Cyberknife, radiosurgery, “Anova” and hypofractionation

To read this post on my blog site and subscribe to future posts, please go to http://www.prost8blog.com. In our local market the NHL Avalanche are back in the playoffs and it is fun to become a fan once in a while of the frozen sport. However, I am tiring of the ad blitz by a local radiation oncology “for profit” organization called Anova that says “you might call it a miracle, we call it Anova” or similar. As a non-radiation oncologist, I will offer my outsider opinion and overview.

imrt

IMRT Treatment Plan

As I have previously posted, there are many ways to ablate prostate tissue. Focusing various sorts of energy on the prostate gland is an evolving field that essentially takes advantage of computerized technology. In essence, the more precisely you can focus a beam (or heat or cold) on the prostate, the more energy you can deliver safely. Most surgeons would argue, of course, that good old formalin, the fixative used to prepare a removed prostate, is the best option (unless they happen to own a radiation therapy machine…). As the dose goes higher, so does the risk of damaging normal tissue, since there is always some scatter. An energy map of a standard IMRT dose plan looks like this. The highest dose is inside the green line, and the other lines called isodose curves depict lower doses going concentrically outward. The map is the result of several different ports being used to target the prostate while reducing the dose to the bladder, rectum and other tissues. (Aren’t computers wonderful?). Now imagine that you link this to a CT scanner that precisely images where the patient is laying on the table each time the treatment begins, and may even check it before each dose is delivered through one window (port), or even that the treatment machine can move constantly delivering doses that are stronger or weaker based on moving lead plates that are brought into the beam to attenuate the amount of radiation. As you can imagine, you can get much more precise delivery to the desired target, and with that, maybe you could deliver higher doses in fewer visits to the radiation therapy facility. 

The reason you can’t deliver all the dose at once, however, is that normal tissues wouldn’t tolerate it. Hence, dating back decades, it was learned that if you delivered a bit each day (fractionated the dose), or sometimes even two times a day, the normal tissues could tolerate the “scatter” better by repairing the DNA damage they got, while cancer cells were less good at repair. The result was less death and destruction to the normal tissue while the cancer was eventually eliminated. In the case of prostate cancer treatments, often the number of “fractions” needed was in the range of 40 or so to get to the final dose needed for prostate death.

BUT… as the technology improved, it became possible to focus better, give a higher dose with each treatment, and reduce the number of treatments. The treatment plans evolved from treating a “box” to treating a “conformal” target,  to treating with the kind of dose distribution shown in the picture. As a result, the total dose could go up, cure rates improved, and then an artistic tension evolved between what you could get away with vis a vis normal tissue, size of each fraction, and total dose. Many studies were done and many are ongoing. A good example is here, in which it was found you could generally safely reduce the number of treatments from 38 to 26 with comparable control rates.

So what about taking it all the way down to 5 treatments using the most precise targeting? This is the promise of what is generally termed stereotactic radiosurgery and one of the instruments is called “cyberknife”. Several reports of trying this are now published, but the results are VERY early. To quote one review, “Five randomized controlled trials have evaluated moderate hypofractionation in >1500 men, with most followed for >4-5 years. The results of these randomized trials are inconsistent. No randomized trials or other rigorous comparisons of extreme hypofractionation with conventional fractionation have been reported. Prospective single-arm studies of extreme hypofractionation appear favorable, but small sample sizes preclude precise estimates of efficacy and short follow-up prevents complication estimates beyond 3-5 years.”

Given that late complications of radiation therapy may take considerable time to develop and may be higher in the group receiving only 5 or 10 treatments, I think it is far too early to be placing ads on television touting this approach. Some version of this article should be required to be a part of any advertising campaign. (be sure you click to read the abstract) Just as with robotic surgery, technologic advances are not always what they seem to be from what you may see on TV. Don’t pull the goalie just yet!

3 Comments

April 25, 2014 · 9:40 am

3 responses to “Cyberknife, radiosurgery, “Anova” and hypofractionation

  1. Geezer

    Never be the first to adopt a new therapy..(Or the last!!!)

  2. Dave Stevens

    I am beginning to wonder if I’ve inadvertently committed a slow-acting suicide by first having robotic surgery followed by IMRT when the robot didn’t work!

    • No way. Doing everything possible to be cured is what everyone does. It is unfortunate that it doesn’t always work and that there are side effects. As one surgeon told me, if the prostate was attached to the elbow, we would simply take it off as soon as a man was done with procreation and this challenge would go away!

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