Saul Rosenberg, pioneer in treating Hodgkin lymphoma, dies at 95

Saul Rosenberg, MD, Maureen Lyles D’Ambrogio Professor Emeritus who pioneered highly successful treatments for Hodgkin lymphoma, a cancer of the lymph nodes, died Sept. 5 at 95.

Collaborating with the late Henry Kaplan, MD, founding chair of Stanford Medicine’s Department of Radiology, Rosenberg gained recognition for targeted radiation on Hodgkin lymphoma in the 1960s. The therapy, which proved successful, paved the way for developing more effective and safe therapies that now lead to the cure of over 90% of patients with Hodgkin lymphoma.

He also developed the first randomized clinical trials in oncology to compare treatments rather than using retrospective or anecdotal data. His colleagues knew him as the founding father of the Stanford Medicine oncology department — the second largest medical department.

“His legacy will live on through the many patients he treated, many of whom he cured; through the hundreds of physicians he trained; and through the ongoing work of the division he founded," said Heather Wakelee, MD, professor of medicine and chief of the oncology division, in an email to colleagues after Rosenberg’s passing.

“Saul contributed so much to the field of oncology and to all who had the privilege of knowing and working with him,” said Lloyd Minor, MD, dean of the School of Medicine. “I am forever grateful to him for the passion, brilliance and leadership he shared with Stanford Medicine for more than five decades. And I know his groundbreaking work will continue to help patients with Hodgkin lymphoma around the world.”

Despite his accomplishments in research, Rosenberg was quoted during his lifetime in several media interviews saying that his greatest advance was the students he left behind: half a century of people to build on his work.

“He influenced many generations of us who can never fill his shoes, but who can walk on the path that he bravely paved for us,” said Ranjana Advani, MD, a professor of oncology and the Saul A. Rosenberg, MD, Professor in Lymphoma. “He inspired and generously supported many of us as his trainees, including myself, an honor which I will never forget.”

Robert Harrington, MD, the Arthur L. Bloomfield Professor in Medicine and chair of the Department of Medicine, said that Rosenberg will be remembered for two programs he initiated: the Saturday morning Hodgkin staging conference, where medical professionals determine a cancer treatment course, and the Hewlett Award program that he oversaw for many years after being the first awardee in 1983.

The early days

Rosenberg was born Aug. 2, 1927, during the Great Depression in Cleveland, Ohio. He attributed his early interest in becoming a doctor to growing up as a child of poor Jewish immigrants living during World War II, he said in a 2016 interview. With few family business acquaintances, the family doctor was the most respected person he knew.

Rosenberg became interested in ionizing radiation and radioactive isotopes at an atomic energy lab before and while attending medical school at Case Western Reserve University in Cleveland, from which he graduated in 1953. He began a residency at Harvard’s Peter Bent Brigham Hospital, but after three months was drafted by the U.S. Navy. He spent the next year as a battalion surgeon with the U.S. Marines in Korea and Japan, among other places.

At a Naval hospital in Corona, California, Rosenberg met Shirley Strahl, whom he married in 1956.

After two years in the Navy, Rosenberg returned to Brigham and became chief resident in 1960. He wanted to practice cancer medicine, but it wasn’t yet a recognized medical field. So he found a program at Memorial Sloan Kettering Cancer Center, where he pursued his interest in lymphoma under Lloyd Craver, MD, a leader in developing techniques for using radiation to treat lymphomas and leukemias.

He also studied under David Karnofsky, MD, a leading cancer chemotherapist. Under their direction, Rosenberg published his first paper in 1961: Using an IBM sorting machine, one of the first computers, he reviewed 1,269 patient charts by analyzing the answer to 240 questions about each patient, allowing him to learn more about lymphoma. The paper earned him recognition in the lymphoma field.

Journey at Stanford

In 1961, Kaplan recruited Rosenberg to Stanford Medicine, the only place that offered a joint appointment in medicine and radiation. Using SLAC’s 2-mile-long linear accelerator as a model, Kaplan and a nuclear physicist developed a 6-foot one used for stronger radiation than what was in use at the time for oncology.

To test whether the treatments worked, in 1962 Rosenberg and Kaplan developed the first randomized clinical trials for oncology. They were the first studies to demonstrate that their radiotherapy could cure certain lymphomas.

The staging conferences — where doctors determined the stage of a patient’s cancer by analyzing biopsies and X-rays, then assign patients to a treatment at random — continue to this day. The team has treated more than 3,000 patients in these trials.

Advani said Rosenberg’s skill with lymphoma patients stood out most about his work: “I think every patient he saw felt that they were the most important person in his life,” she said.

Despite the success of surgery and radiotherapy, Rosenberg and his colleagues were unable to cure all patients. People with metastatic disease — cancer that spreads rapidly throughout the body — needed chemotherapy. At a time when medical professionals were still skeptical of chemotherapy treatment, Rosenberg turned from focusing strictly on radiation treatment to using a combination of radiation and chemotherapy, which significantly increased survival rates.

Leaving a legacy

Rosenberg established the nation’s first Division of Medical Oncology at Stanford Medicine in 1965, acting as chief until 1993.

Also at Stanford Medicine, he developed a patient database that follows patients and their protocols for decades, allowing him and his colleagues him to recognize subsequent effects of radiation. Rosenberg spent the next decades developing therapies that used less and less radiation with the same cure rate.

His observation of the natural history of follicular non-Hodgkin lymphomas — a cancer also of the lymphatic system — and long survival times led him to be a strong advocate of the “watch and wait” approach for patients with low tumor burden follicular lymphoma. It allowed patients to wait until the disease progressed enough that treatment was necessary rather than undergoing therapy at diagnosis, sparing them the side effects while they were still relatively healthy.

Medical oncology blossomed under his efforts. At Stanford Medicine, he chaired an early subcommittee on medical oncology for the American Board of Internal Medicine and was one of the first associate editors of the Journal of Clinical Oncology.

He received dozens of awards for research and teaching, including becoming an elected member of the Institute of Medicine of the National Academy of Sciences and receiving the medal of honor from the American Cancer Society for Outstanding Clinical Research. Rosenberg was the first recipient of several teaching awards: the Arthur L. Bloomfield Award, the Hewlett Award and the Kaiser Award. He became an American Society of Clinical Oncology fellow in 2007.

Rosenberg authored more than 150 peer-reviewed papers, including a classic: “Hodgkin’s disease and other malignant lymphomas,” published in 1970 in the Western Journal of Medicine. For about every paper, he trained a postdoctoral scholar, totaling around 150 who now practice around the world.

In 1996, Rosenberg was recognized as an emeritus professor of medicine and radiation oncology at Stanford Medicine. Late in his career, he began to spend more time away from the office. As his daughter, Anne Miller, wrote in a eulogy: “With [his wife] Shirley by his side, they explored the small villages of Provence, fished the trout streams of Montana and Idaho, and spent summer months and winter days at their beloved home on the shores of Lake Almanor, which they built from the ground up in 1990.”

Until the COVID-19 pandemic, Rosenberg could be found at Stanford Medicine oncology conferences, patient consults and resident trainings, according to Miller. He spent his final years listening to opera, watching the hummingbirds from his balcony and cheering at Stanford University baseball games.

Besides his daughter, Rosenberg is survived by his son, David Rosenberg, and three grandchildren. His wife preceded him in death in 2013.

Colleagues are planning a memorial to honor Rosenberg’s contributions to Stanford Medicine.