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 Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (NCT02645487), a na na study. The primary outcome is Maximal Tolerated Doses.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02645487 |
| Phase | NA |
| Condition | Brain Neoplasms, Adult, Malignant |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 105 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Texas Southwestern Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with brain metastases who have not undergone prior brain irradiation. The condition is listed as adult malignant brain neoplasms. The registry description focuses on patients receiving single-fraction stereotactic radiosurgery.
Intervention
Stereotactic radiosurgery, with dose escalation across dose levels. The record describes escalation when dose-limiting toxicity stays within specified thresholds during follow-up, with escalation to the next level subject to principal investigator discretion.
Comparator
There is no separate control group in the recorded design. Allocation is listed as NA and the model as single group, so the cohort and dose-level labels do not establish a randomized, like-for-like treatment comparison.
Primary question
The primary endpoint is maximal tolerated doses, measured in gray within 90 days. In practical terms, the study asks what dose levels meet the protocol’s dose-limiting-toxicity rules in this population. The registry record does not report a numeric dose result, a selected maximal tolerated dose, or an analysis of the primary endpoint.
This is a dose-finding question rather than a question about comparative treatment effects. The record also lists overall survival, time to progression, local progression rate, and response rate as secondary outcomes. Those outcomes could describe disease course or response, but their presence in the registry does not establish that results were collected or analyzed. Numeric results for them are not reported in the registry record.
3. Trial Design
The registry describes a single-group, dose-escalation study of stereotactic radiosurgery for brain metastases without whole brain radiation. The named intervention is stereotactic radiosurgery, a radiation intervention. Allocation is recorded as NA, masking as none, and the model as single group. The record lists phase as NA. These entries describe the registered design; they do not establish a comparison with a concurrent control group.
The intended population is patients with brain metastases who have not undergone prior brain irradiation. The condition is recorded as adult malignant brain neoplasms. The primary outcome description refers to single-fraction stereotactic radiosurgery and evaluates dose-limiting toxicity within 90 days of the procedure. The study description says dose escalation was guided by prespecified toxicity thresholds and principal investigator discretion. Each cohort had 3 maximum dose levels that could be met by reaching the dose-escalation conditions.
The registry lists an enrollment of 105. The study start date is 2015-12-18, and the primary completion date is 2025-03-23. Its status is active, not recruiting. The sponsor is University of Texas Southwestern Medical Center. These record details do not indicate how many participants completed follow-up or contributed to each outcome.
Adverse-event groups are labeled by cohort and dose level, including Cohort 1 Dose Level 1 through Cohort 4 Dose Level 1. These labels describe the organization of the safety record, not randomized arms. The registry does not report a separate comparator, a randomized allocation procedure, or masking beyond the entry of none. Further operational details, including the rationale for the enrollment target and any changes to the study design, are not reported in the registry record.
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.
Only the first 6 of 9 groups are shown.
Overall Study
| Stage | Cohort 1 Dose Level 1 | Cohort 1 Dose Level 2 | Cohort 1 Dose Level 3 | Cohort 2 Dose Level 1 | Cohort 2 Dose Level 2 | Cohort 2 Dose Level 3 |
|---|---|---|---|---|---|---|
| STARTED | 16 | 12 | 8 | 15 | 14 | 9 |
| Completed Treatment | 13 | 12 | 7 | 14 | 14 | 9 |
| COMPLETED | 6 | 4 | 1 | 6 | 6 | 3 |
| NOT COMPLETED | 10 | 8 | 7 | 9 | 8 | 6 |
Reasons for not completing this period:
| Reason | Cohort 1 Dose Level 1 | Cohort 1 Dose Level 2 | Cohort 1 Dose Level 3 | Cohort 2 Dose Level 1 | Cohort 2 Dose Level 2 | Cohort 2 Dose Level 3 |
|---|---|---|---|---|---|---|
| Death | 7 | 3 | 3 | 8 | 6 | 2 |
| Screen Failure | 3 | 1 | 1 | 1 | 0 | 0 |
| Physician Decision | 0 | 3 | 1 | 0 | 2 | 3 |
| Lost to Follow-up | 0 | 1 | 1 | 0 | 0 | 0 |
| Active Follow Up | 0 | 0 | 1 | 0 | 0 | 1 |
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.
Population: Patients within each cohort and dose level that completed treatment.
Only the first 6 of 10 groups are shown.
| Characteristic | Unit | Cohort 1 Dose Level 1 | Cohort 1 Dose Level 2 | Cohort 1 Dose Level 3 | Cohort 2 Dose Level 1 | Cohort 2 Dose Level 2 | Cohort 2 Dose Level 3 |
|---|---|---|---|---|---|---|---|
| Participants analysed | 13 | 12 | 7 | 14 | 14 | 9 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 10 | 8 | 3 | 12 | 9 | 6 |
| Age, Categorical: >=65 years | Participants | 3 | 4 | 4 | 2 | 5 | 3 |
| Age, Continuous | years | 60.5 (44 to 75) | 59.8 (35 to 80) | 62.1 (32 to 80) | 57.9 (32 to 78) | 58.3 (36 to 75) | 58.6 (42 to 73) |
| Sex: Female, Male: Female | Participants | 6 | 6 | 3 | 7 | 7 | 2 |
| Sex: Female, Male: Male | Participants | 7 | 6 | 4 | 7 | 7 | 7 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 2 | 3 | 0 | 2 | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 13 | 10 | 4 | 14 | 12 | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 | 3 | 2 | 1 |
| Race (NIH/OMB): White | Participants | 12 | 9 | 5 | 11 | 11 | 8 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 0 | 0 | 1 | 0 |
| Region of Enrollment: United States | participants | 13 | 12 | 7 | 14 | 14 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Maximal Tolerated Doses, measured over 90 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | gray |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled “Maximal Tolerated Doses” and uses gray as its unit. Its timeframe is 90 days. The endpoint description defines dose-limiting toxicity within 3-month follow-up as the basis for deciding whether to escalate to the next dose level or regard the maximal tolerated dose as exceeded. The specific clinical definition of dose-limiting toxicity is attributed to the study protocol, but that definition is not reproduced in the registry record.
The described rules use accumulating participant counts: escalation may proceed if the number experiencing dose-limiting toxicity stays within specified limits among the first seven, first nine, first twelve, or first fifteen patients. The description also gives thresholds at which the maximal tolerated dose is considered exceeded. These are decision rules for dose finding, not estimates of treatment benefit. The record notes that escalation to the next level is also subject to principal investigator discretion.
In general, a maximal-tolerated-dose endpoint is used to identify a dose that meets a protocol’s safety-based criteria in the population under study. It is not, by itself, evidence about comparative efficacy or a patient’s likely outcome. The registry record does not report the dose values tested, the dose ultimately selected, counts meeting each decision rule, or a numeric primary-endpoint result. It therefore does not establish which dose level, if any, met the study’s criteria.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a dose-escalation study, not a randomized comparison. Its central statistical question is whether dose levels meet toxicity-based escalation rules within the stated follow-up period. That design can support a dose-finding objective, but it does not provide a direct estimate of how stereotactic radiosurgery compares with another treatment. The record explicitly lists a single-group model, no masking, and no allocation scheme.
The primary endpoint has a defined unit and timeframe: maximal tolerated doses in gray, within 90 days. The registry also provides the decision rules that were intended to govern escalation. However, it does not report the dose values or numeric primary-outcome results. It is therefore not possible to determine from this record what maximal tolerated dose was identified, whether escalation criteria were met, or how many participants experienced dose-limiting toxicity under the protocol definition.
The registry lists 105 as enrollment and includes safety summaries for groups labeled by cohort and dose level. Enrollment is not a substitute for the number analyzed for a particular outcome. The record does not report outcome-specific analysis populations, follow-up completeness, or an account of participants with missing outcome data. The group labels and adverse-event counts should not be interpreted as treatment comparisons: participants at different dose levels are not described as concurrent randomized controls.
Overall survival, time to progression, local progression rate, and response rate are listed as secondary outcomes. No numeric results or analyses for these outcomes are reported in the registry record. Their listing indicates planned outcome categories, but does not establish that an analysis was completed, what definitions were used, or how censoring and missing observations were handled.
In general, a confidence interval describes the range of values compatible with an estimate under a statistical model and its assumptions. No confidence interval or primary-endpoint estimate is reported, so precision cannot be assessed from the registry entry. Likewise, the registry lists zero analyses. This means the posted record does not provide inferential estimates or tests to interpret; it is not a basis for declaring a statistical difference or absence of one.
The serious-adverse-event summaries provide counts for groups and list selected event terms with percentages. Those safety descriptions are distinct from the primary dose-finding result. The record does not make clear the denominator behind each listed event-term percentage, and the percentages should not be treated as comparative risks across randomized groups. The data describe what is posted in the registry, not a causal effect of dose or a comparison with another treatment.
The accompanying planning assumptions describe a two-arm illustration using a two-sided significance level of 0.05, equal allocation, a normal approximation, and fractions of an observed effect. Those assumptions do not describe the registered single-group design. Such illustrations are planning scenarios, not observed power, and cannot supply missing primary results or turn the dose-level groups into randomized comparators.
9. Statistical Methods Explained
Statistical interpretation depends first on matching the method to the question. This registry describes a single-group dose-escalation study. The primary question is dose finding under toxicity-based rules, not estimation of a treatment contrast against a control arm. The recorded allocation is NA and the model is single group. Dose-level cohorts are part of the escalation structure; the record does not describe random assignment among them.
How dose-escalation rules work
In general, a dose-escalation design uses observed toxicities at a dose level to guide whether the next level can be explored. The registry description sets thresholds for the number of dose-limiting toxicities among successive groups of the first seven, first nine, first twelve, or first fifteen participants. It says escalation may occur when toxicity counts remain within those limits, and that the maximal tolerated dose is considered exceeded when specified higher counts occur. The record also states that the principal investigator has discretion over escalation. These are the stated rules; the observed counts needed to apply them are not reported as primary results.
The protocol definition of dose-limiting toxicity matters because it determines which events contribute to the decision. The registry refers readers to the study protocol for that definition but does not reproduce it. Without the event definition and the outcome counts for each applicable dose level, the decision process cannot be independently reconstructed from the registry entry.
What a single-group design can show
In general, a single-group study can describe outcomes observed among participants receiving the intervention and can use a prespecified escalation method to address dose selection. It does not, on its own, separate treatment effects from other explanations for observed outcomes. A concurrent control group can help estimate a comparative effect; no such control is described in this record. Accordingly, survival or progression outcomes, if eventually reported, would need interpretation in the context of this nonrandomized design and the population enrolled.
The cohort and dose-level names in the safety record do not change that design. They identify groups within the dose-escalation record, but do not establish that groups were balanced in baseline characteristics or assigned at random. No like-for-like comparison is reported. Any statistical contrast across these labels would require details about cohort construction and analysis that are not reported in the registry record.
Counts, rates, and uncertainty
A count is the number of participants or events recorded, while a rate or proportion relates a count to a specified denominator. The adverse-event record gives participants at risk and participants affected for serious and other adverse events by group, as well as selected serious-event terms with percentages. The denominator and event-counting conventions for the term percentages are not stated in the record. No additional rate should be inferred without those details.
In general, estimates from small groups can be imprecise, and uncertainty is often expressed with confidence intervals. A confidence interval reflects sampling uncertainty under a model; it does not correct design limitations or unmeasured differences. No confidence intervals or other primary-endpoint uncertainty estimates are reported in the registry record. Thus, the precision of a maximal tolerated dose estimate cannot be evaluated from this entry.
For time-to-event outcomes such as overall survival or time to progression, general analysis methods often account for participants whose event has not been observed by the end of follow-up, a circumstance called censoring. The registry lists these outcome types but does not report an analysis method, event counts, follow-up summaries, or how censoring was handled. The handling of competing events is also not reported in the registry record. No method should be assumed.
Planning assumptions are not trial results
General power calculations ask how often a specified analysis would detect an effect of a chosen size under stated assumptions. The planning assumptions described for the accompanying illustration use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; time-to-event illustrations use total events, while other illustrations use participants per arm. The assumed effect is expressed as a fraction of an observed effect. These are planning conventions, not details of the registered single-group escalation design. They do not represent observed power and do not demonstrate that the study achieved a particular power.
Because no observed effect or primary-endpoint analysis is reported in the registry record, the planning assumptions cannot be read as a result of this trial. In general, a sample-size calculation is conditional on its assumptions about the effect, variability, significance level, and analysis. It does not establish that those assumptions were met, and it cannot replace reporting of the observed endpoint and its uncertainty.
What is needed for reproducibility
Reproducing the primary dose-finding analysis would require the tested dose levels, the number of participants evaluated at each level, the protocol-defined toxicity outcomes during the specified follow-up, and the decisions made under the escalation rules. The registry description gives the rule thresholds but not these results. Reproducing secondary outcome analyses would additionally require outcome definitions, analysis populations, follow-up and censoring details, and the statistical methods used. These details are not reported in the registry record, so a full statistical reanalysis is not possible from the posted entry alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome and four named secondary outcomes: overall survival, time to progression, local progression rate, and response rate. It does not report a multiplicity strategy describing how the risk of false-positive findings across multiple outcomes or analyses would be managed. No hierarchy, adjustment procedure, or distinction between confirmatory and exploratory secondary analyses is reported in the registry record.
The record lists zero analyses. It therefore does not provide statistical tests, effect estimates, confidence intervals, or analysis-specific denominators for the primary or secondary outcomes. The fact that outcomes are listed does not establish that all were measured, analyzed, or reported.
Missing-data methods and analysis populations are not reported in the registry record. The entry does not state how participants who did not complete follow-up were handled, how missing outcome measurements were addressed, or whether analyses used all enrolled participants or a defined subset. It also does not report outcome-specific numbers analyzed. The enrollment of 105 should not be taken to mean that every participant contributed data to each endpoint.
Interim-analysis procedures, stopping rules beyond the described dose-escalation toxicity criteria, and any adjustments to the statistical plan are not reported in the registry record. The record describes escalation thresholds and investigator discretion, but does not provide results showing how those rules were applied. In general, prespecifying analysis populations, missing-data handling, and multiplicity procedures helps readers understand how estimates were selected and how much uncertainty remains. Their absence from the registry entry limits assessment of the analysis process; it does not establish that these procedures were absent from the study protocol.
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 |
|---|---|---|---|
| Cohort 1 Dose Level 1 | 2 | 13 | 15.4% |
| Cohort 1 Dose Level 2 | 6 | 12 | 50.0% |
| Cohort 1 Dose Level 3 | 1 | 7 | 14.3% |
| Cohort 2 Dose Level 1 | 1 | 14 | 7.1% |
| Cohort 2 Dose Level 2 | 7 | 14 | 50.0% |
| Cohort 2 Dose Level 3 | 6 | 9 | 66.7% |
| Cohort 3 Dose Level 1 | 6 | 13 | 46.2% |
| Cohort 3 Dose Level 2 | 3 | 7 | 42.9% |
| Cohort 4 Dose Level 1 | 4 | 7 | 57.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 Dose Level 1 | 7 of 13 |
| Cohort 1 Dose Level 2 | 3 of 12 |
| Cohort 1 Dose Level 3 | 3 of 7 |
| Cohort 2 Dose Level 1 | 8 of 14 |
| Cohort 2 Dose Level 2 | 6 of 14 |
| Cohort 2 Dose Level 3 | 2 of 9 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cohort 1 Dose Level 1 | 13 of 13 |
| Cohort 1 Dose Level 2 | 12 of 12 |
| Cohort 1 Dose Level 3 | 7 of 7 |
| Cohort 2 Dose Level 1 | 13 of 14 |
| Cohort 2 Dose Level 2 | 14 of 14 |
| Cohort 2 Dose Level 3 | 9 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 Dose Level 1 | Cohort 1 Dose Level 2 | Cohort 1 Dose Level 3 | Cohort 2 Dose Level 1 | Cohort 2 Dose Level 2 | Cohort 2 Dose Level 3 |
|---|---|---|---|---|---|---|---|
| Sepsis | Infections and infestations | 0 of 13 | 2 of 12 | 1 of 7 | 0 of 14 | 0 of 14 | 2 of 9 |
| Lung infection | Infections and infestations | 1 of 13 | 1 of 12 | 0 of 7 | 0 of 14 | 1 of 14 | 1 of 9 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 13 | 0 of 12 | 1 of 7 | 0 of 14 | 0 of 14 | 1 of 9 |
| Abdominal pain | Gastrointestinal disorders | 0 of 13 | 0 of 12 | 1 of 7 | 0 of 14 | 2 of 14 | 0 of 9 |
| Intracranial hemorrhage | Nervous system disorders | 0 of 13 | 2 of 12 | 0 of 7 | 0 of 14 | 0 of 14 | 1 of 9 |
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 13 | 0 of 12 | 1 of 7 | 0 of 14 | 1 of 14 | 0 of 9 |
| Anemia | Blood and lymphatic system disorders | 0 of 13 | 0 of 12 | 0 of 7 | 0 of 14 | 0 of 14 | 2 of 9 |
| Constipation | Gastrointestinal disorders | 0 of 13 | 1 of 12 | 1 of 7 | 0 of 14 | 0 of 14 | 0 of 9 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 13 | 0 of 12 | 0 of 7 | 0 of 14 | 1 of 14 | 0 of 9 |
| Encephalopathy | Nervous system disorders | 0 of 13 | 1 of 12 | 0 of 7 | 0 of 14 | 0 of 14 | 1 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 Dose Level 1 | Cohort 1 Dose Level 2 | Cohort 1 Dose Level 3 | Cohort 2 Dose Level 1 | Cohort 2 Dose Level 2 | Cohort 2 Dose Level 3 |
|---|---|---|---|---|---|---|---|
| Hypertension | Vascular disorders | 9 of 13 | 9 of 12 | 5 of 7 | 9 of 14 | 14 of 14 | 9 of 9 |
| Fatigue | General disorders | 10 of 13 | 9 of 12 | 5 of 7 | 13 of 14 | 11 of 14 | 7 of 9 |
| Nausea | Gastrointestinal disorders | 6 of 13 | 10 of 12 | 3 of 7 | 9 of 14 | 11 of 14 | 5 of 9 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 12 of 13 | 6 of 12 | 4 of 7 | 8 of 14 | 7 of 14 | 5 of 9 |
| Headache | Nervous system disorders | 7 of 13 | 8 of 12 | 6 of 7 | 8 of 14 | 8 of 14 | 5 of 9 |
| Constipation | Gastrointestinal disorders | 7 of 13 | 7 of 12 | 4 of 7 | 10 of 14 | 9 of 14 | 4 of 9 |
| Dizziness | Nervous system disorders | 6 of 13 | 6 of 12 | 3 of 7 | 9 of 14 | 8 of 14 | 3 of 9 |
| Anxiety | Psychiatric disorders | 4 of 13 | 6 of 12 | 5 of 7 | 9 of 14 | 5 of 14 | 5 of 9 |
| Insomnia | Psychiatric disorders | 4 of 13 | 6 of 12 | 4 of 7 | 8 of 14 | 6 of 14 | 5 of 9 |
| Blurred vision | Eye disorders | 5 of 13 | 6 of 12 | 1 of 7 | 8 of 14 | 9 of 14 | 3 of 9 |
Serious events with the highest arm-level rate: anemia (22.2%), sepsis (22.2%), intracranial hemorrhage (16.7%), dysphagia (15.4%), dyspnea (15.4%).
The registry’s adverse-event record separates serious adverse events from other adverse events and gives participants at risk and affected within groups labeled by cohort and dose level. The affected counts are not themselves rates, and they should be read alongside the listed at-risk counts rather than as standalone measures. No comparative test or adjusted safety estimate is reported.
The registry lists Anemia and Sepsis at 22.2%, Intracranial hemorrhage at 16.7%, and Dysphagia, Dyspnea, and Lung infection at 15.4% among the top serious-event terms. The record does not specify the denominator or event-counting convention for these term percentages, so they should not be interpreted as directly comparable risks across groups. The listed terms also do not establish that every event was caused by the intervention.
In general, serious adverse events are a safety category, not the same measure as dose-limiting toxicity. The registry’s primary endpoint refers to a protocol-defined dose-limiting toxicity within 90 days, but the protocol definition and primary endpoint results are not reported in the registry record. The serious-event summaries therefore cannot be used to reconstruct the dose-escalation decisions or identify a maximal tolerated dose.
The safety groups are not randomized comparator arms. Differences in their counts cannot by themselves establish that one dose level caused more or fewer events than another. Follow-up completeness, event timing, and adjusted analyses are not reported in the registry record, which further limits interpretation of the safety summaries.
12. What the Result Does, and Does Not, Mean
The registry record identifies a clinically specific statistical aim: evaluate dose levels of single-fraction stereotactic radiosurgery for brain metastases in patients without prior brain irradiation, using dose-limiting toxicity within 90 days to guide escalation. It describes the escalation thresholds and names maximal tolerated doses as the primary outcome. This defines the intended question, but the record does not give the dose values or a numeric outcome.
As a result, the posted registry information does not establish which dose level met the study criteria, whether the maximal tolerated dose was exceeded, or how precise any dose estimate may be. No primary analysis is reported. The secondary outcomes are named, but numeric results for overall survival, time to progression, local progression rate, and response rate are not reported in the registry record.
The safety summaries provide counts by cohort and dose-level labels and list selected serious adverse-event terms with percentages. They offer descriptive safety information in the form recorded, but do not establish causation or a comparison between doses. The terms’ denominators are not reported, and the groups are not described as randomized controls.
In general, a dose-finding result and a comparative treatment effect answer different questions. Identifying a dose that meets a toxicity rule does not establish that it improves survival, disease control, or quality of life. Conversely, an absent numeric result in a registry entry is not evidence that no outcome occurred or that the intervention has no effect. It means the result cannot be assessed from the information recorded there.
The planning assumptions associated with sample-size illustrations are not observed trial findings and are not the registered design. They cannot substitute for a reported endpoint estimate or establish observed power. The appropriate interpretation is therefore limited: the registry describes a single-group dose-escalation study and its intended primary endpoint, while leaving the primary result and secondary outcome analyses unreported.
13. Why This Trial Matters Statistically
Dose-finding studies address a different statistical problem from trials designed primarily to compare treatments. Their escalation rules use accumulating safety information to guide exploration of dose levels. In this record, the primary endpoint is maximal tolerated doses, and the stated toxicity thresholds describe how escalation was intended to proceed. Understanding that structure is essential: the labels for cohorts and dose levels do not create randomized comparisons.
The registry also illustrates why endpoint definitions and results need to be read together. The primary outcome is tied to dose-limiting toxicity within 90 days, but the protocol’s detailed definition and the numeric outcomes are not reported in the registry record. Without the observed toxicity counts and dose values, readers cannot determine how the rule was applied or what dose conclusion followed.
More broadly, a registered study description and a posted analysis are different kinds of evidence. The record gives enrollment, status, outcome names, and a design description, but lists zero analyses. The presence of secondary outcome names or safety summaries does not supply the missing primary analysis. Clear reporting of estimates, uncertainty, analysis populations, and follow-up would allow readers to assess how much the results support the stated dose-finding objective.
This trial is also a useful reminder that planning assumptions are not trial characteristics. A two-arm power illustration does not make a single-group study comparative, and a planning calculation is not observed power. Keeping design, endpoint, and analysis distinct helps prevent a safety-oriented dose-finding question from being mistaken for proof of comparative clinical benefit.
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 most important limitation of the registry entry for statistical interpretation is that it does not report a numeric primary-endpoint result or analysis. The dose values tested, the numbers meeting the dose-limiting-toxicity criteria, and the selected maximal tolerated dose are not reported in the registry record. The protocol definition of dose-limiting toxicity is referenced but not reproduced.
The design is recorded as single group, with allocation listed as NA and masking as none. There is no separate randomized comparator, so the study record does not support a like-for-like estimate of comparative treatment effects. Cohort and dose-level safety labels should not be treated as randomized arms.
Although the record lists enrollment as 105, it does not report outcome-specific analysis populations, follow-up completeness, or missing-data handling. It also does not provide methods for the listed time-to-event outcomes, such as how censoring was handled. Secondary outcome results are not reported, and the registry lists zero analyses.
Safety interpretation is limited because the record does not state the denominator or event-counting convention for the listed serious-event term percentages. It also does not report an analysis relating those events to dose level or establishing causation. The safety counts cannot replace the protocol-defined primary endpoint.
Finally, multiplicity procedures, interim-analysis plans, the rationale for the enrollment target, and details of the statistical analysis plan are not reported in the registry record. These omissions limit assessment of the planned analysis and its implementation. They do not establish that such procedures were absent from the underlying study protocol.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis — NCT02645487.
- Registry record last updated 2026-10-07; status last verified 2026-09.
- Results first posted 2026-10-07.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT02645487 is a single-group dose-escalation study of stereotactic radiosurgery for brain metastases without prior brain irradiation. The condition is listed as adult malignant brain neoplasms; the intervention is stereotactic radiosurgery. The record lists phase and allocation as NA, masking as none, enrollment as 105, and status as active, not recruiting.
The primary outcome is maximal tolerated doses in gray within 90 days, using protocol-described dose-limiting-toxicity thresholds to guide escalation. Secondary outcomes include overall survival, time to progression, local progression rate, and response rate. The registry lists zero analyses and does not report numeric primary-endpoint or secondary-outcome results.
Safety information is organized by cohort and dose level, with serious and other adverse-event counts and selected serious-event terms. The sponsor is University of Texas Southwestern Medical Center. The study start date is 2015-12-18 and the primary completion date is 2025-03-23.