I just sat ...

Today has been one of those days. It wasn't a particularly extraordinary day. Sure it was Father's day, but to be honest we've never been a family that makes a huge fuss over such occasions. Whilst Alison took Jake to play cricket, I went with Adam and Jess to their school's summer fair. On one hand it was nice to be there, watching the kids having fun, enjoying some good weather for a change. And on the other I couldn't really have cared less. I looked around and saw faces of people I knew, people I haven't spoken to for a long time, people who have done a lot for our family, and the only thing that went through my head was a desire not to talk to any of them. My life is so consumed by Adam's illness, it dominates thoughts almost every minute of every day; sometimes it simply becomes the last thing on earth I want to talk about. Particularly with people who cannot know the hellishness of our situation. It doesn't matter what else comes up in conversation, Adam inevitably will. And on days like today it's all too much, so the only thing to do is hide away from the world and let it pass. A bit hard when you're in the middle of a school fair, so instead I just found a bench, parked myself on it … and sat. If you saw me today and thought I was being rather unsociable then I'm sorry, but sometimes needs must. Most times I'm more than happy to talk about Adam; it's nice for people to ask how he's doing, how we're all doing. And then there are days, rare though they are, like today.

As for Adamski himself, he's doing okay, all things considered. I'll put together a proper update in the next couple of days, when I'm ready to talk about him again …

A brief update ...

Sorry that it's been a while since I updated, the truth is I simply haven't felt inclined. I have no good news to impart. Since returning from America we have discovered that Adam has significant bone marrow disease, to the extent that the vaccine trial we had targeted in the US is not a viable option at present.

Adam finished a round of Temozolomide and Irinotecan combination chemotherapy on Saturday. We must now make a decision about what to do when his blood counts have recovered, a process that should take two to three weeks. This chemotherapy might reduce his disease, but there is no guarantee that it will even halt the progression. We could do a second round with the intention of rescanning afterwards, or elect to move to a potentially more potent combination straight away. The downside of this, of course, being the impact on Adam's quality of life and the potentially catastrophic impact on his blood counts that could leave us with very few options even if the chemotherapy itself proved effective. We have to remember that Adam has already been massively pre-treated, having been on continuous therapy for nearly three years.

Thankfully Adam remains pain-free and appears fairly well in himself. He was a bit battered after the bone marrow extraction and surgery to fit a new central line, but tolerated chemotherapy well apart from sporadic nausea during it, and some diarrhea once it had finished.

America, here he comes …

I mouthed off about it on here, thought about it overnight, then asked the hospital to move Adam's bone marrow biopsy and line insertion to Tuesday 15th. As it turns out it's not very likely he'll be going on this school trip to Kew anyway. He isn't due to land back at Heathrow until 6:50am on Thursday morning. I'm not sure he'll be in a fit state for a school trip a few hours later.

I've spent the whole of this past week talking to doctors here and abroad, exchanging emails, investigating clinical trials, reading literature, making plans, and working through possible scenarios. As well as being in regular contact with Adam's consultant at the Royal Marsden and going up to meet one of the research consultants there, I've also been in touch with Penn State Hershey, Children's Hospital of Philadelphia, Baylor College of Medicine, Texas Children's Hospital, and Van Andel Institute. Not entirely surprisingly I've been waking up at 4am and immediately stuff starts going round in my head. Try as I might there's little more sleep to be had once that happens.

So do we know what we're doing yet? Have we got a plan? Err, no. Well sort of. Yes and no. The immediate plan is that Alison and Adam will be flying out to Philadelphia at lunchtime on Bank Holiday Monday, on their way to Penn State Hershey Children's Hospital. One of the options we are seriously considering is a vaccine trial there. As with almost everything we're looking at now it's an early phase clinical trial. In this particular case it's a Phase I trial which means it's actual purpose is to establish tolerability and safety criteria, rather than to see whether it has any effect in treating the disease itself.

A Phase I drug trial almost always involves dose-escalation; that is the drug is given to a certain number of patients at one particular dose level and the side-effects assessed for dose-limiting toxicities (DLTs). If such toxicities are observed the maximum tolerated dose (MTD) has been found. If not, the drug is administered to a different set of patients at an increased dose. And so it continues until the MTD is found or the highest planned dose level is reached without DLTs being observed. If you're going to enrol your child on a Phase I study there is some thinking to do about the dose level at which it is currently accruing patients. Assuming the drug does have some effectiveness (which will only be known after the fact) what might the optimal dose be? The first couple of dose levels are seldom optimal, and neither is the MTD. What tends to happen is effectiveness (if there is any) is a function of dosage up to a certain level, above which higher doses have little or no marginal benefit. So one consideration in choosing whether to participate in a Phase I drug trial is to look at the dose level it is currently recruiting patients at. Keeping in mind you only get one shot, once you've participated at one dose level you can't go back and do it again at another. Which isn't to say enrolling at the first dose level is never the right thing to do. Maybe there isn't time to wait for the dose to escalate further. Maybe, as a result of pre-clinical work, or a different Phase I study, there could be good rationale for doing a lower of dose of one drug rather than a higher dose of another. It's also worth saying that even the first dose level in children is usually a good sized dose, as the drug will already have been used in adults, and the dosing in a paediatric Phase I might start at something like 80% of the normal adult dose.

Anyway, all that was a bit of an aside. The vaccine trial is a little different because all patients get the same amount of vaccine, on the same administration schedule. It's primary objective is still to assess tolerability, but there is no dose escalation. I have had other conversations about Phase I drug trials though - there are a couple running at the Royal Marsden at the moment that Adam would be eligible for. Unfortunately, though they may be the most convenient options, I don't think they're the most promising. Of course we're in unchartered waters now with no proven therapies, so there's almost nothing that's completely clear-cut. There's a new study due to open at the Marsden in the next 6 months or so that will combine an mTOR inhibitor and an IGF1R monoclonal antibody that are currently being trialled as single agents. That might be something that's of interest, but at the moment it hasn't even been determined which solid tumour types will be eligible for enrolment.

The reason for the mad dash to Penn State is that this vaccine is derived from Adam's own blood, which has to be taken before any other treatment is given that might suppress his blood counts. It takes around three to four weeks for the vaccine to be produced. We are really serious about this trial as the next option for Adam, providing (1) his bone marrow biopsies do not show heavy infiltration, and (2) his bony disease does not progress quickly over the next few weeks. So I wanted to get Adam over there as soon as possible, have his blood extracted before we did anything else treatment-wise, and get the production process started. Then when he comes back maybe we can give him a round of chemotherapy (Temozolomide/Irinotecan) in the period during which the vaccine is being made. It will take about three weeks for Adam's blood counts to recover; all these trials, vaccine or otherwise, have eligibility criteria that require platelets and neutrophils to be at a certain level. So recovery from chemo, and vaccine production, can take place at the same time. Well that's the plan at least.

I wouldn't say I've made a nuisance of myself, after all I'm just trying to do the best for my son. But I have been responsible for driving the timescales apace. The doctor in charge of the trial at Penn State has been tremendously responsive. As usual there's always some obstacle to overcome, and in this instance it was the fact that he was busy all day Wednesday, and unavoidably away on Thursday and Friday. On Friday evening we finally settled on a plan, the NB Alliance having taken care of the financial side of things earlier that day. In the end we agreed to do everything in a single day, when ordinarily it would take two. I set about scanning and sending across Adam's medical records, the US doctor set about making sure the hospital could accommodate Adam as such short notice, and our consultant at the Marsden sent across a clinical summary of Adam's care to this point.

So on Monday Alison and Adam will fly out to Philadelphia and then make their way across Pennsylvania to Hershey. They're staying at the Ronald MacDonald House (RMH) on Monday (and Tuesday) night. First thing Tuesday morning when Adam wakes up Alison will put Emla cream on his arms, to numb them in preparation for a cannula to be inserted. At 7am they have to be at the hospital. First off Adam will undergo a physical examination, then he'll have a cannula placed and have blood taken for a full blood count, and to test for a myriad of diseases including HIV and Hepatitis. If there are no problems once those results come back from the lab Alison will then get to sign the consent for the trial itself, and Adam can go down to surgery to have a vascath inserted in his groin. Once he's out of surgery and recovered from the anaesthetic they'll hook him up to an apheresis machine and extract the blood needed to produce the vaccine. Once that's done the vascath will be removed and Adam can go back to the RMH for the night. The return flight to London is scheduled to leave Philadelphia late Wednesday afternoon, getting into Heathrow just before 7am, as I mentioned earlier. Fingers crossed everything goes smoothly to plan. There's certainly no room for any delays, that's for sure! There are undoubtedly parts of this that are not going to be much fun for Adam. In fact they're going to be shit. Having a vascath put in, and removed, for starters; out of all the experiences Adam's had since this journey began that's one he'd pick out as hating more than most. And this will be the fourth time he's had it done. That said, we are trying to make it as much of an adventure as possible, rather than something to fear. A trip to America, choosing what he wants to take, what to watch on the plane. I've told him he's got to keep a diary so he can tell me all about it when he gets back.

I knew if this day came we'd have enough money to take Adam abroad. I also knew what options were out there, having researched quite extensively. The thing I was never quite sure about, however, was whether we'd have the necessary courage and decisiveness. Would we actually be able to get over the mental hurdle that there really wasn't any use sticking around and trying again in the UK? In fact, deciding to take Adam abroad has been one of the simplest decisions ever. After that it's just a question of trying to make the very best of whatever situation we find ourselves in. And at the end of the day that what life's all about, isn't it?

Ineloquent, but true ...

1.	Pisser
	somewhere to go for a piss at the pub
2.	Pisser
	booking the first available slot for Adam's bone marrow biopsy and central line insertion only to subsequently discover it coincides with the day he's supposed to go on his first junior school outing
3.	Pisser
	having to decide whether or not moving said procedures to the following week is the right thing to do under present circumstances

The update after …

The dust has settled a little after Friday's news. We had a pleasant weekend. Truthfully. We did things that we'd have normally done. Friday night we all watched a DVD together. Saturday we went about our business, played some games in the evening. If I've learned anything these past (nearly) three years it's that the way we respond emotionally to bad news, setbacks and worry makes no difference to what comes next. Best to just get on with things as best we can.

The hardest part was always going to be telling the children. No easy way to do it. No good time. And no avoiding it. On Sunday afternoon we went into town and watched the Avengers movie at the cinema. When we got back I called everyone into the front room. We don't do family conferences in our house, so I'm sure they knew immediately and instinctively that something was up. I think I did an okay job. I mean, there's no parental guidance I've seen that comes close to preparing you for having to tell your 8-year old son that his cancer is growing again; or his 10 and 12 year old siblings that their country doesn't have any treatments for their brother and so he has to go to America. There were tears. I'm not ashamed to say some of them were mine.

Today I've been speaking to a number of doctors across the Atlantic, and exchanging emails with others. The origins of a plan are formulating, but we haven't taken any decisive steps yet regarding treatment decisions. That said I don't intend to hang around. It will be a case of here today, gone tomorrow.

A few people have talked to me today about money and fundraising so I thought I'd mention where we're at. Thanks to the money that's already been raised for Adam's Appeal we are safe in the knowledge that as soon as were ready we can head to America without delay. Many of you reading this have contributed to that effort and I thank you all once again. Maybe at times people may have wondered what the money was actually for, or why it hadn't been used. Well it was for this, and we hadn't used it because we hadn't needed to. But now we do, and we will.

If people wish to start raising money again for Adam's Appeal, the Neuroblastoma Alliance UK are now much better equipped to support any fundraising ideas that people might have. I do not know how much money we will need in total. It depends how long Adam needs to spend in America having treatment, which at the moment is indefinitely. It depends what happens to Adam while he's out there, how often he has to stay in the hospital with fevers or infections. Again, another complete unknown.

Alison and I had a brief chat earlier today. We decided that we would prefer it if people didn't do any fundraising for Adam until we have actually taken him out to America for treatment. All the fundraising previously was done to get Adam to America, and it will. If, once he's there, people want to fundraise to help keep him there we would once again be immensely grateful for their support.

Many thanks for all the kind words and good wishes we've received over the past few days. Please continue to keep Adam in your thoughts. We continue to believe ...

The day we hoped would never come ...

It's late on Friday night, and having nothing better to occupy myself with for the next 45 minutes whilst I wait for a professor of clinical oncology from America to return my call I figured I'd try and use the time to productively to write an update for the blog. I'm afraid it doesn't make happy reading.

Adam had an MIBG scan yesterday and the news we received this morning was that there is progressive skeletal disease, and the suspicious lymph node seen on MRI is now also visible on MIBG. The results are those we expected we'd get three months ago when we returned from Germany, but didn't. Now, however, there is no doubt, no alternative explanation, no hiding from the truth. Adam's cancer is growing again, and in the words of his doctor "it doesn't look good."

In truth we had prepared ourselves for bad news. When the technician part way through the scan inquired as to whether Adam had coins in his pocket it didn't take much to figure out they'd seen something that shouldn't have been there. Today's phone call was merely confirmation of everything that we feared. Had that exchange not happened, however, today's news would have come as a big big shock. Adam doesn't look ill, doesn't act ill. Anybody who didn't know he is ill would never guess at the fact. The greatest irony of this moment is he's probably as good as he's ever been right now. Or rather he seems as good as he's ever seemed. I don't think it's merely coincidental that his disease has progressed at the same time as he's grown a full 3cm in the space of just 4 weeks. He's started growing, everything inside him has started growing … neuroblastoma included.

Having talked briefly on the phone with Adam's consultant this morning, I went into the Marsden late afternoon to discuss more fully what to do next. Further tests to check for bone marrow infiltration, and possibly an FDG-PET scan to compare to the one we did last year. Having had his central intravenous access line removed only a matter of weeks ago, Adam will now require a new one to be fitted …

And so to the part that hurts the most right now in the rawness of it all; to think about, and to write. The hickman line removal, going to school regularly, signing up for cricket club. Adam has only just started to taste life as a normal little boy again, and it's all about to get taken away from him. He's been so happy recently, and now we must break his heart.

He's no longer the 5-year-old boy that was diagnosed with cancer all that time ago. He's eight-and-a-half and he's been through so much since then, he's more grown up and a lot more mature. We have to sit down with him and explain the situation, what it means. Back to full-on treatment, back to endless hospital visits, blood draws, infusions, transfusions, scans, tests. We have also to explain to his brother and sister. For our future most certainly now lies beyond these shores. The short time that we had together at home as a family unit after our back-and-forth to Germany is about to come to an abrupt, and indefinite, end.

Over the coming days and weeks a new plan must be put in place. We'll start with trying to select the best treatment option for Adam, and work out the logistics afterwards. There is no way to navigate this other than trying to figure out, in consultation with doctors both here and abroad, the best thing to do and then getting on and doing it. Whatever it involves, wherever it takes us, however much it costs.

America is overwhelmingly our most likely destination. Germany have their own approach for treating relapsed neuroblastoma using haploidentical transplantation. They've seen some very encouraging early results, but such treatment requires as little disease burden as possible to start with. We never got Adam close to remission the first time round, so I don't see how we can have any prospect of it now. Our best shot is surely to try to reduce the new growth as far as possible, and get back to a stable disease state.

I almost wish I could un-know what I know, but that is not possible. I almost wish I could start believing in miracles, but I cannot. At the same time we're not yet devoid of hope. And therein lies the fundamental problem with this country. With its almost complete lack of options, save for more chemotherapy or more radiation, it has nothing to offer families like us. I can look across the pond and see children in America who are alive and well years after relapse or progression. They do one treatment until it ends, or stops working, and then they'll move on to another. But most importantly of all they have a reasonable quality of life to go with it. They go to school, they go to clubs, they enjoy normal social interactions; their lives are not solely about hospitals, treatments, and cancer. For children who do not have fast-growing, ultra-aggressive, disease their neuroblastoma may be treatable as a chronic illness. That's got to be our new hope for Adam. In a sense this is a return to our past hope, in the days before his cancer showed such uniform stability that we dared consider the possibility that it had matured into a benign form.

The fact we live in the UK when we need to be in America, the fact we are liable for any and all treatment costs abroad, means we face enormous challenges to achieve our aim. But the only other choice we have is no choice at all. We will not give up. We will never give up. I think deep down in my heart I always knew it would come to this.

We're ever thankful for all the support we've had in the time since Adam was diagnosed, and the tremendous response we received after we launched Adam's Appeal. I'm afraid we're going to need much more of that support over the weeks and months ahead. It was our most fervent hope that we'd never find ourselves in this situation, but now we have. We know we have some tough times ahead. All we can do is remain strong, do whatever needs to be done, and pray that things work out for us.

Thank you for sticking with us, and please keep our wonderful, beautiful, brave little boy in your thoughts.

Adam, March 2012

Been a long time ...

Adam is doing okay. Last week we had a repeat MRI at the Royal Marsden. It had been six weeks since the previous one which had shown no change five weeks after the MRI in Germany on which the small lesion/node/tumour in Adam's abdomen first appeared. Result this time was also no change. Still there, still the same size, hasn't gone away but most importantly hasn't grown at all either.

That's eleven weeks since 'it' first appeared on 23 January during which time there has been no change at all. It remains impossible to know what it is. However, the longer it remains unchanged, and remembering it did not appear on the last MIBG SPECT scan, the greater the likelihood that it isn't neuroblastoma. We know that it first became apparent following the end of antibody treatment. Therefore were it to be neuroblastoma it grew whilst Adam was on ch14.18 immunotherapy and 13-cis-retinoic acid. For the past eleven weeks it has not grown at all, during which time Adam has been on 13-cis-retinoic acid alone. So either it's not neuroblastoma, 13-cis-RA is more effective alone than when combined with immunotherapy, something innate within Adam's body is stopping it growing further, or something equally weird is occurring.

Come the start of May it will be 3 months since the last MIBG scan (the one that we feared would be devastatingly bad, and wasn't). So we have to decide whether to continue on the same scanning schedule, bearing in mind every one of these scans exposes Adam to yet more radiation. And the next question after that is how long to leave it now before doing another MRI? What do you reckon? I'm thinking somewhere between 6 weeks and 3 months? What would you do?

The start of May will also see the end of Adam's 12th cycle of 13-cis-retinoic acid. I've had a couple of meetings about what to do after, but nothing is settled yet. Nothing is even close to being settled. There isn't a right or wrong answer. We could do nothing and see what happens. Adam has lots of bone and bone marrow disease, an abnormal lymph node imageable by MRI, but despite that there is still a chance he could still be fine if we did nothing else. Problem is we'll only know whether Adam is in that very small group of children who do well despite seemingly responding badly after the fact. There isn't enough known about the biology of those patients whose disease matures and takes a benign course to be able to predict who they are in advance. Current imaging techniques are unable to provide differential diagnoses. Biopsy is almost sure to fail in the case of Adam's bone disease, and the risks outweigh the benefits where the suspicious lesion/lymph node is concerned.

At the other end of the treatment spectrum we could take Adam to America for 6-8 months and enrol him on an early phase clinical trial of an unproven treatment that may (if we had the benefit of hindsight) be completely unnecessary, may (years from now once it's completed and results are published) turn out to be ineffective at treating neuroblastoma, and may in the worst case scenario even end up doing far more harm than good. On the other hand we could get lucky and end up have a more prolonged period of stability by continuing treat. And maybe we hit the jackpot and Adam's disease is miraculous resolved (not that I actually believe that will ever happen).

In the middle is what I'm shooting for, and trying to figure out. Something that doesn't continue to impact too severely on the life of a child who's already been in treatment continuously for nearly three years. Something that let's us be a proper family, at least for a while. Something that has some scientific evidence to support it. Something that has objective reasoning behind it, rather than simply giving us a warm feeling because we're doing something rather than nothing.

If we happened to live reasonably near an institution in America that was doing a Phase I or II clinical trial that had showed early promise I would seriously consider it for Adam, even if it meant one or two days a week in the hospital rather than the classroom. But, of course, we don't. There is a trial that we could enrol Adam on at the Marsden (an mTOR inhibitor study for those who are interested), but I've looked at it and I just don't see the prospective benefit being worth (a) the amount of time we'd have to spend getting blood drawn for pharmacokinetic and pharmacodynamic testing, and (b) the side-effects of mouth ulcers and low blood counts.

There are a couple of ideas that I need to speak further with the doctors about, so we'll see where that takes us. Clearly we want to avoid going outside the UK if at all possible, and failing that to keep any time spent away to an absolute minimum. The only thing we've really ruled out at this stage is relocating full-time to America for the next 6-12 months. Options that may require us to travel back-and-forth are still on the table, but as yet we haven't figured out what's in Adam's best interests regardless of any such logistics. Answers on a postcard anyone?