I think I'll stay until the end of the day ...

Adam's MRI scan passed off without incident. Apart from having to part with his trousers which had metal eyelets at the front there was very little preparation required. No injection, no contrast dye. Adam was given headphones through which he listened to an audio CD and a buzzer in case he needed assistance. He only buzzed the once because, in his own words, "my nose had a really big itch." The scan was all done in less than half-an-hour. Now we wait for the results, I expect we'll receive them next week sometime.

The other noteworthy news from last week is the fact that Adam spent four afternoons at school. The only reason he didn't notch up a full-house was that Friday was an inset day. I don't know if his interest in school was rekindled by having his best friend Georgio to visit after school on the previous three Tuesdays, but come Monday he was ready. The plan was for Adam to go in at the end of lunchtime whilst everybody was out to play; then stay for the hour after during which his class would be doing more interactive activities that Adam, having missed almost 2 years of school, would find easier to join in with.

Having raced through lunch, and dressed in a white cotton shirt and the only pair of Jake's old school trousers that weren't completely threadbare, Adam and his Mum set off for school. As Adam was only going to stay for an hour or so, Alison waited in the staff room at the school. Except when the hour was up Adam decided it wasn't time to go home. His teacher asked Adam whether he would like her to tell Mummy he was ready to go home now. To which Adam responded that he would like to stay until the end of school. And so he did ... much to our pleasant surprise.

And so the pattern continued through Tues, Weds and Thurs. Each day Adam went in towards the end of lunchtime and left school with the rest of his classmates at 3.15pm. On Wednesday I even went to pick him up - the first time I've stood in the playground waiting to collect Adam from school for over 650 days. It felt ... strange.

The retinoic acid Adam has been taking for the past week is leaving him with severe peeling of the skin, but it no longer appears to be sore or bothersome which it certainly was for the first few days. We carry on until Friday, after which he has two weeks off. It's nice to see that his hair is starting to grow back again, things have really accelerated this week and it won't be too much longer before he has a complete (albeit thin) covering. Not that being bald bothers him in the slightest any more, not even at school. I asked him whether anybody mentions the fact that he's got no hair. "Only you Dad" he said "Only you."

Once more unto the scanner, dear friends, once more ...

The MRI scan of Adam's right hip and femur is scheduled for Friday afternoon at 1pm. If the scan shows up an area that can be targeted for biopsy that will be the next step. If, however, the surgical teams feel the disease is too diffuse to make biopsy feasible we will be unable to take Adam to America for hu14.18 antibody treatment. Instead we'll have three options open to us:

(1) Do nothing.

(2) Take Adam to Germany for ch14.18 + IL2 antibody therapy.

(3) Revisit the possibility of enrolling on other clinical trials running in the U.S.

As I've said before option (1) isn't realistic at this time, it's simply too risky. As for option (3) there are no clinical trials that offer any proven results for children such as Adam. Moreover a lot of other trials require evidence of active disease in precisely the same way as the hu14.18 trial. If Adam doesn't qualify for that, he doesn't qualify for them either.

Continuing consolidation therapy, despite the fact we've never had a clear MIBG scan, is the thing to do. So if we can't get a (positive) bone biopsy, to Germany we will go. It's not great, but it's the best we've got right now. We're second-guessing that the biggest threat for Adam at present is the disease we can't see, rather than the disease we can. We're conceding that there isn't anything out there (at the moment) that provides a realistic prospect that Adam will be completely cleared of disease. These are determinations we have to make. The future consequences of them we will have to live with.

Even. Less. Clear ...

Well what do you know? Adam's Gallium Octreotide scan was largely negative. Just a small area of uptake in the right femur that doesn't even correlate precisely with what is seen on his mIBG scan. What does it mean? Well it means that the neuroblastoma cells in Adam's body do not, in the main, take up octreotide. What does that mean? It means just that. Nothing more, nothing less. It barely moves us forward at all. I guess the fact that there were no new areas of uptake distinct from those that exhibit mIBG avidity is a good thing. But it's official, I am now pronouncing it so. Adam is an enigma. The truth, of course, is that neuroblastoma is such a complex, multi-dimensional disease that there are children like Adam for whom modern medicine just doesn't have any answers at present. Relatively speaking there is so much that is still unknown about what neuroblastoma really is, and how/why it behaves like it does.

With these results the 'plan' has an additional, hitherto unmentioned, element; an MRI scan. He's had pretty much every other scan and diagnostic test going, I'm sure he'll hardly noticed if we slip one more into the schedule. The idea is that the MRI scan will focus on the area of the right hip and femur where there is concentration on the octreotide scan and positivity on the mIBG scan too. Essentially it will be looking for viable areas to biopsy, without which we cannot enrol on the American hu14.18 antibody trial.

It's fair to say that the latest scan results make it much more likely that we will not be taking Adam to the States. Not because we don't want to, or because we don't think it would be beneficial. We simply will not be able to. Even if the MRI, which is unlikely to change the picture dramatically, doesn't close the door to biopsy completely there is still a reasonable chance that any sample that is taken won't contain viable, active, disease. No active disease means no trial.

In that case we'd be off to Germany, yes? Well I guess so, although part of me is instinctively resistant to doing something if it is the easiest, or obvious, option. That's not the criteria on which decisions as critical as this need to be made. By the same token overlooking the right option just because it's also the easiest and obvious would be even more dumb. *Sigh*

Whilst we continue to try and figure out what to do for the best, I couldn't sit idly by and have Adam on no active treatment whatsoever. So we've agreed with his doctors that he will start cis-retinoic acid. This consolidation therapy to treat minimal residual disease (as is high-dose/transplant and immunotherapy itself) is designed to induce maturation of neuroblastoma cells rendering them benign. The treatment schedule is two weeks on, during which Adam will be taking 6 capsules (to make up the required 75mg dosage) twice a day, and then two weeks break. A piece of cake to a veteran pill-taker like Adam - he takes them like other kids take smarties. There are not many parents like us who can say they are proud of their son for being a pill-popper! Like everything else cis-retinoic acid (essentially massively high doses of Vitamin A) doesn't come without side-effects. The most obvious and common is severe dryness of the skin, especially face, eyes, and lips, which can become extremely painful and sore. We've already stocked up on copious amounts of Vitamin E cream in preparation. There are other, more severe, side-effects, but these are rare; and Adam's blood results will be regularly monitored for any liver abnormalities. There is also an ongoing debate about possible long-term side-effects ...

One final thing that is definitely worth mentioning, and that to my discredit I could easily have omitted. The Royal Marsden have been incredibly supportive of what we are trying to do in terms of getting the absolute best treatment for Adam. At various points over the last few weeks and months the simplest option by far would've been to turn round and 'encourage' us to take Adam to Germany for the ch14.8 + IL2 trial. Instead they have remained very active, talking to doctors in other countries, facilitating the various additional scans. My feeling is very much that at the end of this period we will know as much as we ever could about what is going on inside Adam. The unfortunate thing is despite everything we have done, and are doing, there's still not actually very much we can say for sure, and the future remains as uncertain as ever. Of course there have been times when I haven't been completely happy; I was very frustrated over the amount of time it took to get the PET and Octreotide scans organised. I've challenged the doctors, offered opinions, made suggestions, and asked some difficult questions (plus a fair few stupid ones as well). And at no time have I heard discouraging noises, or felt like I was being talked down to, or told what to do. It's a very welcome contrast to some of the stories that I've heard from other parents across the UK. Maybe I've just been lucky, maybe sometimes I see through rose-tinted spectacles, or maybe the times they are a-changin'.

Clear. As. Mud ...

Here’s the thing. As a few of you will no doubt already be aware via twitter and facebook, Adam’s FDG-PET scan came back completely clear. No abnormal uptake of the radiotracer was detected anywhere. But what does that really mean? And how does it affect our thinking and plans going forward? The first thing to say is it didn’t entirely surprise me that the scan came back clear, I expected any uptake to be much less widespread and intense than what we see on mIBG scans. It’s definitely a positive result, the best we could have hoped for; but at the same time (unfortunately) it’s neither remarkable nor game-changing.

The scan that Adam has been having regularly for the past 22 months is called an mIBG scan (meta-iodobenzylguanidine). This substance is picked up by receptors on the surface of neuroblastoma cells. For scanning purposes it is radiolabelled i.e. has a radioactive tracer attached to it (usually radioiodine I-123) that can be detected by imaging equipment. It is probably the most specific, most accurate and most widely used of all diagnostic techniques for detecting neuroblastoma. Of course, like almost everything else it’s not infallible. Some children present with non-mIBG avid disease, or their neuroblastoma mutates to become such. It also does not give any information regarding how differentiated the cells are that take up the mIBG; immature, aggressive neuroblastomas, and mature, non-dividing ganglioneuromas, look the same under mIBG scanning. Finally, it cannot tell anything about the metabolic state of tumour cells; fast-growing, or indolent, they will appear identical.

The scan that Adam has on Monday was an FDG-PET scan (fluorine-fluorodeoxyglucose). FDG is a glucose-like compound to which a radioactive tracer (different to that used in mIBG scans) is attached. It’s readily taken up where high amounts of glucose are used – by organs such as the brain and kidneys, but also by tumour cells. Tumour cells metabolize glucose and therefore abnormal FDG uptake is found where there is active cancer.

Putting the two scans together, and considering what this means for Adam things hopefully start to become clearer. Adam still has a lot of disease, his spine, pelvis and femurs are riddled with abnormal cells, as evidenced by his mIBG scan. However, there is currentlylittle going on in those abnormal cells, as evidenced by his FDG-PET scan. The result of the FDG-PET scan is good, but mainly because it would have been bad if there had been significant uptake on it. A clear PET scan is not, and never will be, a substitute for a clear mIBG scan.

I said earlier that I wasn’t surprised by the latest scan results. Although I didn’t necessarily expect the scan to be completely clear, I didn’t expect there to be significant uptake (although it’s always impossible not to worry that something nasty is going to show up). My thinking was that Adam has had stable disease for the best part of twelve months now. If he’s got stable disease that means either treatment is holding it at bay, or the cancer itself hasn’t been doing a whole lot. Reflecting on what he’s had in the last year, and the fact that biologically he was diagnosed with the most aggressive form of neuroblastoma, I think that for some unknown reason his disease has, for now at least, just gone into hibernation. Maybe the MIBG therapy he had in October and January did something – Adam scan results are consistent with responses that have been seen in some other children. We can only speculate because this is the one and only PET scan Adam has had, so at what point his disease first became inactive will forever remain a mystery.

So Adam’s disease is inactive. I’d love to believe that it’s all matured, that the cells have divided as many times as they are going to divide, and that things are now just going to remain in this state. But truthfully, deep-down inside, I don’t believe that for one minute. Maybe one day, but not today.

Even if I did believe it consider this; the majority of children with neuroblastoma do achieve a first remission, their mIBG scans show no evidence of disease (NED). And yet of these children somewhere between 40% and 60% go on to relapse, the neuroblastoma comes back. Despite all the intense, destructive, super-toxic, treatments these children are given residual disease still remains at the end of it. Too small to be detected using current imaging techniques, even the most neuroblastoma specific, the mIBG scan. Yet eventually this residual disease grows and multiplies to become a full-blown, observable, relapse. If a child who is ‘in remission’ has minimal residual disease that can’t be seen, in my own mind I have already decided that Adam has other areas of disease, not showing on any of his scans, but which nonetheless are active and which will, given time, result in new tumours forming. So we have to think about this, as well as what does show up on the mIBG scan. It’s why we put him through high-dose and transplant despite having a positive mIBG scan. It’s why we are starting him on cis-retinoic acid, a super high-dose vitamin A derivative which has been shown to cause differentiation in neuroblastoma cells, turning them into mature cells that will no longer sub-divide. It’s why our next move is to get Adam some form of immunotherapy, the antibody treatment that has proved to be a major breakthrough in the fight to prevent relapse in neuroblastoma patients.

Of the two main possibilities we were looking at the favoured option was a new trial opening up in America using a humanized 14.18 antibody + GM-CSF + cis-retinoic acid. The other was the chimeric (part-human, part-mouse) 14.18 antibody + Interleukin 2 trial in Germany. Adam’s FDG-PET scan now makes it less likely we will be able to go to America for treatment. The trial there requires active disease as evidenced by biopsy. With a clear PET scan that’s something that becomes less likely. It’s also unclear at the moment whether or not there is a site that could be biopsied at all. That’s down to the surgeons at the Marsden, and there was even mention of asking the Royal National Orthopaedic Hospital for an opinion if necessary.

Earlier today Adam was back at the Marsden for a Gallium Octreotide scan. This is another scan that he’s had for the first time. It’s similar to an mIBG scan, but the radioactive tracer is attached to a substance that is taken up by a different set of receptors on the surface of neuroblastoma cells. Theoretically we should expect, and indeed probably hope, to see the same sort of uptake on this scan that we see in the mIBG scan although the intensity may vary. That would be consistent with what we think is going on.

And so there you have it. I know my updates are becoming ever more complicated … but then so is the situation we find ourselves in.

Surprise surprise ...

Surprise surprise. Nobody was willing to swap their own appointment for a noon slot, so we've ended up being stuck with it. The FDG PET scan is at noon on Monday; the Octreotide scan is on Wednesday and Thursday. I spoke with Professor Pearson the head of the children's unit today, who has effectively been consulting on Adam since we reached the end of the road in terms of UK treatment. He was both apologetic and annoyed that these scans have taken so long, but we are where we are and there's nothing to be gained now by me making any more of a fuss about it. I'll just keep this episode tucked away in my back pocket in case it can buy me some goodwill in the future. The Nuclear Medicine team have told us that the fasting period need only be 4 hours instead of 6. So at least we can attempt to wake Adam up early and force feed him his breakfast.

I'm almost certain now that we will also go ahead with the bone biopsy; the only question is whether or not any results obtained by the Royal Marsden would be acceptable as far as the U.S. trial is concerned. It may seem like a no-brainer, I mean it's not as though the Royal Marsden don't know what they're doing, but stranger things have happened. Rules are rules, and it's generally advisable to find out what those rules are upfront rather than have to go through something like this twice because of bureaucratic red-tape. Most likely it will be fine, but best to double-check.

Most other things with Adam remain as they were. No real changes in terms of his general wellness; his bloods are much the same, he's eating, drinking, sleeping, and playing. For the past two Tuesdays Adam's had a friend from school come round to play. This was Adam's best friend during his reception year. The two of them were practically inseparable in the playground during break-times; but Adam hasn't been to school, other than for the odd hour here and there, since July 2009. And yet they played like it was a matter of weeks since they'd been regular pals, not the best part of two years. Yu-Gi-Oh!, beyblades, playstation, football. At bedtime I told Adam it was too late to watch anything on television before he had to go to sleep. Whereas he would normally offer some protest - "I am!" or "Just something short, Dad?" this time he simply looked up at me and said softly "It's ok Dad, you can decide. I had such a hugely enjoyable time today with Georgio." And yes, those really were his words. Spending most of his time in the company of adults has had a profound affect on Adam's vocabulary; some of the phrases he uses are both funny and at the same ever so slightly sad too. But whilst it upsets us that so much of Adam's childhood is being taken from him, for the most part he just gets on with whatever there is for him to get on with.

Grrr ...

There are some things that you have to wonder about. Just received the date for Adam's PET scan. Monday 16th May at midday. Read through the notes ... procedure will take between 2 and 4 hours ... nothing to be eaten for 6 hours beforehand. Could there be a worse time? Instead of eating bananas and nuts on that Monday morning, Adam will be going bananas and nuts. Earlier in the morning and we might have some chance of managing the situation. Later in the afternoon and we might have some chance of getting his breakfast done with the required 6 hours to spare. But nothing to eat from Sunday night until (sometime) Monday afternoon? That's asking for trouble. He'll probably refuse to get on the bed, let alone lie still for an hour.

Needless to say I have been on the phone to the hospital. The complication is that if the PET scan comes first it has to be conducted 48-hours before the Lutetium Dotetate scan; and if it's the other way round there has to be a 7 day gap. This is to prevent the tracer from the first scan interfering with the second. So we are just waiting to see if they can shuffle some other patient(s) around in order to get Adam scanned earlier in the day instead. If not they'd best be prepared ... it's not going to be pleasant. At least Alison will be taking him and not me I suppose.

Whilst it may seem like a triviality in the wider context of having a child with cancer, you'd be surprised just how many 'trivialities' there are that serve to make things that little bit more difficult than they need be.

No news is still no news ...

Still nothing substantive to report.To be honest I'm somewhat annoyed now, given my impatient disposition. Everybody seems to be in agreement that Adam needs to have these additional scans as soon as possible, and yet the wheels keep turning as slow as ever. We got the letter this week from Nuclear Medicine asking us to complete and return the form listing Adam's current medications - a prerequisite to them being able to book an appointment. I'm sure they are busy, I'm sure resources are stretched, I'm sure there are plenty of other patients that need fitting in, I'm sure Easter and the Royal Wedding has had an impact. And you know what? I DON'T CARE. JUST GET THE SCANS DONE SO WE CAN MOVE FORWARD.

It's looking very likely that we will go down the bone biopsy route. As much as I dislike the whole idea of grinding out a piece of Adam's thigh bone, it's the only way we'll know for sure what we're dealing with. If his cancer is still biologically active, but just smouldering, we are almost certainly going to end up in Philadelphia for six months (at least). It would be the best option under these circumstances, and we would need biopsy results in order for Adam to qualify for the trial anyway. My biggest fear is the PET and Lutetium scans are positive and lead us to biopsy, but the biopsy is inconclusive and we therefore can't proceed with the COG (Children's Oncology Group) trial in America. I don't quite know what we'd do in that case.

The little fella is still generally well; except for the fact that he doesn't attend school and has no hair he's a normal little boy. Though if he gets much taller I am going to have to stop referring to him as 'little'. When we checked a couple of weeks ago he was on the 75th percentile for his height (and 50th for his weight). Quite an achievement for a kid with neuroblastoma whose been subject to one of most intensive treatment regimens that modern medicine has to offer. Generally kids aren't supposed to grow, or put on weight, whilst in active treatment. His bloods are continuing to hold at the same levels. If only his platelets got some upward traction they would be as good as they have been since he started treatment.