Monday, April 20, 2009

The Rationale Behind Mammosite

Breast conservation therapy (lumpectomy + axillary node dissection + whole breast irradiation) is an accepted alternative to modified radical mastectomy for the treatment of breast cancer. This determination is based on over twenty years of data. BCT is equivalent to MRM in terms of survival. This is what we tell our patients. The data from multiple randomized controlled trials is incontrovertible. MRM is still a preferred treatment modality in the following clinical scenarios: pregnancy, prior irradiation to the breast, two or more gross foci of cancer in separate quadrants of the same breast,
mammographic findings of diffuse areas suggestive of malignancy, failure to obtain negative margins despite several surgical attempts, collagen vascular diseases. But not every woman needs to undergo a potentially disfiguring mastectomy. The option for less extensive surgical intervention is not only more palatable, but scientifically justified.

But we always like to push the envelope, especially in medicine. The biggest problem with BCT is the necessity for whole breast irradiation. The rationale for radiation therapy is that local recurrence rates after BCT alone were unacceptably high (although survival rates are the same). The NSABP B-06 trial showed that the addition of radiation reduced 10 year local recurrence rates from 53% to 12%. Subsequent studies confirmed the survival benefit of this reduction. So adjuvant radiation therapy is an integral aspect of the BCT trifecta. A surgeon who treats a breast cancer with just a lumpectomy and sentinel node/ax dissection is doing a disservice to his/her patient.

The problem is that radiation therapy is rather inconvenient. It's given over the course of 6 weeks. Every morning, before work, you have to drive into the rad-onc department and get zapped. For some people, this inconvenience outweighs the theoretical benefits; recent studies show that 10-15% of women don't complete the full course of radiation therapy.

So the envelope gets pushed. How can we make radiation therapy shorter and more tolerable? Researchers started looking at where those local recurrences occured in patients who had had BCT. What they found was that 70% of ipsilateral recurrences after BCT were in the neighborhood of the original tumor. So the gears started grinding. And someone came up with the idea of "partial breast irradiation", i.e. just irradiate the breast tissue around the residual tumor bed and you will likely derive an equivalent benefit to whole breast irradiation. Seems reasonable, no?

The Mammosite Balloon is a type of partial breast irradiation delivery system. A balloon catheter is left in the lumpectomy cavity and, after confirming placement with CT scan and US, radiation doses are applied through the balloon over the course of 5 days. At the conclusion of the 5th session, the balloon is removed. And that's it. One week and you're done.

Preliminary evidence is encouraging but we won't have level I evidence (in randomized controlled trials) to support Mammosite-like partial breast irradiation until 2014. So for now, it's strictly an experimental, albeit highly appealing, treatment option.

My question: If local recurrence after BCT seems to be occuring predominantly in the area of the original tumor bed, then why is the solution to use an extremely expensive partial irradiation delivery system instead of just, you know, maybe doing a better, cleaner initial surgery? In breast cancer we talk about the need to get "negative margins" when excising a tumor in a lumpectomy specimen, but we don't put a number on how negative it needs to be. In other words, should you get 1cm clean margin? 2cm? 3mm? Should it be a 1cm gross margin or a full 1cm microscopically? The data is not clear on this point. As long as there is no tumor at the cut edge of the specimen, we are satisfied. In other forms of cancer, expected resection margins are more explicit. If I am doing a right colectomy for cancer, I want at least a 5 cm clean margin. Low rectal tumors need at least a 2 cm distal margin or you aren't doing the patient any good.

So before we dive headlong into a very expensive, labor intensive new technology like Mammosite, shouldn't we first determine the optimal surgical approach to early stage invasive breast cancer? Shouldn't we compare local recurrence rates in specimens with 1cm margins vs. those with 2mm margins? Wouldn't that be a good thing to know? It just seems logical to me; after all, breast cancer is first and foremost a surgical problem.


Enrico said...

What about extremely strong family hx (mother/siblings +findings/death) in spite of acceptable objective criteria for BCT? How does one account for the "maybe" events of a pt's clinical course not being as predictable given significant genetic factors when deciding which modality is appropriate?

I know there isn't a "right" answer, just looking to peek into the thought process :)

Marco said...

What about intraoperative radiotherapy? that can reduce the number of RT sessions needed postop or even give all the needed dose of radiation at the same time of surgery.

Jeffrey Parks MD FACS said...

ceratin genetic predispositions DO present a strong indication for MRM, even prophylactic bilateral MRM.

intraop radiotherapy is even more experimental than mammosite. furthermore, the point of my post here is to ask: if recurrences are in the area of the lumpectomy, then are we doing a good enough lumpectomy to begin with? It doesn't matter how the radiation is given, the fact that cancers tend to recur near the resection bed ought to prompt us to question the adequacy of the initial resection...

Anonymous said...

Here is one study comparing 0-2mm vs >2mm margins: