Trial Outcomes & Findings for Performance and Safety of Biology-Guided Radiotherapy Using the RefleXion Medical Radiotherapy System (BIOGUIDE-X) (NCT NCT04788147)

Results Overview

The primary endpoint determined the number of cases that received the lowest FDG dose of 15 mCi, completed the RMRS image session and established an adequate target activity concentration to enable Biology guided Radiotherapy planning. The starting dose was 15mCi which was determined based upon preliminary physics studies done prior to this study. A FDG dose escalation to 20 mCi was not required.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

30 participants

Primary outcome timeframe

During the RMRS imaging session

Results posted on

2023-10-31

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) Cohort Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, after which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition timepoint: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.
Overall Study STARTED	11	19
Overall Study Enrolled (Received FDG Injection)	8	9
Overall Study COMPLETED	6	9
Overall Study NOT COMPLETED	5	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) Cohort Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, after which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition timepoint: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.
Overall Study Screen Failure	3	10
Overall Study Incomplete RMRS image session	2	0

Baseline Characteristics

Performance and Safety of Biology-Guided Radiotherapy Using the RefleXion Medical Radiotherapy System (BIOGUIDE-X)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) Cohort n=8 Participants Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort n=9 Participants Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Total n=17 Participants Total of all reporting groups
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous Cohort I & Cohort II	68.01 years n=5 Participants	73.0 years n=7 Participants	70.5 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: During the RMRS imaging session

Population: The number of patients that received 15 mCi FDG dose and completed the RMRS image session.

The primary endpoint determined the number of cases that received the lowest FDG dose of 15 mCi, completed the RMRS image session and established an adequate target activity concentration to enable Biology guided Radiotherapy planning. The starting dose was 15mCi which was determined based upon preliminary physics studies done prior to this study. A FDG dose escalation to 20 mCi was not required.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=6 Participants Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort I Recommended RefleXion FDG Dose (RRFD) to Enable the Use of BgRT Planning.	6 Participants	—	—

PRIMARY outcome

Timeframe: After SBRT First Fraction (standard of care) and after SBRT Last Fraction (standard of care)

Population: Cohort II - Emulated Delivery population evaluable scans

The number of scans/fractions where the emulated BgRT dose distribution in a phantom was consistent with the BgRT treatment plan (i.e., 95% of DVH Delivered points for the BTZ and OAR fall within bounded DVH of the approved BgRT plan). There were 9 first fractions and 8 last fractions that were analyzed.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=17 Evaluable Fractions Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort II: Delivery Emulation	16 Evaluable Fractions	—	—

SECONDARY outcome

Timeframe: Immediately after RMRS imaging session

Population: The number of participants that received 15 mCi FDG dose injection and completed the RMRS image session.

This endpoint evaluated percent of cases where there was an agreement between the site investigator SI and an Agreement Standard (AS) for the PET modeling localization decision. Six image comparisons were performed.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=6 Participants Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort I: Endpoint 1 Percent Agreement Between SI and AS for BgRT PET Imaging-only Session	5 Participants	—	—

SECONDARY outcome

Timeframe: Immediately after RMRS imaging session

This endpoint evaluated Percent of cases where there was concordance of the positive "plan proceed" decision between the BgRT PET Imaging-only session and a third-party diagnostic PET/CT.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=6 Participants Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort I Endpoint 2: Percent of Cases X1 PET vs. Third-party Diagnostic PET/CT Image Comparison	5 Participants	—	—

SECONDARY outcome

Timeframe: Immediately after RMRS imaging session

Secondary Endpoint 3 evaluated the percent of cases where X1 PET images generated an Acceptable BgRT plan.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=6 Participants Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort I Endpoint 3: Biology Guided Radiotherapy (BgRT) Plan Generation	4 Participants	—	—

SECONDARY outcome

Timeframe: Immediately after RMRS imaging session

Secondary Endpoint 4 determined the percent of cases where the generated BgRT plan achieved acceptable quality assurance metrics in a physical phantom.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=6 Participants Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort I Endpoint 4: Percent of Cases Where the Intended Dose Distribution of BgRT Plan Was Achieved in the Physical Phantom.	6 Participants	—	—

SECONDARY outcome

Timeframe: Assessed after SBRT First Fraction (standard of care) and after SBRT Last Fraction (standard of care), reported after SBRT Last Fraction.

Population: 17 scans for nine (9) subjects were used to measure the percent of fraction concordance between physical and digital phantoms of emulated BgRT delivery

Number of fractions where there is concordance between the physical and digital phantoms of emulated BgRT delivery derived from human subject PET emissions. Concordance is defined as a standard gamma index with a goal that 90% of pixels meet the 3mm/3% deviation standard.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=17 Fractions Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort II Endpoint 1 Percent of Fractions With Concordance Between Physical and Digital Phantoms	17 Fractions	—	—

SECONDARY outcome

Timeframe: Assessed After PET Pre-Scan 1 and after PET Pre-Scan 2, reported after PET Pre-Scan 2.

Population: Cohort II Inter-observer agreement for Localization decision on RMRS PET Pre-Scan image

Number of Pre-scan images where there is agreement between a site investigator and the agreement standard for the BgRT PET PreScan localization decision (overall percent agreement). Positive percent agreement and negative percent agreement will also be reported.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=18 PET Pre-Scan Image Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort II Endpoint 2 Localization Decision	13 PET Pre-Scan Image	—	—

SECONDARY outcome

Timeframe: Assessed after Last fraction Imaging-only PET scan and Third-party PET/CT scan and reported after Third-party PET/CT scan.

Population: Comparison of short-duration PET CRR01 vs. Third-party Pet/CT

Number of Scans where there is concordance of a positive localization decision between the short-duration PET PreScan and a third-party diagnostic PET/CT scan (positive percent agreement). Overall percent agreement and negative percent agreement will also be reported.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=7 Scans Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort II Endpoint 3 Image Concordance (Cohort II) Positive Agreement	7 Scans	—	—
Cohort II Endpoint 3 Image Concordance (Cohort II) Overall agreement	7 Scans	—	—

SECONDARY outcome

Timeframe: Assessed at 72±24 hours after final FDG injection

Population: TEAE specific to Bladder or Bone Marrow

Number of Participants who experienced AEs related to bladder and bone marrow assessed by complete blood count, urinalysis and AEs specific to bladder and bone marrow determined by Common Terminology Criteria for Adverse Events (CTCAE) v5 at 72±24 hours after final FDG injection.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=9 Participants Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort II Endpoint 4 Toxicity Related to FDG Administrations	0 participants	—	—

SECONDARY outcome

Timeframe: a. Immediately after RMRS imaging-Only sessions b. After acceptable BgRT plan generation c. During BgRT physics Quality Assurance

Population: PET imaging-Only sessions at RRFD that meets BTZ activation concentration threshold for BgRT (5 kBq/ml)

Workflow characterization by 1. Number of participants with PET imaging-Only scans at RRFD that meet the Activity Concentration (AC) threshold for BgRT. 2. Number of participants with PET imaging-Only scans that generate an acceptable BgRT plans. 3. Number of participants with approved BgRT plans that Passed Physics Quality Assurance.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=6 Participants Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort n=9 Participants Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II n=15 Participants Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort II Endpoint 5 Workflow Characterization Number of participants with PET imaging-Only scans at RRFD meeting the AC threshold for BgRT.	6 Participants	9 Participants	15 Participants
Cohort II Endpoint 5 Workflow Characterization b. Number of participants PET imaging sessions which lead to acceptable BgRT plans.	4 Participants	9 Participants	13 Participants
Cohort II Endpoint 5 Workflow Characterization c. Number of participants approved BgRT plans that go on to pass physics quality assurance	4 Participants	9 Participants	13 Participants

SECONDARY outcome

Timeframe: Assessed after PET Pre-Scan 1 prior to First Fraction delivery and after PET Pre-Scan 2 prior to Last Fraction delivery, reported after PET Pre-Scan 2 prior to Last Fraction.

Population: Cohort II (Emulated Delivery Cohort)

Number of PET Pre-Scans on the Day of Fraction Delivery that Elicited a "Pass" Signal Fraction Delivery.

Outcome measures

Outcome measures
Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) n=18 Scans Cohort I: Each participant (5 participants with bone tumor and 3 participants with lung tumor) underwent a CT simulation, then received a single injection of 15 mCi of FDG then underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device. Each participant was then followed up at 72±24 hours after the imaging-only session.	Cohort II: Delivery Emulation Cohort Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.	Combined Cohort I + Cohort II Combined Cohort I (RRFD Cohort) and Cohort II (Emulated Delivery Cohort) to characterize RefleXion system functioning
Cohort II Endpoint 5d Workflow Characterization: PET Evaluations That Elicited a "Pass" Signal	17 Scans	—	—

Adverse Events

Cohort I: Recommended RefleXion FDG Dose (RRFD) Cohort

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort II: Delivery Emulation Cohort

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Debradenise Brooks

RefleXion

Phone: 16504828435

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort I: Recommended RefleXion FDG Dose (RRFD) Cohort n=8 participants at risk Cohort I: All Participants, 5 participants with bone tumor and 3 participants with lung tumor, underwent CT simulations, received single injection of 15 mCi of FDG, underwent back-to-back RefleXion PET Imaging-Only session and third-party diagnostic PET/CT device and was followed up at 72±24 hours.	Cohort II: Delivery Emulation Cohort n=9 participants at risk Cohort II: The RRFD was determined in Cohort 1 as 15 mCi, aftter which enrollment began for Cohort II. In Cohort II each participant, (4 with bone tumor and 5 with lung tumor), underwent RefleXion PET image-only sessions at three different timepoints. Each participant received a FDG injection of 15 mCi, prior to each image acquisition: The timepoints were as follows: 1\. At the time of enrollment: RefleXion PET image-only 2: At SBRT First Fraction (Standard of Care): RefleXion PET Prescan #1 3: At SBRT Last Fraction (Standard of Care): RefleXion PET Prescan #2 plus a Third-party PET/Scan. The participants were then followed-up at 72 ± 24 hours after final FDG injection.
Musculoskeletal and connective tissue disorders Pain in Extremity	12.5% 1/8 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 1/8 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 2 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Musculoskeletal and connective tissue disorders Back Pain	25.0% 2/8 • Number of events 2 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Gastrointestinal disorders Oral Dysthesia	12.5% 1/8 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	0.00% 0/9 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	0.00% 0/9 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Metabolism and nutrition disorders Anorexia	12.5% 1/8 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	0.00% 0/9 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Musculoskeletal and connective tissue disorders Neck Pain	12.5% 1/8 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	0.00% 0/9 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Nervous system disorders Somolence	12.5% 1/8 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	0.00% 0/9 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/8 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Investigations Creatinine Increased	0.00% 0/8 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
General disorders Fatigue	0.00% 0/8 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	22.2% 2/9 • Number of events 2 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Renal and urinary disorders Pollakiuria	0.00% 0/8 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Investigations Platelet count decrease	0.00% 0/8 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Investigations WBC decreased	0.00% 0/8 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Reproductive system and breast disorders Prostatic Obstruction	0.00% 0/8 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
General disorders Anemia	0.00% 0/8 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.
Investigations Lymphocyte count decrease	0.00% 0/8 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.	11.1% 1/9 • Number of events 1 • Cohort I -RRFD: AEs were collected starting at the time of injection of FDG and assessed at 72±24 hours after the end of Imaging-only session. Cohort II -Emulated Delivery: AEs were collected starting at time of first FDG injection and assessed at 72±24 hours after the final FDG injection. Any deaths, SAE, and other adverse events that started at the time of first FDG injection or 72±24 hours after the last FDG injection were collected in this study.