Calypso: Can Radiation Treatment be Improved?

If you look at an illustration of where the prostate gland is located, it’s easy to find. It’s nestled below and against the bladder, and sits in front of the rectal wall (with a layer of tissue in between). Seeing the illustration, your unconscious mind takes for granted that’s where the prostate always stays.

However, the position of the gland is not exactly “written in stone”. Three factors cause it to move around slightly, even when a man is sitting or lying perfectly still:

  1. Breathing – The inhale/exhale motion of the diaphragm at the base of the lungs has a small but measurable effect on prostate position. As the diaphragm rises and falls, it changes the shape of the abdominal cavity. In turn, this has a bearing on the bladder and its prostate neighbor.
  2. Bladder filling – Being directly adjacent, as the bladder fills with urine it affects gland position.
  3. Rectal filling – Bulk in the rectum likewise displaces the prostate to a small degree.

 

Radiation therapy for prostate cancer

 External beam radiation has long been in use as a treatment for prostate cancer (PCa). Historically, it was recommended for older patients who were not considered good surgical candidates. Advantages of beam radiation include noninvasive and low risk of short term side effects (fatigue, bowel irritation, sexual dysfunction). On the other hand, beam radiation has had several hurdles to overcome:

  • Risk of late-onset (3+ years after treatment) urinary, sexual and bowel side effects
  • Risk of late-onset secondary cancers (bladder, colorectal cancer) due to “scatter effect” of ionizing radiation
  • Inability to deliver more radiation if PCa recurs
  • Historically, higher average recurrence rates than for surgery or whole-gland ablation
  • Inability to monitor radiation effectiveness during treatment
  • Inability to evaluate radiation effectiveness for many months, since radiation does not immediately kill cells but interferes with cell DNA over time
  • Establishing ideal dosimetry

Recognizing the scatter effect and its potential to give rise to future colorectal cancer, the injection of an absorbable “hydrogel” into the tissue between the prostate and the rectal wall was created to act as a spacer. This offered some protection since the radiation effect diminishes as it travels. On the other hand, simply targeting the radiation more effectively would be a better solution.

Today’s technologic advances have done just that. Specifically, 3-D conformal beam radiation, intensity modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and proton beam therapy all have greater accuracy, thus diminishing radiation exposure to neighboring structures. However, prostate motion creates a “blurring effect” in terms of delivering the exact same dose to the exact same target during each treatment session, and from one session to the next. To get around this, efforts were devised to “stabilize” (prevent) prostate movement during radiation treatment. These generally increased the length of treatment sessions and created patient discomfort (e.g. inflatable balloon inserted in the rectum).

Tracking prostate position

 Rather than try to restrain prostate motion or physically shield/distance nearby structures, a better approach would be to know exactly where the gland is located from one moment to the next, and adjust the radiation beam’s aim to match it. “The knowledge of organ motion is essential to ensure conformed dose delivery to the target and minimize toxicity to the surrounding organs at risk during prostate radiation therapy,” write authors Lin et al. (2013)[i]

Therefore, a new motion tracking device called the Calypso 4D Localization System™ is the latest effort to assure that prostate radiation acts as an “intelligent bomb”[ii] against prostate cancer. It promises to track the left-to-right, up-and-down motion of the gland in real time during radiation treatments.

To accomplish this, three electromagnetic transponders (the size of a grain of rice) are implanted in the prostate using ultrasound guidance during an outpatient procedure prior to beginning radiation treatments. Then, during each radiation treatment, radiofrequency waves communicate between the Calypso tracking software and the transponders. As the prostate moves slightly in any direction (think of a 3-dimensional graph with an x axis, a y axis and a z axis), the radiation delivery system makes necessary adjustments in real time to aim at the gland. This means less “blurring” of the dosage, maintaining consistency, while avoiding collateral damage to surrounding tissues and organs.

Complex mathematical and physics calculations have assessed the probable extent and direction of prostate movements, to enable Calypso to do its job. Not only has Calypso been in research trials for primary external beam radiation (initial treatment), it is also being tested for radiation to the prostate bed after prostatectomy with high risk patients, where it has been less successful.[iii]

Given the relatively recent entrance of Calypso into radiation therapy for PCa, it is too soon to tell if it will make a significant difference in a) increasing treatment success and b) reducing late-onset side effects and secondary genital cancers. In our opinion, the use of radiation for certain PCa patients may well be their best clinical option. However, radiation is radiation, and it is our belief that there is a more complicated cost-benefits analysis with radiotherapy than with other definitive PCa treatments.


[i] Lin Y, Liu T, Xiaofeng Y et al. Respiratory-Induced Prostate Motion Using Wavelet Decomposition of the Real-Time Electromagnetic Tracking Signal. Int J Radiat Oncol Biol Phys. 2013 Oct 1; 87(2): 370–374.

[ii] Watch the video at https://my.clevelandclinic.org/health/treatments/16826-calypso-4d—prostate-cancer-treatment

[iii]Zhu M, Bharat S, Michalski JM, Gay HA et al. Adaptive radiation therapy for postprostatectomy patients using real-time electromagnetic target motion tracking during external beam radiation therapy. Int J Radiat Oncol Biol Phys. 2013 Mar 15;85(4):1038-44.