Ruminations 2 - Reprieve
Reprieve
March 8, 2007
Yesterday I had meetings with both the surgeon, Dr. Norris, and the oncologist, Dr. Hodi, about the upshot of which more later. In the month between my last surgery and these meetings, I have been giving myself a cram course in cancer immunology because all melanomas are the result of a failure of the immune system.
In my past life I have always avoided studying the immune system because it is, or appears to be, so messy. What I found most fascinating in my cram course was the déjà vu it inspired. In the first half of the 1950’s I was at Westinghouse Research where there was considerable interest in nuclear physics because of Westinghouse’s involvement in nuclear power. At that time new nuclear particles were being discovered and published every week and the zoo of particles was overwhelming. There was no theory relating these particles to each other or capable of making verifiable predictions. The relevant theory did not come along until a decade later – in the 50’s attempts at explanations were an exercise in numerology. I was not there then, but the same thing happened in the 1880’s and 1890’s with atomic spectroscopy – new lines reported every month with no idea what the numbers meant or how to relate them. The spectral lines were not understood until the advent of the Bohr atom and quantum theory more than a decade later.
My crash course persuaded me that immunology today is in the same position that atomic spectroscopy was in the 1890’s and nuclear spectroscopy was in the 1950’s. Lots of data, a confusion of nomenclature and no unifying theory with adequate predictive power, the sine qua non of a maturing science. On the basis of what I have read, I will make a prediction: If I were to show up with any melanoma 20 years from now, I would have a high probability (>80%) of being cured with a series of ‘vaccinations’ that stimulate the appropriate components of the immune system.
The current literature (remembering that the 2007 literature reflects, at best, the facts as known 12 – 18 months prior to the publication date) does not report any clinical trials of any drugs or combination of drugs that has a positive effect on more than 10 – 15% of the study population. There was nothing in the literature I could find that even hinted at or speculated about what distinguished the responding patients from the non-responders. Consequently, I decided on an algorithm for treatment selection: The percentage of the time that the side effects of the treatment are likely to prevent me from doing what I usually do cannot exceed the percentage of likelihood of successful treatment.
Let me at this point interject a plea to all of you, based on my experience in trying to put together my cram course. Please, please, support open source publication. It is an absurdity that I, living on the island and not near a medical school library, cannot access more than the abstracts of papers written describing research that my (and your) tax dollars paid for and that for profit journals want to charge me $20.00 - $50.00 per article to read. Write to your Congressperson and Senators, please! (End of diatribe.)
Unfortunately for me, that is then and this is now. None the less, in my conversations with Drs. Norris and Hodi, I learned a lot that is not obvious from the literature, and, in fact, contradicts some common wisdom. I entered the conversations with the firm intent to decline further radiation therapy on the grounds that violated the algorithm. The literature on melanoma (read cutaneous melanoma since mucousal melanoma is so rare) all agree that radiation therapy reduces the incidence of local recurrence but does not improve life expectancy because of metastases at distant sites. My experience with the first round of radiation therapy did not go as expected. The prediction was that at the end of the six weeks of daily radiation, I would be in considerable pain but that after four to six weeks I would be fully recovered. What actually happened was that I was never in any pain but had so little energy that it was all I could do to move from my bed to my recliner chair and this state lasted for three months and it was three or four more months before I was fully recovered. The idea that I spend the best eight or more months out of my remaining (relatively short) life that incapacitated is unacceptable to me.
Dr. Hodi persuasively explained to me that, for unknown reasons, head and neck cancers are significantly more responsive to radiation that cancers in other locations, with a response rate of 20 – 25% and significant success as measured by stable disease or remission. So, I am again, admittedly reluctantly, going to be talking to the radiation oncologist sometime before the end of the month. It appears from my conversation with Dr. Norris that there is a choice of both radiation modalities (photons or electrons) as well as advances on how the dosage is delivered so that it may not necessitate daily trips to Hyannis or Boston for six weeks. The advantage of electrons over photons is that they penetrate only a few centimeters (all that I need to irradiate the area where the lymph nodes were) and therefore is much easier on the deeper structures in the neck; the disadvantage is that it is much harder on the skin, and my skin is pretty flaky at best.
For both modalities there are now protocols that call for delivering more radiation per session with fewer sessions, which would certainly ease the significant transportation burden. Finding out what treatment, if any, will reduce the long term disability must await the discussions with Dr. McAnaw, the radiation oncologist in Hyannis .
Irrespective of the radiation treatment, Dr. Hodi is currently running two clinical trials of immune system stimulation therapy specifically directed at the pathways that are typical of mucosal melanoma; most, or all, of the other clinical trials underway are directed at another pathway more common to cutaneous melanoma. To be eligible for either trial I have to have ‘measurable disease’, that is a metastasis that shows up radiologically and therefore the effect of the treatment can be measured. While, of course, I would prefer to start such treatment immediately since if it works it will work better on metastases that are too small to be detected radiologically, I fully appreciate the need for this requirement, even as I selfishly wish it could be waved. In order to make sure that I can start the immunologic therapy as soon as practical, we will be doing a PET scan on me every four months. Since the last PET scan was in early December, the next one is only a few weeks away.
One of the things that has been puzzling me are the statistics relating to life expectancy. A five year survival probability of x% is all very well, but exactly when does the clock start? I asked. The clock starts on the cessation of the initial therapy for the condition. In my case, that is when the initial radiation therapy ended, in September of 2005. Consequently, I am already 18 month into the five year period. Since I am now officially ‘disease free’(at least until the next PET scan) I am clearly not in the lower range of 5-year survival predictions. Indeed, I was informed that I have a 20 – 25% chance of remaining disease free for the foreseeable future. We shall see, but there is reason for restrained optimism and no reason for ongoing concern.
More when I know more, in a few weeks.
Cheers,
Tom.
