Dr. Giulio D'Angio, Professor of Radiation Oncology at the University of Pennsylvania and a specialist in children's cancers, received a Gold Medal Award from the American Society for Therapeutic Radiation Oncology at its annual conference in San Antonio, Texas. For nearly a half-century, Dr. D'Angio has been a central contributor to advancements in pediatric oncology, publishing nearly 400 papers in peer-reviewed journals. He was among the first to conceive of many of the terms that the medical community now takes for granted, such as multimodality treatment, adjuvant therapy, clinical trial cooperative groups, and late effects of treatment. He has performed groundbreaking research that has shaped both our understanding and treatment of cancers in children, including Wilms' tumor, leukemia, medulloblastoma, neuroblastoma, and Hodgkins disease. He also has focused attention on the importance of treating the whole child, and not just the disease. As pediatric oncology enters the next century, it must count Dr. D'Angio among those who are responsible for its success. He describes that success in this way: "There is no more encouraging chapter in the history of medicine than what has happened with pediatric oncology in this century. It's amazing that in the course of my lifetime the survival rate for leukemia has gone from 0% to 75 or 80%."
In his early work with Wilms' tumor patients, Dr. D'Angio conceived of the possibilities for using different treatments in combination. At the time, the standard treatment was surgery followed by high doses of radiation therapy -- doses that were much higher than they needed to be, as he discovered through later studies. Chemotherapy was also just coming into use, and Dr. D'Angio recognized that the drug dactinomycin used in conjunction with radiation therapy might be more effective than radiation alone. With his longtime collaborator Dr. Audrey Evans, he conducted animal studies that confirmed his thinking and led to the use of both treatments as a follow-up to surgery. That work paved the way for additional investigations into strategies for using different modalities together. In turn, this helped give rise to the interdisciplinary "team" approach to treating cancer that involves surgeons, medical oncologists and radiation oncologists, which really is the cornerstone of cancer treatment today.
Dr. D'Angio is quick to point out that such discoveries about new treatment approaches were "serendipitous" because today's controlled system of clinical trial protocols did not exist. He helped to change that by initiating the National Wilms' Tumor Study Group thirty years ago, which is still active today. The first study was designed to compare the effectiveness of the chemotherapy drugs dactinomycin and vincristine in treating Wilms' tumor. Dr. D'Angio recalls how a group of interested researchers met in the red carpet room at the United Airlines terminal in Chicago to talk about the possibility of forming a national group that would coordinate the efforts of different institutions. The group would pool their resources -- and patients, since Wilms tumor is relatively rare -- to figure out which chemotherapy drug was best, and perhaps answer other questions about the disease. Dr. D'Angio recalls some of the questions they had in mind: "Was radiation therapy always necessary? Should different stages of the disease be treated differently?" Dr. Audrey Evans and he wrote the protocol for that first intergroup study, and four more have followed since then. Overall, these studies have helped physicians to fine-tune their treatment of Wilms tumor, saving aggressive approaches for high-risk patients while scaling back toxic treatments for lower-risk patients. "It's allowed for the gradual adjustment of treatment to prognostic circumstances," says Dr. D'Angio. "It's one of the most satisfying things I've ever done." And over the course of his career, the survival rate for Wilms tumor has gone from 40% to 90%.
The National Wilms' Tumor Study is constantly held up as a model for other clinical trials. The cooperative approach initiated by Dr. D'Angio and his colleagues thirty years ago has helped to define how pediatric oncology research is conducted in this country. Physicians at different institutions have come together to form large problem-solving groups such as the Children's Cancer Group and the Pediatric Oncology Group. "Cooperative groups really bring science to the bedside," says Dr. D'Angio. "They can move more quickly and more constructively than individual researchers." The fact that this model works, he says, is a tribute to the pediatric oncologists who have made it happen. But it is also a tribute to the forward-thinking approach he took when designing the first Wilms' tumor study in 1969.
Throughout his career, Dr. D'Angio has dedicated himself to finding ways to treat cancer that will cause least harm to the child. When he started his medical career, few children with cancer lived very long. Those who did were often treated with surgery and scaled-down doses of the radiation therapy used with adult patients. No one really knew what children's specific treatment needs were, or how to minimize the long-term side effects that would persist into adulthood. "Survival was the priority," he says, and little thought was given to anything else. Guided by the conviction that "cure is not enough," Dr. D'Angio has worked diligently to tailor treatments to children's needs -- by scaling back certain treatments, eliminating what's unnecessary, and finding more effective approaches -- in order to minimize both their physical "late effects" and psychological toll.
He was among the first to understand that the radiation therapy given to adults could have devastating consequences for children, affecting their growth, mental development, and future ability to have children of their own. He formed the Late Effects Study Group, which involved the University of Pennsylvania Medical Center, M.D. Anderson Cancer Center, and institutions in France, Italy, and England, to investigate such long-term effects in an orderly, systematic way. In 1988, he published the influential paper "Cure Is Not Enough: Late Consequences Associated with Radiation Treatment" in the Journal of the Association of Pediatric Nurses. Through such work, Dr. D'Angio has shaped the approach to the young cancer patient. He has urged physicians to be aware of the potential costs of a cure, and then find ways to work around those drawbacks. To this day, he is involved in research into new treatment approaches that would minimize adverse effects on the developing child. For instance, he is investigating radiation techniques that would treat retinoblastoma and Wilms' tumor effectively without damaging the eye lens and kidney.
Dr. D'Angio's concern for children is not limited to their physical well-being, but also includes their emotional and psychological welfare. He stresses the concept of "total care," or looking out after all of the child's needs as well as their family's. As a member of the Societe d'Oncologie Pediatrique, he was recently part of a Working Committee on Psychosocial Issues that produced a paper that dealt with assistance for terminally ill children with cancer.
When asked how he charted the course of his career, Dr. D'Angio assigns credit to the mentors with whom he worked as a young medical student and doctor. He notes that Dr. William E. Ladd, Chief of Surgery at Boston Children's Hospital, taught him to recognize the delicacy of children's developing tissues. Taking care of the child meant more than having a good bedside manner; it meant treating in ways that would do as little harm as possible. Another early mentor at Boston Children's, Dr. Dick Wittenborg, was among the first to realize that radiation therapy could have permanent effects on children's bone development and growth. "He taught me to think of the adult this child was going to be," says Dr. D'Angio, "and take the good parts of treatment and try to find ways around any bad effects." He also credits pathologist Dr. Sydney Farber with shaping his awareness of the psychosocial aspects of a child's cancer within the family. In addition to discovering how chemicals could be used to induce leukemic remissions, Dr. Farber founded a free clinic for children with cancer that was designed to take care of the whole family's needs. Dr. D'Angio calls these men "seminal influences" who set the course of his career in the late 1940s and 1950s, which he looks back on as an "extraordinarily fruitful and exciting time." He remembers being part of a young, enthusiastic group working to figure out how to achieve cure with as little deformity and disability as possible.
While he says that he feels honored to receive the Gold Medal Award, Dr. D'Angio points out that his "real gold medals" are the young people with whom he works -- not only patients, but also young investigators and doctors. And while he may not realize it, those young physicians look at him with the same awe and respect that he accords his own mentors.