In early June I appeared on a nationwide news show and in a very brief comment indicated that I thought a new approach to radiation therapy in the treatment of primary breast cancer was "not ready for prime time." Subsequently, later in the month, I wrote a blog on the treatment-called TARGIT-where I further outlined my concerns. My primary issue-among some other more technical matters--were that the results of the trial were being promoted to suggest that the treatment was "ready" for moving into clinical use. I wasn't so certain.
During this period of time, I was contacted by someone affiliated with the company that manufacturers the machine used to deliver the radiation, and offered an opportunity to have a discussion with some of the researchers involved in the clinical trials of TARGIT. We accepted their offer.
Last week we had our follow-up call, and I think now is a good time to offer some information regarding that discussion.
First, let me briefly summarize what this is all about.
Radiation therapy to the whole breast after surgery has been a mainstay of "breast conserving treatment" for women with breast cancer for many years. It has allowed doctors to offer women a lumpectomy-assuming the tumor is a reasonable size-at the time of primary treatment, followed by a multiple week course of radiation therapy.
The radiation therapy in this situation is designed to reduce the risk of local recurrence of the breast cancer, and also to essentially "pre-treat" any other small areas of cancer that may be lurking elsewhere in the breast. This treatment approach has proven successful, and reasonable estimates are that about 5-6% of the women treated in this fashion may eventually have a recurrence of the cancer in the treated breast, or perhaps develop a new cancer some time afterwards. That means that the vast majority of women with early stage breast cancer do well after lumpectomy and radiation therapy, with respect to the breast where the initial cancer was diagnosed and treated.
There have been efforts over the past number of years to simplify the radiation therapy for these women with breast cancer. Going back and forth to the radiation center over a 6 or 7 week period of time isn't easy for most women, and impossible for some women who may be disabled, not have transportation or live a great distance from a radiation therapy center.
As a result, alternate approaches have been tried which either give the radiation over a shorter period of time, or use devices placed at the time of surgery which can give the radiation more efficiently or quickly, usually over about a week. The result is that there has been considerable discussion within the medical community over the use of what is called "partial breast radiation," with some doctors using it routinely and others waiting for the results of clinical trials which are currently underway.
The TARGIT treatment takes a somewhat different approach. The treatment itself is again reasonably straightforward, and certainly a lot simpler than traditional radiation therapy in breast cancer.
A women has the cancerous lump removed, and at the time of surgery the TARGIT device-which generates a fairly low level radiation output compared to standard radiation therapy machines-is placed in the site from where the tumor has just been taken out. The radiation is given over a fairly short period of time, as a single dose. After the radiation is administered and while the woman is on the operating table, the surgeon comes back and finishes the operation. That's it. No more radiation is needed for many women, or so the press releases and news reports seemed to indicate.
That's where I started to have some concerns. It was my impression that the reports on TARGIT were underemphasizing the fact that a fair number of women (my rough "back of the envelope" estimate was 22%) who received TARGIT during primary surgery would still have to go on and get whole breast radiation. This was as a result of having more aggressive cancers that the researchers felt would benefit from more intensive treatment. The problem is that for many women, the doctors couldn't know their cancers were more aggressive until looking at the cancer under the microscope. And that usually doesn't happen until after the cancer has been removed and the TARGIT treatment given (there is an alternate approach, but I don't want to repeat here what I have already written in my earlier blog).
Turns out I wasn't far off. The researchers on the phone call agreed that 22% was not an unreasonable number. They agreed that somewhere between 20 and 25% of the women treated with TARGIT in the manner that would probably be the routine practice in the United States would still have to go on to get the traditional radiation therapy over several weeks. But they also emphasized that 75-80% would not.
The other observation that I made in my blog was that this was a group of women who had what we call "favorable" breast cancers. That is, in many of the women the cancers were fairly small, were hormone sensitive, and lymph nodes were not involved.
Again, the researchers on the call agreed. Having such a "select" group of women with more favorable breast cancer was not their intent at the beginning of the trial-as reported in their research paper in the Lancet-but that's the way it worked out, for a number of reasons. They agreed that the results of their trial could not be used to support the use of TARGIT in breast cancer patients who may have larger cancers or other signs of more serious disease.
Perhaps the most contentious issue is whether or not TARGIT is ready for routine deployment as a treatment for breast cancer in this country. In fact, one of the investigators on the call indicated that he was preparing to routinely offer TARGIT treatment for his patients with breast cancer who met the criteria discussed above.
That is still an area where I am not quite comfortable. The researchers make an excellent argument that they have treated enough women over a sufficient period of time to conclude that the treatment is most likely effective. However, there is a long "tradition" of treating early stage breast cancer with whole breast radiation and changing that pattern of care takes very solid evidence-especially since the use of whole breast radiation has been based on prior clinical trial results which are widely accepted and have withstood the test of time.
Please understand that I am not saying that just because we have always done something means we should continue doing it the same way forever, If the evidence is good, then we should change what we are doing. But we shouldn't be quick to abandon a treatment that was built on a foundation of evidence and has proven successful for so many years just because a new gadget comes along. We need to be certain the new approach really works.
In the background of this discussion is the fact that we don't regulate machines that treat patients the same way we regulate medicines used to treat patients.
The FDA has very strict criteria when it comes to approving medicines to treat cancer and other diseases (as reflected in the Avastin® discussion earlier this week). For drugs, companies have to prove both safety and efficacy. For machines, safety and performance-but not necessarily efficacy-are the criteria used for approval. So, there is no process by which the FDA reviews the data and deems the machine effective for use in treating patients with cancer.
It would be great to hear some of the discussions of experts in breast cancer regarding their views on the adequacy of this new TARGIT approach. That might help inform all of us as to whether or not the data are sufficient and compelling to warrant making TARGIT available to more women.
For now, I suspect I am going to remain a bit more conservative and say that a couple of more years of follow-up would be helpful (although the trial has been ongoing for over 10 years, the number of women who have been entered into the trial have increased considerably over just the past couple of years, so the majority have not been followed for a very long time). But I will admit that I am willing to listen to the thoughts of others more expert than I, assuming they do not have a personal interest (financial or otherwise) in this debate.
My bottom line?
The conversation with the researchers was worthwhile, and they acknowledged the validity of some of my concerns-which in fact they had done in their research report, but had not made it into the press releases that accompanied the presentation of the report at the cancer meetings in early June.
I think the most important issue is that women understand that just because they get TARGIT during their surgery, doesn't mean they don't have a fair chance of still requiring whole breast radiation over several weeks if their cancer appears more aggressive when examined under the microscope.
Where we disagree is whether the data is adequate to offer TARGIT as a standard treatment for small, early stage breast cancers at this time. I am not certain it is, but willing to listen to the thoughts of others. What I don't want to have happen is see this treatment (or any other treatment, for that matter) "bootstrapped" into legitimacy, where doctors say they think it works often enough that they believe it works rather relying on the evidence that it works.
Time will tell the outcome of this discussion, but I do think if the trial data remains the same as it is today, and we have a couple of more years of follow-up, it is likely that TARGIT may well become a routine treatment option. And for the women with breast cancer who wouldn't have to come back and forth over weeks for their radiation that would be a huge step forward in the treatment of this disease.
We shall see...
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