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Eli J. Glatstein: A Steward Extraordinaire of Radiation Oncology

2020; Elsevier BV; Volume: 107; Issue: 1 Linguagem: Inglês

10.1016/j.ijrobp.2020.01.016

1879-355X

C. Norman Coleman, Richard T. Hoppe, James M. Metz,

Effects of Radiation Exposure

This memorial tribute could have had hundreds of coauthors and been >30 pages long if those whose lives and careers were influenced by Eli J. Glatstein were each able to contribute. Other tributes and commentaries will expand or complement what is written here,1Coleman CN, Mitchell JB, Hahn SM, et al. Glatstein: Inspiring and provoking critical thinking. Radiati Res., in press.Google Scholar and we hope to be able to capture a good part of what Eli has meant to generations of oncologists and patients. The profound sense of his absence is made tolerable by contemplating his influence on the many, many patients and physicians who (1) have been helped by his keen mind as a master clinician; (2) thought critically about a theme, paradigm, or conventional wisdom that they once held as correct but may not have been quite so after reading an Eli commentary; (3) found his rapier wit to be stinging, humorous, or provocative (the latter as it was meant to be), as well as quite clever and invariably insightful; and (4) saw him as a loyal friend and mentor who served as a conscience of oncology care and who will miss his unmistakable presence. As Eli would tell us, and indeed did so not too long ago as he recognized that he was no longer within the center of radiation oncology, when we think of him it should be a time of celebration, laughter, and enjoyment of what he has left to enrich us. Indeed, every visit with our beloved colleague and friend was special. Eli J. Glatstein, aka “Eli,” was born in Muscatine, Iowa. His father owned a furniture store in which he worked. He learned the necessity and value of an honest day’s work with hometown values. He went to the State University of Iowa and played football. We did not check on his stats, although he would have told us to gather data. Medical school brought him to Stanford, where his insightful perspective slightly jeopardized his grades and his progress. He regaled us with a story of how he did not think too much of his Ob-Gyn clerkship, so he wrote single or few-word answers to the essay questions. When his failing grade required a second time through the clerkship, he admitted with a sigh that the answers were more complete. He passed. After internship in medicine at Cornell University, he served in Vietnam in the US Army, “pacifying villages” he muttered. He did not simply serve: He was awarded a Bronze Star. He told a story of the benefit of his height—the tent he was in collapsed from a combination of a storm and helicopters, and the main tent pole just missed his head as he was lying in his bunk. His thoughts turned to Palo Alto and Stanford, known for its excellence in radiology, where he went to train after Vietnam. It was in the decade from 1967 to 1977 at Stanford as a resident, fellow (2 research years in the United Kingdom), and junior faculty member that he thrived in the oncology programs led by Henry Kaplan and Mal Bagshaw (in radiology/radiation oncology) and Saul Rosenberg (in medicine/oncology). One of his earliest rotations in general radiology residency was in radiation therapy, which immediately captured his interest and enthusiasm. With good fortune, one general radiology resident disliked therapy, so he and Eli were able to fashion their residencies to emphasize their areas of interest. Eli chose radiation oncology, and that was how he became one of us. Stanford was the anchor for his oncology career, built on the malignant lymphomas and relationships with pioneering thinkers, especially Henry Kaplan and Saul Rosenberg, but also Ron Dorfman in pathology, Tom Nelson in staging surgery, and Ron Castellino in radiology. Under Kaplan and Bagshaw’s leadership in radiology, there was strength in clinical care, physics—including the first linear accelerator in North America—and radiobiology. We are fortunate that Eli told his own story about training at Stanford in “As good as it gets—training with Henry Kaplan and Saul Rosenberg during the Stanford studies on Hodgkin's disease and lymphoma”2Glatstein E. As good as it gets—training with Henry Kaplan and Saul Rosenberg during the Stanford studies on Hodgkin's disease and lymphoma.Cancer Biother Radiopharm. 2001; 16: 269-273Crossref PubMed Scopus (5) Google Scholar: A training experience under these physicians was both exhilarating and productive… The strong character traits of Drs. Kaplan and Rosenberg left lasting impressions, not only on other staff, but most especially on the young trainees who learned to accept and appreciate their efforts at excellence. Their method of approach and the gains achieved by it became the paradigm for the study of other malignant diseases. He was indoctrinated in great patient care, the importance of character, and the necessity and know-how to conduct randomized clinical trials. He became a central figure in the group of “lymphomaniacs” with his papers on staging laparotomy (Dr. Glatstein’s curriculum vitae can be found in supplemental information), setting the paradigm for how to carefully understand cancer biology and cancer dissemination. He learned how to approach cancer by doing what Henry Kaplan taught him: “if you want to cure Hodgkin’s disease you have to think like a Reed-Sternberg cell!” Thinking was not just what cancer looked like under the microscope and where it was anatomically, but how its underlying biology influenced its response or resistance to therapy. The anatomic staging approach pioneered for Hodgkin disease was used to study other tumors at Stanford, including non-Hodgkin lymphomas and prostate cancer. Elsewhere, it was the paradigm used for most other cancers, allowing tailored treatment. His hard work, his diligence in caring for patients, his feeling of responsibility for providing the best education and training of residents, his encyclopedic memory for data, and his willingness to listen and change, if warranted, earned the trust of his mentors. He became a world-renowned leader in the treatment of lymphomas and was a senior attending physician in the famous Monday Lymphoma Clinic at Stanford. To achieve that status under Kaplan and Rosenberg required exceptional skills and character. His recognition as an international force in the world of lymphoma was solidified by his selection as the principal investigator for the National Cancer Institute (NCI)-funded international project to study the classification of the non-Hodgkin lymphomas. Thousands of biopsy specimens were reviewed and classified by 6 expert hemato-pathologists, including Henry Rappaport, Karl Lennert, and Bob Lukes, according to their own classifications,. Detailed clinical data were abstracted to provide clinico-pathologic correlations. Although Eli departed from the NCI before the final report was published, the design of the project was his, and it resulted in the “Working Formulation for Clinical Usage” that was used in clinical trials and for classification of lymphoma at many centers until the adoption of the Revised European-American Classification of Lymphoid Neoplasms and World Health Organization classifications. The field of radiation therapy, becoming radiation oncology in the 1960s and 1970s, had a number of “schools” led by master clinicians with their particular approaches. Many were from Europe with the “Herr Professor” model, described by Eli in a paper now in press: “Research-driven radiation oncology: A narrative of the ongoing legacy of Henry S. Kaplan.” We mention it here because it will be his final first-author publication, about which he was truly delighted. It fills in details we will not duplicate in this commentary.3Glatstein EJ, Coleman CN, Pistenmaa DA, et al. Research-driven radiation oncology: A narrative of the ongoing legacy of Henry S. Kaplan. Int J Radiat Oncol Biol Phys, in press.Google Scholar Among the schools of radiation therapy were 2 headed by physician-scientists: Henry Kaplan (and later Mal Bagshaw) of Stanford and Mort Kligerman (and later Jim Fischer) at Yale. Eli did not consider himself a laboratory guy, although that could be debated given his breadth of knowledge supported by endless reading. With the blessing and encouragement of Kaplan, for 2 years Eli studied normal tissue injury under Jack Fowler in the Gray Laboratory in the United Kingdom. He was recruited by Vince DeVita in 1977 to take over the Radiation Oncology Branch at NCI. Vince noted, “I gave him a blank check and he exceeded it!” At that time, the world-renowned NCI Medicine Branch had 5 attendings (the Big Five) who were major leaders in the establishment of science-based medical oncology: Vince DeVita, Bruce Chabner, Robert C. Young, Phil Schein, and George Canellos. Tributes to Eli from them are being prepared for the The Oncologist. Eli’s 14 years at NCI were during a period of explosive growth in oncology, with radiation oncology separating from diagnostic imaging and medical oncology becoming an independent subspecialty of the Board of Internal Medicine. Clinical trials were spearheaded by national cooperative research groups, including international collaborations, particularly with Europe. The Radiation Therapy Oncology Group (which merged to form NRG) was a dominant force. As the NCI Cancer Centers Program grew, spurred by Nixon’s War on Cancer legislated in the National Cancer Act of 1971,4National Cancer Act of 1971.https://www.cancer.gov/about-nci/overview/history/national-cancer-act-1971Date accessed: December 23, 2019Google Scholar the NCI intramural program on the National Institutes of Health campus had a dominant role in what is now called translational research. Eli’s ability as a recruiter and his legend as a mentor were honed at the NCI. The initial clinical team included Joel Tepper, Tim Kinsella, Allen Lichter, Jim Schwade, and medical physicist Benedict Fraass, who developed pioneering programs in 3-dimensional conformal radiation therapy with multileaf collimation, intraoperative radiation therapy, and limb-sparing sarcoma therapy, the latter in conjunction with surgical oncologist Steve Rosenberg. Partnering with radiation biologist Jim Mitchell, they conducted pharmacokinetically directed clinical trials of the halopyrimidines (BUdR and IUdR). Along with medical oncologist/radiation biologist Angelo Russo and surgical oncologist Harvey Pass they developed intraoperative photodynamic therapy. Mitchell and Russo studied glutathione modulation to enhance radiation therapy and studied hyperthermia. Pioneering studies in lung cancer were conducted with John Minna and Dan Ihde and in lymphoma with the Medicine Branch. Eli, the Pied Piper (Fig. 1), recruited medical and pediatric oncologists including Ted Lawrence, Steve Hahn, and Judy Bader into radiation oncology. He trained innumerable future department chairs,3Glatstein EJ, Coleman CN, Pistenmaa DA, et al. Research-driven radiation oncology: A narrative of the ongoing legacy of Henry S. Kaplan. Int J Radiat Oncol Biol Phys, in press.Google Scholar including many of those already mentioned as well as Gillies McKenna and Drew Turissi. There were many other extraordinary trainees and mentees, and we apologize to those not mentioned. Eli’s presence helped build the Radiation Research Program, which is in the extramural component of NCI, and enticed David Pistenmaa, a colleague from Stanford with an MD and PhD in medical physics who had worked on the Stanford pion project, to join NCI. After 14 very productive years at the NCI, Eli moved to Dallas in 1992 with David Pistenmaa to help John Minna establish a cancer center at the University of Texas Southwestern Medical Center. A new Department of Radiation Oncology was established, with Eli its first chairman. He was promised a new radiation oncology facility in 3 years. In conjunction with the clinical program at the Medical Center in Dallas, the Department of Radiation Oncology was going to lead a clinical proton therapy program using the Superconducting Super Collider5SSC Project.https://www.upi.com/Archives/1992/06/16/Superconducting-super-collider-may-help-fight-cancer/9066708667200/Date accessed: December 23, 2019Google Scholar then under construction in Wachsahachie, Texas. Unfortunately, the Superconducting Super Collider project was terminated by Congress in 1993. Because, at the end of 4 years, there was no plan to build the new radiation oncology facility at UT Southwestern (it took 11 years), Eli resigned in early 1996 and moved on to the University of Pennsylvania to become the vice chair of the Department of Radiation Oncology. Eli was recruited by Gillies McKenna, then chair at Penn Medicine, to become vice chair of the Department of Radiation Oncology and to lead its clinical efforts. He stayed at Penn for the remainder of his career (1996-2019). His influence at Penn was extraordinary. He affected virtually every area of the department and set the foundation for a culture that is still flourishing. Eli immediately engaged the residents and junior faculty, becoming a mentor to almost the entire Penn team. He was a stalwart at virtually every teaching and clinical conference in the department. Importantly, he reached out to other multidisciplinary teams, becoming a critical influence in oncology at Penn Medicine. Eli likely affected even more people outside of the department than within it. Eli’s knowledge and leadership shaped Penn radiation oncology into the world-renowned department it is today, and he exemplified the core tenet of culture at Penn Medicine: Excellent is standard. As a mentor and as a giant in the field, he educated and inspired students far and wide, further extending his influence and legacy. The minds he helped shape include those of countless leaders in the field as well as 26 chairs of academic departments who trained immediately under him or served with him as junior faculty. He closely followed the careers of all those he mentored with interest and pride. His principle clinical interests at Penn Medicine were lymphoma, sarcomas, and lung cancer. He was known for his contributions in each of those fields and for his work in radiation biology. In the last 25 years, his primary passion was photodynamic therapy, in which he led pioneering work on intraoperative photodynamic therapy for pleural-based malignant diseases. Although he was a radiation oncologist by training, he was likely best known as an outspoken champion of multidisciplinary treatment for cancer. Eli was always challenging people to think outside the box and to grow as an individual. Eli also enjoyed sharing the things in life he loved most with all those around him: food, movies, and music. He was an encyclopedia of baseball stats. In his spare time, he was a restaurant critic and movie reviewer, contributed to the departmental newsletter, and stimulated discussions about life both before and after conferences. He was always happy to share his perspective and have a friend join him for a meal at one of his favorite restaurants. In fact, he was known to pull out a menu from an inspiring restaurant, put his feet up in clinic, and fantasize about his next meal. In 2018, the department established the Eli Glatstein Professorship in Radiation Oncology to honor his contributions to the department, to Penn Medicine, and to the field of oncology as a whole. Although he had health issues in his final year of life, he was continuously surrounded by those he influenced most: his students, mentees, and great friends. Eli’s written contributions include peer-reviewed publications, books, book chapters, and editorials numbering close to 500. Journal editorial positions numbered 17, including senior editor of the Red Journal for over 20 years. His encyclopedic mind and keen ability to read carefully and analyze data were well known and terrifying to those aiming to bluff or bluster their way toward medical decision making. The memorial commentary in Radiation Research1Coleman CN, Mitchell JB, Hahn SM, et al. Glatstein: Inspiring and provoking critical thinking. Radiati Res., in press.Google Scholar tabulates over 40 publications that are “Eli-isms”—provocative and controversial commentaries that have shaped cancer care. A good number relate to the lymphomas and sarcomas, and many addressed key concepts of the time, often chiding us—even admonishing us—to think about what we are doing. A few of the more memorable titles are “Seduced by oxygen,”6Finkelstein E. Glatstein E. Seduced by oxygen.Int J Radiat Oncol Biol Phys. 1988; 14: 205-207Abstract Full Text PDF PubMed Scopus (10) Google Scholar “Beware the medical-industrial complex,”7Stevens C.W. Glatstein E. Beware the medical-industrial complex.Oncologist. 1996; 1: IV-VCrossref PubMed Google Scholar “Alice and academic oncologists meet in corporate wonderland,”8Stevens C.W. Glatstein E. Alice and academic oncologists meet in corporate wonderland.Oncologist. 1996; 1: IV-VPubMed Google Scholar “Is meta-analysis really meta-physics?”9Machtay M. Kaiser L.R. Glatstein E. Is meta-analysis really meta-physics?.Chest. 1999; 116: 539-542Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar “The return of the snake oil salesmen,”10Glatstein E. The return of the snake oil salesmen.Int J Radiat Oncol Biol Phys. 2003; 55: 561-562Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar “Black, white, or shades of gray?”11Glatstein E. Black, white, or shades of gray?.Int J Radiat Oncol Biol Phys. 2008; 72: 1307Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar “The omega on alpha and beta,”12Glatstein E. The omega on alpha and beta.Int J Radiat Oncol Biol Phys. 2011; 81: 319-320Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar and “The music of V20: a symphony or cacophony?”13Das I.J. Glatstein E. The music of V20: A symphony or cacophony?.Int J Radiat Oncol Biol Phys. 2014; 88: 973-974Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar He had many memorable quotes regarding studies “that should be published in brown ink,” self-important colleagues (he used the proper pronoun, simplified here; “if you buy him/her for what he’s worth and sell him for what he thinks he's/she's worth, you’ll be a rich man”), and respect for people who were excellent overall doctors (often board-certified internists) before or while entering the specialty of radiation oncology (“he/she was educated before he/she was trained”). Eli’s academic accomplishments included Phi Beta Kappa, Alpha Omega Alpha, the Gold Medal from the American Society of Radiation Oncology, the American Society of Clinical Oncology Distinguished Achievement Award, and, perhaps uniquely in oncology, the Muscatine High School Hall of Honor Awardee. As part of the celebration of his 70th birthday, Eli and Norm Coleman published “The road not taken and choices in radiation oncology,”14Coleman C.N. Glatstein E. The road not taken and choices in radiation oncology.Oncologist. 2010; 15: 332-337Crossref PubMed Scopus (3) Google Scholar which summarized much of what Eli was about: “The individual tapestry weaved by choosing the more or less traveled paths during a career results in many pathways that would be called success; however, the one path for which there is no good alternative is that of living and acting with integrity.” The loss of Eli’s encyclopedic, creative, and critical mind and his magnetic personality (both north and south poles!) with the ability to inspire trainees to enter radiation oncology cannot be replaced by any individual. The void he leaves falls on “us” to take up the mantle of the conscience of oncology (Fig. 2). He lived an interesting life and was a steward for our specialty for over 4 decades. Respecting his contributions requires us to be self-critical of the “magic” (ie, things too good to be true or too simple an explanation)—of new treatments, new technologies, and self-interested “breakthroughs.” His legacy is for us to remember and continue his critical thinking, seemingly stern-at-times mentorship, clever wit, and passion for the truth and for us to take care of all of those in our sphere of responsibility—patients, colleagues, coworkers and society—with ethics, inspiration, and integrity. The authors would like to thank Fern Nibauer-Cohen and Lora Furman for providing details on Dr Glatstein’s career; James B. Mitchell for additional details on the NCI years and the photos; and David A. Pistenmaa for additional details on the NCI and University of Texas, Southwestern, and editorial assistance. Download .rtf (1.72 MB) Help with rtf files Supplemental Information