Operating With Scientific Rigor: How Brennan Changed Cancer Surgery

Andrew D. Smith
Published: Sunday, Feb 04, 2018
Sir Murray F. Brennan, MD
Sir Murray F. Brennan, MD
Sir Murray F. Brennan, MD, thought he was joining an empirical science when he began medical school in 1960, but by the time he had completed his residency, he realized that surgery was actually a mishmash of tradition and guesswork.

That is because up until that time no one had ever systematically compared various techniques for most operations. Surgeons used whatever techniques they had learned, whatever techniques were popular, or whatever techniques seemed logical to them.

Brennan made his reputation—and saved many lives—by pioneering the use of rigorous empirical analysis to evaluate alternative strategies and optimize outcomes in surgical oncology. As a result, over the course of more than 4 decades, Brennan and his collaborators published dozens of papers that helped create and refine standards for operating on a wide variety of tumor types.

Unlike nearly everyone else to win a Giants of Cancer Care® award, Brennan’s most important findings may be the negative findings—vivid demonstrations that “obviously beneficial” surgical customs were either a waste of time or a threat to patients. Yet, these negative findings were instrumental in a positive trend that continues to this day: a trend toward less traumatic operations that have shortened recovery times even as they have improved outcomes.

“I started university with the intention of being an engineer. The classes I took were all about rigorous measurement and analysis. I then earned a degree in mathematics and statistics during medical school. When I completed medical school, and saw surgeons operating on gut instinct or medical folklore, I was surprised,” Brennan said. “It didn’t take me too long to realize that I could probably make something useful of myself by taking all these analytical techniques I had learned and applying them to surgery. The only real trick was selling others on the idea and getting myself in the position to do the research I wanted to do.”

Thinking Like an Engineer

Brennan was born in Auckland, New Zealand, in 1940, and raised in the southern part of the country. He was a good student and a good athlete, playing Provincial Rugby (which is just 1 step below the national team).  He was president of the University Student Union and his university’s nominee for a Rhodes scholarship. 

After completing medical school, as well as his internship and residency, at the University of Otago, Dunedin, New Zealand, Brennan stayed on for a year to be an assistant lecturer in physiology and surgery. Then, in 1970, he moved to the United States for a fellowship at Harvard Medical School and Peter Bent Brigham Hospital. Even then, he thought about surgery like an engineer.

“He is probably the most evidence-based surgeon I have ever known,” said Steven Rosenberg, MD, PhD, a previous Giants of Cancer Care® award recipient, who worked with Brennan at Harvard and who now heads the Surgery Branch of the National Cancer Institute (NCI).  “He is a brilliant surgeon and surgical educator with a unique ability to critically analyze large amounts of data before making a decision.”

After 5 years in Boston, Brennan moved to the NCI and Georgetown University. He made a name for himself at the NCI, not only by keeping unusually careful records of each surgery’s many variables, but also by combining those records such that he could see any patterns that emerged organically or when he tried systematic variations.

Between 1975 and 1981, Brennan and several colleagues deliberately tried to use medical treatment alone on patients with Zollinger-Ellison syndrome who would normally undergo surgery. They treated 26 patients with the rare condition, which spurs tumor growth in the pancreas or duodenum, using the histamine receptor agonist, cimetidine, for a mean of 32 months (range, 2-64 months). Only 6 of the patients progressed on cimetidine and required surgery. The rest were maintained on cimetidine, wrote Brennan and his coauthors in a 1982 paper that appeared in Annals of Surgery and ended with a call for a prospective study. Such studies, when they were performed, bore out Brennan’s observation. Medication is now the only treatment for many patients with Zollinger-Ellison syndrome.

Brennan left the NCI after 6 years and moved to New York to begin his ongoing tenure as a professor of surgery at Weill Medical College and to accept the first of many positions at Memorial Sloan Kettering Cancer Center (MSK). He is now the vice president for International Programs and director of the Bobst International Center at MSK.

Defying Tradition With Data

Brennan realized that the sheer volume of patients treated at MSK would speed his efforts to scientifically evaluate surgical techniques. The only problem was that senior colleagues saw little value in controlled trials of seemingly good procedures.

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