Doctors stake careers on stopping a deadly tumor that has stumped science for
by Mary Silva
Dr. Maryam Fouladi heads the Brain Tumor Program. Although they can cure many brain tumors, the team is particularly focused on high-grade gliomas and diffuse intrinsic pontine gliomas, for which there are currently no cures.
Among the list of unwelcome, invasive, aberrant growths that can take up residence in a child’s brain, a few rise to the top for their ability to do harm.
Doctors call them “high-grade” tumors, so named because in the numbering scheme assigned to such growths, 1 or 2 means a tumor is treatable and chances of survival, quite good. One labeled 3 or 4 is high-grade, with a far poorer prognosis.
Maryam Fouladi, MD, came to Cincinnati Children’s in 2008 to lead the Brain Tumor Program in our Cancer and Blood Diseases Institute. The program cares for and cures many children with brain tumors. Fouladi and her team are especially interested, however, in the tumors labeled 3 and 4.
“My objective in coming here was to develop treatments for the worst and highest-risk brain tumors — high-grade gliomas and diffuse intrinsic pontine glioma, both of which have a terrible prognosis,” Fouladi says.
Terrible seems an understatement. These gliomas arise in the brain stem, the part of the brain that controls life-giving functions like breathing and circulation. Because of where they grow, they cannot be removed. And they grow rapidly. Nearly all patients with diffuse intrinsic pontine glioma (DIPG) die within two years of diagnosis.
MANY PEOPLE, A SINGLE PURPOSE
Working to save the children whose lives these tumors destroy is a team of more than 40 people - basic and translational scientists, neurosurgeons, neuroradiologists, pathologists, neuro-oncologists, nurses, social workers – the list goes on.
“We have a comprehensive program with every subspecialty you could imagine for a child with a brain tumor,” Fouladi says. “In one sentence, our mission statement is to cure DIPGs in 10 years. And in the meantime, to increase survival and decrease toxicities for these kids with the poorest prognosis.”
Brain stem tumors are what drew Fouladi to becoming a neuro-oncologist. She remembers as a pediatric resident hearing her mentor tell a family that their child with a DIPG was going to die no matter what the doctors did.
“I was shocked,” she recalls. “It was 1993, and I couldn’t believe that was all we could do. It became my goal to be part of a generation that helps find a cure.”
Yet despite steady effort, science has remained largely confounded by the tumors. “We have made no strides in literally 40 years,” Fouladi says.
Recently, however, there has been progress in understanding the biology of brain stem tumors, fueled largely by families who have lost children to the disease.
FAMILIES STEP FORWARD
As with most rare pediatric diseases, public research funding for study of these tumors has been difficult to come by. So organizations begun by families of DIPG patients, such as The Cure Starts Now Foundation and the DIPG Collaborative, have stepped up.
“We are enormously lucky that the DIPG Collaborative and the Cure Starts Now have funded our work to the tune of $600,000 in the past 21/2 years,” Fouladi says, “and have pledged their continuing support.”
That funding helped create an international DIPG registry, a database of information about DIPG patients. Participants include an international who’s who of experts in DIPG who share data, imaging, pathology, and research findings. The resulting wealth of information is opening new windows of discovery.
“In the two years since the registry was created, we have enrolled 400 patients, with 900 more committed to enroll, from over 30 institutions in the U.S., Canada and Australia,” says Fouladi, who leads the effort. “And we are now working to link with a European registry.”
Dr. Mariko DeWire developed a brain donation program for patients who die from high-grade brain tumors. Tissue from those donations has helped researchers take giant steps in understanding and treating the tumors.
A GAME-CHANGING PROGRAM
The registry will connect to another remarkable resource developed by Mariko DeWire, MD, who joined Cincinnati Children’s just over two years ago. The program collects donated brain and tumor tissue from children who die from DIPG and other high-grade brain tumors.
Called simply “the autopsy study,” it is modeled on a program DeWire was involved with during her fellowship at St. Jude’s Hospital. In the Cincinnati Children’s program, the brain is removed within 24 hours of death and goes directly to the laboratory, where it is imaged for extent of invasiveness. The tumor tissue is removed, sequenced for genomic analysis and used to grow additional tumor cells for research.
FIGHTING BACK – AND GIVING BACK
The push for the study came primarily from parents, who see it as a way to fight back against a disease that shows no mercy. Although most children stricken with DIPG are between the ages of 5 and 7, DeWire also has teenage and young adult patients who ask to donate their brains. “They want to see some good come from their situation,” she says. “Doing this is their way of helping those who come after them.”
Some parents stay in touch with the project even after their child dies. “They have told me they feel as though their child is still living, and it gives them great comfort,” says DeWire.
In just over a year, our doctors have performed 18 autopsies, and already the program is proving its scientific value. Information from the autopsies is helping our scientists make giant steps forward in understanding the tumors and identifying potential treatments.
THE POWER OF MANY
Moving from potential treatments to actual remedies is a process riddled with regulatory obstacles. Fouladi works to ease the process as Chair of the Pediatric Brain Tumor Consortium, an NIH-funded group of 11 of the country’s top brain tumor programs. Members use their scientific clout to get promising treatments into clinical trials as quickly as possible. In April 2014, the group received a five-year renewal grant of $13 million, funding they will put toward their research activities.
Fouladi is heartened by what scientists here and elsewhere have learned in just the few years since tumor donation programs and the DIPG registry began.
“Our researchers are developing a comprehensive understanding of the biology of these tumors, and are translating what they find into the clinic.
“We have learned that these tumors are different from adult tumors. They have changes that could be targeted by some of the drugs we are developing now,” she says. “For the first time in 40 years, we are focusing on real possibilities for treating these children.”
‘A Joy and a Privilege’
Social workers (from left) Mandy Bley, Bridget Kikta, and Maureen Donnelly work with children in the Brain Tumor Program, and their families.
The social work team in the Brain Tumor Program finds they are the students; their families, the teachers
Beyond the researchers looking for answers and the physicians and nurses who provide expert care, the Brain Tumor Program includes dozens of clinical support staff. They include child life specialists, psychologists, school intervention specialists, and social workers.
They are part of the Patient and Family Wellness Center within the Cancer and Blood Diseases Institute. From the moment a child is diagnosed, these individuals play an integral part in the patient’s and family’s experience.
Social workers Mandy Bley, LISW-S, Bridget Kikta, LSW, and Maureen Donnelly, LISW-S, work specifically with families in the Brain Tumor Program. “Our relationship with the child and the family is key. We see them every time they come to clinic,” Bley says. “It’s an opportunity to validate the experiences they are having in their journey.”
That journey is life-changing, says Kikta, even when a child’s tumor can be treated or cured.
“Life is different in many ways for these families,” she says, “Children often suffer deficits, and that comes with a new set of challenges.”
The team walks a fine line between acknowledging the experience of cancer and helping children live as normally as possible.
Bley paraphrases a line from the book, The Fault in our Stars. “These kids are not their disease. They are bigger than that. There is a joy and privilege in getting to know who they are, what’s important to them, and how they interact with the world.”
Because of this, the social workers say, children of every age want to find meaning in their experience. A young adult or teenager might choose to donate their brain for research, write a poetry book or become a champion for research. Younger children, says Bley, “Have their own way to make their mark. They might have a lemonade stand to raise money or create a picture book about their experience.” The Program has developed special outings and groups for families to meet and share their experiences.
“Often, the families stay in touch after a child passes away,” Donnelly says. “They want to hear about the research being done that is going to further knowledge and lead to a cure – they find that comforting. Families who have donated their child’s brain for research often share their decision publicly, to encourage other families.”
When asked about the value of their work, the team’s response is unanimous.
“This job has shown me how much good is in the world,” says Kikta. “In the face of the most horrible things, there are families who will walk through fire for their children. There are foundations started by people who have lost someone they care deeply about, and they choose to pay it forward by contributing to research.”
Adds Bley, “I am forever inspired how in hard moments, families find a way to take the next step and keep going. To be able to witness that is a privilege.”
Lauren Hill, photographed with her physician, Dr. Mariko DeWire. Lauren fulfilled her dream of playing as a freshman in Mount St. Joseph University’s season opener basketball game in Cincinnati on November 2, 2014. She had been diagnosed with a fatal diffuse intrinsic pontine glioma (DIPG) brain tumor one year earlier.
What follows are excerpts from a paper written by Lauren Hill for an English class in her senior year of high school, April 2014. Lauren was diagnosed with the fatal DIPG tumor in November 2013. Throughout the course of her cancer, she has been an outspoken proponent of research funding for childhood cancers in general, and for DIPG in particular, raising more than $1 million for DIPG research.
“Being diagnosed with DIPG is like giving someone a best-if-used-by date. Children affected with this disease are given a few months to two years at best to live, deprived the luxury of having a long and healthy life. Parents of the diagnosed are in absolute shock and devastated at the terribly short amount of time their child has been predicted to live. What makes the situation worse is that there is nothing anyone can do to stop it from happening. It is like being tied to train tracks, looking down the dark path like a deer frozen in front of the oncoming headlights, the DIPG freight train is always moving and stops for no one. This terminal pediatric brain cancer is perhaps the most baffling to researchers because virtually no progress has been made in thirty years.
DIPG research is in short supply of tumor samples because this disease is inoperable and only affects less than 200 people a year in the United States alone. Many parents are asked to donate their child’s tumor after they succumb to this terrible disease and this provides researchers the tissue samples they need to develop more knowledge and better strategies for combating DIPG. However for many children diagnosed with DIPG, these treatments will not come quick enough.
It is sad to think that drug companies are willing to shell out research money for cancer treatments that give seventy-five year olds a few more years to live but overlook the causes of those who will not even reach double digits in their lifetime.
Children are the future of the world. What happens to them is far more important than what happens to an aging elderly. The impact of DIPG has not reached enough people and the knowledge of this disease needs to be spread. Researching this disease should be of the upmost (sic) importance in the world of cancer research because if DIPG can be cured, all cancers can be cured. It is now time that the stories of tragedy turn into stories of triumph… It is time for a change in research, a change in the methods of cancer treatment, and a change in the heartbreaking prognosis of DIPG.”