Trial Outcomes & Findings for Stereotactic Radiation Therapy With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases (NCT NCT00377156)

Last Updated: 2022-09-16

Results Overview

The primary endpoint was cognitive deterioration (progression), defined as a decline of greater than 1 SD from baseline on at least 1 of 7 cognitive tests (all tests are standardized based on published norms and transformed so that higher values represent improved cognition) at the 3-month post-SRS evaluation. The number of participants who experienced cognitive deterioration by 3 months is reported for each arm below. For primary analysis of the 3-month cognitive deterioration endpoint, the Fisher exact 2-group binomial test was used to compare the proportion of evaluable patients with 3-month cognitive deterioration between the 2 groups.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

213 participants

Primary outcome timeframe

3 months post radiosurgery

Results posted on

2022-09-16

Participant Flow

At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. 70 patients accrued by ACOSOG Z0300 were included in the power calculation and also included for this study.

Participant milestones

Participant milestones
Measure	Arm I (SRS) Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Arm II (SRS+WBRT) Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.\> \> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Overall Study STARTED	111	102
Overall Study COMPLETED	63	48
Overall Study NOT COMPLETED	48	54

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (SRS) Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Arm II (SRS+WBRT) Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.\> \> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Overall Study Death	23	19
Overall Study Withdrawal by Subject	16	24
Overall Study Had follow-up <90 d	3	6
Overall Study Cancellation	1	0
Overall Study Refused testing	0	1
Overall Study Ineligible	0	1
Overall Study Disability or language problem	0	1
Overall Study Other	5	2

Baseline Characteristics

Stereotactic Radiation Therapy With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (SRS) n=111 Participants Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Arm II (SRS+WBRT) n=102 Participants Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.\> \> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.	Total n=213 Participants Total of all reporting groups
Age, Continuous	59.8 years STANDARD_DEVIATION 10.4 • n=5 Participants	61.4 years STANDARD_DEVIATION 10.6 • n=7 Participants	60.6 years STANDARD_DEVIATION 10.5 • n=5 Participants
Age, Customized 18 to 59	53 Participants n=5 Participants	44 Participants n=7 Participants	97 Participants n=5 Participants
Age, Customized >= 60	58 Participants n=5 Participants	58 Participants n=7 Participants	116 Participants n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	47 Participants n=7 Participants	104 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	55 Participants n=7 Participants	109 Participants n=5 Participants
Region of Enrollment Canada	23 participants n=5 Participants	22 participants n=7 Participants	45 participants n=5 Participants
Region of Enrollment United States	88 participants n=5 Participants	80 participants n=7 Participants	168 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months post radiosurgery

Population: Patients who died prior to the 3-month evaluation, who did not return for the 3-month evaluation or a subsequent evaluation, or who did not complete the required baseline tests were excluded from the analysis population for the primary end point.

Outcome measures

Outcome measures
Measure	Arm I (SRS) n=63 Participants Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Arm II (SRS+WBRT) n=48 Participants Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.\> \> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Neurocognitive Progression as Measured by the Number of Participants With Cognitive Deterioration by 3 Months	40 Participants	44 Participants

SECONDARY outcome

Timeframe: Up to 3 months

Number of Participants with Local and Distant Tumor Control up to 3 months is defined as....

Outcome measures

Outcome measures
Measure	Arm I (SRS) n=105 Participants Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Arm II (SRS+WBRT) n=95 Participants Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.\> \> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Number of Participants With Local and Distant Tumor Control up to 3 Months	79 Participants	89 Participants

SECONDARY outcome

Timeframe: From Baseline to 3-Month Evaluation

Population: All patients in the SRS and SRS+WBRT groups that had a baseline and 3-month QOL score were used in this analysis.

Quality of Life was assessed using the Functional Assessment of Cancer Therapy-Brain, for which the range is from 0 to 200 and higher scores indicate better QOL. The Quality of Life (QOL) scores were transformed to a 0- to 100-point scale (with 100 being most favorable), in which a 10-point change was considered clinically significant. Intergroup changes in QOL scores were compared using a 2-sample t test.

Outcome measures

Outcome measures
Measure	Arm I (SRS) n=65 Participants Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Arm II (SRS+WBRT) n=50 Participants Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.\> \> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Overall Quality of Life, as Measured by Mean Change From Baseline [3 Month]	-0.1 QOL score change from baseline points Interval -4.8 to 4.5	-12 QOL score change from baseline points Interval -17.5 to -6.6

SECONDARY outcome

Timeframe: From baseline to 12 months

Population: Patients who survived for at least 12 months and had at least one cognitive assessment on or after 365 days were included in this analysis.

Long-Term Neurocognitive Status \> To ascertain in patients with one to three brain metastases whether there is better long-term neurocognitive status in patients who receive SRS alone (Arm A) compared to patients who receive SRS combined with WBRT (Arm B). Long-term survival status is defined as evaluable patients who survived for at least 12 months and had at least one cognitive assessment on or after 365 days.

Outcome measures

Outcome measures
Measure	Arm I (SRS) n=10 Participants Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Arm II (SRS+WBRT) n=18 Participants Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.\> \> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Long-Term Neurocognitive Status (Long-Term Cognitive Status), as Measured by Percentage of Long-term Survivors With Cognitive Deterioration at 12 Months	60 percentage of participants	94.44 percentage of participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: A survival comparison was performed on an intention-to-treat basis using the entire study population.

Overall survival, defined as the time from randomization until death due to any cause, was compared between the groups using stratified log-rank tests.

Outcome measures

Outcome measures
Measure	Arm I (SRS) n=111 Participants Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Arm II (SRS+WBRT) n=102 Participants Patients undergo stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT) received 22 Gy in a single fraction if lesions were less than 2.0cm or 18 Gy if lesions were 2 to 2.9 cm in maximum diameter.\> \> Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Overall Survival	10.4 months Interval 0.0 to 62.5	7.4 months Interval 0.0 to 60.9

Adverse Events

Arm I (SRS)

Serious events: 8 serious events

Other events: 45 other events

Deaths: 5 deaths

Arm II (SRS+WBRT)

Serious events: 11 serious events

Other events: 53 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Paul Brown, M.D.

Mayo Clinic

Phone: 507-538-0948

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm I (SRS) n=68 participants at risk Patients undergo stereotactic radiosurgery (SRS) received 24 Gy in a single fraction if lesions were less than 2.0cm or 20 Gy if lesions were 2 to 2.9 cm in maximum diameter.	Arm II (SRS+WBRT) n=64 participants at risk Patients randomly assigned to SRS plus WBRT received 30 GY in 12 fractions of 2.5-Gy WBRT delivered 5 days a week. Whole brain radiotherapy began within 14 days of SRS.
Ear and labyrinth disorders Hearing loss	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Gastrointestinal disorders Nausea	1.5% 1/68 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	0.00% 0/64 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Gastrointestinal disorders Vomiting	1.5% 1/68 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	0.00% 0/64 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
General disorders Death	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	4.7% 3/64 • Number of events 6 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
General disorders Disease progression	4.4% 3/68 • Number of events 6 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	3.1% 2/64 • Number of events 3 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
General disorders Fatigue	1.5% 1/68 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	0.00% 0/64 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Infections and infestations Bladder infection	1.5% 1/68 • Number of events 1 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	0.00% 0/64 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Infections and infestations Bronchitis	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Infections and infestations Encephalitis infection	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 1 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Investigations Alanine aminotransferase increased	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Investigations Alkaline phosphatase increased	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Investigations Bilirubin increased	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Investigations Leukocyte count decreased	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Investigations Neutrophil count decreased	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Investigations Platelet count decreased	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Nervous system disorders Central nervous system necrosis	1.5% 1/68 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	0.00% 0/64 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Nervous system disorders Cognitive disturbance	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Nervous system disorders Encephalopathy	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	0.00% 0/68 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.5% 1/68 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	0.00% 0/64 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.5% 1/68 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	1.6% 1/64 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.
Vascular disorders Thrombosis	1.5% 1/68 • Number of events 2 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.	0.00% 0/64 • Up to 60 months from the start of treatment All patients that began treatment and were assessed at least once for adverse events are included in this analysis. Adverse Events were collected at weeks 6 and 12 after radiation treatment, and at months 6, 9, 12, 16, 24, 36, 48, and 60 after radiation treatment.