In 1986, Zietman joined Harvard Medical School as a research fellow; thirty years later, he is Harvard's Jenot and William Shipley Professor of Radiation Oncology and director of the school's Radiation Oncology Residency Program. Zietman has also treated patients as a radiation oncologist at Massachusetts General Hospital since 1991.
"Conscience-based care" is how Zietman describes the model of patient care he strives to practice and promote throughout the field. "We should practice with our conscience and from the evidence," he said in a recent interview, stressing the importance for clinicians to couple "a devotion to evidence" with the requirement that they "treat patients with what they need, rather than what we need." Similarly, his research often considers the value, as well as the effectiveness, of cancer treatment. He has attempted, for example, to clarify whether or not proton therapy fosters superior outcomes compared to other therapies for localized prostate cancer. He has strongly advocated that those with the lowest risk form of this disease be spared from treatment altogether.

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Zietman has led multiple clinical trials examining the efficacy of therapy in GU cancers, including the use of androgen deprivation or radiation dose escalation for localized prostate cancer and chemo-radiation in bladder cancer.
Zietman's dedication to improving patient care can be seen in the ways he integrates research with service. When the NCI initiated its GU Protocol Steering Committee, Zietman was named its Co-chair for Radiation Oncology, a role he continues today as he and the committee help coordinate NCI's clinical trials effort for GU cancers. Zietman also helped establish the multidisciplinary GU Cancer Symposium, a joint effort of ASTRO, the Society for Urologic Oncology and the American Society for Clinical Oncology. He has been integral in helping write multiple national guidelines for prostate and bladder cancer treatment and editorials to give perspective on treatments new and old.
Since being named as Editor-in-Chief of ASTRO's flagship journal, the International Journal of Radiation Oncology • Biology • Physics, in 2011, Zietman has made strides in diversifying the journal's editorial board and editorial focus while simultaneously elevating the caliber and reputation of the journal. Zietman's leadership with the Red Journal has proved a natural continuation of his service to ASTRO. After leading the program committee for ASTRO's Annual Meeting and leading ASTRO's Education Council for four years, he was elected President and Chair of the society by its membership. Zietman credits his time with ASTRO's Board of Directors as the place where he learned the powerful role of policy in shaping health outcomes and the ability of specialty societies to influence these policies.