Joseph V. Simone: In Memoriam (1935–2021)
Authors: James R. Downing, Ching-Hon Pui
Journal: Clinical Cancer Research (2021)

He was a poet. A prodigious writer. A giant in the world of pediatric oncology. Those of us in the field of cancer research, as well as patients around the globe, owe a tremendous debt of gratitude to Joseph “Joe” Simone.A first-generation American who was born amid the Great Depression, Joe defied the odds. He attended Loyola University Chicago Stritch School of Medicine, which was named after the Catholic cardinal who urged actor Danny Thomas to found St. Jude Children's Research Hospital in Memphis, Tennessee. Was it coincidence or serendipity that Joe's first post, and the one that set him on a trajectory for greatness, would be located at St. Jude?In 1967, he and his wife and three daughters squeezed into a 1963 VW Beetle and headed for Memphis. There, Joe joined the staff of a small, upstart hospital that had been in existence for only 5 years.At the helm of St. Jude was another visionary who shared Joe's passion and enthusiasm for integrating basic research and clinical care. Dr. Donald Pinkel had already instituted Total Therapy, an unorthodox series of clinical trials for pediatric acute lymphoblastic leukemia (ALL). During the 1960s, most clinicians viewed ALL as universally fatal. Treatment consisted of a succession of chemotherapy agents, which induced only temporary remissions. In defiance of medical convention, Don created a regimen that combined multiple anticancer drugs with radiation treatment. Each Total Therapy study built upon lessons learned in preceding clinical trials.When Joe arrived at St. Jude, he immediately joined the Total Therapy team, working on the series' fourth study. He and Don subsequently designed the world-renowned Total Therapy Study V, which featured combination remission induction, prophylactic central nervous system–directed therapy, and post-remission combination chemotherapy in MTDs (Simone and colleagues, Cancer 1972;30:1488–94). The results were dramatic: 32 of 35 patients attained remission, half of them becoming long-term survivors who were eventually declared cured.Even at this early date, with progressive improvement in the survival rates of children with this disease, Joe had already advocated for the use of randomized trials to improve the efficacy and reduce the toxicity of therapy (Simone and colleagues, Cancer 1975;35:25–35). In fact, he performed the first study on the prognostic factor analysis of childhood ALL. Among the 363 children treated in the Total Therapy studies between 1962 and 1971, Joe found that initial leukocyte count above 100,000/mm3, spleen enlargement greater than 5 cm, mediastinal involvement, age over 10 years, and African-American ancestry were associated with a poor prognosis (Simone and colleagues, Cancer 1975;36:2099–108). This study led to the era of “modern therapy,” using risk-directed therapy to avoid over- or undertreatment. It also marked the first time clinicians had safely and successfully ceased therapy in a significant number of patients with ALL (Simone, Br J Haematol 1976;32:465–72).Joe moved his family to the South during a tumultuous time in American history. Eight months after his arrival, Dr. Martin Luther King Jr led a march through the streets of Memphis to support striking sanitation workers. Joe and several of his colleagues took part in the event, which dissipated when riots erupted. As he was returning to the hospital, Joe picked up two of the discarded placards emblazoned with the words, “Honor King: End Racism!” and “Union Justice Now!” Joe kept those signs as poignant reminders of the event and its significance. His journal entries indicate he was profoundly affected by King's assassination the following week. To help heal the wounds of racial division in the city, Joe worked with others at St. Jude to establish a clinic for poor children, which was followed by creation of the MAP South Project and the federal Special Supplemental Nutrition Program for Women, Infants, and Children, a program that exists to this day.Joe quickly rose through the ranks to lead the hospital's leukemia program, later serving as associate director for clinical research. He brought scientific attention to St. Jude by entering the Pediatric Oncology Group in 1981. In 1983, he was named to succeed Dr. Alvin Mauer as the hospital's third director. For the next 9 years, Joe shepherded the hospital through an unprecedented time of growth. Under his leadership, St. Jude instituted a human immunodeficiency virus/AIDS clinical program, dramatically elevated its research, and created one of the world's largest long-term follow-up clinics for childhood cancer survivors. Joe paved the way for St. Jude to be a charter member of the National Comprehensive Cancer Network, of which he was a founding chair. It was also during his tenure that the hospital considered and, ultimately, rejected an offer to relocate to Washington University in St. Louis.In 1992, Joe accepted a position as physician-in-chief at Memorial Sloan Kettering Cancer Center (New York, NY), where he developed a cancer disease management system and a regional clinical cancer network. He then moved to Utah to serve as senior clinical director at the Huntsman Cancer Institute (Salt Lake City, UT) and later to Florida to hold a leadership position at the University of Florida's Shands Cancer Center (Gainesville, FL). When he retired from academia, he founded Simone Consulting.A member of the American Association for Cancer Research (AACR) since 1972, Joe served on the organization's Board of Directors, published in its journals, and spoke at its annual meetings. For his accomplishments, the AACR bestowed upon him the Richard and Hinda Rosenthal Foundation Award.Joe also served as a member of the Board of Scientific Advisors of the NCI and the external advisory committees of 12 NCI-designated cancer centers. “If you've seen one cancer center, you've seen one cancer center,” he frequently quipped when discussing their attributes and idiosyncrasies.He chaired the Institute of Medicine's National Cancer Policy Board, the Cancer Clinical Investigators Review, and NCI's Cancer Center Review Committee. He was also a president of the Association of American Cancer Institutes and vice chair of the Pediatric Oncology Group.Among his awards and honors, Joe was elected to the Association of American Physicians. The American Society of Clinical Oncology (ASCO) awarded him the Distinguished Service Award for Scientific Achievement in 2002, the Public Service Award in 2006, and the ASCO-American Cancer Society Award in 2010. ASCO also named an award in his honor: the Joseph V. Simone Award and Lecture for Excellence in Quality and Safety in the Care of Patients with Cancer.Joe authored countless personal journal entries, estimated at more than 1.3 million words, and poems, some of which appear in the 2015 edition of Collected Poems. He also penned hundreds of pithy columns in the OncOpinion section of Oncology Times. Perhaps his most well-known work is Simone's Maxims, which was born as a 1999 editorial and matured into a book that was expanded and updated in 2012. Simone's Maxims Updated and Expanded: Understanding Today's Academic Medical Centers has become a bible for leaders of academic medical centers. The tenets in this guide are at once funny, thought-provoking and, often, revelatory. They include such aphorisms as: And, importantly: “Academic medicine is a noble calling.” Joe Simone exemplified that statement, to the benefit of students, scientists, clinicians, academicians, and childhood cancer survivors worldwide. He left this world, and the scientific community, better than he found it.There can be no greater legacy.