In Memoriam: Giulio D'Angio, MD, May 2, 1922-September 14, 2018

Abstract

On the 14th of September 2018, we lost a colleague, mentor, teacher, and friend, Giulio D'Angio, the father of pediatric radiation oncology and 1999 American Society for Radiation Oncology Gold Medal recipient. He died peacefully at home surrounded by his family. Dr D'Angio's impact on and influence in the fields of pediatric oncology and pediatric radiation oncology were unmatched. During his long and fruitful life, Dan achieved much, encouraged many, and passed his knowledge and wisdom to countless students, residents, and colleagues. This is in addition to the countless patients who have benefited from his knowledge. Born on May 2, 1922, Dan was a true giant in several medical specialties: diagnostic radiology, radiation oncology, pediatric oncology, and cancer survivorship. The second son of Italian immigrants, Dan was raised in Brooklyn, New York, and earned an undergraduate degree at Columbia University. He applied for admission to Harvard Medical School (HMS) during the era of widespread anti-Semitic and anti-Italian Roman Catholic restrictive admissions quotas. After an interview with Harvard's director of medical school admissions, Dr Worth Hale, where he was advised that there were restrictions on admitting “too many students whose names end in vowels” he was admitted to HMS, where, as he said, he was “the only Italian-American in his class.” His training was interrupted by World War II; he served in the Pacific theatre and had a brief stint in Florence to study the classics before returning to Boston. He was trained by world-renowned surgeons, radiologists, and other physicians and then joined the nascent efforts at Boston Children's Hospital with Sidney Farber to usher in the era of chemotherapy for cancer. One of Dan's most important early contributions was demonstrating how radiation therapy and chemotherapy can act synergistically, and he was responsible for some of the first cures of metastatic Wilms tumor in children. In an interview with Dr Edward C. Halperin for the American Society for Radiation Oncology History Committee, Dan was asked how he became interested in radiation oncology as he had been orientated toward diagnostic radiology. He replied“Yes, that was the training. You did both diagnostic and therapeutic radiology. There was no such thing as separate training in radiation oncology. It didn't exist. In those days, radiation therapy in Boston, as in most major cities, was a black hole. It was really terrible. If you got cutaneous erythema with 250 kV x-rays with large-field radiation, it was evidence of malpractice. So you can imagine what happened to the skin of a lady who had postoperative chest wall radiation therapy after a radical mastectomy, she got a lot of radiation and a lot of erythema! Anyhow, the Korean War broke out and the man who was in charge of radiation therapy was called to the colors to go off into the Navy. Dr Max Ritvowe, who was the chief of the program, called me in one day and said, “D'Angio, I've been watching you.” “Yes, sir,” he said. “You hate radiation therapy the least among all the residents, so you're in charge.” That was it. That was absolutely it. We had truly only a smattering of exposure. And then through complicated false reports that I was leaving the Boston City Hospital, Dick Wittenborg [Martin “Dick” Wittenborg, 1914-1969, published important papers on the effect of radiation therapy on the growing spines of children and on the management of neuroblastoma], who was one of the real pioneers in pediatric radiation therapy, called me and said, “How would you like to do radiation therapy at the Children's Hospital?” and I loved the Children's. I had done my internship there in surgery with Dr Robert E. Gross [Robert E. Gross, 1905-1988, served on the HMS faculty for over 40 years and was a pioneer in pediatric surgery], so going back to the Children's was almost a dream. In many ways, the lack of training was a help because you had no precedents, you had no fixed ideas as to what to do. It was all new. And just at that time, effective chemotherapy was just coming into the picture, so the development of the combined therapy was due largely to Dr Sidney Farber who believed in coordinated care, total care and that dictum about cure not being enough for children. So all of that just was part of the air I breathed. I didn't have to manufacture anything personally; it was the way things were done. And it turned out to be quite successful—not because of me, but because of the model.” When Dr Halperin asked what gave him the most satisfaction in his professional life, Dr D'Angio replied, without hesitation, “To get a letter from one of my patients saying that she's had a baby.” Perhaps Dan's most important professional achievements arose from his humble and collegial spirit. Dan had the vision to bring multidisciplinary investigators together by founding the National Wilms Tumor Study Group in 1969. Although combination therapy was able to bring about cures in this pediatric tumor, Dan recognized the harmful effects of radiation therapy on young children and courageously organized the first randomized clinical trial that reduced the use of this curative, but sometimes harmful, modality. He was proven correct, and subsequent clinical trials adhered to his famous admonition to oncologists: “Cure is not enough.” As pediatric oncologists became more successful, he led the efforts to understand the harmful consequences of cancer therapy in young children and organized efforts to avoid them. Early in his career, he learned from Dr Farber that families with a sick child require consideration of total care and sought ways to reduce the psychosocial and economic burdens of childhood cancer. The lessons from his leadership have been applied across the landscape of pediatric cancers and have had an impact on the care of patients and families. Dan became the Chairman of Radiation Therapy at the University of Minnesota in 1964 and then served as Chairman of Radiation Therapy at the Memorial Sloane Kettering Cancer Center in 1968. After being recruited to the University of Pennsylvania and Children's Hospital of Philadelphia in 1976, he solidified his life-long collaboration with Dr Audrey Evans and had an immeasurable impact on children and families in the Philadelphia region. Working with Dr C. Everett Koop, they described the remarkable spontaneous regression of an identifiable subset of neuroblastoma in infants, and together they developed the Evans-D'Angio staging system for neuroblastoma that is the basis for the staging system we use today. Drs D'Angio and Evans were married just before her 80th birthday, and they were inseparable partners. Dan led the Childhood Cancer Research Center at Children's Hospital of Philadelphia and built the foundation for the current “bench-to-bedside and back” research efforts across our campus today. He was the founder of several currently robust organizations, including the Society for Pediatric Radiology, the Pediatric Radiation Oncology Society, the Histiocyte Society, and the Late Effects Study Group, which ultimately led to the Office of Cancer Survivorship at the National Institutes of Health. He mentored hundreds of young investigators from across the world, creating what could be called Dan and Audrey's international family, and published over 500 manuscripts, some of which remain absolute classics in the field. Dan had an international impact. He became a full member of International Society of Pediatric Oncology (SIOP) during the 4th SIOP Annual Meeting held in Manchester in 1972, 4 years after the Society was founded. He was among the first North American doctors accepted as a full member in the Society. Since then, the story of this society has been marked by his presence, by his extraordinary stature as a clinical scientist, by his vision, by his determination and commitment, but above all, by his unique capacity for building global human and scientific networks, which represent one of his main legacies to the Society. He served SIOP as president between 1986 and 1988, edited for many years its international journal, and promoted a series of worldwide collaborative research and education efforts. His last contribution to SIOP is dated in 2015, at the age of 93, when he published in a special 50-page edition of Pediatric Blood and Cancer, the “History of SIOP.” Finally, on October 12, 2017, in Washington, during the opening ceremony of the 48th Annual Meeting, SIOP acknowledged his tremendous contribution to the field of pediatric oncology and to the life of the Society with a special prize: the Lifetime Achievement Award. Needless to say, Dr Audrey Evans was a co-recipient. Although he had many professional achievements, Dan was internationally known as the ultimate bow-tied gentleman—kind, polite, and always most interested in what others had to say. His family always came first, and he was blessed with 2 sons, 2 grandchildren, and 2 great-grandchildren who enjoyed visits to his Rittenhouse Square balcony. A voracious reader, he could hold court on a remarkable breadth of subjects, from the arts to military history, and readily shared his books with others. Dr Evans composed a fitting epitaph: “Dan's eyes have closed. They will open in a better world than this. Our love travels with him. He will be greatly missed.”