July 15, 2012 - By Krista Conger
Saul Rosenberg and the late Henry Kaplan helped pioneer treatments for Hodgkin's disease. On July 13-14, Stanford celebrated the 50th anniversary of the clinical trials for the therapy.
Gil Troutman is an extremely fortunate man.
In 1971, he was a new father and he had received what, only a few years earlier, would have been a death sentence: a diagnosis of Hodgkin's disease, a malignancy of the lymph nodes.
Troutman, who was then 27 and a resident of San Carlos, Calif., was tipped off by his doctor that research was under way at Stanford that had recently shown some success in treating the disorder. It relied on targeted radiation from a linear accelerator designed for medical use.
That therapy, which was pioneered in 1962 by radiologist Henry Kaplan, MD, and oncologist Saul Rosenberg, MD, had transformed a once-fatal disease into a highly curable one.
Fifty years after the Stanford Lymphoma Program (now known as the Lymphoma and Hodgkin's Disease Research Program at the Stanford Cancer Institute) began clinical trials of this new radiation treatment, Stanford researchers and practitioners marked this milestone with a symposium and patient reunion on July 13-14. Troutman, his wife, Fran, and his son, Jeff (himself a Hodgkin's survivor and Stanford patient) joined a throng of former patients, trainees and colleagues to celebrate the anniversary of the initiation of the study, and the role played by Rosenberg since his arrival at Stanford 51 years ago. (Kaplan died in 1984.)
"It's very simple," said Troutman. "Without Dr. Rosenberg, I would not be here today. It means everything to me: My life, my lifestyle, my family. The ability to watch first my son, and then my grandchildren, grow up."
"The cure rates for Hodgkin's disease have gone from vanishingly small to about 90 percent," said Richard Hoppe, MD, the Henry S. Kaplan-Harry Lebeson Professor of Cancer Biology. "At the time, these prospective, randomized clinical trials for lymphoma conducted by Drs. Rosenberg and Kaplan were some of the first in the world. As researchers around the world adopted this approach, we've furthered our understanding of lymphomas and developed new concepts of therapy, including advances in the way we use radiation, to new combinations of chemotherapeutic drugs, to monoclonal antibodies and immunotherapy." In fact, one chemotherapy regimen is known simply as the Stanford 5.
"My time at Stanford has been a blessing," said Rosenberg, the Maureen Lyles D'Ambrogio Professor Emeritus, who noted that the successes he and others have had in treating Hodgkin's disease didn't come as the result of a single breakthrough, but rather as a series of incremental advances. "None of our findings were initially dramatic or exciting. Progress was very gradual as we observed the effect of changes in therapies or techniques on complications and outcomes. Without the patients who participated in our trials of new treatments and allowed us to observe them over decades, none of this would have been possible."
Gil Troutman and his son, Jeff, are among the patients with Hodgkin's disease who benefitted from treatments developed at Stanford.
Kaplan recruited Rosenberg, who had trained as a radiobiologist and an internist, to Stanford in 1961 from Peter Bent Brigham Hospital, Boston. Rosenberg had previously completed a fellowship at New York's Memorial Sloan-Kettering Cancer Center, in which he established the technique of carefully evaluating and recording the outcomes of various lymphoma therapies — an approach that would be critical to the success of the trials at Stanford.
When Kaplan and Rosenberg began their Hodgkin's disease clinical trials, in which Gil Troutman would later participate, the concept of radiation for cancer treatment was in its infancy. The advent of a medical linear accelerator at Stanford in 1955 had allowed Kaplan to treat his first patient with external radiation therapy — a young boy with a tumor in his eye called retinoblastoma. The boy survived with vision intact. Kaplan wondered whether a similar therapy aimed at cancerous lymph nodes would work for Hodgkin's disease.
Troutman recalled his treatment in 1971. "In those days, Dr. Kaplan was doing a study to compare the effectiveness of radiation alone, with radiation plus chemotherapy. I was in the radiation-only group. I lay on a table with lead blocks over parts of my chest, and they gave me total nodal radiation from my chin to my abdomen."
The treatment was successful — for a time. "Everything seemed clear," said Troutman, who moved to the East Coast soon after completing the treatment. But his symptoms shortly recurred. Oncologists at Massachusetts General Hospital put him on a variety of chemotherapy options, including a regimen called MOPP and a single-drug treatment with a compound called vinblastine. Neither eradicated the disease, however, and all of the treatments left him nauseated and exhausted. When Troutman relocated back to California in 1975, he again turned to Stanford for help.
"Dr. Rosenberg said, 'You know, we've got some new experimental chemotherapy drugs, if you're interested in participating in a clinical trial,'" said Troutman. "I said, 'Go for it.'" The quartet of medications — adriamycin, bleomycin, vinblastine and dacarbazine (also known as ABVD) — did the trick.
"I went for my three-month, my six-month, my annual check-up with Dr. Rosenberg, and everything's been fine," said Troutman. But even after 25 years, the family's ordeal was not over. In 2000, Gil's son, Jeff, then 29, began to cough. He lost energy and was unusually tired. "Hodgkin's disease only rarely runs in families, so my doctor was doubtful that was the issue," said Jeff. The doctor was wrong.
"Within one week, I had my diagnosis," said Jeff. "That was the first time in my life I'd seen my dad cry."
"We were really shocked," said Gil. "But there was never any question; he was going to Stanford for treatment." To Stanford, and to Rosenberg.
Jeff underwent a new treatment — called the Stanford 5 because it was the fifth protocol — which incorporates six separate chemotherapeutic drugs. Jeff had three rounds of the Stanford 5 plus four weeks of radiation. The experience was difficult, but left Jeff with fewer long-term side effects than those experienced by his father.
"I felt terrible, but I was nowhere near as sick as he was. I was even able to father my own children after my treatment," said Jeff, who now has an 8-year-old daughter and a 5-year-old son. (Many earlier treatments left patients sterile.) "I owe a tremendous debt to Dr. Rosenberg for making it possible to have the family I have."
"Patients like Gil and Jeff become friends," said Rosenberg. "After so many years we don't talk as much about their disease, but more about their families and lives. It's like a conversation with good friends. That's really a blessing."
"We have a long history with Dr. Rosenberg," said Gil Troutman. "Jeff and I go in together now for check-ups, and it's always wonderful to see him. He keeps saying he's going to retire, but I hope it's not true."
Rosenberg's influence extends beyond lymphoma, however. "He essentially established the field of medical oncology at Stanford," said Hoppe, "and he has mentored many, many other oncologists who now lead similar programs around the country. He's been a wonderful professor and teacher, and it's a joy for the medical students to have the opportunity to learn from him."
Sometimes Jeff Troutman even helps with the instruction by volunteering to be a sample patient for trainees. "Dr. Rosenberg is always on the lookout to see if the doctors he's bringing through can locate a lymph node in my armpit that's still swollen," said Jeff. "It's a privilege to see him sharing his knowledge and information with others. I don't know if an uncle is the right term, but Dr. Rosenberg is a family friend. He always says the same thing: 'I'm sorry to say that you're in great shape. I'll see you in a year if I haven't retired or died.'"
"There are three things that someone like me leaves behind: my children, my students and trainees, and my patients and their families," said Rosenberg. "These wonderful results continue to expand and grow over time. Nothing can be more satisfying."
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