First person profile: Leslie L. Robison, PhD

Still, when Dr. Bhatia says that Dr. Robison, “has written the book on childhood cancer survivorship” and points to his “tremendous vision and clarity of thought,” she is not simply speaking as a friend but reflecting a view held widely in the oncology world. Dr. Robison played key leadership roles in developing both the national Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study. Those 2 cohorts, which follow the outcomes of more than 40,000 childhood cancer survivors, have influenced general consensus guidelines for treatment and long-term follow-up care in these patients throughout their lives. Chair of the Department of Epidemiology and Cancer Control at St. Jude Children's Research Hospital in Memphis, Tennessee, and associate director of the St. Jude Comprehensive Cancer Center, he has authored more than 750 peer-reviewed publications. Among other national awards, he received the American Cancer Society's 2016 Medal of Honor, which is given to leaders who have made the most valuable contributions and impact in saving lives from cancer through basic research, clinical research, and cancer control. In 2019, the American Association for Cancer Research (AACR) awarded his team at St. Jude the AACR Team Science Award for its innovative research. According to Dr. Robison, he stumbled into the profession by happenstance. As a University of California Los Angeles undergraduate in need of a job, he took a research assistant position with the National Cancer Institute's (NCI) Children's Cancer Study Group at the University of Southern California Medical School. “I fell into this incredibly supportive network of researchers that really led to my career,” he says. It was there that Dr. Robison was first exposed to clinical trial protocols and collaborative research and ultimately decided to focus on epidemiology. He went on to receive his master's and doctoral degrees in public health and epidemiology from the University of Minnesota in 1979 and 1982, respectively. Dr. Robison credits Mark Nesbit Jr, MD, an international leader in pediatric oncology at the University of Minnesota, with training him and helping him to navigate the field. “He was an incredibly supportive mentor who not only gave me opportunities in new areas of pediatric oncology research but also made sure career-wise that I was on a very strong academic path,” he says. Dr. Robison's dissertation focused on long-term effects in pediatric patients with acute lymphoblastic leukemia who had been randomized to 4 different chemotherapy regimens. “We realized that in order to really understand the implications of being diagnosed and treated for cancer in children, we needed large numbers of survivors,” Dr. Robison says. With that in mind, he proposed the CCSS in the late 1980s while he was working as an associate professor in the Department of Pediatrics at the University of Minnesota Medical School. A multicenter collaboration, the CCSS included institutions from across the United States and Canada and received a major NCI grant to initiate the cohort, which launched in 1994. Baseline data were collected for more than 14,000 child and adolescent survivors and 4000 of their siblings, who were then followed longitudinally. Because significant advances in pediatric cancer therapy have occurred in the past 30 years, a second group of approximately 10,000 survivors diagnosed between 1987 and 1999 were later recruited along with approximately 1000 of their siblings. “It gave us incredible new insights for this population,” Dr. Robison says. The CCSS's original aim was to characterize the delayed effects of pediatric cancer treatment, which include risks of second cancers, organ dysfunction, cardiopulmonary problems, reduced growth and development, decreased fertility, and early death. Long-term effects vary according to many different factors such as the type and duration of therapy, type of cancer, family history, and genetics. The study's participants continue to complete comprehensive questionnaires about their health and other issues, and investigators are still publishing research results. Moreover, because of the initiative's success, “many other groups across the globe decided to follow the same path that Les had started,” Dr. Bhatia says, pointing to British, Nordic, Dutch, and Swiss childhood cancer survivor studies as examples. After 20 years as principal investigator of the CCSS, Dr. Robison stepped down in 2014. His St. Jude colleague Greg Armstrong, MD, MSCE, assumed the role and leads a research group that now comprises 35 member academic medical centers. However, Dr. Robison's work to better understand pediatric cancer survivors did not stop there. In another effort to clinically assess outcomes for pediatric cancer patients, he, along with his colleague Melissa Hudson, MD, had begun to build the St. Jude Lifetime Cohort Study in 2005 and launched it in 2007. For the study, every pediatric cancer patient treated at St. Jude who has survived 5 or more years is brought back to the hospital's Memphis location for 3 to 4 days of comprehensive clinical assessments throughout their life. The cohort now includes approximately 6000 patients who return for these evaluations every 3 to 4 years. More than 140 publications have resulted from the study's findings, including the first comprehensive picture of the chronic disease burden for pediatric cancer survivors, which was published in The Lancet in 2017.1 “It was the first time we described how massive the disease morbidity and burden is for this population,” he says. Among many other findings, the study indicated that by the age of 45 years, pediatric cancer survivors on average will have experienced 17 different chronic health conditions, including 3 to 4 conditions ranked as severely disabling or life-altering. Research generated by both the CCSS and the St. Jude Lifetime Cohort Study has been the basis for many of the long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers recommended by the NCI's Children's Oncology Group.2 The research also has helped investigators to understand the underlying influence of genetics on patients' long-term outcomes. Toward that end, scientists have developed the St. Jude Life Genomics Project, an effort aimed at understanding the genetic interplay between therapy exposure in children and adolescent cancer survivors and their long-term outcomes. They have completed whole genome/whole exome sequencing of more than 4500 survivors to understand not only the genetic risk of certain cancers but also the risk of adverse outcomes related to treatment, such as the development of second cancers. A study the group published in the Journal of Clinical Oncology shows the frequency and distribution of major genetic mutations and predisposition genes in this population.3 Some patients develop multiple subsequent neoplasms that are closely tied to treatment exposures such as radiation, and these may be tied to their genetic risk for both their primary and subsequent cancers according to Dr. Robison. He notes that approximately 12% of childhood cancer survivors carry a genetic mutation that is considered pathogenic or likely pathogenic. “Some survivors with exactly the same treatment exposure will have adverse outcomes while others won't, and we know there are many other issues at play such as the ability of individuals to metabolize the drugs and to repair DNA damage from some of these exposures,” Dr. Robison says. In an effort to speed progress in the field, researchers are now putting all of the treatment, outcome, and genetic data gleaned from the St. Jude Lifetime Cohort and the St. Jude Life Genomics Project onto the St. Jude Cloud. As a result, researchers from around the world will have access to the data for their own studies into how to better treat and screen both current and future pediatric cancer survivors. “It's an innovative platform with visualization and analytic tools that makes the data easily available,” Dr. Robison adds. Looking ahead, he considers the main challenge in the field to be implementation of the vast knowledge that they have accumulated. “We understand who's at risk, but we need to translate that knowledge into clinically actionable interventions,” he says. With approximately 500,000 childhood cancer survivors nationwide, that is a tall order. The vast majority will survive more than 5 years, and an overwhelming number are cured and become long-term survivors. Generally, however, they eventually stop seeing their pediatric oncologists and are cared for instead by internists and family practice physicians who know little about recommendations for screening and prevention in this high-risk population. “It's unrealistic to expect them to be experts,” Dr. Robison says. “We need to learn how to empower survivors and to improve easy access to guidelines for internal medicine physicians who are managing these patients.” Dr. Robison rarely takes his eye off his overriding mission of improving survivors' lives and admits that it leaves him little time for outside interests. “Work and family are enough for me,” he says. “I have a wife, 2 daughters, and 5 grandchildren—and when I'm not working, it's the time we spend together as a family.”

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