Stanford University School of Medicine
Radiation Oncology
Billy W. Loo, Jr., M.D., Ph.D. is a Professor of Radiation Oncology, a member of the Molecular Imaging Program at Stanford (MIPS) in the Department of Radiology, and a member of the Stanford Cancer Institute, in the School of Medicine. He is a physician-scientist Radiation Oncologist and Bioengineer who directs the Thoracic Radiation Oncology Program at Stanford. His clinical specialties are state-of-the-art radiation therapy for lung/thoracic cancers, including stereotactic ablative radiotherapy (SABR) and 4-D image-guided radiation therapy for lung tumors. Dr. Loo is a recognized expert in thoracic cancers serving on multiple national committees (including as writing member, chair, or vice-chair) that publish clinical guidelines on the treatment of lung cancer and other thoracic malignancies, including the National Comprehensive Cancer Network (NCCN), American College of Radiology (ACR), and American Society of Radiation Oncology (ASTRO). His clinical research is in clinical trials and implementation of new treatment techniques for lung cancer, and development of new medical imaging methods for measuring organ function and predicting response to cancer treatment. As part of this work, he leads a clinical and preclinical research program in molecular imaging, particularly using novel PET tracers for tumor hypoxia (EF5), tumor proliferation (FLT), and neuroinflammation (PBR06). He also co-leads clinical trials of novel applications of SABR including treatment of pulmonary emphysema and cardiac arrhythmias. Since conceiving of a fundamentally new approach to delivering ultra-rapid, ultra-precise radiation therapy, pluridirectional high-energy agile scanning electronic radiotherapy (PHASER), Dr. Loo's major laboratory research focus has been to co-lead a collaborative effort between the Stanford Cancer Institute and SLAC National Accelerator Laboratory to develop PHASER into a transformative yet clinically practical technology. This program comprises both technology development and fundamental research on the radiobiology of extremely rapid FLASH radiation therapy to optimize the biological therapeutic index. Dr. Loo received his MD from University of California, Davis and his PhD in Bioengineering from University of California, San Francisco and Berkeley. He completed his Radiation Oncology residency training at Stanford University. He is certified by the American Board of Radiology in Radiation Oncology.

Moderator of 1 Session

Session Type
Live E-Poster Discussions
Date
Thu, 02.12.2021
Session Time
17:20 - 18:20
Room
Station 03

Presenter of 1 Presentation

FLASH: Path to Clinical Translation

Session Type
FLASH Modalities Track
Date
Thu, 02.12.2021
Session Time
09:10 - 09:40
Room
Hall C
Lecture Time
09:10 - 09:35

Abstract

Abstract Body

FLASH radiation therapy is rapidly progressing to human clinical trials. This presentation will review the preclinical data from the perspective of key questions needed for clinical translation. It will also summarize the technological basis, current and under development, for ongoing and future clinical trials of FLASH radiation therapy.

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Author Of 4 Presentations

FLASH: Path to Clinical Translation

Session Type
FLASH Modalities Track
Date
Thu, 02.12.2021
Session Time
09:10 - 09:40
Room
Hall C
Lecture Time
09:10 - 09:35

Abstract

Abstract Body

FLASH radiation therapy is rapidly progressing to human clinical trials. This presentation will review the preclinical data from the perspective of key questions needed for clinical translation. It will also summarize the technological basis, current and under development, for ongoing and future clinical trials of FLASH radiation therapy.

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RAPID CONVALESCENT PLASMA STERILIZATION USING HIGH DOSE RATE ELECTRON RADIATION

Session Type
FLASH in the Clinic Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
14:50 - 15:50
Room
Room 2.31
Lecture Time
15:00 - 15:10

Abstract

Background and Aims

Passive antibody administration through convalescent plasma has shown benefit in treating COVID-19 in the early stages of the disease in patients >65 years old, and in other viral outbreaks. A practical, rapid method to sterilize convalescent plasma while also maintaining antibody function would be valuable for safe treatment in future viral pandemics. Plasma sterilization by irradiation requires kGy of dose to deactivate bacteria and viruses of concern. Conventional lab-based irradiators would require days to reach such doses, while ultra-high dose rate irradiation (FLASH) would require minutes. We present a proof-of-concept on sterilizing plasma with 25 kGy in approximately 3 minutes without damaging the antibodies in the plasma.

Methods

A Varian Trilogy LINAC was configured for 16 MeV FLASH electron irradiation. Frozen aliquots of convalescent plasma from patients with COVID-19 were placed in a 3D printed holder submerged in liquid aiming to preserve sample temperature (RT, 4C or -20C). The number of pulses was estimated with EBT-XD film. Samples were irradiated with a dose of 25 kGy in ~33,330 pulses over 185 seconds. Antibody binding against the receptor-binding domain (RBD) of the S1 region of SARS-CoV-2 was measured by ELISA pre- and post-irradiation.

Results

Frozen plasma aliquots from 10 COVID-19 convalescent plasma donors were irradiated in frozen state to 25 kGy dose. IgG antibody binding against SARS-CoV-2 RBD after irradiation remained at 90.8% of non-irradiated samples (Figure; OD 1.25 vs. 1.36, p< 0.0003).

frpt image.jpg

Conclusions

FLASH irradiation allows for rapid sterilization of blood plasma from potential pathogens while largely preserving antibody binding function and specificity.

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REAL-TIME OPTICAL OXIMETRY UNDER IRRADIATION

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
18:00 - 19:00
Room
Room 2.15
Lecture Time
19:00 - 19:10

Abstract

Background and Aims

Transient changes in oxygen tension in tissues taking place during FLASH radiotherapy may explain its biological effects. However, because the kinetics of oxygen depletion and recovery occur on a very short timescale, it is challenging to measure these effects in vivo using existing methods. Here we developed a real-time optical oximetry system with millisecond temporal resolution to elucidate early radiochemistry under irradiation.

Methods

Oxygen measurements were performed in vitro using the phosphorescence quenching method and a water-soluble molecular nanoprobe (Fig. 1). An epifluorescence fiber-coupled system was designed and built. The system was validated using a standard dissolved oxygen meter. The changes in oxygen per unit dose (G-value) were quantified in response to irradiation by 320 kVp x-ray and 16 MeV electron beam at dose rates ranging from 0.04 Gy/s to 100 Gy/s.

mainfig_signal decay.png

Results

Transient oxygen depletion of phosphate buffer solution under standard kV X-ray irradiation was continuously measured every millisecond (Fig. 2). The samples at normoxia with oxygen concentration of 150–240 µM had constant G-value of 0.54 uM/Gy, however hypoxic samples (15 µM and below) had significantly lower G-values (Fig. 3).

contmeas-xray1.png

oxygen depletion (μm_gy) michaelismenten.png

Conclusions

Our observations suggest that oxygen depletion rate decreases under hypoxia, with the measured data being a good fit to Michaelis-Menten kinetics. Future works will measure oxygen depletion kinetics of biomimetic lipid emulsions and in vivo mice under irradiation. We anticipate that the proposed method will capture crucial millisecond-order oxygen change after individual e-beam pulses.

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3D HIGH SPEED RF BEAM SCANNER FOR HADRON THERAPY OF CANCER

Session Type
FLASH Modalities Track (Oral Presentations)
Date
Thu, 02.12.2021
Session Time
15:10 - 16:10
Room
Hall C
Lecture Time
16:00 - 16:10

Abstract

Background and Aims

Treatment of cancer using actively scanned hadron pencil beams (protons and light ions) has major clinical advantages over treatments using photons. However, current methods used to adjust beam energies by degrading the beam are not compatible with the high dose rates needed for FLASH therapy. We are pursuing the demonstration of a compact accelerator technology to rapidly scan the energy and the trajectory of the hadron pencil beam to deposit the desired dose at FLASH dose rates.

Methods

We utilize RF energy modulation and deflection to enable a dose delivery of 50 Gy/L/s. Very fast irradiation presents many benefits to patients: (1) it solves the issue of patient motion and thus removes the need for tracking organ motion during irradiation (motion-adapted radiation therapy); it implies single- or hypofractionated treatments which will (2) increase dramatically patient throughput and (3) present biological benefits.

Results

We will present key innovations for energy modulation and lateral steering, including the design, optimization, and testing of critical components of an RF accelerator, RF deflector, and a PMQ. We have modeled dose deposition in phantoms with realistic beam parameters. We will also present our approach to integrating these technologies at a clinical beamline, monitoring dose deposition on a phantom target, and utilizing this information for treatment planning.

Conclusions

The scanner can be adjusted to cover the depth and lateral extent of the tumor while maintaining the quality of the pencil beam. Scanner operation in a clinical setting will provide definitive proof that the approach is viable and compatible with high dose rate FLASH.

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