Vienna, Austria

ESTRO 2023

Session Item

May 15
15:00 - 16:00
Stolz 1
Jan Bussink, The Netherlands;
Shing Fung Lee, Singapore
15:00 - 16:00
BIOGUIDE-X: A First-in-Human Study of the Performance and Safety of Biology-Guided Radiotherapy
Lucas Vitzthum, USA


BIOGUIDE-X: A First-in-Human Study of the Performance and Safety of Biology-Guided Radiotherapy

Lucas Vitzthum1, Murat Surucu2, Michael Gensheimer2, Nataliya Kovalchuk2, Bin Han2, Daniel Pham2, Daniel Chang3, Shervin Shirvani4, Didem Aksoy4, Arjun Maniyedath4, Manoj Narayanan5, Angela Da Silva5, Samuel Mazin6, Karine Al Feghali4, Puneeth Iyengar7, Tu Dan7, Arnold Pompos7, Robert Timmerman7, Orhan Öz8, Bin Cai7, Aurelie Garant7

1Stanford University School of Medicine , Radiation Oncology, Stanford, USA; 2Stanford University School of Medicine, Radiation Oncology, Stanford, USA; 3University of Michigan School of Medicine, Radiation Oncology, Ann Arbor, USA; 4RefleXion Medical, Clinical and Medical Affairs, Hayward, USA; 5RefleXion Medical, Research and Development,, Hayward, USA; 6RefleXion Medical, Corporate, Hayward, USA; 7UT Southwestern Medical Center, Radiation Oncology, Dallas, USA; 8UT Southwestern Medical Center, Radiology, Dallas, USA

Show Affiliations
Purpose or Objective

Biology-guided radiotherapy (BgRT) is a novel tracked dose delivery modality that uses real-time positron emission tomography (PET) to guide radiotherapy beamlets. Human subject data demonstrating accurate targeting with BgRT has not yet been presented. The BIOGUIDE-X study was performed with sequential cohorts of participants to (1) Identify the fluorodeoxyglucose (FDG) dose for BgRT on the RefleXion® X1 system and (2) Confirm that the emulated dose distribution of BgRT at delivery timepoints was consistent with a physician-approved radiotherapy plan.

Material and Methods

This single-arm, open-label, prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (≥2cm and ≤5cm) in the lung or bone. For Cohort I, a modified 3 + 3 design was used to determine the FDG dose that would result in adequate FDG activity for BgRT functioning. For Cohort II, PET imaging data were collected on the X1 before the first and last fractions among patients undergoing conventional stereotactic ablative body radiotherapy. BgRT dose distributions were modeled on the patient’s CT anatomy using the collected PET data at each fraction, a process termed ‘emulated delivery’. A dose distribution was scored as accurate if 95% of dose volume histogram (DVH) points in the emulated delivery fell within the boundaries of the BgRT plan’s bounded DVH. Secondary endpoints included the deliverability of emulated fluence, safety of multiple FDG administrations, and BgRT workflow feasibility.


Cohort I study results demonstrated that adequate FDG activity was achieved in 6/6 (100.0%) of evaluable participants with the first injected dose level of 15 mCi FDG. In Cohort II, 4 patients with lung tumors and 5 with bone tumors were enrolled, and evaluable emulated delivery data points were collected for 17 treatment fractions. Sixteen of the 17 emulations resulted in BgRT dose distributions that were accurate with respect to the approved BgRT plan. The 17th data point was just below the 95% threshold for accuracy (DVH Score = 94.6%). All emulated fluences were physically deliverable. No toxicities were attributed to multiple FDG administrations.


BgRT is a novel radiotherapy modality in which a radiolabeled tumor can act as its own fiducial for radiotherapy targeting. This study is the first human validation of real-time BgRT dosimetry. The investigation demonstrated that 15 mCi FDG provides adequate activity for BgRT planning and delivery. Emulated BgRT dose distributions calculated from continuously acquired real-time PET data were accurate and machine-deliverable. The safety of multiple FDG administrations and the feasibility of the BgRT workflow were also confirmed.