Wednesday, January 6, 2016

Bye-bye Chemotherapy, Hello TP53!

Chapter 15: starting a new life
There are quite a few developments to report — First, the happiest news: I saw my big chief oncologist on Monday 4 January and we agreed that I am stopping chemotherapy now, having had six cycles of chemotherapy, rather than the full eight cycles that was pencilled in five months ago. Happy happy happy!
Here's the clinical information that underlay this decision. In my latest CT scan, taken on 30th December 2015, the evidence of a secondary tumour in one of the vertebrae of my spine had gone away; my stomach wall looked thin (which is a good thing); and a couple of lymph nodes are potential causes for concern - one of them has plumped up a little since the last scan, and another has become visible that was not visible before. The plump lymph nodes are not necessarily cancerous - they could just be plump because they are busy doing their job. So this seems like a 1-1 draw. I asked my doctor to talk me through the decision to have chemotherapy, which we took five months ago, and to update the decision making to this week's situation. Five months ago I drew, on the basis of what the doctors told me, a quality of life graph like this: showing quality of life versus time without chemotherapy (red) and with (green). The deal, five months ago, was that chemo might reduce quality of life by 20% or so for 6 months, and in return there might be some extension of life, with perhaps a steeper downturn in quality of life at the end; the median extension of life was a remarkably small 2 months, but if you get to be in the lucky right hand half of the distribution [indicated vaguely by dotted lines] you might get a bigger life extension. The doctor recommended trading in the 20% over 6 months in return for the expected life extension. So, this week, I asked the doctor to help me update the graph to the present situation, having completed 6 cycles, and considering whether or not to have another two. He told me that there was considerable uncertainty, no strong evidence of a benefit from cycles 7 and 8, and that other hospitals would recommend only 6 cycles not 8. He said there is good evidence that the bulk of the benefit of chemo comes from the first 3 or 4 cycles. He said it was credible that the benefit of cycles 7 and 8 was no greater than the 6 weeks of life which I'd be devoting to chemo, if I went ahead, and he said that he would be sympathetic if I said 'let's stop', based on my judgement of the expected loss of quality of life. So I said "let's stop" (yippee!). Except first, to put the decision in context, I also asked the doctor to update for me my projected survival curve, which at my time of diagnosis looked something like this, with a central summary of "you might die roughly 12 to 18 months after diagnosis", accompanied by the tail-probability summary: "very unlikely to live more than 2 years after diagnosis". I asked whether the new data and observations over the last five months led him to update these projections. He said, essentially, "no, not yet"; I will have another CT scan in 6 weeks, and that might enable a change of view; and also the fact that I have responded well to the chemo means I am somewhat less likely to be in the left half of the distribution and more likely to be in the right. But my updated prognosis remains "likely to die 12 to 18 months after diagnosis", which means roughly 6 to 12 months from now (with a slim possibility of 18 months). With such small durations on the cards it definitely feels the right decision to stop chemo, to stop being a patient, and get back to feeling fit and having maximum fun as soon as possible. I'd like to thank the Addenbrookes staff for doing a super job of scheduling the CT scan and getting the results analysed in time for my clinic this week; and all the Oncology day unit team for being so lovely during my chemo visits.
The second somewhat shocking development – at least to those who know me – is the acquisition of a new car (also on 4 Jan 2015). This is the first car I have owned since 1991, when, living in LA (where it would of course be against The Constitution not to drive) I owned a tiny red convertible. We have bought a brand new Skoda Fabia. Our main motivation for having a car is so that my wife can learn to drive. Maybe we will go for some road-trips or car-assisted holidays too.
The third piece of news is medical again. As I mentioned in Chapter 10, I enrolled in a research study to attempt to measure my cancer using DNA markers in the blood, I gave research blood every month, and I volunteered to have an extra gastroscopy so that samples of my tumour could be taken away and sequenced. I cycled to the hospital today to hear how the research was going. Surprisingly there was simultaneous good news and bad news: My in-stomach tumour had reduced so much by the time of the gastroscopy that none of the biopsies that were removed from me contained enough tumour tissue to get the required DNA samples! Good news for me and my chemo, but not such good news for the research project. The research team had gone back to my other biopsies that were taken from my peritoneum and that had been fixed in paraffin (which is not good news for the DNA boffins), and pulled out DNA sequences for just 50 genes, including ones that were likely to be mutated in cancers. As I said in Chapter 10, a single gene, called TP53, is mutated in more than 50% of human cancers, and it turns out that TP53 (exon 5) is mutated in mine. All this trouble, just because of one nucleotide! The research team are now thinking of setting up a diagnostic process where I give them a monthly blood sample and they use DNA probes specific to my TP53 mutation to return a month by month measurement that may indicate what my tumours are up to. This seems like a very good deal to me.
The fourth piece of news is an update to our parade of wonderfully-successful film viewings. Courtesy of BBC iplayer we watched the delightful Come as you are, which gets five stars. We also watched the Royal Tenenbaums, which gets two stars.

In closing, here is a data update...
Blood measurements (Haemoglobin, and various white blood counts) before and during six cycles of chemotherapy.

Saturday, January 2, 2016

Cycle 6 - and maybe I have had enough of this

Chapter 14 - Pattern spotting
Today is Saturday 2nd January, and Cycle six ended on Wednesday just three days ago. Happily the hospital have given me a week off, which I am looking forward to, before probably restarting with cycle seven next Thursday.
Once you have completed six cycles of chemotherapy, you have enough data to spot some patterns. Of course these may be coincidences.
My main side-effects are, in no particular order:
  1. sore spots in my mouth, especially my lips; here I have spotted a pattern: even if I am super careful not to bite my lips, I get sore spots about day 13 of the cycle, and then
    • they get steadily worse and more painful if I'm on the original high dose of chemo; or
    • they get worse for a few days then heal after about 7 days if I'm on the new lower dose.
  2. tiredness; here the pattern is that every cycle I am more tired, and tired for longer. In cycle 6 I've had a substantial nap during the day on pretty much every day of the cycle, and even now that I'm a few days into my "week off", I still feel washed out.
  3. runny noses and colds; here the pattern is that I got them a lot in the first few high-dose cycles, and I don't seem to be getting them so much in the last two low-dose cycles - hurray! I do still get a runny nose when out in the cold, but it's not bad.
  4. Three Torrin-creations in Lego
    the skin of my fingertips falling apart - especially my right finger and thumb, which I use for many important tasks, including taking Lego apart for Torrin. For this side-effect, there is no pattern. The skin is shiny and cracking all the time.
I was given a third CT scan on Wednesday 30th December, to help my doctors decide what to do next. The default is that cycles 7 and 8 will roll along and ruin much of January. I'm hoping that the doctors will have a reason for stopping my chemotherapy now, however, because I have had enough of being tired; I shouldn't complain - I am sure it could be much worse; but I would like to feel well again and have some fun, and I am optimistic that stopping chemotherapy will let me do that.
We have managed to have some fun in the last two weeks, in spite of the chemo. Having got a good handle on my capabilities during cycle 5, we planned a perfectly timed holiday in North Wales in cycle 6, over Christmas, and had great fun on the beach and on a couple of hills, where we enjoyed generous quantities of sun, rain, wind, and sand.
We also enjoyed watching a remarkably good brace of movies.
I'll list here all the movies we've seen in the last month or two, giving star-ratings out of five to highlight the brilliant ones.
The first remarkably good film we saw was Mission Impossible - Rogue Nation, which I thought was possibly the best action movie I've ever seen. After watching it, I re-watched the original Tom Cruise Mission Impossible and found it slow and dull in comparison. ☆☆☆☆☆
Next we saw Bridge of Spies, which was quite a good film, and certainly gave some interesting ideas about how to be a negotiator. ☆☆☆
For our third trip to the big screen we saw Star Wars - the Force Awakens, which was a million times as good as George Lucas's last three Star Warses. I really liked the way they used Han Solo, and the new relationships that they threw us into, and the way that lots more epic personal history has washed by [between episodes six and seven] without being shown. My main complaint is that the film seemed really flickery: I felt I could often see the frame rate ☆☆☆☆☆
Back at home we had a disappointing evening watching The Imitation Game, which is a dud in so many ways - it is criminal how they have replaced Turing's life by fiction. The fiction is far more Hollywood, with ridiculous personal conflicts and drama, such as the notion that Turing was put in charge of the project, overruling his boss; and his boss marching in and dramatically switching off the Bombe while it was in the middle of a computation; and the idea that they were working on code-breaking for ages, including building Bombes, then had the brainwave that one might try to crack messages by guessing what the plaintext was. Awful.
Our next DVD about a Cambridge boffin was Theory of Everything , which was tenderly made and wonderfully acted. ☆☆☆☆
Our next two wonderful successes on DVD were both found by following amazon-recommendations from Ken Loach's lovely film about four young scots, The Angel's Share , [☆☆☆☆]
which led us to the absolutely delightful Sunshine on Leith , which is a musical based on the music of the Proclaimers. This film made me cry with happiness not because the three love stories in it were very interesting (they weren't) but because the film is so exuberantly founded on a deep (and perhaps nationalistic?) love of the music of the Proclaimers, which I share. The film is a love-song to the Proclaimers. After we watched this film, everywhere we drove in our borrowed car, we listened to five Proclaimers albums [ Sunshine on Leith , This is the Story , Hit the Highway , Restless Soul , and Life With You ] on continuous-playing shuffle. Glorious! ☆☆☆☆☆
The second amazon-recommendation (based on Angel's Share) was the best film of all, at least in terms of laughs per minute, and perhaps overall: What we did on our holiday - another Scottish film featuring Billy Connolly and three super child actors, and an awesomely funny script highly reminiscent of Parenthood [one of my favourite films of all time] and Little Miss Sunshine . ☆☆☆☆☆
Our sequence of DVD hits continued with the absolutely delightful The Grand Budapest Hotel , which reminded me of the best Harold Lloyd films with its whimsy and speed. ☆☆☆☆☆
Next, An Inspector Calls proved to be a surprisingly gripping watch. ☆☆☆
We tried to continue the joy of viewing The Grand Budapest Hotel by watching the same director's Rushmore but we found it really disappointing. It was somewhat quirky and memorable, but the central love-triangle premise was that the demure teacher-lady-widow, who was both perfect and characterless, was romantically attracted both to a deluded moron of a 15-year old and to a rich 50-year-old jerk. This made no sense, and it was impossible to resonate with any of the characters.
Things picked up with the next DVD: Belle , based on a true story of a mixed-race girl who became a lady in the house of the Lord Chief Justice at the time when the slave trade was going strong, and people of colour were, for upper class snobs, untouchable. Like the Turing film, this film about Belle is heavily fictionalised, but at least the film makers had the honesty to say "based on a true story" in the opening credits. ☆☆☆☆
Last, we watched A Little Chaos , about King Louis 14, his court, and some gardeners making the gardens at Versailles. Alan Rickman does a lovely King, and the scene praised by critics in which the bereaved King has an incognito chat in the garden was indeed nice, but I felt a bit disappointed that we didn't see more of the grandeur and behind the scenes difficulty of the creation of the gardens. The masterpiece garden of Kate Winslet was a disappointment after all the anticipation, given that this was what the whole film was about. And her brainwave, near the beginning of the film, that the fountains in that garden could be fed by perpetually recycled water was most irritating to a physicist, since there was no talk of any pump, only a nonsensical assertion that the "pressure" could be used to recycle the water back to the top. ☆☆
OK, I'll sign out now. Except for completeness, I suppose I should mention the happy news which came out at New Year, that I've just been awarded a knighthood. Many thanks to all my supporters and to my family!

Thursday, December 3, 2015

Cycle 5 - getting the hang of chemotherapy

Chapter 13 - Starting to get the hang of chemotherapy [Friday 4 December]
At the start of each cycle, my infusions of "E" and "C" are accompanied by loads of steroids, which produce various side-effects including Hmmm, maybe this isn't a nice topic to open a blog post with... Let's skip over the details and just say that after five rounds of experimentation, I've figured out how to take preemptive Senna and Movicol to manage this one.

In cycle 5, my chemotherapy doses have been reduced for the second time. Apparently this is normal: they start off with doses that they think are likely to be too big for the patient, then watch for side-effects and reduce the doses by roughly 20% at a time. My dose of capecitabine (the toxin I take daily in pill form) was 1300 mg twice daily in cycle 1 and is now 800 mg twice daily.

Whereas in cycle 4 I felt washed out for almost the whole cycle, in cycle 5, I perked up from last Saturday (day 10) to today (day 16), which is great. Ramesh and I spent a day at Torrin's primary school (day 9) helping out with "Maths day". You can see Torrin enjoyed having his parents in school! I went down to London last Wednesday (day 7) for a meeting at Google Deep Mind about using machine learning to enhance climate science and to see Book of Mormon; and then again this Wednesday to give a talk about Why Making Good Energy Policy is Difficult in the House of Lords.

Here is a graph of my haemoglobin and white blood cell measurements. The green and blue lines delimit the "normal range" for each indicator. The brown line at the bottom indicates infusion days that begin each 3-week cycle. The yellow line shows whether I was taking capecitabine.



The interesting features are: (1) the low haemoglobin [June] that kicked off the investigations that led to my cancer being diagnosed; (2) bouts of neutropenia (low white blood counts) at the end of most of the chemo cycles; (3) monocytes are baby neutrophils, so high monocyte counts are a good sign of (temporary) recovery.

What else is going on?

The Huntingdon Road safety campaign #EddingtonSafety has not produced any positive results yet, but we haven't given up hope.

The children have been ill a lot recently; Eriska has followed up a lengthy snotty cold by contracting hand, foot and mouth disease. The doctors tell me to avoid contact if possible, which is sad, because it's nice to cuddle her.

Last night we had an evening out at a new Thai restaurant, Thaikhun, in Cambridge. Yum. Tonight we are planning a night out - thanks very much to Nanny for the babysitting! - to see Bridge of Spies at the cinema.

Monday, November 9, 2015

Time off for bad behaviour

Chapter 12 - a welcome break between cycles 4 and 5

Today I went to the clinic for my pre-infusion check-up and to my delight my symptoms [exhaustion] have been bad enough that, again, I get to have a one-week delay and indeed more than one week off from chemo drugs. Hurray!

Other cancer news... I had a second CT scan during cycle 3, and heard the results today. The purpose of the CT scan was to try to measure the progress of the cancer. Some people have cancers markers that can be measured weekly (e.g. the concentration of something in the blood), but I was told in the first couple of months that I don't have any markers, and the cancer didn't really show up at all on the first CT scan, so there was little expectation that the second CT scan would give much information. However, three things did show up:
a) the elasticity of the stomach has changed; in scan 1, the stomach didn't distend when I drank the obligatory 4 glasses of water; in scan 2 it distended much more. This is deemed a promising sign of the chemotherapy working as intended.
b) the lymph nodes that showed up enlarged in scan 1 are a bit smaller in scan 2.
c) there is a new secondary in a vertebra in my spine.
So, a 2-1 score, overall.

Other non-cancer news... We were privileged to have two memorable movie-nights-out: Last night we went to London for the UK premiere of HUMAN, the awesome new film by Yann Arthur-Bertrand [a big thank-you to Nanny for baby-sitting all day!]; and a couple of weeks ago a local Cambridge start-up [FeatureSpace] invited us to the Cambridge premiere of Spectre. Fun!

Yann Arthur-Bertrand presents HUMAN Ramesh and David dressed up as Bond girl and Bond

Sunday, November 1, 2015

The fourth cycle of chemotherapy

Chapter 11 – Mid-way through cycle 4

Cycle 3 finished without any problems, except for ongoing pain in the infusion vein in
my left arm. Sometimes the thought that I voluntarily connect my vein for several hours to a plastic tube passing litres and litres of chemicals strikes me as terribly odd and queasy-making.

Cycle 4, right arm.

Today is day 11.
This time I haven't had much in the way of runny noses and coughing, but feeling-weak-and-washed-out has lasted much longer than the canonical "first 4 or 5 days" that I was hoping for. I feel breathless and exhausted when I walk up two flights of stairs. It's a lot like when I had anaemia (a few months ago) but going by the blood test I had 14 days ago, I think it is unlikely that I'm anaemic. Presumably the whole body is just being successfully beaten up by the chemo. My leg muscles ache as if I have got sports injuries in all of them.

I've been keeping myself busy (1) giving one lecture for a new MPhil course in the department;
and (2) working with other local parents on The Campaign for Safer Cycling
and Walking to and from the North West Cambridge Development
["#EddingtonSafety"].
I have made five youtube videos and learned how to put them into a playlist.



I've been using Facebook and Twitter, and our Petition has gathered over 300 signatures, including roughly 100 from University members.

I've been a bit manic about this campaign, and haven't rested enough. Today I stayed in bed all day.

So:  last cycle I kept my mind off cancer by working on the climate-cooperation Comment in Nature, which seems to have fallen on deaf ears; this cycle, I kept myself busy by campaigning for Cambridge University to actually build decent walking and cycling links, like it said it would do in its grand fluffy sustainable plans for the development. I've probably overdone it a bit. I don't have much oomph in my tanks. But I am optimistic that Cambridge University will hear our message and do the right thing.  If they don't then I genuinely fear that one of the children at the new University of Cambridge Primary School is going to be killed on Huntingdon Road.

As day 11 gives way to day 12, I find I have a steadily growing sore spot on my lips.
Tomorrow I will go to see my GP and ask him if all this aching body stuff is
normal, and is there any way to stop my lips from falling apart?

Then on day 13 I will put on my gown and will go to the Senate House to make
a "remark" at a "discussion".

Monday, October 12, 2015

The third cycle of chemotherapy

Chapter 10 – Mid-way through Cycle 3
As I said in my last post, my doctors suspended my chemo pills for a little over a week, and delayed the cycle-3 infusion by one week. Wow, it was lovely! Within 24 hours of stopping the pills I could feel my body's self-healing working again. The mouth ulcers healed up. My runny nose stopped being runny. I would be in great shape if it weren't for the chemo!

In the one-week gap, the hospital arranged for me to have an extra gastroscopy for the benefit of a research project I'm enrolled in. The project (called OCCAMS) is about attempting to measure the progress of a cancer by measuring tiny DNA signals in the blood. (Whereas some of my friends with cancer have cancer-markers that can be measured on a weekly basis, to reveal how things are going, in my case we are flying blind - there is no measure of cancer-up or cancer-down.) To help them use my blood in the study, they wanted to genome-sequence a sample of my cancer cells. So I popped in to a special research ward for an extra gastroscopy, which went smoothly. I'm looking forward to learning which mutation started the cancer - one fascinating thing I learnt about cancer is that a single gene, called TP53, is mutated in more than 50% of human cancers! Conceivably, knowing about the genome of my cancer might help me look into novel targeted therapies that might work better than the blunderbuss that is conventional chemotherapy.

Cycle 3 has been going a bit better than cycle 2. I have developed a runny nose and a cough again, but not quite so runny and cough as last time. My left-arm vein, which they infused me in for cycles 1 and 3, is sore and tender. I feel quite tired a lot of the time, but I have been getting some good work done. The pinnacle of the last year, from the work point of view, came last Friday when I went down to London for a press briefing for a Nature Comment piece that I wrote with Stoft, Cramton, and Ockenfels. As I said on my other blog, I view this article as the most important thing I have ever written. When I wrote Sustainable Energy - without the hot air, I wanted to improve and transform the public discussion of energy options, and I was delighted with the outcome; but that was just a book about energy arithmetic, and lots of other people have explained energy arithmetic before me and since me. Our Nature Comment, in contrast, makes a point that very few people are making, and if people listened carefully to our argument, I think it could be a game-changer for international negotiations.

I was really happy with how the press briefing went, and the Comment was published today. I'm grateful to the staff at Nature for recognising that we had an important message and helping us express it clearly in one and a half pages.

Anyway, halfway through cycle 3... What's coming up this week is a pneumonia vaccination, a check-up with my GP, a flu vaccination, and a CT-scan at the hospital to measure the unmeasurable (i.e., my cancer, which as far as we know doesn't show up on CT scans).

Apart from these four exciting outings, I'll mainly hunker down and work at home.

I'm eating well, and have a good appetite for snacks during the day as well as mealtimes. I've got my old juicer working and have been making lovely apple and carrot and ginger juice daily. I still feel tired and grey much of the time, and I do find myself wondering whether I'd be better off stopping chemotherapy.

At some point I think I will put some effort into researching the latest news about targeted cancer therapies. I've heard about quite a few - monoclonal antibodies, aspirin, warfarin... - but right now I can't be bothered to do the reading.

Instead I'm working on another work project - a completely different project, all about statistics, international standards, and how poor statistical protocols incentivise falsification of data.

Monday, September 21, 2015

Neutropaenia and other side-effects

Your normal neutrophil count is between 2,000 and 7,500 per cubic millimetre of blood. When you don't have enough neutrophils you are said to be neutropaenic.
A Red Admiral in our garden on a very sunny Sunday. Notice her black and white stripey antenna!

Chapter 9 - the medicine cupboard is not big enough
In the first few days of chemotherapy, we designated a bedside cupboard for the nasty medicines, and fitted a padlock to it. Eriska is fascinated and loves to rattle and pull the lock. 
As my side-effects multiply, the proliferation of prescribed medicines is remarkable. 
During cycle two (of which I have reached day 19 of 21) I had a perpetual runny nose, and I felt washed out more of the time. As in cycle 1, I was prescribed antibiotics for a week. At about 7 days, I developed a couple of sore patches on and inside my lip. One of them was simply caused by my accidentally biting myself while enjoying a delicious meal provided by a kind neighbour. They were the sort of sore patches that I'd normally expect to heal up and go away, but they stayed and grew and became steadily more painful. So, last week, I went to my GP, who prescribed mouthwash 2 and goop 1, and who encouraged me to phone the hospital; the hospital said "come on in", so, after a lovely bike ride, I spent most of the next day waiting to be seen, and then was given mouthwash number 3 and a new antiviral medicine and was advised to use goop number 2. The antiviral thing is five tablets per day, on top of the 8 tablets per day of capecitabine (cytotoxin), 4 tablets per day of omeprazole (to reduce stomach acidity), and 2 iron pills per day (to reverse my anaemia).   
The viral infections have been making me feel quite glum - aching teeth, sore ulcers both keeping me awake at night; ulcers sometimes very painful while eating; general grottiness.  
Today I went in to the hospital for my end-of-cycle check-up and told them how I was feeling. The doctor prescribed mouthwash number 4 (to replace mouthwash 3) and mouth-spray number 1, and put me on a new course of antibiotics (2 pills per day). He also recommended using over-the-counter goop number 3. And told me to stop taking the chemotherapy pills for a few days, to give me a chance to recover.  (Hurray!) 
It turns out my neutrophil count has dropped in the last 12 days to 0.48 billion per litre. (Normal range is 2-7.5 billion per litre.) So I'm especially vulnerable to infection, and my next chemo cycle is being postponed a week, because of both the neutropenia and the slow-to-heal mouth ulcers.  I've been told if I have any signs of having a temperature, I should not even wait to phone the emergency number, I should just go straight to the hospital as quick as possible.  

To cheer myself up, I aim to read a Lord Peter Wimsey novel.