Extensive Stage Small Cell Lung Carcinoma, Limited Stage Small Cell Lung Carcinoma
Conditions
Brief summary
This randomized phase II/III trial studies how well whole-brain radiation therapy works and compares it with or without hippocampal avoidance in treating patients with small cell lung cancer that is found in one lung, the tissues between the lungs, and nearby lymph nodes only (limited stage) or has spread outside of the lung in which it began or to other parts of the body (extensive stage). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The hippocampus is part of the brain that is important for memory. Avoiding the hippocampus during whole-brain radiation could decrease the chance of side effects on memory and thinking. It is not yet known whether giving whole-brain radiation therapy is more effective with or without hippocampal avoidance in treating patients with small cell lung cancer.
Detailed description
PRIMARY OBJECTIVES: I. Determine whether the 12-month intracranial relapse rate following hippocampal avoidance (HA)-prophylactic cranial irradiation (PCI) is non-inferior compared to the rate following PCI for patients with small cell lung cancer (SCLC). (Randomized Phase II Component \[Non-Inferiority\]) II. Determine whether HA-PCI reduces the likelihood of 6-month deterioration from baseline in Hopkins Verbal Learning Test (HVLT)-Revised (R) delayed recall compared to PCI for patients with SCLC. (Phase III Component \[Efficacy\]) SECONDARY OBJECTIVES: I. Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, Controlled Oral Word Association (COWA) test, and Trail Making Test (TMT) parts A and B), after PCI versus HA-PCI in SCLC. II. Compare time to cognitive failure as separately measured by each test (HVLT-R for Total Recall and Delayed Recognition, COWA test, and TMT parts A and B), after PCI versus HA-PCI for SCLC. III. Compare patient-reported cognitive functioning and other quality of life domains (assessed by the European Organization for Research and Treatment of Cancer \[EORTC\] Quality of Life Questionnaire (QLQ)-Core \[C\]30 and BN20) between PCI versus HA-PCI for patients with SCLC. IV. Compare overall survival after PCI versus HA-PCI for patients with SCLC. V. Compare 12-month intracranial relapse rate (at completion of phase III) and time to intracranial relapse after PCI versus HA-PCI for patients with SCLC. VI. Evaluate adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. VII. Correlate changes in health-related quality of life (HRQOL) domains with changes in cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC. VIII. Assess cost-effectiveness of HA-PCI (intensity modulated radiation therapy \[IMRT\]) and PCI (3-dimensional conformal radiation therapy \[3DCRT\]) using the EuroQual (EQ)-5-Dimensions (5D)-5L. IX. Correlate miRNA signatures with cognitive failure in SCLC patients who received PCI and HA-PCI. X. Evaluate Apolipoprotein E (APOE) genotyping as potential predictor of neurocognitive decline, hippocampal atrophy after brain irradiation and/or differential benefit from hippocampal avoidance. XI. Evaluate baseline MR imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI. TERTIARY OBJECTIVES: I. Collect serum, whole blood, and urine for future translational research analyses. II. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo PCI using 3DCRT daily for 2 weeks. ARM II: Patients undergo PCI with HA using IMRT daily for 2 weeks. After completion of study treatment, patients are followed every 3 months for 1 year, then every 6 months until 3 years and then annually until death.
Interventions
daily fractions
RADIATIONIntensity-Modulated Radiation Therapy
daily fractions
Sponsors
NRG Oncology
National Cancer Institute (NCI)
Radiation Therapy Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\[prior to Step 1 registration\]: * Histologic proof or unequivocal cytologic proof (fine needle aspiration, biopsy or two positive sputa) of SCLC within 250 days prior to Step 1 registration * High-grade neuroendocrine carcinoma or combined SCLC and NSCLC is permitted. * Patients must have received chemotherapy and be registered to Step 1 registration no earlier than 7 days and no later than 56 days after completing chemotherapy. Note: * Post-chemotherapy restaging imaging must be completed no more than 56 days prior to Step 1 registration. * For patients with extensive-stage small cell lung cancer who are being considered for consolidative thoracic radiotherapy after chemotherapy, concomitant administration of consolidative thoracic radiotherapy and protocol-specified prophylactic cranial irradiation with or without hippocampal avoidance is permitted. * Patients must have a gadolinium contrast-enhanced three-dimensional (3D), spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan. To yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE or TFE axial MRI scan must use the smallest possible axial slice thickness not exceeding 1.5 mm. * This MRI must be obtained within 56 days prior to Step 1 registration. Note: The MRI study is mandatory irrespective of randomization to the experimental or control arm of this study. * Prior to chemotherapy +/- thoracic radiotherapy, patients must be defined as limited-stage or extensive-stage SCLC after clinical staging evaluation involving the following: 1. History/physical examination; 2. CT of the chest and abdomen with contrast (does not have to be done if the patient has had a positron emission tomography (PET) / CT scan prior to initiating chemotherapy or thoracic radiotherapy); 3. MRI of the brain with contrast or diagnostic head CT with contrast; 4. For patients without evidence of extensive-stage SCLC on chest and abdomen CT and brain MRI or head CT, a PET/CT or bone scan is required to confirm limited-stage SCLC. * After chemotherapy, patients must be restaged prior to Step 1 registration using the same diagnostic work-up as required pre-chemotherapy. Repeat PET/CT or bone scan is not required. Patients must have: * History/physical examination within 30 days of Step 1 registration; * No CNS metastases (Repeat MRI required) within 56 days prior to Step 1 registration; * No progression in any site; * Radiographic partial or complete response to chemotherapy in at least one disease site within 56 days prior to Step 1 registration. 1. If PET/CT was obtained prior to chemotherapy, either a repeat PET/CT or CT of the chest and abdomen with contrast can be obtained for response assessment. 2. Patients who underwent resection for limited-stage SCLC prior to chemotherapy and have no radiographically evident disease for response assessment remain eligible if post-chemotherapy imaging demonstrates no progression. * Zubrod performance status 0-2 within 30 days prior to Step 1 registration. * Women of childbearing potential must have a negative qualitative serum pregnancy test =\< 14 days prior to Step 1 registration. * Patients who are primary English or French speakers are eligible * Patients must sign a study-specific informed consent prior to study entry Inclusion Criteria \[prior to Step 2 registration\]: * The following baseline neurocognitive assessments must be completed and uploaded within 10 calendar days after or at the time of Step 1 registration: HVLT-R (recall, delayed recall, and recognition), TMT (Parts A and B), and COWA. The neurocognitive assessments will be uploaded into the NRG Oncology Rave System for evaluation by Neurocognitive Co-Chair. Once the upload is complete, within 3 business days, a notification email will be sent to the site to proceed to Step 2 registration. At minimum, the HVLT-R delayed recall must be able to be scored (i.e. completed without error) in order to be eligible. * Patients must have a baseline raw score greater than 2 on the HVLT-R delayed recall as determined by central assessment by the Neurocognitive Co-Chair.
Exclusion criteria
* Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields * Radiographic evidence of central nervous system (CNS) metastases * Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt * Planned concurrent chemotherapy during PCI * Concurrent atezolizumab permitted * Concomitant invasive malignancy or invasive malignancy within the past five years other than non-melanomatous skin cancer; history of in situ carcinoma (e.g. ductal carcinoma in situ of breast, in situ carcinoma of the cervix, vulva or larynx) is permitted * Contraindication to MR imaging, such as implanted metal devices or foreign bodies or severe claustrophobia * Severe, active comorbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration * Uncontrolled, clinically significant cardiac arrhythmias * HIV positive with CD4 count \< 200 cells/microliter; 1. Note: Patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to Step 1 registration. 2. Note: HIV testing is not required for eligibility for this protocol. * Pregnant or lactating women or women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III) | Baseline and six months | The HVLT-R delayed recall test assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials to recall after a 20-minute delay. The score is the sum of the number of words correctly recalled and ranges from 0 to 36, with a higher score indicating better functioning. Deterioration is defined a decrease from baseline of at least 3 points. |
| Number of Participants With Intracranial Relapse at 12 Months (Phase II) | From baseline to 12 months | Intracranial relapse, defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Neurocognitive Failure (Phase III) | Randomization to date of failure, death, or last known follow-up whichever occurred first. Maximum follow-up at time of analysis was 7.2 years. | Neurocognitive failure is defined as the first instance of neurocognitive decline in any of six assessments, as determined my reliable change index: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Trail Making Test (TMT) part A, TMT part B, and Controlled Oral Word Association (COWA). Failure time is defined as time from randomization to failure, death (competing event), or last follow-up (censored). Neurocognitive failure rates are estimated using the cumulative incidence method. The distributions of failure times are compared, which is reported in the statistical analysis results. Six-month rates are reported here. Analysis occurred after all patients had been on study for at least six months. |
| Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III) | Baseline, 3, 6, 12 months. | The HVLT-R Total Recall score assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials. Raw score is the sum of the number of targets correctly recalled, ranging from 0 to 36. Higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 5 points. |
| Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III) | Baseline, 3, 12 months. | The HVLT-R Delayed Recall test assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials, this test requires recalling the 12 targets after a 20-minute delay. Raw scores are sum of the number of targets correctly recalled. The score ranges from 0 to 12. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 3 points. Six-month results are reported as the primary endpoint. |
| Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III) | Baseline, 3, 6, 12 months. | The HVLT-R Delayed Recognition assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials and recalling the 12 targets after a 20-minute delay, the test involves then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are the sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified. The score ranges from -12 to 12 for recognition. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 2 points. |
| Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III) | Baseline, 3, 6, 12 months. | The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A, reported here), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order. The score is the amount of time, in seconds, that it takes the patient to complete the maze. The range for Part A is 0 to 180 (3 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 12 seconds. |
| Number of Participants With Deterioration in TMT Part B Score (Phase III) | Baseline, 3, 6, 12 months. | The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the second part (Part B, reported here), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete the maze. The score range for Part B is 0 to 300 (5 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 26 seconds. |
| Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III) | Baseline, 3, 6, 12 months. | The COWA is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter. Patients are given 1 minute to name as many words as possible beginning with the designated letter. The procedure is then repeated for the remaining two letters. Two alternate forms of the COWA are employed to minimize practice effects. The score is the sum of the correct responses with a range of 0 to infinity. A higher score indicates better functioning. Deterioration is defined an increase from baseline of at least 12 words. |
| Number of Participants by Highest Grade Adverse Event Reported (Phase III) | From start of treatment to last known follow-up . Maximum follow-up time was 7.2 years. | Common Terminology Criteria for Adverse Events (version 5) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. |
| Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III) | Baseline, 3, 6, 12 months. | The QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. Global Health Status is considered a measure of overall quality of life and is calculated from two questions whose raw scores are averaged and then transformed to a range of 0 (worst) to 100 (best). Deterioration is defined a reduction of 10% from baseline. |
| Number of Participants With Deterioration in EORTC QLQ-C30 Global Health Status (Phase III) | Baseline,18, 24 months. | The QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. Global Health Status is considered a measure of overall quality of life and is calculated from two questions whose raw scores are averaged and then transformed to a range of 0 (worst) to 100 (best). Deterioration is defined a reduction of 10% from baseline. |
| Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III) | Baseline, 3, 6, 12 months. | The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline. |
| Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III) | Baseline, 3, 6, 12 months. | The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline. |
| Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III) | Baseline, 3, 6, 12 months. | The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline. |
| Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III) | Baseline, 3, 6, 12 months. | The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline. |
| Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III) | Baseline, 3, 6, 12 months. | The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline. |
| Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III) | Baseline, 3, 6, 12 months. | The EORTC QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration. |
| Number of Participants With Deterioration in EORTC QLQ-BN20 Motor Dysfunction Score (Phase III) | Baseline,18, 24 months. | The EORTC QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration. |
| Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III) | Baseline, 3, 6, 12 months. | The QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration. |
| Correlation of Quality of Life and Neurocognitive Function (NCF) Measures at 6 Months | 6 months | The Pearson correlation coefficient was calculated for EORTC QLQ-C30 (physical, role, emotional, cognitive, and social functioning domains and global health status) and QLQ-BN20 (motor dysfunction and communication deficit) versus the standardized neurocognitive function (HVLT-R total recall, HVLT-R delayed recall, HVLT-R delayed recognition, COWA, TMT parts A and B) and the Clinical Trial Battery Composite (CTB Comp) score (mean of the z-scores for the six NCF scores) for all patients, treatment arms combined. The Pearson correlation coefficient is computed for each pair of measurements, resulting in 48 correlation coefficients. Possible values range from -1 (negatively correlated) to 1(positively correlated), with 0 indicating no correlation. A correlation with a value in range -0.35 to 0.35 is considered weak and is indicated by "0" in the table. Because of the large number of comparisons, only individual correlation coefficients outside that range are listed here. |
| Incremental Cost-per Quality-adjusted Life Year (QALY) (Cost-effectiveness as Measured by the EQ-5D (Phase III) | Baseline to two years | The incremental cost per quality-adjusted life year (QALY) ratio will be calculated as total cost of the PCI with HA using IMRT arm (Arm 2) minus total cost of the PCI using 3DCRT arm (Arm 1), divided by the quality adjusted survival of the Arm 1 patients minus the quality adjusted survival of Arm 2 patients. |
| Overall Survival (Phase III) | From the date of randomization to the date of death or last follow-up. Maximum follow-up time at time of analysis was 7.2 years. | Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 8 months. |
| Intracranial Relapse Rate (Phase III) | From date of randomization to date of intracranial relapse, death, or last known follow-up, whichever occurred first. Maximum follow-up at time of analysis was 7.2 years. | Intracranial relapse is defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast. Time to intracranial relapse is defined as time from randomization to the date of first intracranial relapse, last known follow-up (censored), or death without intracranial relapse (competing risk), whichever occurred first. Intracranial relapse rates are estimated using the cumulative incidence method. The distributions of intracranial relapse times are compared between the arms, which is reported in the statistical analysis results. One-year rates are provided here. Analysis occurred at time of the phase III primary analysis. |
| White Matter Injury and Hippocampal Volume on Neurocognitive Function (Phase III) | Baseline to 6 months | Pearson correlation coefficients will be used to assess the effect of hippocampal volume and FLAIR volume change on baseline neurocognitive function, as measured by the HVLT-R, COWA, and TMT, separately for each arm. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORVinai Gondi
NRG Oncology
Participant flow
Pre-assignment details
Patients were screened in order to determine whether their neurocognitive functioning was healthy enough to participate. This was defined as a score of 2 or higher on the Delayed Recall subscale of the Hopkins Verbal Learning Test (HVLT). HVLT testing was done after initial enrollment, but prior to randomization. Of 418 participants screened, 393 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| PCI Using 3DCRT Prophylactic cranial irradiation (PCI) using three-dimensional conformal radiation therapy (3DCRT) for 2 weeks, 5 fractions/week. | 196 |
| PCI With HA Using IMRT PCI with hippocampal avoidance (HA) using intensity-modulated radiation therapy (IMRT) for 2 weeks, 5 fractions/week. | 197 |
| Total | 393 |
Baseline characteristics
| Characteristic | PCI Using 3DCRT | PCI With HA Using IMRT | Total |
|---|---|---|---|
| Age, Continuous | 64 years | 65 years | 64 years |
| Age, Customized Age (years) ≤ 49 | 12 Participants | 8 Participants | 20 Participants |
| Age, Customized Age (years) 50-59 | 49 Participants | 37 Participants | 86 Participants |
| Age, Customized Age (years) 60-69 | 75 Participants | 102 Participants | 177 Participants |
| Age, Customized Age (years) ≥ 70 | 60 Participants | 50 Participants | 110 Participants |
| Education level Advanced degree | 14 Participants | 9 Participants | 23 Participants |
| Education level Bachelor's degree | 23 Participants | 23 Participants | 46 Participants |
| Education level Grade school | 9 Participants | 2 Participants | 11 Participants |
| Education level High school graduate or GED | 73 Participants | 79 Participants | 152 Participants |
| Education level More than grade school and did not graduate high school | 30 Participants | 17 Participants | 47 Participants |
| Education level Some college or associate's degree | 46 Participants | 64 Participants | 110 Participants |
| Education level Unknown | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 185 Participants | 190 Participants | 375 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 6 Participants | 13 Participants |
| Extent of disease Extensive stage disease (ED) | 54 Participants | 64 Participants | 118 Participants |
| Extent of disease Limited stage disease (LD) | 142 Participants | 133 Participants | 275 Participants |
| Planned concurrent memantine use No | 96 Participants | 102 Participants | 198 Participants |
| Planned concurrent memantine use Yes | 100 Participants | 95 Participants | 195 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 10 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) White | 175 Participants | 180 Participants | 355 Participants |
| Sex: Female, Male Female | 127 Participants | 114 Participants | 241 Participants |
| Sex: Female, Male Male | 69 Participants | 83 Participants | 152 Participants |
| Smoking status (self-reported) Current smoker | 106 Participants | 110 Participants | 216 Participants |
| Smoking status (self-reported) Former smoker | 62 Participants | 61 Participants | 123 Participants |
| Smoking status (self-reported) Never smoked | 5 Participants | 5 Participants | 10 Participants |
| Smoking status (self-reported) Unknown | 23 Participants | 21 Participants | 44 Participants |
| Zubrod performance status 0 | 79 Participants | 83 Participants | 162 Participants |
| Zubrod performance status 1 | 100 Participants | 105 Participants | 205 Participants |
| Zubrod performance status 2 | 17 Participants | 9 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 118 / 196 | 112 / 197 |
| other Total, other adverse events | 154 / 191 | 152 / 189 |
| serious Total, serious adverse events | 26 / 191 | 17 / 189 |
Outcome results
Primary
Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III)
The HVLT-R delayed recall test assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials to recall after a 20-minute delay. The score is the sum of the number of words correctly recalled and ranges from 0 to 36, with a higher score indicating better functioning. Deterioration is defined a decrease from baseline of at least 3 points.
Time frame: Baseline and six months
Population: Randomized patients with score at baseline and 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III) | 33 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III) | 27 Participants |
Comparison: Proportion of participants with deterioration in HVLT-R delayed recall score at six months: Null hypothesis = No difference between the arms; Alternative hypothesis = Arm 2 will have less deterioration than Arm 1. Ninety-eight evaluable participants per arm at six months provides 80% statistical power to detect a 14.5% absolute difference between the arms in proportion of participants with deterioration at six months using a one-sided Fisher's exact test.p-value: 0.28Fisher Exact
Primary
Number of Participants With Intracranial Relapse at 12 Months (Phase II)
Intracranial relapse, defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast.
Time frame: From baseline to 12 months
Population: Phase II randomized participants on study for at least one year.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Intracranial Relapse at 12 Months (Phase II) | 16 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Intracranial Relapse at 12 Months (Phase II) | 12 Participants |
p-value: 0.003Test of binomial proportions
Secondary
Correlation of Quality of Life and Neurocognitive Function (NCF) Measures at 6 Months
The Pearson correlation coefficient was calculated for EORTC QLQ-C30 (physical, role, emotional, cognitive, and social functioning domains and global health status) and QLQ-BN20 (motor dysfunction and communication deficit) versus the standardized neurocognitive function (HVLT-R total recall, HVLT-R delayed recall, HVLT-R delayed recognition, COWA, TMT parts A and B) and the Clinical Trial Battery Composite (CTB Comp) score (mean of the z-scores for the six NCF scores) for all patients, treatment arms combined. The Pearson correlation coefficient is computed for each pair of measurements, resulting in 48 correlation coefficients. Possible values range from -1 (negatively correlated) to 1(positively correlated), with 0 indicating no correlation. A correlation with a value in range -0.35 to 0.35 is considered weak and is indicated by 0 in the table. Because of the large number of comparisons, only individual correlation coefficients outside that range are listed here.
Time frame: 6 months
Population: Randomized participants with values at 6 months. The protocol specifies that the treatment arms are combined into a single group for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Correlation of Quality of Life and Neurocognitive Function (NCF) Measures at 6 Months | EORTC QLQ-C30 Physical functioning vs. NCF CTB Comp Score | 0.3619 correlation coefficient |
| PCI Using 3DCRT (Arm 1) | Correlation of Quality of Life and Neurocognitive Function (NCF) Measures at 6 Months | All others | 0 correlation coefficient |
Secondary
Incremental Cost-per Quality-adjusted Life Year (QALY) (Cost-effectiveness as Measured by the EQ-5D (Phase III)
The incremental cost per quality-adjusted life year (QALY) ratio will be calculated as total cost of the PCI with HA using IMRT arm (Arm 2) minus total cost of the PCI using 3DCRT arm (Arm 1), divided by the quality adjusted survival of the Arm 1 patients minus the quality adjusted survival of Arm 2 patients.
Time frame: Baseline to two years
Secondary
Intracranial Relapse Rate (Phase III)
Intracranial relapse is defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast. Time to intracranial relapse is defined as time from randomization to the date of first intracranial relapse, last known follow-up (censored), or death without intracranial relapse (competing risk), whichever occurred first. Intracranial relapse rates are estimated using the cumulative incidence method. The distributions of intracranial relapse times are compared between the arms, which is reported in the statistical analysis results. One-year rates are provided here. Analysis occurred at time of the phase III primary analysis.
Time frame: From date of randomization to date of intracranial relapse, death, or last known follow-up, whichever occurred first. Maximum follow-up at time of analysis was 7.2 years.
Population: Randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PCI Using 3DCRT (Arm 1) | Intracranial Relapse Rate (Phase III) | 15.9 percentage of participants |
| PCI With HA Using IMRT (Arm 1) | Intracranial Relapse Rate (Phase III) | 15.7 percentage of participants |
p-value: 0.93Gray's test
Secondary
Number of Participants by Highest Grade Adverse Event Reported (Phase III)
Common Terminology Criteria for Adverse Events (version 5) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
Time frame: From start of treatment to last known follow-up . Maximum follow-up time was 7.2 years.
Population: Randomized participants who received radiation therapy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 2 | 78 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 4 | 12 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 3 | 47 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 5 | 1 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 1 | 27 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 5 | 3 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 1 | 30 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 2 | 75 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 3 | 47 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants by Highest Grade Adverse Event Reported (Phase III) | Grade 4 | 8 Participants |
Secondary
Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)
The COWA is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter. Patients are given 1 minute to name as many words as possible beginning with the designated letter. The procedure is then repeated for the remaining two letters. Two alternate forms of the COWA are employed to minimize practice effects. The score is the sum of the correct responses with a range of 0 to infinity. A higher score indicates better functioning. Deterioration is defined an increase from baseline of at least 12 words.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)
The COWA is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter. Patients are given 1 minute to name as many words as possible beginning with the designated letter. The procedure is then repeated for the remaining two letters. Two alternate forms of the COWA are employed to minimize practice effects. The score is the sum of the correct responses with a range of 0 to infinity. A higher score indicates better functioning. Deterioration is defined an increase from baseline of at least 12 words.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III) | 3 months | 13 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III) | 6 months | 3 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III) | 12 months | 7 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III) | 3 months | 24 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III) | 6 months | 12 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III) | 12 months | 14 Participants |
Comparison: 3 monthsp-value: 0.043Chi-squared
Comparison: 6 monthsp-value: 0.017Fisher Exact
Comparison: 12-monthp-value: 0.057Chi-squared
Secondary
Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)
The QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)
The QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III) | 3 months | 50 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III) | 6 months | 45 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III) | 12 months | 31 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III) | 3 months | 40 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III) | 6 months | 42 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III) | 12 months | 28 Participants |
Comparison: 3 monthsp-value: 0.35Chi-squared
Comparison: 6 monthsp-value: 0.99Chi-squared
Comparison: 12 monthsp-value: 0.94Chi-squared
Secondary
Number of Participants With Deterioration in EORTC QLQ-BN20 Motor Dysfunction Score (Phase III)
The EORTC QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III) | 3 months | 58 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III) | 6 months | 41 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III) | 12 months | 37 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III) | 6 months | 55 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III) | 3 months | 45 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III) | 12 months | 30 Participants |
Comparison: 3 months.p-value: 0.16Chi-squared
Comparison: 6 months. Assuming 50% of patients experience deterioration at 6 months, based on a prior study (RTOG-0212), a sample size of 198 participants per arm provides 94% power to detect a 50% relative reduction (50% on Arm 1 vs. 25% on Arm 2) in decline at 6 months using Fisher's exact test with a two-sided alpha=0.05.p-value: 0.017Chi-squared
Comparison: 12-monthp-value: 0.56Chi-squared
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III) | 3 months | 46 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III) | 6 months | 31 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III) | 12 months | 19 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III) | 3 months | 41 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III) | 6 months | 33 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III) | 12 months | 19 Participants |
Comparison: 3 monthsp-value: 0.7Chi-squared
Comparison: 6 monthsp-value: 0.52Chi-squared
Comparison: 12 monthsp-value: 0.73Chi-squared
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Global Health Status (Phase III)
The QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. Global Health Status is considered a measure of overall quality of life and is calculated from two questions whose raw scores are averaged and then transformed to a range of 0 (worst) to 100 (best). Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III) | 3 months | 39 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III) | 6 months | 30 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III) | 12 months | 25 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III) | 3 months | 60 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III) | 6 months | 46 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III) | 12 months | 28 Participants |
Comparison: 3 monthsp-value: 0.0021Chi-squared
Comparison: 6 monthsp-value: 0.007Chi-squared
Comparison: 12 monthsp-value: 0.35Chi-squared
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III) | 3 months | 54 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III) | 6 months | 30 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III) | 12 months | 20 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III) | 3 months | 56 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III) | 6 months | 41 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III) | 12 months | 24 Participants |
Comparison: 6 monthsp-value: 0.062Chi-squared
Comparison: 3 monthsp-value: 0.55Chi-squared
Comparison: 12 monthsp-value: 0.32Chi-squared
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III) | 3 months | 39 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III) | 6 months | 21 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III) | 12 months | 17 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III) | 3 months | 46 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III) | 6 months | 30 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III) | 12 months | 13 Participants |
Comparison: 3 monthsp-value: 0.28Chi-squared
Comparison: 6 monthsp-value: 0.094Chi-squared
p-value: 0.61Chi-squared
Secondary
Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)
The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III)
The EORTC QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III) | 3 months | 57 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III) | 6 months | 49 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III) | 12 months | 37 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III) | 3 months | 60 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III) | 6 months | 51 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III) | 12 months | 41 Participants |
p-value: 0.44Chi-squared
p-value: 0.45Chi-squared
p-value: 0.25Chi-squared
Secondary
Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III)
The QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. Global Health Status is considered a measure of overall quality of life and is calculated from two questions whose raw scores are averaged and then transformed to a range of 0 (worst) to 100 (best). Deterioration is defined a reduction of 10% from baseline.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III) | 3 months | 57 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III) | 6 months | 39 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III) | 12 months | 22 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III) | 3 months | 67 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III) | 6 months | 43 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III) | 12 months | 26 Participants |
Comparison: 3 monthsp-value: 0.1Chi-squared
Comparison: 6 monthsp-value: 0.33Chi-squared
Comparison: 12 monthsp-value: 0.29Chi-squared
Secondary
Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)
The HVLT-R Delayed Recall test assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials, this test requires recalling the 12 targets after a 20-minute delay. Raw scores are sum of the number of targets correctly recalled. The score ranges from 0 to 12. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 3 points.
Time frame: Baseline, 18, 24 months.
Secondary
Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)
The HVLT-R Delayed Recall test assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials, this test requires recalling the 12 targets after a 20-minute delay. Raw scores are sum of the number of targets correctly recalled. The score ranges from 0 to 12. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 3 points. Six-month results are reported as the primary endpoint.
Time frame: Baseline, 3, 12 months.
Population: Randomized patients with HVLT-R Delayed Recall score at baseline and: 3 or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III) | 3 months | 40 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III) | 12 months | 23 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III) | 3 months | 34 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III) | 12 months | 19 Participants |
Comparison: 3 monthsp-value: 0.56Chi-squared
Comparison: 12 monthsp-value: 0.75Chi-squared
Secondary
Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)
The HVLT-R Delayed Recognition assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials and recalling the 12 targets after a 20-minute delay, the test involves then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are the sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified. The score ranges from -12 to 12 for recognition. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 2 points.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and: 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III) | 3 months | 49 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III) | 6 months | 11 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III) | 12 months | 19 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III) | 3 months | 45 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III) | 6 months | 11 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III) | 12 months | 22 Participants |
Comparison: 3 monthsp-value: 0.81Chi-squared
Comparison: 6 monthsp-value: 0.93Chi-squared
Comparison: 12 monthsp-value: 0.35Chi-squared
Secondary
Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)
The HVLT-R Delayed Recognition assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials and recalling the 12 targets after a 20-minute delay, the test involves then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are the sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified. The score ranges from -12 to 12 for recognition. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 2 points.
Time frame: Baseline, 18, 24 months.
Secondary
Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)
he HVLT-R Total Recall score assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials. Raw score is the sum of the number of targets correctly recalled, ranging from 0 to 36. Higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 5 points.
Time frame: Baseline,18, 24 months.
Secondary
Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)
The HVLT-R Total Recall score assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials. Raw score is the sum of the number of targets correctly recalled, ranging from 0 to 36. Higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 5 points.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III) | 3 months | 47 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III) | 6 months | 33 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III) | 12 months | 20 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III) | 3 months | 47 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III) | 6 months | 35 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III) | 12 months | 17 Participants |
Comparison: 3 monthsp-value: 0.78Chi-squared
Comparison: 6 monthsp-value: 0.63Chi-squared
Comparison: 12 monthsp-value: 0.84Chi-squared
Secondary
Number of Participants With Deterioration in TMT Part B Score (Phase III)
The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the second part (Part B, reported here), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete the maze. The score range for Part B is 0 to 300 (5 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 26 seconds. If reporting a score on a scale, please include the unabbreviated scale title, the minimum and maximum values, and whether higher scores mean a better or worse outcome.
Time frame: Baseline, 18, 24 months.
Secondary
Number of Participants With Deterioration in TMT Part B Score (Phase III)
The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the second part (Part B, reported here), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete the maze. The score range for Part B is 0 to 300 (5 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 26 seconds.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with score at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in TMT Part B Score (Phase III) | 3 months | 43 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in TMT Part B Score (Phase III) | 6 months | 26 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in TMT Part B Score (Phase III) | 12 months | 22 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in TMT Part B Score (Phase III) | 3 months | 38 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in TMT Part B Score (Phase III) | 6 months | 38 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in TMT Part B Score (Phase III) | 12 months | 19 Participants |
Comparison: 3 monthsp-value: 0.71Chi-squared
Comparison: 6 monthsp-value: 0.079Chi-squared
Comparison: 12 monthsp-value: 0.85Chi-squared
Secondary
Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)
The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A, reported here), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order. The score is the amount of time, in seconds, that it takes the patient to complete the maze. The range for Part A is 0 to 180 (3 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 12 seconds.
Time frame: Baseline, 3, 6, 12 months.
Population: Randomized patients with TMT Part A at baseline and 3, 6, or 12 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III) | 3 months | 27 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III) | 6 months | 21 Participants |
| PCI Using 3DCRT (Arm 1) | Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III) | 12 months | 22 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III) | 3 months | 30 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III) | 6 months | 26 Participants |
| PCI With HA Using IMRT (Arm 1) | Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III) | 12 months | 14 Participants |
Comparison: 3 monthsp-value: 0.54Chi-squared
Comparison: 6 monthsp-value: 0.43Chi-squared
Comparison: 12 monthsp-value: 0.25Chi-squared
Secondary
Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)
The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A, reported here), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order. The score is the amount of time, in seconds, that it takes the patient to complete the maze. The range for Part A is 0 to 180 (3 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 12 seconds.
Time frame: Baseline, 18, 24 months.
Secondary
Overall Survival (Phase III)
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 8 months.
Time frame: From the date of randomization to the date of death or last follow-up. Maximum follow-up time at time of analysis was 7.2 years.
Population: Randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PCI Using 3DCRT (Arm 1) | Overall Survival (Phase III) | 24.9 months |
| PCI With HA Using IMRT (Arm 1) | Overall Survival (Phase III) | 20.7 months |
p-value: 0.79Log Rank
Secondary
Percentage of Participants With Neurocognitive Failure (Phase III)
Neurocognitive failure is defined as the first instance of neurocognitive decline in any of six assessments, as determined my reliable change index: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Trail Making Test (TMT) part A, TMT part B, and Controlled Oral Word Association (COWA). Failure time is defined as time from randomization to failure, death (competing event), or last follow-up (censored). Neurocognitive failure rates are estimated using the cumulative incidence method. The distributions of failure times are compared, which is reported in the statistical analysis results. Six-month rates are reported here. Analysis occurred after all patients had been on study for at least six months.
Time frame: Randomization to date of failure, death, or last known follow-up whichever occurred first. Maximum follow-up at time of analysis was 7.2 years.
Population: Randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PCI Using 3DCRT (Arm 1) | Percentage of Participants With Neurocognitive Failure (Phase III) | 57.0 percentage of participants |
| PCI With HA Using IMRT (Arm 1) | Percentage of Participants With Neurocognitive Failure (Phase III) | 52.7 percentage of participants |
p-value: 0.0598Gray's test
Secondary
White Matter Injury and Hippocampal Volume on Neurocognitive Function (Phase III)
Pearson correlation coefficients will be used to assess the effect of hippocampal volume and FLAIR volume change on baseline neurocognitive function, as measured by the HVLT-R, COWA, and TMT, separately for each arm.
Time frame: Baseline to 6 months