"What's the prognosis?"

The examination under anaesthetic last week revealed that the tumours in Asa’s eyes have halved in size in the left eye and more than halved in the right eye since he began chemo.

Retina scans showing tumours before and after the first two cycles of systemic chemotherapy.

The retcam images show how the tumours have shrunk, and also changes in texture from diffuse blobs to gnarly, calcified masses.

 

This is encouraging, but there’s still a lot of cause for concern.

For one thing, systemic chemo has its greatest effects in the first cycles.  So unfortunately we can’t expect this rate of shrinkage to continue through the remaining 4 cycles of chemo. As the ophthalmologist told us, the remaining chemotherapy is to prevent relapse.

The other cause for concern is seeding. 

In the images, the constellations of little spots around the tumours are “seeds”: tumours-in-the-making that, if they’re not attacked, will grow bigger.  These are a worry because (a) they’re so many of them and (b) they’re not well supplied by blood vessels, the way the big tumours were, so they won’t respond as well to systemic chemo, which relies on the circulatory system to deliver the drugs.

The seeds can be attacked in a variety of ways, including laser and cyrotherapy.

But there’s a delicate balance to be struck between the benefits these treatments can bring in terms of destroying the seeds, and the collateral damage they can cause in the process.  Aggressive use of laser, for instance, might inactivate the seeds, but could also further detach the retina, which would cause problems of its own.

This is part of the reason why, after this first course of chemotherapy ends, Asa’s going to need to be examined under anaesthetic every month or 2 months for the next few years.  The doctors will be trying to keep these seeds under control, using an appropriate level of focused therapy.

Where we are now

The day after the examination under anaesthetic, Asa received his third dose of chemo.  

Now we have three down; three more to go.

Asa and parents at the new Royal London Hospital, in Whitechapel

Last week Asa's blood counts -- specifically, his neutrophil count -- didn't return to normal in time for him to undergo his eye exam and begin the 3rd round of chemo. Our medical appointments were pushed back a week, and in the meantime we've enjoyed a lull, waiting things out, and hoping the neutrophils are climbing, but also getting more time and space to reflect on life than we've had for the last couple of months.

The first time Asa’s neutrophils fell below 1.0, during the first cycle of chemo, we were thrown into a panic, and half expected him to break out in spots or immediately develop a fever.  Since then we’ve learned that the danger is manageable.

Neutrophils are one component of white blood cells, which indicate your body's ability to withstand infections.  The chemo drugs Asa is taking inhibit his ability to produce white blood cells, and consequently his immune system is seriously depressed for a while after each dose.  During the first cycle they plunged after 9 days, and then returned to normal by day 20 or so. This time they fell more rapidly and stayed down for longer. 

The implications for our day to day life aren't all that great: We've been taking precautions to protect him from infections, and we don't get out much: an excursion to the shops every now and then or a walk in the countryside when the weather's fine is about as adventurous as we get.

One of the precautions we take – keeping Asa (and sometimes Selam) penned in

This has become our normal routine now, so we're used to it.  And so far we've been lucky this time around -- no fevers, no scary coughs, no inflammation around the Hickman line.…

The downside of up

At first, the absence of crisis was a bit difficult to deal with.  When you've been putting out fires for weeks on end, it feels weird not to have an emergency on your hands.  And the first week or so after Asa's appetite returned, when he seemed to be pulling back and was acting (as he still is now) pretty much like any other toddler, saw us struggling much more than we'd expected, with worries bubbling up.  Your mind goes strange places under these circumstances -- you start wondering how long all this treatment is going to last.  How you’ll get your own career back on track.  How nice it would be to return to Ethiopia.  And what it would be like if Asa were really to lose his sight….

We started searching for more information from other families who had children with Rb, and how things had worked out for them. 

This has been a sobering exercise, and the stories make difficult reading.  The first 6 months of chemo are never the end of the road, at least in the cases we've heard about.  There are long periods when children are getting regular eye exams under anaesthetic, doctors are spotting new tumours, and children are receiving focused therapies like cryo, laser, and radioactive plaque… 

And sometimes, after all this, removal of one or both eyes is necessary.

The blog that we've learned most from is Fintan Tadgh's.  Maintained by his parents James and Fiona, it tells the story of their journey from Fintan’s diagnosis in 2007, when he was 6 months old, through an EUA last week, at the age of 4.

Fintan and his family have been through a lot, and learned a lot, over the years.  Following them through this, reading a year's worth of posts each evening last week, we empathised as they took a roller coaster ride through periods when it looked like Fintan’s cancer was on the ebb, through times when it was resurgent, and through many and various treatments, all of which they suffered with great strength and dignity.

At the moment, we can’t tell how closely Asa’s story will resemble Fintan’s.  We expect we’ll get more information when we see Mr Reddy, the consultant ophthalogist at the Royal London Hospital on Wednesday.  And while we’re hoping for good news on how the chemo’s working, we know that this won’t be the final judgment, and there are likely to be more surprises ahead.

For the time being, we’ve attained a certain amount of equanimity, and the past few days have been as good as any I can remember of late. 

Asa's been developing in new and surprising ways: imitating sounds, walking more confidently each day, fussing for our attention (are we spoiling him??), and kissing us (wetly and smack on the mouth).   

And we've felt more lighthearted than we have for a long time, one sign of which is our ability to laugh at things that would have caused us to freak out just a week or two ago -- for example, me tracking dog shit into the house one day… Not a great move at the best of times, but especially not when you've got a severely immune compromised toddler in the house. 

The second cycle

 

Two weeks ago, Asa had his second dose of chemotherapy. So far, the second cycle has been much easier than the first. We’ve managed to stay at home except for short visits to hospital, and we've largely succeeded in controlling Asa's discomfort. 

Part of the reason for this is that we’ve been giving him potassium supplements to head off hypokalaemia, whereas the first time around it was several days before we began using potassium. But a bigger reason is that the dosage of the most potent of the drugs he is on – Vincristine – has been halved.

Halving the dosage of this drug is a big deal, because our most immediate challenge is managing the side-effects of the chemo drugs.

In the first cycle that meant trying to distract him from pain.  This time it's mainly meant trying to get him to eat. 

Asa feeding Jed feeding Asa....  Oranges are the only food he's never refused.

Expecting that Asa might have difficulty feeding, we had a naso-gastric tube inserted just a couple of days after the second dose of chemo.  The tube is useful not only for topping him up with food when he’s not taking anything by mouth, but also for giving him anti-nausea medicines and potassium syrup (which can themselves be nauseating to swallow).

Thankfully, he has been breastfeeding well throughout.

In this way we’ve been able to get him through the rough first few days of the cycle, until his appetite starts to revive.

Blood counts

Next week, we'll learn whether the drugs have been working – whether the cancer is receding.  On Wednesday, the staff at the Retinoblastoma Service in London will examine Asa’s eyes, and assess how much the tumours have shrunk since he began chemo.

For the time being, the main indication we have of how the medicines are working is Asa's blood counts.  These give us an idea of how effectively the drugs are inhibiting the reproduction of fast-developing cells throughout his body (including the cancer). 

The blood components that are most important to keep track of are haemoglobin (red blood cells) and platelets. Haemoglobin carries oxygen to cells, and platelets help the blood to clot.  They’re important not only because they serve as an index of the drugs’ action, but also because if they fall below critical levels, one needs transfusion.

Platelet and haemoglobin counts for cycles 1 and 2 of chemotherapy. 
Cut off points for transfusion are 30 for platelets and 7 for Hb.

Yesterday Asa's haemoglobin levels dropped into the danger zone for the first time, and today he received blood transfusion at our local hospital. 

This is something we'd been hoping to avoid.  But, as with so many other choices we’ve had to make recently, transfusion is much better than the alternative – seeing him become more anaemic, and increasing the risk of spontaneous bleeding.

Who are you calling anaemic?

Asa hadn’t shown any of the lethargy that often accompanies anaemia.  In fact, even during the days when he wasn’t eating, he looked and behaved much like any other toddler, ebullient and energetic.

But it was a pinker, better perfused Asa who emerged from hospital this afternoon, with 200 ml more red blood cells in his system than before.

Taking a walk in the hospital corridor during transfusion

 

In the past week Asa began to stand by himself, and to walk confidently when his hands were being held. 

It’s a source of wonder to us that, despite all he’s going through, Asa should be developing as fast as he is. 

During a week-long stay in hospital last month, he began saying, “Dada”.  He claps his hands and applauds himself when he’s succeeded in stacking hoops onto a pole (one of his favourite games).  And his babbling becomes more florid and melodic each day.

All of this buoys us up, and keeps us optimistic.  

As my mum observed, in some ways it’s easier for those of us who are with Asa day to day than for those who aren’t, because we see the happy times as well as the sad ones.  Those happy moments are in large part what keep us going – them, and the love and support we receive from friends and family.

Many thanks to all who sent birthday wishes to Asa.  And to everyone who's reached out to us. 

Today is day 20 of Asa's first round of chemotherapy.  I last wrote on day 4, and since then we've had some ups and downs.  

For about 5 days Asa was very distressed and uncomfortable, and could be distracted from the discomfort only fleetingly.  His appetite was faltering, and then dropped off almost to nothing.  For two or three days following he was limp, too weak at one point even to roll over in bed.  When he was left to himself, he'd either sleep or stare blankly at whatever was before his eyes.  When he was moved, he'd feel pain, and protest.

A couple of days in to the distress and discomfort, we took Asa into hospital to get him checked out.  Paracetamol, even at the highest doses recommended for infants, wasn't having any effect; we imagined we might be sent home with some more powerful painkillers.

As it happened, we were in hospital for the following week.  Admitted with hypokalaemia (low potassium), he was immediately hooked up to a potassium drip, and it took several days for his blood potassium levels to stabilise.

It was during that week in hospital that he transitioned from the chronic discomfort to the -- even more worrying -- weakness and limpness.  He'd been eating very little, and in retrospect it seems clear that his energy levels were very low.  Our only consolation was that he was still breastfeeding. 

When he lost interest in the breast, we started to realise that the option a doctor had spoken of when we were admitted, a naso-gastric tube -- which at the time had seemed distasteful -- actually sounded pretty good.

Seeing the tube inserted through Asa's nose and into his stomach was one of the less pleasant experiences of my life. 

But over the following days, as we learned the basics of NG tube care and maintenance, pouring and pushing formula milk and various drugs down it 3 or 4 times a day, Asa made a remarkable comeback.


Only the night before last -- about 60 hours after he'd been readmitted to hospital with a fever and placed on prophylactic antibiotics -- did the tube come out (it was starting to leak from the outside end; its shelf life of 2 weeks was almost passed). 

But by that time, his appetite -- even if not back to pre-chemo levels -- was much improved, and he'd become once again the lively little man we knew and loved.

Last night (February 3) he and Selam got back from hospital, and had dinner at home, and Asa crawled around on the floor and babbled at us; and went to sleep. 

And today he is one year old.

Asa, home again, on his birthday

Starting chemo

On Sunday we took Asa back to London to begin chemotherapy.  The first doses of drugs were given on Monday, and we returned home late the following day.  During the stay in hospital we had an opportunity to reflect on the pros and cons of Asa's condition versus other kinds of cancers, and the treatment regimen he's on.

One thing was vividly impressed on us: Asa isn't the first or the last child to have cancer; his isn't the worst or the best case that's been seen; and the treatment regimen he's on isn't the most or the least radical that's been used.  In short, we gained a sense of the ordinariness of what, a week ago, seemed like an exotic diagnosis.  And the normality of a course of treatment that, after the doctors announced it a few days ago, seemed to make removal of his eyes look like an attractive option. 

"Everyone here has a Hickman"

A Hickman line is a port used for delivering drugs directly into veins, and for taking blood out of them.  It’s like a permanent IV – one that can be kept open for months or years, with a plastic stopper to cap it.  In Asa’s case the plastic tube enters his body on the left side of his torso, and snakes under his skin to the jugular vein in his neck, where it enters his bloodstream.

Asa's Hickman line, exposed during a change of dressings.

On our first evening in the hospital, Malachi, an 8-year-old boy whom we met outside the ward kitchen, pulled his shirt up to show us his Hickman – his 'wiggly', as the nurses call it – as if it was nothing at all. He looked very much like a normal 8-year-old boy, cautious around strangers, but with a brightness in his eyes that showed he was observing you carefully.  He had been on the ward for almost a month, receiving treatment for cancer.

Angela, a nurse who has seen dozens of children with cancer, noted that compared to leukaemia and other childhood cancers, retinoblatoma has a very high cure rate, and requires less radical treatment. 

Angela's take on retinoblastoma: 

"If you've got to have cancer as a child, this is the one to have."

A cure worse than the disease?

When we first thought about Asa's treatment options, systemic chemotherapy seemed like the least attractive choice.  The drugs are toxic – the technical term for them is cytotoxins, cell-killers – and the common side effects, including hair loss, impaired intestinal function, and erosion of the mucosa of the mouth, are directly related to their function of short-circuiting the growth of rapidly-developing cells throughout the body, including but not limited to cancers.

Samples of Asa's blood, and a syringe of Vincristine,
one of the three chemotherapy drugs he's taking.

Giving repeated doses of these drugs to children who are undergoing rapid development seems like madness, and a recipe for long-term health problems. 

Perhaps, in the future, it will be seen as madness.  But at the moment there are no other good options.  In Asa's case, the tumours in his eyes are too big to be treated any other way. If his eyes were removed, he would still be advised to take a protective course of chemo to mop up cancers that might be hanging out elsewhere in the body – and the dosage and duration would be the same as for the chemo that would have been prescribed first off. 

Rates of bilateral enucleation (removal of both eyes) after chemo are low these days, our doctor tells us – around 2% – so preemptive enucleation has nothing to recommend it.  And lasers and other more focused therapies just aren't adequate to the job – unless, that is, the tumours are shrunk by chemo first.

That, then, is the course of therapy he's getting: Chemo to do the tumour-shrinking, followed by focused therapies to attack the tumours when they're down.

Frequent blood tests are going to be necessary to track progress over the coming months. And the progress we expect to see is of a strange sort. Low blood counts are desired, because they are direct indications of the drugs' action.  At the same time, they will serve to show how Asa's body as a whole is being assailed by these toxins, with results being anemia, vulnerability to infections, and liability to spontaneous bleeding. 

A long course of treatment

One of the unpleasant implications of all this for Asa is that he will be a patient for much of his childhood – under close medical surveillance until 5 years and beyond.  For the next 6 months he will be spending more time in hospital than in nursery school.

The unpleasantness of this prospect is tempered by the fact that the medical system here in the UK is a particularly humane one. Regular home visits by community nurses will minimize the amount of time he has to spend in hospital.  And technological and clinical innovations make therapy less painful than it used to be.

The Hickman line is a case in point: On Monday night, I witnessed a nurse pushing a dose of anti-nausea drugs down Asa’s Hickman line while he slept.  If he didn’t have the Hickman, this would have required a painful injection, or the equally painful installation of an IV catheter.  As it was, Asa barely stirred as the drugs entered his veins.  Changing his nappy is now a more invasive procedure than administering intravenous drugs.

None of this makes the immediate challenge of helping Asa through chemotherapy any smaller.  Two days after the drugs entered his bloodstream, he is already clearly suffering.  As I’m writing this, at 3 AM on Thursday, Asa has been crying most of the night and with a new intensity; and despite frequent attempts to get him to eat, he’s accepted very little food since we returned from hospital.

Amidst all this we try to bear in mind that his suffering is less than that of other children. 

But it's scant consolation, faced with a child who's suffering, to reflect that other children suffer even more.

_____

A postscript on developmental effects of chemo in infancy: Dr Judith Kingston, the consultant managing Asa's care, has seen hundreds of children with cancer go through chemo, and attests that long-term effects on development are very rare.  The oldest children who went through this as infants are now in their 20s, so there's still a possibility of later-life problems.  But there’s reason to be hopeful.  If anyone has good information on this, please let us know.

Asa's status, and the way forward

Yesterday Selam, my mother, and I took Asa to London for assessment by retinoblastoma specialists.  In due course I’ll describe the health workers we met there.  Our first impressions are that they’re brilliant people who wear their knowledge and expertise lightly.  Based on the examinations they carried out and on what they told us, we’re now in a much better position to understand the stage of the disease and the treatment that’s necessary.

The stage of the disease

The International Classification for Intraocular Retinoblatoma grades severity on a scale from A to E.  A represents the best outcome, where chances of preserving vision are very good, and E represents the worst, where the eye must be removed to prevent metastasis. 

Asa is a D in both eyes.  There are multiple tumours in each eye, and they are large.  One indication of their size is that, while ocular tumours are conventionally described in millimeters, those in Asa’s eyes were described to us in centimeters: The largest in the left eye is 1.9 x 1.3 cm, and that in the right eye is 1.3 x 0.5 cm. 

The tumour in his right eye, while smaller, is more disadvantageously positioned, already impinging on the crucial area between the fovea and the optic nerve, and interfering with Asa’s sight.  The long-term chances of saving vision are therefore greater for the left eye than the right.

The left eye, however, is far from well: there are seeds – tiny pieces of tumour – that have already split off into the vitreous area of the eye, and should these grow, they would likely cause blindness in the left eye too.

Retcam image of left eye.  The mass at the bottom is the largest tumour; the spots and clouds above are subsidiary tumours.

Had the disease in each eye been fractionally worse, the doctors would have recommended removal of Asa’s eyes.  We’re grateful that they did not.  And we’re grateful too that there’s no evidence of the cancer having spread outside the eye.

What treatment do they have for this?

For children with bilateral retinoblastoma (cancer in both eyes) the standard treatment is systemic chemotherapy to shrink the tumours, accompanied by more focused therapies to attack them once they have shrunk. 

The first round of treatments will begin next week, and last about 5 months.  This includes 6 cycles of chemo, each lasting 3 weeks.  After every 2 cycles, he’ll be evaluated, and lasers or cryo may be used to attack the tumours. 

During the chemo, Asa is going to be delicate: We’re going to have to take special care to protect him from infection and to preserve his appetite.  His blood counts will need close monitoring, and if they plunge very low he may need blood transfusion.

A team effort

To pull all this off, we’ve been offered the help of a large team, including 

-- community nurses who will visit Asa at home each week to check blood counts and change the dressings on the shunt that will be used to funnel drugs into him;

-- paediatricians at our local hospital, whom we can call upon to manage any infections that Asa picks up along the way;

-- oncologists and ophthalmologists in London. 

We’ll also be relying on Asa’s own resilience and adaptability.  On love and support from friends and family.  And on God.

With help from these sources we pray Asa will overcome the cancer and retain his sight. 

There’s a long road ahead.

Asa's eyes

When Asa was 5 or 6 months old, Selam noticed something about his eyes.  Under certain light conditions, they would reflect light back, the way cat’s eyes do. 

“This child has animal’s eyes,” she said.

Neither Kuri nor I thought much of it.  It was amusing, we thought; a trick of the light; not a cause for alarm.

When I arrived in Ethiopia 3 days ago, Selam had just come across some information online that suggested this could be a sign of disease.  Whiteness at the back of the pupils is a characteristic of retinoblastoma, a cancer of the eye.  It’s rare, but more common in infants than adults.

Another sign of the disease is that in flash photographs with “red eye”, the eyes of affected children appear yellow or white rather than red. 

Going through old photos, Selam noted that this “yellow eye” phenomenon showed up for Asa in photos from 3 or 4 months ago.

The earliest photo of Asa showing "yellow eye". Note the contrast with Asa's companion Mekdas, who has red eye.

Yesterday morning we took Asa to an ophthalmologist in Addis Ababa who examined his eyes and corroborated the possibility of retinoblastoma.  In the afternoon he got an ultrasound, which confirmed the diagnosis.  Present in both eyes, it’s more advanced in the left eye than the right.

Left untreated, retinoblastoma can kill within 2 years.  Each year, 40 or 50 children are diagnosed in the UK, and 1 or 2 die.  As with other cancers, the prognosis depends largely on the stage of the disease.

In Asa’s case, we don’t yet know the stage of the disease.  A CT scan today should tell us more.  At the least, his vision is likely to be impaired.

But Asa shows no other signs of illness.  He looks and sounds like a normal, healthy child: inquisitive, playful, alert to everything around him. 

Within the last two days he’s made great progress in getting around on two feet, yesterday walking across the living room holding his mother’s hand. 

He’s begun to say, “Mama,” using the word to call Selam to him, or as a response when she says his name.

It’s remarkable to be told by a doctor that your child losing his sight is a good outcome.  It will take some time for us to see things from this perspective. Right now, scenarios worse than blindness are difficult to contemplate.

On Monday we’ll fly to England to seek treatment there.

We’re hoping and praying that Asa’s sight will be preserved.  And when we reflect on it, we recognize that we would love him just as much had he been born blind.