Where there’s a Will, there’s a way

The Frost family were reluctant tabloid headliners in spring 2017. ‘Tot shocks docs,’ declared the Sun newspaper. ‘Boy’s aggressive brain tumour shrinks thanks to CANNABIS compound, parents claim,’ it continued.

The boy in question, William, now seven, did indeed experience remarkable results in tackling a terminal condition after taking cannabis oil.

But the Frosts were somewhat uncomfortable with their moment of red top heat.

The message that ‘cannabis cures cancer’, as the story seemed to pronounce to the world, could be dangerous and misleading; and the column inches devoted to William didn’t reveal the full picture of his journey.

Dad Stephen has since made it his mission to help uncover the true facts about the potential role cannabis can play in fighting paediatric brain tumours.

The family’s charity, Make William Well, has helped to raise £100,000 to support ground-breaking research on the topic; and Stephen is now a regular speaker at insight- sharing events focused on childhood cancers and their possible links to cannabis treatments.

“It’s been so much of a rollercoaster over the last few years that our emotions are almost blunted or exhausted. You can’t really describe how it feels,” he says over the noise of a busy coffee shop near the family home.

“We were basically told he had a brain tumour and probably had five years to live. It was utterly devastating.”

It all started innocuously with little signs; the type fretted over by young parents but downplayed by doctors. William was 18 months old and had just started nursery when he began experiencing sickness and teething issues commonly seen in toddlers.

But he was also finding balancing unusually difficult for a child of his age, and walking with his head tilted to one side.

After several trips to the GP, he was referred to the local eye, ear, nose and throat (EENT) department.

But his parents felt a looming sense that his condition was more serious than the speculated ear problem.

“My wife had been on the headsmart.org.uk website, which supports the early diagnosis of brain tumours, and William had some of the symptoms. Then one night I picked him up and he threw up on me for no apparent reason. That was it, we thought there was something seriously not right here.

“We went to accident and emergency and after a week of tests in which they could find nothing wrong with him, they finally agreed to do an MRI scan. That’s when they found the tumour.

“We were told it was terminal and that there was a five year survival rate. If he had surgery and they could get it out then he might have a chance at longer than that. But if they didn’t, then it would be much shorter.”

The tumour was around the size of a golf ball, near to the centre of his brain. It was diagnosed as a ‘grade three anaplastic ependymoma of the fourth ventricle’. Within days, William was taken into surgery at Queens Medical Centre, Nottingham, and the tumour was removed.

Due to its proximity to critical nerves, however, he was left with partial paralysis on his left hand side. This meant he couldn’t move this side of his face, or swallow properly, and had to be tube fed.

Because of the grade of the tumour there was a significant chance it would likely come back so further treatment was required. William started chemotherapy, but was unable to tolerate the full planned 13 months of treatment.

He was already deaf in his left side, possibly as a result of surgery, and was beginning to lose high tone hearing in his right side, likely due to the chemotherapy. Treatment therefore ceased after nine months.

But the family received the welcomed news that tumour had been “fully resected” and there was no sign of regrowth.

Stephen says: “I don’t think the outlook ever really changed but we were hopeful. We pushed the idea that it could return to the back of our minds and hoped that we’d got it. As a parent, if you’re told its fully resected and your child’s had chemo too, you kind of hope that that’s it. But obviously the cancer was a particularly nasty one.

“He was still a bit wobbly on his feet at the time, but he made a good fight of doing the things other children get up to at that age, like going to playgroup and so on.”

When his balance problems worsened, their underlying fears that the tumour would regrow were realised – and this time it was in an even more precarious place, tangled around the brain stem.

The only option was a “very risky” surgery, which successfully removed most, but not all, of the tumour. The family were then told that William could be considered for Proton Beam Therapy in America. This is a less damaging form of radiotherapy than that offered in the UK.

Yet, although the NHS had approved funding, the centre in America ultimately denied treatment him due to his tracheostomy and the possible complications of travelling to America.

In the meantime, the tumour had regrown exponentially since the surgery. William was fast-tracked onto a six week course of radiotherapy during which sickness was a constant issue.

But the tumour was increasing in size and, despite going through another round of chemotherapy, it’s growth could not be stopped. Doctors gave the family the heart-breaking news that there were no other treatment options available.

“They said, ‘unfortunately that’s it’ and they gave us details of a hospice. We were told that William only had six months maximum left and wouldn’t live to see Christmas.”

And so began a desperate hunt for alternatives beyond what was available on the NHS.

One glimmer of hope was that William’s tumour had the correct profile for the ketogenic diet to possibly have an effect. This is a high-fat, adequate-protein, low- carbohydrate diet sometimes used to control severe childhood epilepsy.

But Stephen and his wife’s search also brought them to CBD.

“We didn’t know at the time if it was possible to go down the THC route, or how we could get hold of it, or CBD that we could trust. This was in 2016 before CBD had become readily available.

“We spoke to our consultant who couldn’t recommend it and said not to bother with it because it hadn’t been through preliminary trials.” Ignoring this advice, they found a private clinic offering a synthetic CBD treatment, which they decided to try in conjunction with the ketogenic diet.

“This was the only way we could get hold of what we could trust was CBD and they charged us a lot of money for quite a small amount.

Then six months after being told nothing more could be done for William, they noticed an improvement in his condition.

An MRI scan revealed that his tumour had shrunk to around a third of its original size.

“We don’t know what worked exactly, but we know the tumour shrank. Was it the CBD? Was it a combination of this and the ketogenic diet? Radiotherapists even argue that it could be delayed effects from the radiotherapy, which would be surprising given how long after the radiotherapy it occurred.

“We don’t know whether there was a synergistic effect between the CBD, the diet and the delayed effects of the radiotherapy.”

The tumour remained stable at its reduced size for around 18 months until scans showed that it had started growing again. William underwent another surgery, removing almost all of the tumour, before more chemotherapy.

He continued on cannabinoids and the ketogenic diet and, by late last year, his scans were clear.

He now takes a non-synthetic CBD product containing more cannabinoids than his previous regime, with the aim of killing the remains of the tumour.

He is also undergoing metronomic chemotherapy (lower dosage with less side-effects) continuing on the ketogenic diet alongside his dad.

“We hope this will keep it under control but I’ve also read certain lab-based studies that suggest it can actually be killed by cannabinoids. That’s the hope.”

The family’s charity, Make William Well, has teamed up with Brain Tumour Charity to raise funds for vital research that could ultimately shape treatments for other children like William.

It has helped to raise over £100,000 for ongoing research led by the Children’s Brain Tumour Research Centre at the University of Nottingham.

The research aims to answer the question: Is there a role for cannabidiol in the treatment of children’s brain tumours? The researchers say: “CBD is widely used by brain tumour patients, sometimes with considerable success. But, we need to objectively understand how CBD affects the cells, and why the results patients and families are reporting occur.

“This knowledge is essential in order to determine what the therapeutic dose of CBD might be. Without this, clinicians or families may inadvertently be too conservative or liberal in their dosage, and not achieve optimum results for the patient.”

Stephen is hopeful that other cannabinoids, including THC, might also be included in such research in future.

“From the outset in pushing for this, our aim was to get all cannabinoids researched so that eventually they can be issued free of charge on the NHS once they’ve gone through the clinical trials.”

Specific areas of the soon-to-be-concluded lab-based studies include to what extent oxygen levels in tumour cells treated with CBD, have on markers within the cell which indicate the beginning of the process of cell death.

Also, some patients are taking cannabis oil as an adjuvant therapy (applied after an initial cancer treatment) for their brain tumour.

The treatment is to take the oil for CBD three days on and three days off. But it is not yet understood how this action affects tumour cells. Furthermore, the researchers have investigated in further detail how CBD affects the cell receptors, to better understand the effect the drug has on tumour cells.

According to the researchers: “This research could have considerable clinical benefits, and therefore it is very important that any conclusions we draw are able to stand up to international scientific scrutiny.

“To achieve this, we are now in the process of detailed examining all  of our data from the project.”

The findings are expected imminently, from a study which is underpinned by global collaboration.

Lead researcher Professor Richard Grundy visited The University of Western Australia as part of the study to learn first-hand about their CBD research studies focussing on medulloblastoma.

He spent time with Dr Clara Andradas Arias, an international post-doctoral researcher in the Brain Tumour Research Lab at Telethon Kids Institute in Perth.

This international collaboration has enabled the sharing of data on how CBD affects cells in paediatric tumours. Further studies include a planned ketogenic diet and CBD clinical trial, which is hopefully taking place this year.

More generally, as UK health authorities continue to call for more evidence of the medical benefits of cannabis, Stephen would like to see investment in “adaptive clinical trials”.

These are trials in which modifications in response to the participant’s outcomes and other factors such as side effects are allowed after it has begun, without its validity or integrity being questioned.

They are distinct from ‘double-blind, placebo-controlled clinical trials’ which are considered the gold standard in medical testing and typically relied upon by the pharmaceutical industry to prove the benefits of new drugs.

Doctors and campaigners who advocate medicinal cannabis argue that such trials are not compatible with cannabis medicine. They argue that the plant is too complex and is not a single molecule pharmaceutical product that these trials are designed for.

They also point to the growing body of observational and case study data supporting the use of medicinal cannabis to treat various conditions.

Stephen says: “Why are such clinical trials the gold standard? They take too long, are too expensive and clearly haven’t been very good in terms of coming up with effective treatments for childhood brain tumours.

“Adaptive clinical trials, which are far cheaper and produce faster results, should be carried out on a multitude of cannabinoids. This way more children could be given the opportunity of sooner access to paid- for quality assured medicinal cannabis products under close clinical supervision.

“I believe the current system of gold standard trials has failed our children – only one drug has ever been specifically developed to treat a childhood brain tumour.

“There are hundreds of papers written about cannabinoids and the evidence that it works in the lab is overwhelming. But there just aren’t the gold standard clinical trials.

“There are just four drugs that have ever been developed specifically for childhood brain tumours, the rest are hand-me-down treatments from adult cancers, which are very different biologically to their childhood equivalents.

“We are cutting, burning, and poisoning our children with decades old inappropriate approaches when cannabinoids are starting to be shown to be potentially effective but are currently a long way off being prescribed on the NHS.

“I believe there needs to be a sea-change in the way we go about looking for childhood cancer cures and I believe that pushing for adaptive clinical trials is the way forward.”

While continuing to push for research, Stephen is also regularly contacted by parents of other children facing similar challenges to William.

“I try to help, and I get a lot of questions about dosages, but I would never recommend one thing or the other. There’s generally massive confusion out there about cannabis medicine.

“A lot of people think, like I did before we went through all this, that the whole medicinal cannabis campaign is just led by people wanting to legalise marijuana for recreational use.

“They don’t see the evidence which proves that it can work on brain tumours, certainly in the lab. For whatever reason, the clinical research isn’t getting done and that’s now why we’re campaigning.

“Its one thing getting it legalised, but without the research you’re still not going to know about the dosages or side- effects. If I was a doctor I wouldn’t want to give a drug that hadn’t been through clinical trials. Also, different cannabinoids could have different effects on different cancers. This is where the research needs to go and in a way that reflects the complexities of the plant.

“What we want to do with Make William Well is to say ‘there is a potential new advancement here, let’s get the focus on kids.’ Three years ago I didn’t think we’d have a chance of getting a research study done, yet we proposed it, the centre agreed to it and we helped to raise the funds to do it. After that we didn’t think there was a cat in hell’s chance that we’d ever be looking at clinical trials, but now that’s hopefully realistic as well.”

To donate to Make William Well visit www.makewilliamwell.com.