By Shana R. Spindler, PhD
If you asked a doctor 50 years ago what the average prognosis was for a child with cancer, the answer would have been a grim 30 percent chance at a five-year survival. That is not so today. Thanks to the ingenuity of researchers and doctors, the average survival rate from childhood cancer has skyrocketed to more than 80 percent. But along with this success come potential complications later in life for these patients. Today, nearly one in every 640 adults between the ages of 20 and 39 years received cancer treatment at a young age. On April 17, 2013, experts gathered in an NICHD Exchange meeting to discuss how to best care for this growing population of survivors.
The Childhood Cancer Survivor Study, an extensive follow-up of over 14,000 childhood cancer patients and 4,000 of their siblings, has enabled doctors to identify common themes in the aftermath of cancer treatment. Dr. Maya Lodish, deputy program director for the NIH fellowship program in pediatric endocrinology, kicked off the discussion with a presentation of some of the most prevalent late effects after cancer treatment. Among the long-term problems are endocrine complications, metabolic syndromes, cardiovascular disease, diabetes, and secondary cancers. Many of these conditions are dependent upon the type and intensity of treatment given.
But perhaps what resonated most throughout Dr. Lodish’s talk was that researchers are clearly shifting a portion of attention to making post-treatment life as normal as possible. With better prognosis rates, parents are now asking quality-of-life questions, like “Can my child participate in sports?” or “Will my child be a normal height?” Understanding how different treatment options can increase or decrease risk for chronic conditions later in life can influence therapy choices.
One particular concern, reproductive health, is at the heart of the NICHD mission. Now that people with childhood cancer are living well beyond childhood, into and past puberty, the question of fertility is an important one. Just like many other health conditions after cancer treatment, the effect on fertility is dependent upon a list of factors, including age, gender, disease, treatment type, administrative method, and treatment duration.
While advances have been made for egg, embryo, or sperm preservation, young children who have not yet reached puberty still have few options. Current efforts are examining reproductive tissue preservation for post-treatment grafts back into the patient, but researchers are debating the risk of tissue contamination with cancer cells as well as ethical concerns associated with embryo and tissue preservation. The fact that doctors are even grappling with these issues is “a milestone,” said Dr. Charisee Lamar, program director of Reproductive Neuroendocrinology and Fertility Preservation Programs as well as meeting presenter on post-treatment fertility issues.
The better we understand the underlying cell biology in pathological conditions, the better researchers and doctors can predict these late effects for each individual. In the third talk of the Exchange meeting, Dr. Lorette C. Javois, health scientist administrator of the NICHD Developmental Biology and Structural Variation Branch, argued that information gleaned from studying the co-occurrence of birth defects and pediatric cancer will benefit the pediatric cancer community. Several lines of evidence, from clinical observations to registry linkage to case-controlled studies, show that some birth defects and pediatric cancers share common etiologies. For example, children who carry a chromosomal defect are ten times more likely to have acute lymphoblastic or myeloid leukemia.
Dr. Javois boils it down to the “embryonic toolkit,” a set of four signal transduction pathways that, in one way or another, control most of embryonic development. Cell movement and morphogenesis—a simplified view of development—are two activities tightly tied to cancer. Developmental biologists and oncologists have indeed found themselves studying the same genes, which begs the question: can cancer treatments aid in the minimization of birth defect progression and vice versa?
Dr. Constantine Stratakis, scientific director of the NICHD Division of Intramural Research, is one to argue that a genetic component of pediatric cancer is prominent. Dr. Stratakis wrapped up the meeting with a review of case report examples showing that pediatric cancer, specifically associated with Cushing syndrome, is rooted in genetic disease. Sometimes the genetic component is not obvious and requires digging deep in family trees to identify affected relatives, or determining if improperly spliced proteins localize to the wrong compartment of cells. His lab has now identified several genes associated with Cushing syndrome, and he will likely identify more in the years to come.
The long-term remission for many pediatric cancers is not quite at 100 percent, but it’s getting close. The chronic conditions from treatment are being identified and studied, but we still have a long way to go. NICHD fellows have the unique opportunity to think about these problems while examining the very basic biology of the cell. Perhaps recent advancements in cancer biology can shed light on questions in embryonic and fetal development. Or maybe a mutation in one of the genes involved in making the Zebrafish lateral line is a contributing culprit in a childhood cancer. At the NICHD and around the world, these conversations are ongoing. As one attendee put it: “This is a very exciting period of time that we’re living in.”