This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BEST) for Radionecrosis After Radiosurgery for Brain Metastases (NCT02490878), a randomized phase 2 study. The primary outcome is Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02490878 |
| Phase | Phase 2 |
| Condition | Radionecrosis, Brain Metastases |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alliance for Clinical Trials in Oncology |
| Results posted | Yes |
2. Clinical Question
Population
Patients with symptomatic brain radionecrosis following radiosurgery for brain metastases. The primary-outcome population was defined more narrowly: eligible patients who began protocol treatment and had a baseline assessment plus at least one subsequent assessment within the first 8 weeks.
Intervention
Bevacizumab added to corticosteroid therapy. The arm description specifies bevacizumab 10 mg/kg intravenously on days 1 and 15 of a 28-day cycle for 4 cycles. Corticosteroids were to be tapered every 5 days as tolerated after study treatment began.
Comparator
Placebo added to corticosteroid therapy. The registry record describes an intravenous placebo on days 1 and 15 of a 28-day cycle for 4 cycles, with corticosteroids tapered every 5 days as tolerated after study treatment began.
Primary question
Does adding bevacizumab to corticosteroids lead to a greater change in the MD Anderson Symptom Inventory Brain Tumor Symptom Severity Score than adding placebo to corticosteroids? The registry lists assessments at baseline and weeks 2, 4, 6 and 8, but it does not report the arm-level scores or a treatment comparison.
The clinical rationale described in the registry record is to investigate whether adding bevacizumab can improve symptoms and reduce treatment-induced symptoms compared with corticosteroid therapy alone. The hypothesized benefits are stated as objectives, not as findings. The trial also registered secondary outcomes covering toxicity, quality-of-life measures, progression-free survival, time to maximum radiographic response and time to stopping corticosteroids. The posted information does not establish whether any of these outcomes favored either arm.
3. Trial Design
This was a randomized, double-masked, parallel-group phase II study comparing corticosteroids plus bevacizumab with corticosteroids plus placebo. The registry record lists enrollment of 19 and trial status as terminated. The start is recorded as 2016-04, and primary completion as 2019-02-01. The reason for termination is not reported in the registry record.
The active-treatment arm received bevacizumab with corticosteroids; the comparator arm received placebo with corticosteroids. Both descriptions specify treatment on days 1 and 15 over 28-day cycles, with corticosteroids tapered every 5 days as tolerated after study treatment began. The registry arm descriptions are incomplete in the record, so further details about treatment delivery or tapering cannot be established from them.
The primary outcome was change in the MD Anderson Symptom Inventory Brain Tumor Symptom Severity Score, measured at baseline and weeks 2, 4, 6 and 8. The analysis population was defined as eligible patients who began protocol treatment, had a baseline assessment and completed at least one subsequent assessment within the first 8 weeks. The registry record does not report how many participants met this definition or the number assessed at each visit.
Secondary outcomes included toxicity assessed with CTCAE Version 4.0; three quality-of-life or symptom measures; progression-free survival; time to maximum radiographic response; and time to stopping corticosteroids. Although the registry lists outcome measures, it lists no statistical analyses. Randomization and masking describe the intended design, but the registry record does not report details such as the randomization procedure, allocation concealment, or how masking was maintained.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 40 patients underwent pre-screening. Only 19 underwent randomization.
Overall Study
| Stage | Arm A: Bevacizumab | Arm B: Placebo |
|---|---|---|
| STARTED | 10 | 9 |
| Eligible Participants | 10 | 8 |
| COMPLETED | 10 | 6 |
| NOT COMPLETED | 0 | 3 |
Reasons for not completing this period:
| Reason | Arm A: Bevacizumab | Arm B: Placebo |
|---|---|---|
| deemed ineligible | 0 | 1 |
| progression prior to treatment | 0 | 1 |
| only submitted baseline QOL | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All eligible patients that began protocol treatment and were assessed at baseline and at least one subsequent time within the first 8 weeks were included in this analysis.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Arm A: Bevacizumab | Arm B: Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 6 | 16 | |
| Age, Customized: Age group – <= 65 years | Participants | 7 | 5 | 12 |
| Age, Customized: Age group – > 65 years | Participants | 3 | 1 | 4 |
| Sex: Female, Male: Female | Participants | 6 | 4 | 10 |
| Sex: Female, Male: Male | Participants | 4 | 2 | 6 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 7 | 5 | 12 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
| Prior whole brain radiotherapy: Yes | Participants | 5 | 1 | 6 |
| Prior whole brain radiotherapy: No | Participants | 5 | 5 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Change in M. D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) Symptom Severity Score, measured over Baseline, 2, 4, 6 and 8 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in the MD Anderson Symptom Inventory Brain Tumor Symptom Severity Score. This patient-reported measure assesses symptom severity and the interference of symptoms with daily living. It contains 28 items, including 9 items specific to brain tumors. Each item ranges from 0, representing the best condition, to 10, representing the worst condition. A symptom-severity subscale score is calculated as the average of its items when the specified minimum number of items has been completed.
The registry lists assessment at baseline and weeks 2, 4, 6 and 8. Change from baseline is intended to describe how symptom severity shifts during the assessment period. The registry's endpoint description states that a negative change in score from baseline indicates a worsening score. That stated direction matters when reading any eventual estimate: direction should be interpreted according to the registry definition rather than assumed from the scale's item anchors alone.
A patient-reported symptom measure is relevant to this question because the stated aim concerns symptoms and their effects on daily life. However, the registry record does not report arm-level means, standard deviations, change estimates, uncertainty intervals, or a between-arm comparison. It is therefore not possible to describe the observed magnitude or precision of change from the information recorded.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a randomized comparison intended to assess whether bevacizumab added to corticosteroids changes symptom severity relative to placebo added to corticosteroids. It does not report the primary-outcome results needed to answer that comparison. In particular, there are no posted arm-level means or standard deviations for the MDASI-BT symptom-severity score, no estimated difference between arms, and no confidence interval or p-value. The registry record lists no statistical analyses.
The outcome was to be assessed at baseline and weeks 2, 4, 6 and 8. Multiple assessment times can describe the course of symptoms, but a result at one visit would not automatically represent the pattern across all visits. The registry record does not identify a single time point or a prespecified summary across time as the sole treatment contrast. Its stated reason for not reducing the primary outcome to one comparison is that the outcome has several categories or time points. Without reported estimates, the treatment pattern cannot be characterized.
Enrollment is listed as 19, and the trial is marked terminated. These registry entries provide context about the record but do not establish why the trial ended, how many participants contributed primary-outcome data, or whether the planned assessments were completed. The reason for termination and the number assessed at each time are not reported in the registry record. Enrollment alone cannot substitute for the analysis population specified for the endpoint.
The serious adverse event record reports affected participants by arm and counts of deaths. These descriptive safety counts should be read separately from the missing symptom comparison. They do not provide a randomized estimate of symptom benefit, and they do not resolve how the primary outcome changed over time. The listed serious-event terms and percentages likewise do not include enough arm-specific context to compare the terms between groups.
General statistical interpretation: an estimate describes the size and direction of a comparison, while a confidence interval conveys the range of values compatible with the data under the analysis assumptions. A p-value addresses compatibility with a specified null model; it does not measure the size or clinical importance of an effect. None of these inferential quantities is reported for the primary endpoint in the registry record. Consequently, no conclusion about the comparative symptom results or their precision can be drawn from the posted outcome information.
9. Statistical Methods Explained
What does randomization contribute?
Randomization assigns participants to treatment groups using a chance-based process. In general, it is intended to reduce systematic differences between groups at enrollment, so that a comparison can more credibly be attributed to the assigned treatment strategy than a nonrandomized comparison could. It does not guarantee that groups will be identical, especially in a small trial. The registry describes this study as randomized, double-masked and parallel-group, but does not report the randomization method, allocation concealment details, or masking procedures. Those aspects cannot be evaluated from the registry record.
What is the treatment contrast?
The registered contrast is bevacizumab plus corticosteroids versus placebo plus corticosteroids. This is an add-on comparison: corticosteroids are part of both arms, while bevacizumab is replaced by placebo in the comparator. Therefore, the intended comparison concerns the addition of bevacizumab within the registered corticosteroid-treatment approach, not bevacizumab versus no treatment. The registry describes a corticosteroid taper in both arms, but further details of the treatment protocol are not fully reported in the arm descriptions.
How should a change score be understood?
A change score compares a participant's score at a follow-up assessment with that participant's baseline score. Comparing change between randomized groups can account for the starting score in a direct way, although the interpretation depends on the chosen analysis and the data available. The registry identifies a mean change outcome and standard deviation as the measure and dispersion, but does not post the group values or describe the exact statistical model. The endpoint definition states that a negative change means a worsening score. Because the score uses items anchored from best to worst, keeping the registry's explicit change-direction definition in view is important.
Why do repeated assessments matter?
The primary outcome is scheduled at baseline and weeks 2, 4, 6 and 8. Repeated assessments can reveal whether group differences are consistent, change over time, or appear only at particular visits. Statistical approaches for repeated measurements can account for the correlation between observations from the same participant; those observations are not generally independent. The registry record does not report whether a repeated-measures model, separate visit-specific comparisons, or another approach was planned or used. It also does not report the primary time point, if any, designated for the main comparison.
What do a mean and standard deviation describe?
General statistical explanation: the mean describes the average score or change in a group. The standard deviation describes variability among individual observations around that group average. Neither one alone gives the uncertainty of a between-group treatment estimate. A confidence interval for a contrast would help show how precisely the difference was estimated. The registry identifies the mean and standard deviation as the endpoint summary, but no such results or confidence intervals are posted.
What can the planning illustration tell readers?
The registry record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also states that the illustration considers a stated fraction of the observed effect, with participant counts per arm for non-time-to-event outcomes and total event counts for time-to-event outcomes. This is a planning framework, not observed power. No numerical illustration is reported in the record summarized for this trial, and no primary-outcome effect estimate is posted from which to interpret such an illustration. The record does not report the trial's own sample-size justification or statistical design assumptions.
What is not available for evaluating the analysis?
The registry lists no statistical analyses. It therefore does not describe an adjusted or unadjusted primary model, covariates, handling of repeated measurements, missing-data method, or planned contrasts. These omissions are material because the endpoint has several assessment times and because the analysis population requires baseline and follow-up data. General statistical explanation: missing outcome data can reduce precision and can bias a comparison if the availability of measurements is related to participants' outcomes or treatment assignment. The direction and size of any such effect depend on the missingness pattern and analysis assumptions; neither can be assessed without the participant-level flow and analysis details.
The record also includes secondary outcomes, which raises the general issue of multiplicity: testing many outcomes or time points can increase the chance of at least one apparently notable result under a collection of null hypotheses. A prespecified hierarchy, adjustment method, or clear distinction between primary and exploratory analyses can help readers interpret multiple tests. No multiplicity strategy is reported in the registry record. Since no analysis results are listed, there are no reported tests to evaluate for multiplicity or to interpret as confirmatory.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary symptom-severity outcome at baseline and weeks 2, 4, 6 and 8, alongside several secondary outcomes. It does not report a multiplicity strategy, such as a hierarchy among outcomes, an adjustment for multiple comparisons, or a designation of particular time points as primary. The registry record also states that the primary outcome has several categories or time points and was not reduced to one comparison. Without a reported plan and results, the degree to which multiple testing was considered cannot be assessed.
The primary analysis population is defined as eligible participants who began protocol treatment and had baseline and at least one subsequent assessment within the first 8 weeks. The record does not report the number meeting this definition, the number with measurements at each visit, reasons for missing assessments, or how missing values were handled. It also does not report whether analyses included all randomized participants or used another analysis population.
General statistical explanation: an analysis restricted to participants with observed follow-up can differ from an analysis that makes assumptions about missing outcomes. If follow-up availability is related to prognosis, symptoms, treatment, or adverse events, complete-case results may not represent the randomized groups as intended. Methods for addressing missing data rely on assumptions, which should be stated and evaluated where possible. The registry record does not report an approach or sensitivity analyses, so the impact of missing data is unknown.
The record lists no statistical analyses. Thus, it does not identify the primary model, planned contrasts, covariate adjustment, or the handling of the multiple assessment times. These details are not reported in the registry record and should not be inferred from the randomized design alone.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm A: Bevacizumab | 3 | 10 | 30.0% |
| Arm B: Placebo | 6 | 8 | 75.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A: Bevacizumab | 0 of 10 |
| Arm B: Placebo | 1 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A: Bevacizumab | 10 of 10 |
| Arm B: Placebo | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A: Bevacizumab | Arm B: Placebo |
|---|---|---|---|
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | 0 of 10 | 2 of 8 |
| Seizure | Nervous system disorders | 0 of 10 | 2 of 8 |
| Confusion | Psychiatric disorders | 1 of 10 | 1 of 8 |
| Fever | General disorders | 1 of 10 | 0 of 8 |
| Infections and infestations - Oth spec | Infections and infestations | 0 of 10 | 1 of 8 |
| Lung infection | Infections and infestations | 0 of 10 | 1 of 8 |
| Sepsis | Infections and infestations | 0 of 10 | 1 of 8 |
| Alanine aminotransferase increased | Investigations | 0 of 10 | 1 of 8 |
| CPK increased | Investigations | 0 of 10 | 1 of 8 |
| Hyperglycemia | Metabolism and nutrition disorders | 1 of 10 | 0 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A: Bevacizumab | Arm B: Placebo |
|---|---|---|---|
| Hypertension | Vascular disorders | 7 of 10 | 7 of 8 |
| Fatigue | General disorders | 4 of 10 | 4 of 8 |
| Gait disturbance | General disorders | 2 of 10 | 1 of 8 |
| Fall | Injury, poisoning and procedural complications | 1 of 10 | 2 of 8 |
| Hyperglycemia | Metabolism and nutrition disorders | 2 of 10 | 1 of 8 |
| Proteinuria | Renal and urinary disorders | 1 of 10 | 2 of 8 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 3 of 10 | 0 of 8 |
| Hypotension | Vascular disorders | 1 of 10 | 2 of 8 |
| Thromboembolic event | Vascular disorders | 1 of 10 | 2 of 8 |
| Blurred vision | Eye disorders | 1 of 10 | 1 of 8 |
Serious events with the highest arm-level rate: muscle weakness lower limb (25.0%), seizure (25.0%), infections and infestations - oth spec (12.5%), lung infection (12.5%), sepsis (12.5%).
The registry reports serious adverse events for Arm A, Bevacizumab, and Arm B, Placebo. Serious events affected 3 of 10 participants at risk in Arm A and 6 of 8 at risk in Arm B. Other adverse events affected 10 of 10 at risk in Arm A and 8 of 8 at risk in Arm B. The record lists 0 deaths in Arm A and 1 in Arm B. These are descriptive counts recorded for the safety population; they are not estimates of the primary symptom outcome.
The serious-event terms listed include muscle weakness lower limb and seizure, each reported as 25.0%, and infections and infestations - Oth spec, lung infection, sepsis, and alanine aminotransferase increased, each reported as 12.5%. The record does not identify the treatment arm associated with each term in this list, so the term percentages should not be interpreted as arm-specific comparisons.
General statistical explanation: counts of participants affected and counts of event terms are different summaries, and one participant may experience more than one event. The registry record does not provide enough detail to determine the number of events per participant, timing, duration, attribution, or severity grading for each listed term. The safety counts are not adjusted for differences in exposure or follow-up time. They are therefore useful as a descriptive registry snapshot, not as a complete comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The registry record establishes the intended question: whether adding bevacizumab to corticosteroids changes symptom severity compared with adding placebo to corticosteroids in patients with symptomatic brain radionecrosis after radiosurgery for brain metastases. It records a randomized, double-masked phase II design and identifies a patient-reported primary outcome. Those design features describe how the comparison was intended to be conducted; they do not, by themselves, establish the direction or size of any treatment difference.
The posted record does not include arm-level primary-outcome results, a between-arm estimate, a confidence interval, or a p-value. It also lists no statistical analyses. As a result, the registry record does not establish whether symptoms improved or worsened in either arm, whether the arms differed, or how precisely a difference was estimated. The stated hypothesis that bevacizumab might reduce treatment-induced toxicities and improve neurologic impairments is a rationale for the study, not a result.
The enrollment of 19 and terminated status are relevant context, but the reason for termination is not reported in the registry record. The total enrollment entry does not specify how many participants began treatment, contributed endpoint data, or completed each assessment. The endpoint population definition requires baseline and follow-up assessment, and its size is not reported.
The recorded serious adverse event counts provide descriptive safety information, but cannot establish a full comparative safety profile. The registry does not provide the arm attribution for the serious-event term percentages in the listed summary, nor does it give detailed event timing or exposure-adjusted rates.
General statistical explanation: absence of a reported estimate is not evidence that the treatments had the same effect. Equally, a stated hypothesis or trial design is not evidence that one treatment performed better. Interpretation requires outcome estimates and uncertainty, details of the analysis population and missing data, and a clear analysis plan. Those elements are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial poses a clinically specific statistical question: whether adding an agent to a shared corticosteroid regimen changes patient-reported symptom severity. An add-on design helps focus the comparison on the contrast between bevacizumab and placebo within the registered treatment approach. The primary measure also captures symptoms and their interference with daily life, rather than relying solely on a radiographic outcome.
The endpoint's repeated assessments make the analysis question more complex than a single end-of-study comparison. Symptom scores are listed at baseline and weeks 2, 4, 6 and 8, so the timing and handling of repeated observations matter. A statistical plan would ordinarily clarify which comparison is primary, how the correlation among measurements is handled, and how incomplete follow-up is addressed. The registry record does not report those details or any analysis results.
The record is also a useful example of the distinction between a trial's stated rationale and evidence from its results. The study hypothesis proposes symptom improvement and reduced treatment-induced symptoms, but those aims cannot substitute for estimates. The termination status and enrollment entry do not supply an explanation for the outcome record or its analysis population.
For biostatistical interpretation, the central limitation is not merely the absence of a p-value. Without group summaries, an estimated contrast and its uncertainty, readers cannot evaluate magnitude, direction, or precision. The registry's safety summaries add descriptive context, but do not answer the efficacy question or amount to a complete safety comparison. This record therefore illustrates why transparent reporting of estimates, analysis populations, missing-data handling, and prespecified comparisons is essential to interpreting a randomized clinical trial.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record is insufficient to reconstruct the primary-outcome analysis. It reports the measure, its assessment schedule, and the intended analysis population, but no scores, group summaries, treatment contrast, confidence interval, or p-value. It lists no statistical analyses. The main comparative symptom question therefore remains unanswered by the posted results.
The primary endpoint includes several assessment times, but the record does not report a designated primary time point, a repeated-measures method, or the planned contrast across visits. It also does not state how incomplete questionnaires or missing follow-up assessments were handled. The number of participants with data at each visit and the number meeting the endpoint population definition are not reported in the registry record.
The registry identifies enrollment as 19 and the study status as terminated, but does not report the reason for termination. It does not provide a participant flow describing screening, treatment initiation, withdrawal, or follow-up completion. The arm descriptions are incomplete, limiting the treatment-delivery detail that can be confirmed from this record.
The safety information is also limited. The record gives counts of participants affected and a list of serious-event terms with percentages, but does not map each listed term to an arm or report event timing, duration, attribution, or exposure-adjusted rates. The listed counts should not be treated as a comprehensive comparative safety analysis.
Finally, no multiplicity strategy or sample-size justification for the trial is reported in the registry record. The planning illustration described in the record is not a substitute for the trial's own design rationale or for an observed treatment estimate. These gaps constrain assessment of both the statistical methods and the evidential strength of the trial results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BEST) for Radionecrosis After Radiosurgery for Brain Metastases — NCT02490878.
- Registry record last updated 2023-03-23; status last verified 2023-02.
- Results first posted 2021-08-06.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02490878 is a randomized, double-masked, parallel-group phase II study of bevacizumab plus corticosteroids versus placebo plus corticosteroids for symptomatic brain radionecrosis following radiosurgery for brain metastases. Enrollment is listed as 19; the record marks the trial terminated. The primary outcome is change in the MDASI-BT Symptom Severity Score, assessed at baseline and weeks 2, 4, 6 and 8.
The registry record lists secondary outcomes covering toxicity, quality of life and symptom measures, progression-free survival, radiographic response timing, and time to stopping corticosteroids. It also reports descriptive serious adverse event counts. No statistical analyses or primary-outcome results are listed. The reason for termination, analysis results, and details of missing-data handling are not reported in the registry record.