Emerging Technologies in Prostate Cancer Radiation Therapy: Improving the Therapeutic Window

Matthew C. Biagioli, MD, MS; Sarah E. Hoffe, MD

Disclosures

Cancer Control. 2010;17(4):223-32. 

In This Article

Prostate Motion and Image-guided Radiation Therapy

Integration of more conformal radiation techniques with smaller radiation fields into the clinical setting has necessitated a better understanding of the location of the prostate during treatment. A multitude of imaging and localization techniques have been investigated to explore these issues. Although a typical margin of 0.4 cm to 1 cm is created around the prostate to generate a target for IMRT treatment, evidence has shown that the prostate can move as much as 1 to 2 cm on a day-to-day basis (Fig 2).[34,35] Cine-magnetic resonance imaging (cine-MRI) has demonstrated that this prostate motion is mostly due to varying degrees of rectal filling,[36] although bladder filling can contribute as well.[37] Thus, radiation oncologists must design a treatment strategy that will account for motion that occurs between daily treatments (interfraction motion) and that which occurs during the treatment itself (intrafraction motion). The fact that prostate motion could result in potential geographical misses and lead to worse clinical outcomes was demonstrated by de Crevoisier et al.[38] They found that patients who had a distended rectum at the time of treatment planning CT had > 30% worse PSA outcomes compared with those who did not.

Figure 2.

A-B. (A) Initial planning CT scan demonstrating empty rectum, and (B) CT just prior to treatment delivery demonstrating prostate displacement from gas in rectum.

In the era prior to advanced treatment technologies, large margins around the prostate were employed using skin markers and bony landmarks to align radiation fields. Studies using repeated CT scans or implantable markers showed that the prostate location poorly correlated with these landmarks.[34,36,39,40] It was quickly realized that other imaging modalities needed to be deployed during daily radiation delivery in what is now known as IGRT. One of the first imaging types used was abdominal ultrasound. Each day prior to treatment, a technologist performed an abdominal ultrasound to localize the prostate and make shifts in the patient's position in relation to the radiation field. However, this technique is user-dependent, and the ultrasound probe can displace the prostate, thus questioning its clinical accuracy.[41–43]

Because the use of abdominal ultrasound generated significant controversy regarding its accuracy, other imaging modalities have been explored. Metallic markers known as fiducials inserted interstitially into the prostate under rectal ultrasound have been used as a surrogate target for the prostate because of their easy visibility with x-ray imaging (Fig 3). Verification of the prostate position using fiducial markers, along with kilavoltage or megavoltage x-ray systems built into the treatment machine, has significantly improved the accuracy of prostate radiation therapy by reducing treatment setup and organ motion errors and eliminating user dependency.[44,45] To further improve the accuracy of treatment delivery, verification of fiducial marker location using CT was investigated since CT images acquired in the treatment room allow definition of position and shape of the prostate relative to the surrounding normal tissue not visible on x-ray imaging. One of the first available in-room CT systems is known as CT on rails. This system requires that the patient be moved between the CT scanner and the treatment machine on a track while remaining in the treatment position. Though conceptually strong, CT on rails has been compared with fiducial markers imaged with x-rays. Significant disagreement was found between the two systems that contributed to the lag time between image acquisition.[46] To overcome this problem, work was done to create a CT system built into the treatment machine that does not require patient movement and decreases acquisition time, resulting in the development of cone beam CT (CBCT). CBCT of the treatment area can be obtained just prior to treatment delivery, and alignment can be performed on the prostate and surrounding tissue. However, several investigators have reported considerable inter-user variability with this method of anatomical alignment, and the use of fiducial markers with CBCT is recommended.[47,48]

Figure 3.

A-C. (A-B) Implantable fiducial markers as seen on orthogonal kV x-rays just prior to treatment, and (C) with kilavoltage x-ray systems built into the treatment machine.

Though the study of prostate positional variation between daily fractions has resulted in improved accuracy of radiation delivery to the prostate, the above techniques do not take into account intrafraction variations that can occur during the actual radiation delivery. IMRT treatments to the prostate can take 10 to 25 minutes to deliver depending on the system used. Gas or stool that moves into the lower rectum during treatment delivery can potentially cause overdosing of the rectum and subsequent underdosing of the prostate.

The Calypso system (Calypso Medical Technologies, Inc; Seattle, WA) is a 4D radiation target positioning device that continuously monitors the location of three implanted electromagnetic beacon transponders at the rate of 10 Hz and permits 3D tracking. This system allows for continuous determination of prostate motion during the delivery of radiation in which treatment can be halted if the prostate moves outside of a set threshold distance for a predetermined period of time. Kupelian et al[49] were the first to report on the clinical use of this system in the context of a multi-institutional study for the treatment of prostate cancer. In the 41 patients evaluated, they found that continuous prostate motion was unpredictable. Prostate displacements of ≥ 3 and ≥ 5 mm for cumulative durations of at least 30 seconds were observed during 41% and 15% of treatments, respectively. Among individual patients, the number of treatments with prostate displacements of ≥ 3 and ≥ 5 mm ranged from 3% to 87% and 0% to 56%, respectively. This initial study demonstrated that prostate motion during treatment can be significant. Further investigation is needed to evaluate whether its active monitoring can result in improved outcomes.

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