Trial Outcomes & Findings for Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases (NCT NCT03391362)

Last Updated: 2026-07-14

Results Overview

Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic progressive disease).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

Target enrollment

100 participants

Primary outcome timeframe

12 months

Results posted on

2026-07-14

Participant Flow

Participants were recruited at Brigham and Women's Hospital / Dana-Farber Cancer Institute as well as at Beth Israel Deaconess Medical Center, Milford Regional Medical Center, and South Shore Health. All patients were assessed for eligibility before being approached by their treating physician regarding participation in the study. Study enrollment occurred between February 2018 and April 2023.

Participant milestones

Participant milestones
Measure	Stereotactic Radiation * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Overall Study STARTED	100
Overall Study COMPLETED	100
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions
Age, Continuous	68 Years n=9 Participants
Sex: Female, Male Female	55 Participants n=9 Participants
Sex: Female, Male Male	45 Participants n=9 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants
Race (NIH/OMB) Asian	2 Participants n=9 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants
Race (NIH/OMB) Black or African American	5 Participants n=9 Participants
Race (NIH/OMB) White	89 Participants n=9 Participants
Race (NIH/OMB) More than one race	4 Participants n=9 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=9 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	94 Participants n=9 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=9 Participants
Primary Site of Malignancy SCLC Primary	96 Participants n=9 Participants
Primary Site of Malignancy Extrathoracic Primary	4 Participants n=9 Participants
Karnofsky Performance Status <70	6 Participants n=9 Participants
Karnofsky Performance Status 70-80	48 Participants n=9 Participants
Karnofsky Performance Status 90-100	40 Participants n=9 Participants
Karnofsky Performance Status Unknown	6 Participants n=9 Participants
Smoking Status Never	11 Participants n=9 Participants
Smoking Status Current	12 Participants n=9 Participants
Smoking Status Prior	77 Participants n=9 Participants
Number of Brain Metastases	2 Metastases n=9 Participants
Size of Largest Brain Metastasis	12 millimeters n=9 Participants
Neurologic Symptoms at Diagnosis Yes	68 Participants n=9 Participants
Neurologic Symptoms at Diagnosis No	32 Participants n=9 Participants
Seizures at Diagnosis No	96 Participants n=9 Participants
Seizures at Diagnosis Yes	4 Participants n=9 Participants
Distant Extracranial Metastases No	57 Participants n=9 Participants
Distant Extracranial Metastases Yes	43 Participants n=9 Participants
Systemic Therapy for Metastatic Disease Prior to Study Registration No	17 Participants n=9 Participants
Systemic Therapy for Metastatic Disease Prior to Study Registration Yes	83 Participants n=9 Participants
Intracranial Resection Prior to Study Registration No	84 Participants n=9 Participants
Intracranial Resection Prior to Study Registration Yes	16 Participants n=9 Participants
Dexamethasone Use No	83 Participants n=9 Participants
Dexamethasone Use Yes	17 Participants n=9 Participants

PRIMARY outcome

Timeframe: 12 months

Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic progressive disease).

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Neurologic Mortality	11.0 percentage of participants Interval 5.8 to 18.1

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Population: 16 patients remained alive at time of analysis

Death from any cause cumulative incidence estimate assessed at 1 year and 2 year

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
All-cause Mortality 1-Year Estimate	59.0 percentage of participants Interval 49.6 to 68.7
All-cause Mortality 2-Year Estimate	81.9 percentage of participants Interval 73.2 to 89.2

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Questionnaire - MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Hopkins Verbal Learning Test -Revised (HVLT-R). Scores are transformed into Z scores.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Trail Making Test Part A and B (TMT). Scores are transformed into Z scores.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Controlled Oral Word Association Test (COWAT). Scores are transformed into Z scores.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Mini Mental Status Examination (MMSE). Scored 0 to 30. Higher scores indicate better cognitive function

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Questionnaire - EQ-5D. A patient reported quality of life questionnaire

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Karnofsky performance status. Scale ranges from 0 to 100, with higher scores indicating better function.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

1 and 2 year estimates of first appearance of new brain metastases (on radiographic assessment)

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
One and Two Year Incidence of New Brain Metastases 1-Year Estimate	59.0 percentage of participants Interval 48.6 to 68.0
One and Two Year Incidence of New Brain Metastases 2-Year Estimate	60.2 percentage of participants Interval 49.7 to 69.2

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Population: 1 and 2-Year cumulative incidence estimates of local recurrence in brain metastases treated on study on a per patient basis.

Per patient radiographic assessment of first event of local recurrence in the brain metastases treated with radiation on trial. One- and 2-Year estimates.

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Incidence of Existing Brain Metastases 1 Year Estimate	15.0 percentage of participants Interval 8.8 to 22.7
Incidence of Existing Brain Metastases 2 Year Estimate	17.1 percentage of participants Interval 3.8 to 20.4

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Per patient radiographic assessment of first event of radiation necrosis in the brain metastases treated with radiation on trial. One- and 2-Year cumulative incidence estimates.

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Incidence of Development of Radiographic Radiation Necrosis 1 Year Estimate	6.0 percentage of participants Interval 2.4 to 11.9
Incidence of Development of Radiographic Radiation Necrosis 2 Year Estimate	8.1 percentage of participants Interval 3.7 to 14.5

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Per patient radiographic assessment of first event of leptomeningeal disease. One- and 2-Year estimates.

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Incidence of Development of Leptomeningeal Disease 1 Year Estimate	7.0 percentage of participants Interval 3.1 to 13.1
Incidence of Development of Leptomeningeal Disease 2 Year Estimate	9.0 percentage of participants Interval 4.4 to 15.7

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Per patient clinical assessment of first use of neurosurgical resection / craniotomy as salvage therapy in metastases treated with radiation on trial. One- and 2-Year estimates.

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Incidence of Salvage Craniotomy 1 Year Estimates	4.0 percentage of participants Interval 1.3 to 9.2
Incidence of Salvage Craniotomy 2 Year Estimates	7.1 percentage of participants Interval 3.1 to 13.3

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Per patient clinical assessment of first use of salvage brain-directed stereotactic radiation. 1- and 2-Year estimates.

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Incidence of Additional CNS-directed Radiotherapeutic Treatments (Stereotactic Radiation) After the Initial Course 1 Year Estimate	37.0 percentage of participants Interval 27.5 to 46.5
Incidence of Additional CNS-directed Radiotherapeutic Treatments (Stereotactic Radiation) After the Initial Course 2 Year Estimate	39.1 percentage of participants Interval 29.4 to 48.6

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Per patient clinical assessment of first post-treatment seizure as assessed during routine study visits and via medical record review. 1 and 2-Year estimates.

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Incidence of Seizures 1 Year Estimates	7.0 percentage of participants Interval 3.1 to 13.1
Incidence of Seizures 2 Year Estimates	12.2 percentage of participants Interval 6.6 to 19.6

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Per patient assessment of first event of symptomatic radiation necrosis in the brain metastases treated with radiation on trial. 1- and 2-Year estimates.

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Incidence of Symptomatic Radiation Necrosis 1 Year Estimate	3.0 percentage of participants Interval 0.8 to 7.9
Incidence of Symptomatic Radiation Necrosis 2 Year Estimate	5.4 percentage of participants Interval 1.9 to 11.4

SECONDARY outcome

Timeframe: 2-years

Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic progressive disease).

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Incidence of Neurologic Death at 2 Years	20.3 percentage of participants Interval 12.7 to 29.1

SECONDARY outcome

Timeframe: Until death or loss to follow up, up to 24 months

Per patient clinical assessment of first use of salvage whole brain radiation. One- and 2-Year estimates.

Outcome measures

Outcome measures
Measure	Stereotactic Radiation n=100 Participants * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Incidence of Additional CNS-directed Radiotherapeutic Treatments (Whole Brain Radiation) After the Initial Course 1 Year Estimate	21.0 percentage of participants Interval 13.6 to 29.5
Incidence of Additional CNS-directed Radiotherapeutic Treatments (Whole Brain Radiation) After the Initial Course 2 Year Estimate	22.4 percentage of participants Interval 14.6 to 31.2

Adverse Events

Stereotactic Radiation

Serious events: 9 serious events

Other events: 94 other events

Deaths: 84 deaths

Serious adverse events

Serious adverse events
Measure	Stereotactic Radiation n=100 participants at risk * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Nervous system disorders Radiation Necrosis	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.0% 1/100 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Seizure	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Musculoskeletal and connective tissue disorders Back pain	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Headache	2.0% 2/100 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Gastrointestinal disorders Gastroesophageal reflux disease	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Atelectasis	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Gastrointestinal disorders Esophagitis	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Systemic Disease Progression	3.0% 3/100 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	1.0% 1/100 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.

Other adverse events

Other adverse events
Measure	Stereotactic Radiation n=100 participants at risk * Stereotactic radiation will begin within 14 days of the MRI used for radiation planning * Lesions \<2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction * Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction * Lesions \>3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions Stereotactic Radiation: Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases
Cardiac disorders Sinus bradycardia	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Ear and labyrinth disorders Hearing impaired	2.0% 2/100 • Number of events 2 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Ear and labyrinth disorders Tinnitus	2.0% 2/100 • Number of events 2 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Eye disorders Blurred vision	6.0% 6/100 • Number of events 6 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Eye disorders Dry Eye	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Gastrointestinal disorders Diarrhea	3.0% 3/100 • Number of events 3 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Gastrointestinal disorders Dry Mouth	3.0% 3/100 • Number of events 3 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Gastrointestinal disorders Fecal incontinence	3.0% 3/100 • Number of events 3 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Gastrointestinal disorders Nausea	12.0% 12/100 • Number of events 12 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
General disorders Edema face	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
General disorders Edema limbs	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
General disorders Fatigue	17.0% 17/100 • Number of events 17 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
General disorders Gait disturbance	5.0% 5/100 • Number of events 5 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
General disorders Irritability	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Injury, poisoning and procedural complications Fall	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Investigations Weight loss	2.0% 2/100 • Number of events 2 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Metabolism and nutrition disorders Anorexia	9.0% 9/100 • Number of events 9 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Musculoskeletal and connective tissue disorders Back pain	4.0% 4/100 • Number of events 4 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	6.0% 6/100 • Number of events 6 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Musculoskeletal and connective tissue disorders Muscle weakness in lower limb	3.0% 3/100 • Number of events 3 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	5.0% 5/100 • Number of events 5 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Musculoskeletal and connective tissue disorders Neck pain	3.0% 3/100 • Number of events 3 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Musculoskeletal and connective tissue disorders Pain in extremity	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Musculoskeletal and connective tissue disorders Trismus	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Ataxia	3.0% 3/100 • Number of events 3 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Cognitive disturbance	4.0% 4/100 • Number of events 4 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Dizziness	4.0% 4/100 • Number of events 4 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Dysarthria	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Dysgeusia	2.0% 2/100 • Number of events 2 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Edema cerebral	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Headache	13.0% 13/100 • Number of events 13 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Intracranial hemorrhage	2.0% 2/100 • Number of events 2 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Memory impairment	3.0% 3/100 • Number of events 3 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Myelitis	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Paresthesia	4.0% 4/100 • Number of events 4 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Peripheral sensory neuropathy	4.0% 4/100 • Number of events 4 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Seizure	7.0% 7/100 • Number of events 7 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Syncope	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Nervous system disorders Trigeminal nerve disorder	2.0% 2/100 • Number of events 2 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Psychiatric disorders Anxiety	3.0% 3/100 • Number of events 3 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Psychiatric disorders Confusion	2.0% 2/100 • Number of events 2 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Psychiatric disorders Depression	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Psychiatric disorders Insomnia	7.0% 7/100 • Number of events 7 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Renal and urinary disorders Urinary incontinence	2.0% 2/100 • Number of events 2 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Cough	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Hoarseness	1.0% 1/100 • Number of events 1 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.
Skin and subcutaneous tissue disorders Alopecia	3.0% 3/100 • Number of events 3 • From enrollment until end of follow-up (duration of patient survival post-treatment), on average 2 years. Data were collected at each visit, approximately every 8 weeks for the first 9 months of study participation and then approximately every 3 months thereafter for duration of patient time on study (until death of off study for any other reason), approximately 2 years.

Additional Information

Ayal Aizer, MD, MHS

Brigham and Women's Hospital

Phone: (617) 732-7560

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place