Weeks 193 & 194: signs of cancer growth again

Written by Lars Haakon Soraas

Weeks 193 and 194 in the war on lung cancer have passed. Here are the highlights:

  • As people familiar with this blog will know, we measure tumor markers CEA and NSE regularly. And both have declined nicely after Dyanne got chemo in end of March. However, it appears they are now both on the rise again. Charts of both are pasted in at the end of this blog post.
  • We would have liked CEA to have fallen further. But it did not. When Dyanne got chemo in December, CEA fell from 99 to 7. This time CEA has fallen from 37 to 17 and it seems unlikely to fall any further. Why is the nadir higher this time? We can’t know for sure, but there are at least three possible explanations: the dose of chemo Dyanne got this time was lower than the dose she got in December; some of the repurposed drugs and supplements we added in December-February somehow contributed to the fall in CEA; or there are now simply more cancer cells that are resistant to the chemo. If we knew which of these explanations was the correct one (if any of them are…), it would have helped us decide next steps. However, we are unlikely to find out before we have to make some new decisions on treatment. I guess this is what they call “decisions under uncertainty”.
  • Some more analysis has been done on the tumor that was removed from the neck in December 2018. A pathologist in Oslo has looked at it some more and made some interesting findings. The most interesting is that he believes that the earlier conclusion that was drawn, that the cancer had transformed to “large cell neuroendocrine carcinoma” (LCNEC) was not really correct. He believes there are actually two distinct tumor cell populations: One that consists of small cell lung cancer (SCLC) cells, and one that consists of squamous cell carcinoma.(SCC). Interestingly, the SCC cells are positive for the tumor marker CEA, while the SCLC cells are positive for the tumor marker NSE. So it seems that when we track CEA and NSE in the blood, they actually correspond to two distinct tumor cell populations. An interesting question that has arisen from this finding is this: which of the mutations that have been identified in Dyanne’s tumor exist in each of these tumor cell populations? The EGFR and maybe also the TP53 mutations are probably in all the cancer cells. And the RB1 loss is certainly in the SCLC cells, and probably not in the SCC cells. But what about the PTEN and PIK3CA mutations? It would have been interesting to find out which cells harbour these mutations. If anyone knows how this can be done, then please do let us know (email: ). For all wanna-be pathologists, the images of the various stainings the pathologist has done are attached to this post.
  • Based on the latest development, Dyanne has started on mifepristone and also tetrathiomolybdate. Dyanne has been on both these drugs before, but stopped for various reasons. We are giving these drugs another go and hope they can help control the cancer.
  • Dyanne did a CT scan this week and we should get results in a few days. Annoyingly, the hospital had only scheduled to take images of the lungs, and not further down, including the liver. Luckily Dyanne managed to convince them that they obviously also had to take pictures of the liver as she has metastasis there. On top of this, they have now managed to compare the CT scan with a CT scan that was done 4 years ago, and not the most recent scan from March. The reason is that the hospital has moved the follow-up of lung cancer patients from one location (Radiumhospitalet) to another location (Ullevål). And it seems neither the IT systems or the people speak at these two locations speak with each other.
  • Dyanne has generally been in very good shape the past two weeks.

We are considering next steps when it comes to treatment. One approach we are considering (and, to some extent, already doing) is chemotherapy in an “adaptive” manner, following the work of Dr Robert Gatenby at Moffitt (Florida, US). In short, his approach involves only giving a new chemo infusion once there are signs that cancer is growing back (e.g. as seen by an increase in tumor markers). This is, essentially, what we did already: Dyanne got chemo in December and the second round of chemo was only given in March when both scans and tumor markers showed cancer was growing again. The purpose is basically to allow the cancer cells which are sensitive to the chemo treatment to grow back again. If one gives chemo in too high doses too frequently, there is a high likelihood that the cancer cells that are sensitive to chemo will be wiped out and replaced by cancer cells that are resistant to chemo.

Implementing such an approach in reality is, of course, challenging. In our case, for instance, when should one give the next round of chemo? When CEA is back at 37? Or 99? Or should some other decision point be used? No one knows what the answer to these questions are and so judgement has to be used. Luckily, we are getting some good guidance from Dr Gatenby himself, and some of his colleagues.

We are also looking into a number of other options. Time will show what we land on.

CEA – the red dots indicate when chemo was given
NSE – the red dots indicate when chemo was given

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