A conversation with Nicholas Foreman, MD

Nicholas Foreman, MDNicholas Foreman, MD, is director of pediatric neuro-oncology at Children’s Hospital Colorado and one of only 35 pediatric neuro-oncologists in the United States. He holds the $2 million Seebaum/Tschetter Chair in Pediatric Neuro-oncology and is co-chair of the national Children’s Oncology Group/Pediatric Oncology Group Ependymoma Subcommittee, which is working to develop new national protocols for studying the biological underpinnings of childhood brain tumors.

C3: What is the primary focus of your research?

Foreman: Along with Rajeev Vibhakar, I run a lab working to develop new therapies for resistant brain tumors in children. We’ll often do small trials internally ourselves; then those are taken to the Pediatric Oncology Experimental Trials Consortium, which comprises eight institutions. We’re looking at the role of micro-RNAs [ribonucleic acid] in brain tumor activity. Micro-RNAs are recently discovered small molecules that regulate activity within the cell.

C3: Are there major differences between the brain tumors in children and those in adults?

Foreman: In adults, brain tumors are most often spread from somewhere else in the body, whereas in children the tumor is primary in the brain. There are types of tumors in children that are incredibly rare in adults and conversely, adult tumors that are rare in children. As we and others have shown, in pediatric brain tumors there are genes that are “turned on” that should have been shut off in the womb or shortly after birth. These genes drive the tumor growth. If we can reduce the tumor burden, often the child’s innate control of growth can aid in cure. This is not an advantage that adults have.

C3: Why aren’t there more pediatric neuro-oncologists in practice?

Foreman: It’s partly becasue pediatric brain tumors are relatively rare, affecting only three in 100,000 children per year. It’s also difficult to recruit people because few doctors are trained in both neurology and oncology. The problem is getting people who are not trained in both disciplines to be comfortable working in management of both. We’re one of a limited number of centers that offer a final-year fellowship in neuro-oncology.

Another challenge is the treatment. If you cure a child with leukemia, the child is cured. In neuro-oncology, you can cure the disease, but the treatment can cause hurt. Many changes in therapies are as much directed at reducing the hurt as they are in actually increasing survival.

C3: What changes in therapies are helping to mitigate the hurt that accompanies the cure?

Foreman: Jenny Madden in our group is leading a study to reduce radiation doses to those with medulloblastoma and Meg Macy, also in our group, is leading an exciting new effort to reduce radiation injury when it occurs.

C3: So not all brain tumors in children are terminal?

Foreman: Right. The cure rate has actually come up quite a bit. We actually cure about two-thirds of the children we see at the Cancer Center, which is actually a doubling of the survival over the 25 years I’ve been doing this. The cure rates in children are significantly higher than in adults.

C3: What is a current challenge in your field?

Foreman: I’m trying to persuade the FDA to reverse its standard for biopsying a tumor of the brain stem called diffuse pontine glioma, which is 100 percent fatal. The current standard is not to biopsy the tumor, which makes up 10 percent of childhood brain tumors. There have been hundreds of Phase I trials where we literally have to guess what therapy might be effective because we have no information about the biology of the tumor. However, all of these trials have failed. We can only really make progress with actual biological knowledge. Our laboratory has helped develop new techniques so we can obtain a large amount of biological information on very small biopsies. In conjunction with Dr. Michael Handler in neurosurgery, we’re attempting to have the American Society of Neurosurgery join us in reversing this standard.

C3: What does a $2 million endowed chair enable you to do?

Foreman: Thanks to a group of concerned families affected by the disease, I can explore new therapies without having to secure funding. We’ve explored new therapies in four children with radiation injury and showed that a new therapy could reverse the damage.