Chemo infusion number 6 is in the books, and it was a relatively informative day at the same time. Two horizons are coming into focus:

1. The chemo is taking a toll on Sherri’s blood counts; not unexpected, but reaching the edges of normal limits.
2. Results are back on the genetic profiling of the pancreatic tumors, with several interesting mutations detected.

Blood Counts: A typical chemo regimen is designed to put misbehaving cells in the cell block, but they say collateral damage of up to 20% in certain good-cell neighborhoods is inevitable.  So let me get this straight; cancer’s law enforcement accidentally puts 20% of your upstanding citizens in the slammer, and that’s normal? That would be like the Cancer Congress just arbitrarily furloughing another 20% of the essential workforce every two weeks. Oh, yeah.

So to be more specific, Sherri’s white blood counts are at the lower limit; hemoglobin, hematocrit, and platelets are below normal ranges; and red blood count is low. No surprise (that’s why they check it every time) and it’s not critical quite yet, but we’re trending toward shaky ground. So we’ll need to make a few changes. First up: skip an extra week before the next treatment.

Genomic Alterations: I was just thinking the other day: what if the excessive proliferation and tumor formation was due to the amplification or overexpression of ERBB2? Clearly a mutation in the kinase domain of ERBB2, such as in ERBB2 L755S, could be an activating mutation capable of inducing oncogenic transformation in cell cultures. Well it turns out I was right! And not only that, but it turns out she has the ERBB2 R678Q missense mutation within the cytoplasmic domain of the HER2 protein, in the region of the nuclear localization signal and the region required for interaction with KPNB1 and EEA1… I’m thinking that would be in the region of amino acids 676 to 689-ish… I kid you not! (well, no that’s a lie. I got it from the report. See below.)

There is quite a bit more of this in a 17 page report from Foundation Medicine, who conducted their FoundationOne™ screening. In fact, they detected several genomic alterations that have FDA-approved therapies in use for other (non-pancreatic) tumor types, and identified a number of clinical trials underway that apply them to pancreatic. All you biotech gurus, medical researchers and practitioners, and extremely advanced hobbyists that we are proud to call our friends, let me know if you want to see this report and I’ll email you a copy!

We are happy to have this information. Our village will find something useful to do with it!

Next Steps: We’ve moved the next chemo trickle charge to a different date. We are waiting three weeks instead of two, so the next infusion will be on Nov 21. Our hope is that this will give Sherri’s system a little extra time to boost those platelets back up (unless someone can bring us a wheel barrow of real marrow, and say it 5 times, quickly…). Also this change will reset our normal two-week cycle to be out of sync with Thanksgiving and Christmas, when we will likely be trying to venture out a bit.

In the meantime, let’s all set our clocks back at different times this weekend just to keep things interesting.

The Genetics Risk Assessment Program (RAP) Rap:

Met with the team in clinical genetics

Identified the genes using nothing but phonetics

Ask me to name them and it will be pathetic | you’ll regret it | don’t go there just forget it.

 

There’s no silver-bullet story, yo

We’ll tell you ’bout the glory, tho’

No mystery in the history | no  family-tree story | not to worry

 

Not passed down through the generations

Gotta find the configurations

Of the gene mutations | with the formation | for annihilation

 

Or in less artistic language, we received the results of Sherri’s genetic profile this week, and they were relatively inconclusive. There were no gene mutations identified that have any known correlation with cancer. This is good in that there is no indication that family members might share a predisposition to the cancers that Sherri has contracted. On the other hand, it doesn’t give us any additional actionable information to work with.

Still pending is additional profiling of the tumor cells for useful genetic information, but this is a separate process.

Meanwhile, we are back at FCCC for cocktails.

Live from Fox Chase Cancer Center.

Today we received results of yesterday’s CAT scan to follow up on Sherri’s progress after 3 chemo treatments. It’s pretty good news, folks.  To cut to the chase, the report summary says:

IMPRESSION:

1. Decrease in size of multiple hepatic metastases.

2. Decrease in size or resolution of small pulmonary metastases.

3. Apparent increase in size of pancreatic head mass may be due to technical differences.

4. Decrease in size of portacaval lymph node consistent with treatment effect for metastatic disease.

The interpreting radiologist’s name is Dr. Milestone. Poetic, ain’t it?

Here is our understanding of what this means. The tumors on Sherri’s liver have decreased by about one third (and to my eye, the biggest one has dramatically reduced). The small tumors that were apparent on her lungs are all but undetectable – only a few can be found, and they are smaller than before. The pancreatic mass seems slightly larger, but the docs are skeptical of this appearance because the original CAT scan used a different technique that didn’t provide as accurate a measurement in this region. Also reduction in the liver normally follows reduction in the pancreas. Finally, the lymph node that was assumed to contain cancer cells due to inflammation is also shrinking. Nothing new is showing up in other organs.  For comparison, during the month prior to the first scan, one of the liver masses almost doubled in size.

Our oncology team is very pleased with this result, and one of them dubbed this an “amazing” result for only 3 treatments. Not really all that surprising given the blast of cosmic pancreas-kicking prayer vibes you’ve all been sending. Way to go people! Keep those amazing results coming!

So we”ll stay the course for now and continue to work toward a complete smack-down of this nuisance. Infusion number 4 is underway.