Wednesday, September 21, 2011

Just to Clarify some Questions which have Arisen...

This will be a bit of a "technical" post about her disease, in response to some queries. Don't read it if you are not in to scenarios and details and would rather focus on Meagan as a person and the life she enjoys today.

Meagan's disease is at this point incurable. And therefore likely terminal, in some undefined timeframe. For the moment it is controlled. That means we don't expect her imminent demise, in fact at this point it looks probable she will be here for the holidays, something that means a lot to her. But controlled in the context of melanoma means you really only focus on the short term - it speaks nothing to any long term prognosis. Because she has a quite active disease, and melanoma is known for being capricious, unpredictable in its behavior and can "jail break" (surge and grow rapidly), one just has to be cautious in looking too far ahead and assuming anything.

Thanks to radiation treatments, the current tumors seem to be responding (shrinking), and the ones in her brain for sure are shrinking as a result of the last treatment. We don't know yet if her spinal tumors are responding; there is a temptation to extrapolate and assume that if the brain tumors responded, then it's likely that the spinal tumors will as well. But we won't know that for sure until her spine is rescanned (in the next 45 days or so). It's not safe to assume that any particular treatment is working until you have hard data (a scan) confirming an impact and it's not safe to assume that the trajectory will remain the same over time.

Melanoma has somewhat of a reputation for radiation resistance. It can be effective initially, but then can mutate or survive and continue to grow after initially shrinking. Even if the tumor has shrunk, some melanoma cells can survive. It can also return to a treated area. In the case of the brain, her tumors are being "spot welded" as Dr. Vermeulen likes to say. This means that the focal point of the radiation beam is the tumor itself and as a result of the technology the radiation burden/dose on the rest of the gray matter is not large. Obviously the more tumors which emerge (and even beyond the newly discovered ones we fully expect others to occur down the road) the more difficult it becomes. You can still spot weld them with the Cyber knife or Gamma knife, but the burden/dose on the rest of the gray matter starts to increase. So you start killing off more gray matter, and that causes long term impacts. One thing that can happen is that instead of 1-2 brain tumors emerging, there can be a lot which pop up. The Gamma knife can handle up to about 6. Beyond that they would recommend whole brain radiation. Once you go to whole brain radiation, you get one shot at that. There is only so much radiation the brain can take, and once you've had the whole brain treatment, and you get another tumor, it's game over. So that is why it is crucial to find some systemic way to stop the melanoma from spreading - and given there is nothing like that currently out there, why melanoma is considered one of the most deadly cancers.

With regard to her spinal tumors, she has been treated in two areas of her spine. We hope the treatment is working in those areas. Because she has an active disease it is highly probable that the disease will spread into other parts of her spinal column through the epidural space. If it sticks and grows in those areas, which we will discover through a scan or through symptoms she experiences, they will be able to treat those areas with the Tomo therapy radiation. But like the whole brain radiation, you get one shot at each area. The spine can only tolerate so much radiation. So if the cancer reemerges in a previously treated area, they cannot treat it anymore.

So that's why radiation is considered local control and palliative treatment  - it is short term and not a cure. It buys you some time.

She does have numerous small tumors on her lungs. For now, those are causing no problems, and are not being treated, although they could be zapped. Aside from a couple skin tumors, the melanoma has not shown up in other vital organs.

Absent a new drug discovery  - and at this point I have not been able to find anything in the pipeline which would suit Meagan - the only hope for a systemic cure to stop the melanoma in its tracks is a form of chemotherapy. The Temodar did not work for her. It has worked for a very small percentage of people, and those people have remained free of disease for a period of time - they aren't considered cured, but their status is referred to as NED (No Evidence of Disease). Dr. Kaplan has indicated he wants to try to new chemotherapy called Abraxane. Whether it is used alone (single agent) or in combination with some other drug (such as Avastin), it still has a pretty low chance of success. Even if it has some initial success  - melanoma shows an ability to adapt and get past it. For some, and there are anecdotal stories out there, it has worked to stop the growth. It hasn't proved its efficacy in large, controlled studies, but at this point it hardly matters; if there is a chance and there is nothing else, why not try it, especially if the side effects are manageable.

The only drug out there which has a reliable track record of producing durable responses in a limited number of patients is Interleukin-2. Generally 6% of patients will have a complete response and another 12% will have a partial response. This is a particularly nasty drug with major side effects. Even if you wanted to try it, you have to be off steroids (which Meagan is not due to her brain tumors and regular brain radiation treatment which causes swelling). Because of her seizure risk, it becomes less viable as an alternative. So unfortunately, IL-2 alone or in combination with some of the new agents being developed in clinical trials is off the table for her. At least until she has no brain tumors emerge for a significant period of time and is able to go off steroids and anti-seizure meds.

That's the picture as I see it. Very slim chance of Abraxane controlling the disease. Continued radiation of emerging tumors to control them as long as we can. Then at some point, the disease moves from controlled to uncontrolled, and runs its course. So we buy time and enjoy every minute of that time we can.

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