Transformative Technology for FLASH Radiation Therapy.

The general concept of radiation therapy used in conventional cancer treatment is to increase the therapeutic index by creating a physical dose differential between tumors and normal tissues through precision dose targeting, image guidance, and radiation beams that deliver a radiation dose with high conformality, e.g., protons and ions. However, the treatment and cure are still limited by normal tissue radiation toxicity, with the corresponding side effects. A fundamentally different paradigm for increasing the therapeutic index of radiation therapy has emerged recently, supported by preclinical research, and based on the FLASH radiation effect. FLASH radiation therapy (FLASH-RT) is an ultra-high-dose-rate delivery of a therapeutic radiation dose within a fraction of a second. Experimental studies have shown that normal tissues seem to be universally spared at these high dose rates, whereas tumors are not. While dose delivery conditions to achieve a FLASH effect are not yet fully characterized, it is currently estimated that doses delivered in less than 200 ms produce normal-tissue-sparing effects, yet effectively kill tumor cells. Despite a great opportunity, there are many technical challenges for the accelerator community to create the required dose rates with novel compact accelerators to ensure the safe delivery of FLASH radiation beams.
Competing Interests: Billy W. Loo Jr. is an employee of Stanford University School of Medicine. Dr. Billy W. Loo Jr. has received research support from Varian Medical Systems. He is a co-founder and board member of TibaRay. Reinhard Schulte is employed by Loma Linda University, School of Medicine. Dr. Schulte has received research funding by Grant R44CA257178 “Ultrafast and Precise External Beam Monitor for FLASH and Other Advanced Radiation Therapy Modalities” from the National Cancer Institute awarded to Peter Friedman (PI), Integrated Sensors, LLC. The funder had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The United States Government has rights to patents pursuant to Contract No. DE-AC52–07NA27344 between the United States Department of Energy and Lawrence Livermore National Security, LLC for the operation of Lawrence Livermore National Laboratory. For SES, Opcondys, Inc. is a for-profit company and may profit from the technologies described in this paper.