First person profile: Quynh-Thu Le, MD

One of her early third-year rotations in medical school led Quynh-Thu Le, MD, on an unexpected career path that paved the way for her to serve as chair of the Department of Radiation Oncology at Stanford University. Dr Le could not have foreseen herself in this position, largely because before that rotation in the early 1990s, she did not know that radiation oncology existed. What she knew was that she wanted to be a clinician and to work with patients. She was told that radiation oncology was a great specialty for learning the most fundamental skills necessary for being a good clinician: preparing a good patient history and performing a physical examination.

She fell in love with the specialty, and that rotation set the stage for a career in radiation oncology, which she has practiced at Stanford University since completing her medical degree (1993) and her residency in radiation oncology (1997) at the University of California San Francisco (UCSF) School of Medicine. She also completed an internal medicine residency at the Alameda County Highland Hospital in 1994. Along with chairing the Department of Radiation Oncology, Dr Le codirects the Radiation Biology Program at the Stanford Cancer Institute and is the Katharine Dexter McCormick and Stanley McCormick Memorial Professor.

She credits Karen Fu, MD (a prior head and neck cancer radiation oncologist at UCSF, who helped to further refine her career to focus on head and neck cancers); Amato Giaccia, PhD (a professor of radiation oncology in the Division of Radiation and Cancer Biology at Stanford), and Albert C. Koong, MD, PhD (division head and chair of the Department of Radiation Oncology at MD Anderson Cancer Center and a prior Stanford faculty member), who encouraged her toward research; and Richard Hoppe, MD (a prior chair of radiation oncology at Stanford), who gave her the opportunity to grow into her current leadership role.

Each step of the way, Dr Le took the reins of opportunities presented to her and steered them into groundbreaking research and effective leadership focused on advancing the care of patients with cancer.

Dr Le is on the forefront of confronting some of the thorniest challenges of improving the efficacy and safety of radiation therapy in the treatment of head and neck cancers. She describes her research as focusing on three main areas.

The first is working to develop biomarkers to improve the precise delivery of radiation therapy. This includes identifying radiation-resistant tumors to avoid unnecessary treatment.

The second is looking at how to optimize radiation and systemic therapy for different types of head and neck cancers. As leader of the Head and Neck Cancer Committee of the NRG Oncology Group in developing and conducting several phase 2 and 3 clinical trials, she has shed light on numerous issues in this area. First, cetuximab cannot replace cisplatin in unselected patients with human papillomavirus (HPV)–positive oropharyngeal cancer. Second, radiation dose de-escalation in patients at low risk is feasible but unfortunately yields a high rate of locoregional failure in comparison with standard radiation doses. Third, durvalumab with radiation is inferior to cetuximab with radiation in patients with cancer who are HPV-negative and cannot tolerate cisplatin. In other research, she is focused on harmonizing the testing for Epstein–Barr virus DNA to use it as a biomarker for selecting patients for treatment escalation or de-escalation in a large phase 2–3 international study. Dr Le’s recent research is focused on the immunomodulatory effect of Galectin-1 in head and neck cancer (especially with radiation) and the preclinical testing of a novel therapy that modulates the gene expression of Galectin-1 while simultaneously enhancing the radiation sensitivity of cancer.

The third is working with her team to develop treatment strategies to protect the salivary glands by preserving the functioning of saliva stem cells after radiation so that they can regenerate after treatment. A phase 1 clinical trial currently underway is testing the use of a repurposed drug to maintain the activation of an enzyme found in saliva stem cells throughout the course of radiation treatment. The study is built on prior research in which the researchers identified pathways that distinguish the saliva stem/progenitor cells from the terminally differentiated cells. Keeping certain pathways of these cells activated during radiation and chemotherapy aims to prevent the death of some of the saliva stem/progenitor cells.

Dr Le’s involvement in numerous smaller clinical trials at Stanford eventually led to her involvement in larger cooperative trials, which, in turn, raised her visibility as a clinician researcher and leader in cancer research. In one of her first leadership positions for advancing oncologic clinical research, she led the Head and Neck Cancer Committee of the NRG Oncology Group of the National Cancer Institute–sponsored National Clinical Trial Network for 10 years. In 2021, she was appointed as one of the three NRG Oncology Group chairs and later was selected as the chair of the board of directors. In this role, she is charged with overseeing the NRG Oncology Group board of directors as well as several committees to develop and conduct large phase 2 and 3 clinical trials in a range of tumor areas.

Dr Le credits her years of leadership as chair of the Department of Radiation Oncology as helping her to meet the challenge of leading the NRG Oncology Group. A key challenge she focuses on is figuring out the best way to work with all the smart people engaged in the group across North America to advance the next generation of clinical trials that ultimately will change practice and move the field forward. These diverse researchers are national and international experts in their respective fields and, unlike the members of her department, do not report directly to her. “You need to figure how to get people stimulated and engaged and to leverage their strength and creativity in order to bring out the best in them,” she says. “The wonderful thing about these colleagues is that they are all leaders in their fields and are all mission driven, so it is really a pleasure to work with them.”

Mission-driven describes the trajectory of Dr Le’s career, which arcs from her early childhood years in Vietnam (where she was born) to the present. As a daughter of parents who fled Vietnam at the end of the Vietnam War and came to the United States in 1981 as refugees, she absorbed the immigrant’s desire to improve one’s situation, which propelled her toward higher education at the California Institute of Technology (Caltech). Having a father who was a physician helped to steer her toward medicine. The rest is a history still in the making and one that continues to leave its marks on the field of oncology, especially radiation oncology.

In 2015, Dr Lee received the Distinguished Alumni Award from Caltech. She became a fellow of the American Society of Therapeutic Radiation Oncology (ASTRO) in 2014 and of the American College of Radiology in 2011. In 2014, she was inducted as a member into the Institute of Medicine, which is now known as the National Academy of Medicine. She is the recipient of numerous awards, including the American Society of Clinical Oncology Clinical Research Development Award (2002–2005), ASTRO Junior Faculty Research Fellowship (2000–2002), and the Radiologic Society of Northern American Resident Award (1997). She also has been honored for her teaching.