Genetic mutant

I went to Baltimore today to get genetic test results from my doctors at Johns Hopkins. The results were somewhat inconclusive. It seems that my case is unusual even among unusual cases of cancer.

The first test was for microsatellite instability. They examined the DNA of my cancer cells to check for excessive repeats in the base sequences. Two of the five markers they examined were unstable, qualifying the specimen as having high microsatellite instability (MSI-H). That result is suggestive of a hereditary factor. It's also correlated with a better prognosis: "Colorectal carcinomas with no indication of microsatellite instability (MSS) have been associated with worse stage-specific survival after surgical and adjuvant therapies than those with MSI-H."

The second test looked at the expression of protein production in the cancer cells. With high microsatellite instability they expect certain proteins to be missing from those cells. However, my results showed that all of the proteins they checked were present. It's possible that the proteins were present but nonfunctional due to mutations or misfolding.

Since these first two tests suggest a hereditary cause but are inconclusive themselves, the next step is to examine certain genes from my normal tissue. There are four genes known to be involved in hereditary colorectal cancers and defects in two of those genes produce 90% of the cases. So they will start by checking those first two genes.

I'm not sure whether being diagnosed with hereditary colorectal cancer would be good news or bad. The average prognosis is better, but it also means a greater chance of recurrence and a greater risk for my relatives. The information is also interesting to the doctors at Johns Hopkins academically and might help direct treatment some day in the future.

Reevaluation

After a year on Xeloda plus Avastin, my CEA has reached the normal range and stayed there for a month. I took a week off from chemotherapy to share a vacation with my family (mother, three sisters, two brothers-in-law, one niece, three nephews, and my girlfriend) in Florida.

By the end of the week I felt something surprising: normalcy. My energy level is good, my appetite is solid, my skin condition is closer to normal. My previously tumor-ravaged hip joint didn't give me any trouble in miles of walking per day. My mental capacities are slowly improving enough so that I started a fresh batch of computer simulations for work, something I haven't done since declaring my cancer returned in June 2006. I don't feel like I have cancer anymore.

We are continuing with chemotherapy and that alone will be enough to make me feel sick for the coming months. But we have quietly reached the milestone where it's worthwhile to reevaluate the state of my body and look for a basis of hope that good health can last beyond a few weeks or months.

There will be a flood of information coming and it will keep me busy running medical errands. I will receive genetic test results from Johns Hopkins University next week. The following day I will get a radioactive injection for a full body bone scan. I will return to the National Institutes of Health for CT and PET scans. And we'll continue to watch my CEA and see whether it rebounds or stays low.

I'm starting to think about what to do with myself if we declare my cancer in remission and stop treatment. The first time I reached remission we thought I might be cured and treated it as a cause for celebration. This time I'm reluctant to hope for being cured. But for all the unexpected tragedies in life, isn't it possible to sometimes find an unexpected miracle?

Cancer quantified

Since starting treatment more than three years ago, our main measurement of its effectiveness has been the level of carcinoembryonic antigen (CEA) in my blood. CEA is a protein involved in cell adhesion that is normally present in a developing fetus but not in an adult. A plot of CEA versus time shows the history of my cancer's ebb and flow.


A normal CEA level is below 2.5 ng/mL. Higher levels can be produced by gastrointestinal cancers, and levels above 20 ng/mL are associated with metastatic tumors. Note that the vertical scale is logarithmic, not linear, so each major tick is ten times higher than the one below. My CEA was at 23 when diagnosed in August 2004.

Colectomy (removal of the lower colon) and FOLFOX chemotherapy reduced my CEA to normal. A laparoscopic examination showed that I still had many small tumors remaining, so in May 2005 surgeons removed my peritoneum (a membrane covering organs in the abdomen) and diseased parts of many other organs. Then they applied direct, heated chemotherapy to kill any remaining cancer cells.

The surgery seemed successful, but in early 2006 my CEA shot back up to worrying levels. CAT scans and PET scans confirmed that tumors were growing in several spots, particularly around the pelvis. We started chemotherapy with Erbitux and Camptosar, but the cancer kept growing.

In November 2006 we tried the oral chemotherapy Xeloda plus Avastin. The cancer responded well, and my CEA has dropped from a high of 160 ng/mL down to normal. We are continuing chemotherapy since a normal CEA does not necessarily mean that all the cancer is gone. I'll get scans again in a few weeks to see if those have cleared.