitial sources has motivated intensive investigation of dosimetry techniques for more accurately estimating clinical dose distributions, a development that has greatly benefited from AAPM's leadership and consensus building.² Parallel developments in computational and experimental dosimetry³ have reduced physical dose specification uncertainty to the 3% to 5% level (k=1) for ¹²⁵I brachytherapy.¹⁹ Another emerging development is the application of Monte Carlo-based dose calculations to treatment planning,^20,21 which will eliminate major uncertainties in clinical dose specification due to tissue heterogeneities, interseed attenuation, and applicator shielding effects.

While brachytherapy usually is an invasive procedure limited to surgically accessible tumor sites, it is able to safely deliver much higher biological equivalent doses than IMRT.²² HDR brachytherapy is able to deliver very large fraction sizes safely while, at the other end of the spectrum, permanent seed brachytherapy (the ultimate form of hyperfractionation) supports delivery of very high physical doses due to repair of normal tissue sublethal damage. Credit is often given to brachytherapy's superior targeting accuracy and conformality (direct insertion of sources into target tissue versus external fiducial alignment and minimum impact of tissue motion), which is widely assumed to make planning target volume (PTV) expansions unnecessary. For brachytherapy to retain these competitive advantages, the following scientific issues require urgent attention.

Geometric uncertainty, and its role in determining PTV margins, has been extensively studied in external-beam radiation therapy in contrast to brachytherapy,²³ where relatively little data is available.²² Image-guided radiotherapy (IGRT) techniques have markedly improved external-beam precision.²⁴ Brachytherapy-like hypofractionated regimens have been successfully delivered to patients with lung²⁵ and prostate cancers²⁶ using external beam IGRT. To use brachytherapy safely for highly conformal treatment of well-defined target volumes, a better understanding of the interplay between organ delineation errors, seed and applicator positioning uncertainties, and intrafractional tissue motion are needed. For permanent brachytherapy, a better understanding of normal and target-tissue response to the ultralow dose rates, along with the modulating effects of geometric uncertainties, are required to be able to extend permanent seed brachytherapy to new treatment sites without mounting dose-seeking phase I and II clinical trials.

Since brachytherapy is a surgical intervention, it deforms and displaces tissues in a highly localized and nonlinear fashion. These problems hinder accurate registration of pretreatment biological images onto intraoperatively available images or preclude accurate summation of biological doses from individual brachytherapy fractions. Deformable image registration is a promising solution to this problem and has been demonstrated in both prostate²⁷ and gynecological²⁸ brachytherapy applications. However, many challenging problems remain to be solved, including general and patient-specific validation of such registrations.²⁹

Despite substantial progress in single-source brachytherapy dosimetry, current table-based dose computation algorithms model patients as uniform water spheres of water, neglecting tissue density and composition heterogeneities and applicator- and source-shielding effects. This approximation results in large differences between the dose distribution actually delivered to the patient and that calculated by the treatment planning system, particularly for low-energy sources. This topic is discussed below.