Stacie Schaible with WFLA News Channel 8 in Tampa Bay sat down with the Matthews family to share some of Because of Ezra’s story of battling neuroblastoma.
A week ago, we hung out at All Children’s Hospital in St Pete to see 3 year old Sofia Anderson ring the oncology floor bell. All Children’s does this every time a kid finishes upfront cancer treatment, and Friday marked the end of over a year of treatment for Sofia – she’s cancer free!
One of the main things Because of Ezra is focusing our research funding on is stopping neuroblastoma relapse. Historically, over half of kids who beat neuroblastoma relapse – but through the work of the NMTRC, a 25+ hospital national research consortium we work closely with, we’re changing that story. Sofia’s next step is getting on the DFMO trial we’re helping to fund, which we hope is stopping relapse. Results of the DFMO trials which have already been completed are hugely promising, and we’re thrilled Sofia will be able to get on this trial at the same hospital Ezra was treated at 6 years ago, All Children’s Hospital.
We’ve become good friends with Catalina and Patrick Anderson, Sofia’s parents, and Cat has joined Because of Ezra as the founding member of our Parent Advisory Board. Hanging out with their son Aiden and Sofia is always a good time. Plus, our five year old Charley may have a small crush on Sofia. 🙂 The Andersons have also helped us launch our Because of _____ program, raising awareness and fundraising Because of Sofia. They’re a force to be reckoned with against neuroblastoma, and we’re so grateful to be beating up this stupid cancer with them.
A history of the NMTRC’s genomic-based treatment for childhood cancer, and a new paradigm for today.
The launch of a new clinical trial called PEDS-PLAN in September of 2015 marks a paradigm shift in childhood cancer treatment and precision medicine — the first time DNA and RNA sequencing are being done in newly diagnosed patients. This article will take a look at the last five years of genomic research in childhood cancer done by the Neuroblastoma Medullablastoma Translational Research Consortium (NMTRC), and what it means for the future of precision medicine.
If you follow the clinical research world, you’ve heard of personalized medicine, or precision medicine, or molecularly guided therapy (MGT), or genomics. They’re different terms for what is generally the same concept — personalizing treatment per patient based on specific genetic or molecular analysis. In childhood cancer, genomics is being used to beat cancer on a kid by kid basis.
Because of Ezra is a non-profit my wife Robyn and I founded in 2011, dedicated to finding and funding a cure for neuroblastoma and other types of childhood cancers. 2016 will be our 6th operating year, after losing our son Ezra to neuroblastoma in 2010. By the end of 2015, we will have given over $700,000 directly to patient-affecting childhood cancer research.
These past 5 years, we’ve been working closely with the NMTRC, an international consortium of 25 hospitals (and growing) conducting clinical trials and research with a shared goal to ours — beating neuroblastoma and other childhood cancers. Much of the NMTRC’s work, in partnership with Dell and TGen, has been in leading genomics research in childhood cancer. (Full disclosure: this author sits on the Executive Board for the NMTRC, and Because of Ezra supports various NMTRC trials financially.)
Some background on genomics: the human genome was first completely mapped in 2003. It took 10 years, and $1 billion. Today, in 2015, TGen can process a patient’s genome in 6 hours. The cost is in the thousands. The sharply dropping costs and speed of genomics have opened a new world of research. There is much work to be done still — we could map the genome in 2003, and now can do so quickly and cost effectively, but what do we do with that data? That is what is being researched worldwide now — across many malady types.
Genomics in cancer is exciting. Cancer kills because a group of cells are mutated, and keep duplicating without stopping. Your body is supposed to maintain a state of equilibrium (called homeostasis) as you go about your life. Cancer cells ignore this, and keep duplicating. The mutations that make cancer cells keep going are what cancer genomics look at. And the goal is to then treat with a drug targeted to that specific mutation — knocking out the tumor with a precise medicine, rather than a blanket chemo hoping to destroy the tumor.
While sequencing can be done at most hospitals today, it is important to understand what depth of sequencing is done for each child, and how this information is being interpreted. The NMTRC’s molecular tumor board has developed significant expertise over the last 5 years in the analysis of the genomic sequencing, to make the most informed clinical decisions for children. This is truly the key to best personalized care, taking into account the previous medical treatments, the current condition of the patient and wishes of the family.
The NMTRC, chaired by Dr Giselle Sholler, first started clinically looking at genomics in childhood cancer with a trial opened in 2010. They’d noticed in treating children with neuroblastoma since 2005, kids all had very different tumor profiles. With genomics starting to be clinically relevant, a trial idea was formed.
Dr Giselle Sholler, Chair of the NMTRC, and one of her patients. Photo credit: Spectrum Health.
The pilot trial (NCT01109238, completed), opened in April 2010, enrolling 5 children to test if it was possible to support “real-time” (quick enough to treat with) treatment decisions through mRNA expression data genome-wide in neuroblastoma biopsies. At the end of that trial, the process was able to be completed in 12 days. This was the first genomic-based personalized medicine childhood cancer trial in neuroblastoma. (Results published here). It’s important to note, the most accurate and deepest data for determining best treatments comes when using both RNA and DNA expression and sequencing. However, in 2010 the tech wasn’t yet able to support doing all of that quickly enough to get “real-time” data for making treatment decisions. But RNA expression could be done quick enough, so it was time for a new trial, one actually treating kids.
The following year, in 2011, a Phase I trial (NMTRC 001, NCT01355679, completed) opened with a larger enrollment of 14 children fighting neuroblastoma, to test the feasibility and safety of actually treating kids with these individualized therapies. (Results published here). Now, the NMTRC was treating children using the data generated by their RNA expression profiles (what the first trial tested if was possible). In addition, as research, DNA mutation panels were done (these look at 50 common DNA mutations for cancer) to see if they’d be feasible / useful to add to the data gathered.
A significant partnership with Dell (along with an initial commitment of $4m, which has continued to grow over the years), brought Dell’s cloud supercomputing power to help analyze the data.
In May of 2012, we had written a blog update about the rapidly increasing speed and relevance of using genomics in realtime treatment, after discussions at the 2012 NMTRC Symposium:
This year focused heavily on personalized medicine trials, or targeted treatments. To explain, a little history — chemotherapy, which was only discovered in 1942, is the main treatment for cancer. Chemotherapy is poison — in fact, the first chemo was mustard gas, which was injected into patients after folks during World War 1 noticed it suppressed blood production. Because cancer grows faster than normal cells, the chemo kills cancer faster than it kills the body (is the hope), and then the body recovers (is the hope). You know all those pictures you see of bald, skinny, hollow eyed cancer patients? That’s not cancer doing that — it’s chemo. Of course, it’s the best we’ve had until now.
Since mapping the human genome, we can now attempt to target therapy. The NMTRC’s work is focusing on (among other things — and this is a high level overview) taking a biopsy of a tumor, identifying it’s mutations, and treating with a chemotherapy [sic — this could be various drugs] which will target ONLY these mutations — making the treatment go from systemic (poisoning the entire body) to targeted (poisoning only the tumors). It’s showing a lot of promise.
There’s a LOT of information, and up until recently it could take 17 days from biopsy to a list of targeted drugs (these are FDA approved drugs). Dell has stepped up this year to a long-term commitment to the NMTRC’s work with millions of dollars of hardware and systems analyzing. This has already cut over 2/3 of the processing time down — from 17 days to roughly 5 days.
Building on the past three years of research and continuing at, for the clinical research world, a rapid pace, a third personalized medicine trial by the NMTRC (NMTRC 008, NCT01802567, ongoing, but not recruiting participants) was opened, accruing 48 kids. The partnership with Dell suggested the hope to complete an RNA expression profile, a DNA Mutation Panel, genomic analysis and report generation, a tumor board held with treatment decision, and treatment review completed and start of treatment — all within 21 days of a child’s biopsy/surgical resection date. It worked.
Between 2013 and 2014, Dell continued to increase technology and speed, and where sequencing an entire DNA exome (important because it tests allyour DNA mutations, not just a common set) used to take 2 months (not fast enough to be used while treating children, or “clinically relevant”), it could now be completed in 2 weeks. Additionally, TGen became the first CLIA certified lab to have RNA sequencing available, in September of 2014. CLIA certification is needed to use RNA sequencing for treatment decisions. These major advances led the NMTRC to open a new trial.
In 2014, a 4th trial was opened (NMTRC 009, NCT02162732, currently recruiting participants). 48 children with cancer would be the goal to test again, now with full DNA exomes being completed, as well as RNA sequencing (remember, sequencing is a much deeper look than expression profile). This study would determine feasibility of using tumor samples to assess genomic sequencing using predictive modeling to make real-time treatment decisions for children with relapsed/refractory cancers. The entire DNA exome was now being sequenced (more powerful than a DNA mutation panel alone), RNA was sequenced, and the data was analyzed and a treatment decision made.
Watch this video to see how TGen and Dell are collaborating with Dr Sholler and the NMTRC to beat kids’ cancer.
A new paradigm in treating children with neuroblastoma.
In 2012, the ASCO Post wrote:
Although Dr. Sholler’s trials are the first attempt in personalized medicine for children with relapsed disease, if successful, genomic-based medicine for pediatric patients with cancer may eventually be used in the front-line setting, where the greatest chance for cure may be possible.
Today, that goal is being realized. Just 5 years after the NMTRC began clinical trials to research moleculary guided therapy in childhood cancer, in September of 2015 a new trial opened incorporating MGT into upfront therapy (PEDS-PLAN, NCT02559778, currently recruiting participants). This trial represents a new paradigm in treating children with neuroblastoma, based on and uniting the work the NMTRC has done with personalized medicine and a drug called DFMO, which hopes to stop neuroblastoma relapse. The trial, called Pediatric Precision Laboratory Advanced Neuroblastoma Therapy (PEDS-PLAN), suggests using molecularly guided therapy in combination with current standard therapy (COG protocol), followed by maintenance therapy with DFMO in subjects with newly diagnosed high risk neuroblastoma.
This is the first time DNA and RNA sequencing are being done in newly diagnosed patients.
A targeted agent (drug) is added to standard of care therapy. Because it is known from experience the expression profiles of tumors change throughout a child’s treatment, they do the RNA and DNA sequencing again after the 4th cycle of chemotherapy, when the tumor is removed. Using precision medicine in this way, in upfront therapy, truly gives the greatest chance for a cure. It’s expensive — full exome sequencing currently costs around $12,000, and RNA sequencing around $7,200. Dell has graciously committed to covering these costs during this trial.
Genomics is an exciting weapon in battling disease, and precision medicine has an army of advocates moving it forward. Not the least of these is thePrecision Medicine Initiative launched in January of 2015 by President Obama. The Precision Medicine Initiative’s mission is to enable a new era of medicine through research, technology, and policies that empower patients, researchers, and providers to work together toward development of individualized treatments.
Others are also carrying this work forward, even in childhood cancer. St. Jude and Washington University have launched the Pediatric Cancer Genome Project. Columbia University Medical Center is now sequencingevery pediatric cancer patient’s tumor. As the NMTRC marks five years into childhood cancer genomics research, more continue to join the battle.
A new trial, the NEPENTHE trial (Next-generation PersonalizedNeuroblastoma Therapy) is slated to begin in 2016. However, this trial is using only a DNA mutation panel for the results, not full exome sequencing. Their RNA sequencing is not being done in a CLIA certified lab, and therefore won’t be used to make treatment decision — critical in pediatrics, given the low mutation rate. Scientifically, this study will answer the target question for those drugs, but a concern will be how well these single or double agent treatments without chemo will affect relapsed neuroblastoma.
Collaboration is crucial to moving work like this forward. The NMTRC now has trials operating in over 25 institutions across the US and internationally. Partners like TGen in Phoenix and Dell in Austin add to the passion and expertise being directed to beating childhood cancer with genomics.
Precision medicine generates vast amounts of data. Converting that data into actionable (and effective) clinical outcomes is a very nuanced and learned approach. The physicians and scientists in the NMTRC continue to learn how best to make use of these new approaches, having worked through the process over 80 times now (data, rules, tumor boards to determine best treatment options).
Mature rules have been developed to determine what pathways and drugs are clinically relevant in neuroblastoma. Technical partners are refining analytics and sequencing processes, and speed keeps increasing. Advances in mobile and cloud computing will continue to offer more relevant and available data, and easier ways to digest it for use in the clinic (treating kids). The next five years are just as exciting as what’s happened already.
I wish Ezra could have been diagnosed today instead of in 2009. And of course I don’t mean that — if we’re granting wishes I’d wish he never experienced a single minute knowing what cancer feels like. I can’t help but feel proud, and energized, seeing the huge leaps in treatment and research in the 6 years since Ezra was diagnosed with stage 4 neuroblastoma. Robyn and I know in some small way, Ezra’s name will one day be one of so many whose stories led to a cure. With incredible and caring physicians and resaerchers like those in the NMTRC, and other passionate advocates like ourselves (hi BeatNB!), we will beat neuroblastoma.
If you’d like to be a part of this work being done to cure childhood cancer, we welcome your involvement. If you are a parent seeking information on any of these clinical trials (or anyone else with a comment), you can reach us atbecauseofezra.org/contact. You can support financially atbecauseofezra.org/give. Because of Ezra, Inc is a 501(c)(3) tax-exempt organization with the Internal Revenue Service. Our EIN is 27–4013571.
↑ Ezra. For more of his story, read becauseofezra.org/why.
Brighthouse Networks Enterprise Solutions and Because of Ezra, partnering to cure childhood cancer
Brighthouse Networks Enterprise Solutions (BHNES) chose Because of Ezra as the beneficiary for their 2nd annual Charity Classic golf tournament. We spent the day at the beautiful Saddlebrook Resort in Wesley Chapel, FL. Yesterday, Brighthouse Networks Enterprise Solutions presented Because of Ezra with a check for $90,000! This money goes straight to childhood cancer research. We are so incredibly grateful.
BHNES have been incredible supporters of Because of Ezra – yesterday’s event marked over $170,000 they’ve raised toward beating childhood cancer with us. Between BHNES and their incredible patrons – the many sponsors of the event, we’ve been humbled at the support. BHNES have connected with the research we are doing with the NMTRC, and our cause in a deep way, and know our story and mission well. It is an honor to be partnered with a group who delves into our workings and sees the promise this research is showing.
Over 100 golfers came and the feedback was the same as last year – many golfers said this was one of the best tournaments they’ve ever been to. Sherrin Smyers of Eventrics did a brilliant job of event planning. We owe huge thanks to Craig Cowden, Brian Zelenka, and the entire team at Brighthouse Networks Enterprise Solutions. These are caring professionals.
As I’m writing this, I’m in a conference room with a dozen doctors, parent advocates, and medical professionals discussing one of the most promising trials we’re helping to fund. The results are groundbreaking, and this room is full of people who are truly bringing hope to families who are fighting neuroblastoma today, and those who will tomorrow.
Brighthouse Networks Enterprise Solutions, and all our supporters, are making this possible. We can’t say enough how deeply thankful we are. It takes all of us. Thank you.
We were honored to receive a $17,710.75 check from West Pharmaceuticals last week as the result of their West Without Borders campaign for the Clearwater location in 2015. I regret we didn’t get a photo of the rest of the room above – over 130 employees for months raised funds and awareness, coming together to greatly support or mission of finding and funding a cure for neuroblastoma and other childhood cancers. Amazing!
Earlier this year, we spoke to the team at West, sharing stories of the children being affected by the research Because of Ezra is helping to fund, and sharing our own story. Seeing so many caring and compassionate people was wonderful – the West team takes their commitment to heart. Thanks to Debbie and Holly for making our visits great (and for showing Charley around!).
West Pharmaceuticals over the past 10 years has raised over $2.5m dollars for a variety of charities located around the globe through West without Borders and other campaigns. Because of Ezra is grateful to the West team (especially our sister-in-law, Nicole Matthews, pictured above!) for their effort and support.
On Tuesday we watched a scientist tear up at a dinner party.
Around twenty years ago, Dr Andre Bachmann started working with a drug called DFMO in Hawaii. In the early 2000s, he recognized the fact DFMO inhibited something called ODC could make it a good drug to treat neuroblastoma, and started working on that, in a lab.
In 2008, at a conference in San Diego, the father of a boy with neuroblastoma introduced Dr Bachmann to Dr Giselle Sholler of the NMTRC, who was doing some promising work in clinical neuroblastoma research. Less than two years later, in 2010, the first clinical trial of DFMO opened. In 2012 a Phase II opened.
Because of Ezra is helping to fund this trial, and although results cannot be shared of ongoing clinical trials, they are encouraging. Neuroblastoma has such a high rate of relapse, remission is termed “no evidence of disease” because its thought we just can’t detect residual disease. These DFMO trials are hoping to stop relapse.
For Lily-Mae (in the picture with her mom Jude), who is 15 months cancer free now, there is incredible hope. At dinner in Grand Rapids, Michigan on Tuesday, for the first time, Dr Bachmann watched a patient (Lily-Mae) take a DFMO pill, with a sip of water. That simple sip, 20 years in the making, may be helping children to beat neuroblastoma cancer. The hope is, this pill is stopping Lily-Mae’s cancer from coming back.
This is what we’re doing. #thismatters
This past Tuesday was the first ever Charity Classic by Bright House Networks Enterprise Solutions (BHNES), benefitting Because of Ezra – to the tune of $86,000+. It was a beautiful day at Saddlebrook Resort north of Tampa (check out more photos on the Because of Ezra Facebook page), with a dozen companies sponsoring including BHNES and Platinum Sponsor Cisco. The teams played 18 holes, wrapping up just as the sun was going down, then enjoyed a great reception.
We continue to be amazed at the community around us, and are honored and humbled to partner with Bright House Networks Enterprise Solutions. Their leadership, including Chief Network Office and SVP Craig Cowden, were warm and caring throughout the planning process and the event itself. You could tell this was a personal connection for them – a refreshing realization and one we’re grateful for! From our first phone call with BHNES, we knew they were connected to our mission of curing childhood cancer. Because of Ezra is proud to work toward a cure with BHNES.
Golfers from across the country flew in to participate, and we heard feedback from many of them it was one of the best tournaments they’d been to. BHNES puts on a classy event (big thanks to Brian and Sherrin as well for their long hours and expertise!), from the t-shirts and golf jackets to the Callaway golf bag prizes to the shish-ka-bob stations between holes.
We’re grateful to all the sponsoring companies for their support, and of course to BHNES as well. We left with many more people having heard of Because of Ezra, and over $86,000 which will directly affect children going through cancer treatment today.
From all of us at Because of Ezra, and kids like Lily-Mae,
We received this email the other day, and were moved to tears (good ones!) by it. Thanks, Meshelle, for letting Ezra’s story be a part of yours. It means so much.
“Honestly, I can’t remember how I heard about Ezra’s story, but I can tell you exactly where I was… that is forever engraved into my consciousness. I was at home and about five weeks into my maternity leave after delivering my second child. There was a rare moment of silence where both, our oldest 18 month old and our newest member, were both napping away. I remember opening the website and seeing a blog simply titled ‘Relapse.’ It was August 30, 2010. I often describe that day as the day that Pandora’s box was opened, learning things that I could never forget and finding a depth of sadness that I didn’t know existed. It was the day where I was overcome by a tornado of opposing feelings, one side knew the extreme peace and happiness that comes with bringing a new child into this world, and the other side was overcome with sadness and anger that there was something dangerous that was silently stealing children from their families. I have two children, how did I not know about the world of childhood cancer? I spent all day catching up on Ezra’s story. I allowed your words to pierce the perfect little bubble that I lived in, and I allowed myself to feel sadness for you… soon enough that sadness turned into anger and outrage. It just didn’t make sense to me how so many kids were affected by cancer and how so few people seemed to know about it.
By the time the November 8th blog post ‘Ezra David Matthews‘ was uploaded I had already returned to work. I sat at my desk and cried for you, for the loss of Ezra, and for the fact that the light of the world was diminished a bit more. My first thoughts were more of a series of questions, each one of them beginning with why; why them? (I didn’t know you at all but you all came across as the most loving people on the planet… and it wasn’t like you hadn’t been through enough.), why Ezra?, why not one of my kids? That last question stopped me cold as the stark realization that it could be one of my children washed over me. There is no rhyme or reason to this. It was not enough for me to be angry, to say this sucks and move on with my life… I had to do something. I had a degree already, but it was in Philosophy, and I’m pretty sure that a cure for neuroblastoma couldn’t be found in Aristotle… so I went back to school. I took an extremely rigorous course load that well prepared me to take the MCAT, which I did and now I’m working on changing the world. Medical School isn’t easy, but I can guarantee it’s a cakewalk compared to fighting cancer. My course of study has led me down the clinical research path.
‘Please, be changed because of this. Recognize the flawed world we live in, and work to help the ones you can. Really work. Recognize the hurt in the world, and recognize the grace that gives us a chance to still be beautiful.’
I was changed because of Ezra. It’s hard not to be changed by something of this magnitude. I get up and go to school because I can. My kids are happy and healthy and my husband is extremely supportive. I am alive, and because of that, because of Ezra, I will work my hardest to make a change in the world of pediatric cancer.
P.S. The picture I sent is of me and my youngest Laila… she was the one I was on maternity leave with when I first read your story.”
Sometimes we get communication from people which is so powerful we just have to share it. A woman named Stephanie sent us the picture above, of her stethoscope for nursing school. It has Because of Ezra engraved on it, as well as a cross and her initials. Stephanie said this in her message to us:
I received my stethoscope in the mail today! I wanted to make sure the engraving was something that meant something important to me. I engraved Because of Ezra on it along with a cross and my initials. This organization pushed me even more to pursue my dream of nursing – specifically in pediatric oncology where I hope to end up in the future. Now everyday I go to nursing school, I will always see the reminder of exactly what I’m working for and the little boy that changed my life and made me who I am! #EzraMatthews #800days #weLOVEweHOPEweFIGHT
Stephanie – we are so proud to know Ezra’s story touched you enough to move you to this career in nursing with an emphasis on pediatric oncology. It’s beautiful to see Ezra’s story (and so many of the other kids fighting neuroblastoma) affecting lives and change like this.
Thank you – you’re making a difference.
Tampa runners, joggers, lovers of the pavement, and haters of cancer – come run the Gasparilla Distance Classic with us!
EVERYONE can do this – runs range from a 5K jog, strollers jog, or run… all the way up to a half marathon. We’re doing it a little different this year – check the link below to create your own fundraising page (it’s super easy – just press the big green “Become a Fundraiser” button)!
All funds raised benefit Because of Ezra to support our mission of funding relevant research into a cure for neuroblastoma, the most common form of pediatric cancer. $50 or more raised gets you one of our awesome t-shirts – $750 or more raised gets you a pair of custom Nike running shoes in BoE colors!
Come on out and run with us – we’d love to see the most runners ever this year! If you can’t make it, please share the event so your runner / walker / stroller friends can come out. If you can’t make it, you can also donate toward someone running by pressing the Donate button below.
Sign up at http://stayclassy.org/gasparilla.