Trial Outcomes & Findings for Lymphocyte Depletion and Change in Lymphocyte Functionality (NCT NCT04273893)

Last Updated: 2024-12-10

Results Overview

Mean percentage difference of measured absolute lymphocyte counts between the baseline and at each time points for the two separate arms

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

Target enrollment

55 participants

Primary outcome timeframe

Baseline to End of SBRT (up to 12 days), 4 weeks after SBRT (up to 1.5 months) and 6 months after SBRT (up to 10 months)

Results posted on

2024-12-10

Participant Flow

Participants were recruited based on physician referral at one academic medical center between February 2020 and April 2023. Participants were randomized with equal allocation to each ordering (optimize SBRT ARM or Standard SBRT ARM) using a stratified block randomization scheme with varying block sizes. Randomization occurred prior to start of treatment.

Two participants were discontinued from the study before treatment but after randomization. One participant became ineligible after discovering new medical history information and the other participant withdrew consent.

Participant milestones

Participant milestones
Measure	SBRT Additional Treatment Planning Dose Optimization Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. SBRT with additional treatment planning dose optimization: Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials.	SBRT With Standard of Care Planning Only Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) SBRT with standard of care planning only: Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC)
Overall Study STARTED	26	27
Overall Study Completed Treatment	25	26
Overall Study Completed 4 Week Follow Up	25	25
Overall Study COMPLETED	24	19
Overall Study NOT COMPLETED	2	8

Reasons for withdrawal

Reasons for withdrawal
Measure	SBRT Additional Treatment Planning Dose Optimization Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. SBRT with additional treatment planning dose optimization: Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials.	SBRT With Standard of Care Planning Only Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) SBRT with standard of care planning only: Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC)
Overall Study Withdrawal by Subject	0	2
Overall Study Treatment of Disease Progression	0	2
Overall Study Death	1	2
Overall Study Lost to Follow-up	0	2
Overall Study Physician Decision	1	0

Baseline Characteristics

Lymphocyte Depletion and Change in Lymphocyte Functionality

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SBRT Additional Treatment Planning Dose Optimization n=27 Participants Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. SBRT with additional treatment planning dose optimization: Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials.	SBRT With Standard of Care Planning Only n=28 Participants Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) SBRT with standard of care planning only: Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC)	Total n=55 Participants Total of all reporting groups
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	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	12 Participants n=7 Participants	27 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	27 Participants n=5 Participants	27 Participants n=7 Participants	54 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants	27 Participants n=7 Participants	51 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants	28 participants n=7 Participants	55 participants n=5 Participants
Lung Lesion Location Central	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Lung Lesion Location Peripheral	18 Participants n=5 Participants	22 Participants n=7 Participants	40 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to End of SBRT (up to 12 days), 4 weeks after SBRT (up to 1.5 months) and 6 months after SBRT (up to 10 months)

Population: Participants completing the CBC with Differential lab test to obtain absolute lymphocyte count results. A few participants missed the lab test or discontinued from the study for various reason resulting no lab data for a particular timepoint.

Mean percentage difference of measured absolute lymphocyte counts between the baseline and at each time points for the two separate arms

Outcome measures

Outcome measures
Measure	SBRT Additional Treatment Planning Dose Optimization n=25 Participants Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. SBRT with additional treatment planning dose optimization: Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials.	SBRT With Standard of Care Planning Only n=26 Participants Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) SBRT with standard of care planning only: Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC)
Impact of Lymphocyte-Sparing SBRT Planning Objectives on Post-SBRT Lymphocyte Count Between Baseline and End of SBRT	-15 Percentage from baseline Standard Deviation 18	-30 Percentage from baseline Standard Deviation 21
Impact of Lymphocyte-Sparing SBRT Planning Objectives on Post-SBRT Lymphocyte Count Between Baseline and 4 weeks after SBRT	-22 Percentage from baseline Standard Deviation 24	-34 Percentage from baseline Standard Deviation 18
Impact of Lymphocyte-Sparing SBRT Planning Objectives on Post-SBRT Lymphocyte Count Between Baseline and 6 months after SBRT	-15 Percentage from baseline Standard Deviation 29	-24 Percentage from baseline Standard Deviation 22

PRIMARY outcome

Timeframe: Baseline to End of SBRT (up to 12 days), 4 weeks after SBRT (up to 1.5 months) and 6 months after SBRT (up to 10 months)

Median of the difference between predicted value and observed measurement of lymphocyte absolute counts.

Outcome measures

Outcome measures
Measure	SBRT Additional Treatment Planning Dose Optimization n=25 Participants Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. SBRT with additional treatment planning dose optimization: Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials.	SBRT With Standard of Care Planning Only n=26 Participants Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) SBRT with standard of care planning only: Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC)
Determine if an Algorithm Can Predict the Magnitude of Post SBRT Lymphocyte Depletion Prospectively for Participants With NSCLC End of SBRT	0.14 10^9 cell/L Interval 0.06 to 0.27	0.18 10^9 cell/L Interval 0.08 to 0.38
Determine if an Algorithm Can Predict the Magnitude of Post SBRT Lymphocyte Depletion Prospectively for Participants With NSCLC 4 Weeks after SBRT	0.27 10^9 cell/L Interval 0.18 to 0.4	0.18 10^9 cell/L Interval 0.08 to 0.3
Determine if an Algorithm Can Predict the Magnitude of Post SBRT Lymphocyte Depletion Prospectively for Participants With NSCLC 6 Months after SBRT	0.23 10^9 cell/L Interval 0.14 to 0.41	0.21 10^9 cell/L Interval 0.14 to 0.46

Adverse Events

SBRT Additional Treatment Planning Dose Optimization

Serious events: 10 serious events

Other events: 24 other events

Deaths: 1 deaths

SBRT With Standard of Care Planning Only

Serious events: 7 serious events

Other events: 26 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

UVA Radiation Oncology Clinical Research Coordinator

University of Virginia

Phone: 434-243-0008

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	SBRT Additional Treatment Planning Dose Optimization n=26 participants at risk Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. SBRT with additional treatment planning dose optimization: Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials.	SBRT With Standard of Care Planning Only n=27 participants at risk Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) SBRT with standard of care planning only: Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC)
Gastrointestinal disorders Abdominal pain	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Aspiration	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Nervous system disorders Dizziness	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Dyspnea	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	7.4% 2/27 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Nervous system disorders Encephalopathy	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
General disorders Flu like symptoms	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Cardiac disorders Heart failure	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Metabolism and nutrition disorders Hyperglycemia	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Metabolism and nutrition disorders Hyponatremia	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Hypoxia	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Nervous system disorders Intracranial hemorrhage	7.7% 2/26 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Infections and infestations Lung infection	19.2% 5/26 • Number of events 5 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	14.8% 4/27 • Number of events 4 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Cardiac disorders Mobitz (type) II atrioventricular block	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Cardiac disorders Myocardial infarction	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
General disorders Non-cardiac chest pain	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Productive cough	7.7% 2/26 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Infections and infestations Sepsis	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Nervous system disorders Stroke	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Infections and infestations Upper respiratory infection	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Infections and infestations Urinary tract infection	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Pleural Effusion	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)

Measure	SBRT Additional Treatment Planning Dose Optimization n=26 participants at risk Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. SBRT with additional treatment planning dose optimization: Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials.	SBRT With Standard of Care Planning Only n=27 participants at risk Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) SBRT with standard of care planning only: Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC)
Gastrointestinal disorders Anal hemorrhage	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Metabolism and nutrition disorders Anorexia	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	7.4% 2/27 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Atelectasis	11.5% 3/26 • Number of events 3 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	29.6% 8/27 • Number of events 8 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Blood and lymphatic system disorders Lymphadenopathy	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Cardiac disorders Cardiac disorders - Other, specify	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Gastrointestinal disorders Constipation	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Cough	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Gastrointestinal disorders Diarrhea	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	7.4% 2/27 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Nervous system disorders Dizziness	7.7% 2/26 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Skin and subcutaneous tissue disorders Dry skin	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Nervous system disorders Dysgeusia	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Dyspnea	15.4% 4/26 • Number of events 6 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	29.6% 8/27 • Number of events 10 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
General disorders Edema limbs	11.5% 3/26 • Number of events 3 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	14.8% 4/27 • Number of events 4 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Endocrine disorders Endocrine disorders - Other, specify	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
General disorders Fatigue	30.8% 8/26 • Number of events 8 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	33.3% 9/27 • Number of events 9 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
General disorders Fever	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Injury, poisoning and procedural complications Fracture	11.5% 3/26 • Number of events 3 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Musculoskeletal and connective tissue disorders Generalized muscle weakness	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Nervous system disorders Headache	11.5% 3/26 • Number of events 3 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Hoarseness	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Hypoxia	11.5% 3/26 • Number of events 3 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	11.1% 3/27 • Number of events 4 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Infections and infestations Lung infection	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Gastrointestinal disorders Nausea	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
General disorders Non-cardiac chest pain	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	14.8% 4/27 • Number of events 4 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
General disorders Pain	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Nervous system disorders Paresthesia	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	23.1% 6/26 • Number of events 6 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	11.1% 3/27 • Number of events 3 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	26.9% 7/26 • Number of events 7 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	37.0% 10/27 • Number of events 10 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Productive cough	7.7% 2/26 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	22.2% 6/27 • Number of events 6 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	38.5% 10/26 • Number of events 10 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	37.0% 10/27 • Number of events 10 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Eye disorders Retinal detachment	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Sore throat	7.7% 2/26 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Renal and urinary disorders Urinary frequency	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Injury, poisoning and procedural complications Venous injury	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Investigations Weight loss	7.7% 2/26 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	0.00% 0/27 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Wheezing	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Bronchiolectasis	3.8% 1/26 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/26 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)
Gastrointestinal disorders Abdominal pain	7.7% 2/26 • Number of events 2 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)	3.7% 1/27 • Number of events 1 • From the time informed consent is obtained until 6 months after completion of SBRT (up to 11months)