NNECOS Supported Awards Through Conquer Cancer The ASCO Foundation

2020 Conquer Cancer Young Investigator Award Award Term: 7/1/2020‐6/30/2021

Supported by: Northern New England Clinical Oncology Society (NNECOS)

Xingzhe Dillon Li, MD, MPH

Memorial Sloan Kettering Cancer Center

“Probing dynamic changes in DNA damage and innate immune responses of normal tissue and the tumor microenvironment following proton FLASH radiation”

Mentored by: Samuel Bakhoum, MD, PhD

Layperson Summary

Radiation therapy remains a cornerstone in the modern era of cancer treatment as 60% of all cancer patients may need radiation treatment at certain point. Radiation is a form of high energy X‐ray that can kill tumor cells by damaging their DNA. Radiation may also injure the DNA of normal cells near the tumor, causing radiation related side effects. Despite the technical advances in radiation delivery over the past century, the side effects associated with conventional radiation treatment still adversely impact the quality of life in our patients.

Limited by the side effects, we cannot routinely deliver highly curative dose of radiation or combine radiation with other very effective but also toxic treatments such as chemotherapy or immunotherapy.

Proton therapy is an advanced form of radiation therapy using proton particles flying at 2/3 speed of the light to kill tumor cells. Proton therapy has shown great potential in sparing normal tissue from radiation related side effects due to the physical nature of proton beam. Recently, FLASH radiation, a way of ultra‐fast delivery of high dose radiation, has gained great interests among radiation oncologists due to its promising normal tissue sparing effect.

The exact mechanisms of such normal tissue sparing effect (FLASH effect) remain poorly understood, limiting its translation into clinical practice. My research aims to study the FLASH effect using proton radiation, combining the two most powerful technical advances in radiation oncology during the past few decades. I aim to find out how proton radiation delivered in FLASH rate can potentially lead to even greater normal tissues sparing by causing less DNA damage and less acute inflammatory responses in normal tissue near the tumor.

My goal is to use the evidence generated by my studies to support first in human clinical trials using proton FLASH radiation. If proton FLASH radiation causes significantly fewer side effects in human subjects, it will allow combination of such radiation with cancer drugs such as immunotherapy to greatly enhance the chance for cure. In addition, proton FLASH radiation can be delivered in less than 1 second, compared to conventional radiation which is usually delivered over weeks. All these potentials of proton FLASH radiation may translate to safer, better and much faster radiation treatment, which will ultimately lead to meaningful benefit in the care of our patients across all cancer types.Biography

Dr. Xingzhe Li grew up in a small town in Inner Mongolia. He attended Peking University in Beijing, the top ranked university in China, where he received undergraduate degree in biomedical sciences and graduated summa cum Laude in 2007. He then joined Dr. Ramanujan Hegde’s lab at the National Institutes of Health to study membrane protein biology as an Intramural Research and Training Award recipient, which led to co‐authorship of a seminal paper in Nature. He then received an MPH degree from the University of Cincinnati prior to attending medical school at the University of Kentucky College of Medicine, where he graduated top of his class with numerous honors including Alpha Omega Alpha (AOA) and Gold Humanism Honor Society (GHHS). His research during medical school in DNA damage response and clinical radiation oncology led to multiple publications in Cell Reports, Int J Radiat Oncol Biol Phys, etc. He then completed a transitional year internship at Santa Clara Valley Medical Center, where he was named the Intern of the Year, prior to joining the Radiation Oncology Residency Program at Memorial Sloan Kettering Cancer Center. He continues to perform research during residency training focusing on particle therapies such as proton therapy and radiation toxicities. Dr. Li is committed to research in both basic science and clinical oncology, with strong interests in improving the therapeutic index of cancer treatment through better understanding of normal tissue sparing mechanisms such as ultra‐fast (FLASH) radiation and particle therapies. Dr. Li plans to continue his research endeavor as an academic radiation oncologist with basic, translational and clinical research focuses in thoracic radiation oncology, head and neck radiation oncology and radiation toxicities.