Trial Outcomes & Findings for Radiation Therapy in Preventing Central Nervous System (CNS) Metastases in Patients With Non-Small Cell Lung Cancer (NCT NCT00048997)

NCT ID: NCT00048997

Last Updated: 2018-06-08

Results Overview

Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 12 months.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 356 participants
• Primary outcome timeframe: From randomization to last follow-up. Analysis occurred after all patients had been on study for at least 12 months. Maximum follow-up at time of analysis was 96 months.
• Results posted on: 2018-06-08

Participant Flow

Participant milestones

Measure	Prophylactic Cranial Irradiation (PCI) PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation Observation
Overall Study STARTED	176	180
Overall Study COMPLETED	163	177
Overall Study NOT COMPLETED	13	3

Reasons for withdrawal

Measure	Prophylactic Cranial Irradiation (PCI) PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation Observation
Overall Study Protocol Violation	7	2
Overall Study Withdrawal by Subject	6	1

Baseline Characteristics

Radiation Therapy in Preventing Central Nervous System (CNS) Metastases in Patients With Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Prophylactic Cranial Irradiation (PCI) n=163 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=177 Participants Observation.	Total n=340 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	60 years n=7 Participants	61 years n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	67 Participants n=7 Participants	127 Participants n=5 Participants
Sex: Female, Male Male	103 Participants n=5 Participants	110 Participants n=7 Participants	213 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to last follow-up. Analysis occurred after all patients had been on study for at least 12 months. Maximum follow-up at time of analysis was 96 months.

Population: All eligible patients

Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 12 months.

Outcome measures

Measure	Prophylactic Cranial Irradiation (PCI) n=163 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=177 Participants Observation
Overall Survival	28.5 months Interval 23.6 to 34.9	25.3 months Interval 21.0 to 32.2

SECONDARY outcome

Timeframe: Baseline and one year post study entry

Population: All eligible patients with a baseline and 12 month HVLT-R assessment.

The HVLT-R assesses verbal learning and memory. It incorporates 6 different forms to mitigate practice effects of repeated administrations. Each form includes 12 nouns (targets) with 4 words drawn from 3 semantic categories, which differ across the 6 forms. The recall part of the test involves memorizing a list of 12 targets for 3 consecutive trials for immediate recall. The raw score is derived by summing the number of targets correctly recalled and ranges from 0 to 36 with a higher score indicating better functioning. A patient was classified with deterioration if there was a statistically significant decrease in score from baseline to one year as determined by the method of reliable change index.

Outcome measures

Measure	Prophylactic Cranial Irradiation (PCI) n=38 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=45 Participants Observation
Percentage of Subjects With Deterioration in the Hopkins Verbal Learning Test - Revised (HVLT-R) Recall Score at One Year	26 percentage of participants Interval 13.0 to 43.0	7 percentage of participants Interval 1.0 to 18.0

SECONDARY outcome

Timeframe: Baseline and one year post study entry

Population: All eligible patients with a baseline and 12 month HVLT-R assessment.

The HVLT-R assesses verbal learning and memory. It incorporates 6 different forms to mitigate practice effects of repeated administrations. Each form includes 12 nouns (targets) with 4 words drawn from 3 semantic categories, which differ across the 6 forms. The delayed recall part of the test involves memorizing a list of 12 targets and recalling them after a 20-minute delay. The raw score is derived by summing the number of targets correctly recalled and ranges from 0 to 12 with a higher score indicating better functioning. A patient was classified with deterioration if there was a statistically significant decrease in score from baseline to one year as determined by the method of reliable change index.

Outcome measures

Measure	Prophylactic Cranial Irradiation (PCI) n=31 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=40 Participants Observation
Percentage of Subjects With Deterioration in the Hopkins Verbal Learning Test - Revised (HVLT-R) Delayed Recall Score at One Year	32 percentage of participants Interval 17.0 to 51.0	5 percentage of participants Interval 1.0 to 17.0

SECONDARY outcome

Timeframe: Baseline and one year from randomization

Population: All eligible patients with a baseline and 12 month EORTC QLQ-C30 global health status score

The EORTC QLQ is an integrated system for assessing the health-related quality of life (QOL) of cancer patients participating in international clinical trials. The QLQ Core-30 (QLQ-C30 ) is a 30-item self-report questionnaire that has patients rate the items on a 4-point scale, with 1 "not at all" to 4 "very much" and is composed of both multi-item scales and single-item measures, including 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea and vomiting, pain), a global health status, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0-100. A high score for the global health status represents a high QOL. An increase from baseline to one year by >= 10 points was considered deterioration.

Outcome measures

Measure	Prophylactic Cranial Irradiation (PCI) n=37 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=47 Participants Observation
Percentage of Subjects With Deterioration in Global Health Status From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) at One Year	22 percentage of participants Interval 1.0 to 38.0	34 percentage of participants Interval 21.0 to 49.0

SECONDARY outcome

Timeframe: Baseline and one year from randomization

Population: All eligible patients with a baseline and 12 month EORTC QLQ-C30 cognitive functioning score

The EORTC QLQ is an integrated system for assessing the health-related quality of life (QOL) of cancer patients participating in international clinical trials. The QLQ Core-30 (QLQ-C30 ) is a 30-item self-report questionnaire that has patients rate the items on a 4-point scale, with 1 "not at all" to 4 "very much" and is composed of both multi-item scales and single-item measures, including 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea and vomiting, pain), a global health status, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0-100. A high score for a functional status represents a high QOL. An increase from baseline to one year by >= 10 points was considered deterioration.

Outcome measures

Measure	Prophylactic Cranial Irradiation (PCI) n=37 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=47 Participants Observation
Percentage of Subjects With Deterioration in Cognitive Functioning From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) at One Year	41 percentage of participants Interval 25.0 to 58.0	25 percentage of participants Interval 14.0 to 40.0

SECONDARY outcome

Timeframe: Baseline and one year from randomization

Population: All eligible patients with a baseline and 12 month EORTC QLQ-C30 cognitive fatigue score

The EORTC QLQ is an integrated system for assessing the health-related quality of life (QOL) of cancer patients participating in international clinical trials. The QLQ Core-30 (QLQ-C30 ) is a 30-item self-report questionnaire that has patients rate the items on a 4-point scale, with 1 "not at all" to 4 "very much" and is composed of both multi-item scales and single-item measures, including 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea and vomiting, pain), a global health status, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0-100. A high score for a symptom scale/item represents a high level of symptomatology/problems. An increase from baseline to one year by >= 10 points was considered deterioration.

Outcome measures

Measure	Prophylactic Cranial Irradiation (PCI) n=38 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=47 Participants Observation
Percentage of Subjects With Deterioration in Fatigue From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) at One Year	34 percentage of participants Interval 20.0 to 51.0	28 percentage of participants Interval 16.0 to 43.0

SECONDARY outcome

Timeframe: Baseline and one year from randomization

Population: All eligible patients with a baseline and 12 month EORTC QLQ-B20 future uncertainty score

The EORTC QLQ-B20 is a 20-item self-report that assesses 11 symptom scales/items such as future uncertainty, visual disorder, motor dysfunction, and communication deficit. Items are presented as questions on a scale ranging from 1 = "not at all" to 4 = "very much." It is meant for use among brain cancer patients varying in disease stage and treatment modality (i.e. surgery, chemotherapy, radiotherapy, etc.) and should always be complemented by the QLQ-C30. The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0 to 100. A high score for a symptom scale/item represents a high level of symptomatology/problems. An increase from baseline to one year by >= 10 points was considered deterioration.

Outcome measures

Measure	Prophylactic Cranial Irradiation (PCI) n=38 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=47 Participants Observation
Percentage of Subjects With Deterioration in Future Uncertainty From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain-20 (EORTC QLQ-B20) at One Year	16 percentage of participants Interval 6.0 to 31.0	21 percentage of participants Interval 11.0 to 36.0

SECONDARY outcome

Timeframe: Baseline and one year from randomization

Population: All eligible patients with a baseline and 12 month EORTC QLQ-B20 communications deficit score

The EORTC QLQ-B20 is a 20-item self-report that assesses 11 symptom scales/items such as future uncertainty, visual disorder, motor dysfunction, and communication deficit. Items are presented as questions on a scale ranging from 1 = "not at all" to 4 = "very much." It is meant for use among brain cancer patients varying in disease stage and treatment modality (i.e. surgery, chemotherapy, radiotherapy, etc.) and should always be complemented by the QLQ-C30. The raw score is calculated as the mean of component items. This score is then standardized such that all of the scales and single-item measures range in score from 0 to 100. A high score for a symptom scale/item represents a high level of symptomatology/problems. An increase from baseline to one year by >= 10 points was considered deterioration.

Outcome measures

Measure	Prophylactic Cranial Irradiation (PCI) n=38 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=47 Participants Observation
Percentage of Subjects With Deterioration in Communications Deficit From the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain-20 (EORTC QLQ-B20) at One Year	39 percentage of participants Interval 24.0 to 57.0	23 percentage of participants Interval 12.0 to 38.0

SECONDARY outcome

Timeframe: From randomization to one year (Scans given at 6 and 12 months and additionally at other times within the time frame if clinically indicated.)

Population: Eligible patients

The presence of metastases were determined by computerized tomography (CT) of the brain with and without contrast or by magnetic resonance imaging (MRI) of the brain with and without gadolinium, using the same method that was done prior to study entry.

Outcome measures

Measure	Prophylactic Cranial Irradiation (PCI) n=163 Participants PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy.	Observation n=177 Participants Observation
Number of Subjects With Central Nervous System (CNS) Metastases in the First Year	15 Participants	36 Participants

Adverse Events

Prophylactic Cranial Irradiation (PCI)

Serious events: 5 serious events

Other events: 83 other events

Deaths: 0 deaths

Serious adverse events

Measure	Prophylactic Cranial Irradiation (PCI) n=163 participants at risk PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy..
General disorders Pain-Other	0.61% 1/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Nervous system disorders Ataxia (incoordination)	0.61% 1/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Psychiatric disorders Mood alteration-depression	0.61% 1/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	0.61% 1/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Vascular disorders Hemorrhage-Other	0.61% 1/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.

Other adverse events

Measure	Prophylactic Cranial Irradiation (PCI) n=163 participants at risk PCI is given to the whole brain in a dose of 2 Gy per fraction, 5 days per week, for 3 weeks for a total dose of 30 Gy..
Gastrointestinal disorders Nausea	11.0% 18/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
General disorders Fatigue (lethargy, malaise, asthenia)	31.3% 51/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
General disorders Late RT Toxicity: Other: NOS	16.6% 27/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Injury, poisoning and procedural complications Late RT Toxicity: Skin: NOS	7.4% 12/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Metabolism and nutrition disorders Anorexia	10.4% 17/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Nervous system disorders Headache	8.6% 14/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Nervous system disorders Late RT Toxicity: Brain: NOS	9.2% 15/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Nervous system disorders Memory loss	5.5% 9/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.
Skin and subcutaneous tissue disorders Alopecia	23.3% 38/163 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). Adverse events are compiled for all eligible patients on the prophylactic cranial irradiation arm who received protocol treatment. Adverse events were not collected on the observation arm and therefore that arm is not shown.

Additional Information

Wendy Seiferheld

Radiation Therapy Oncology Group (RTOG)

Email: seiferheldw@nrgoncology.org

Results disclosure agreements

• Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
• Publication restrictions are in place

Restriction type: OTHER