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 Temozolomide and Radiation Therapy in Treating Patients With Brain Metastasis Secondary to Non-Small Cell Lung Cancer (NCT00080938), a na phase 2 study. The primary outcome is Number of Patients With Intracranial Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00080938 |
| Phase | Phase 2 |
| Condition | Lung Cancer, Metastatic Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 26 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eastern Cooperative Oncology Group |
| Results posted | Yes |
2. Clinical Question
Population
Patients with brain metastasis from non-small cell lung cancer were the study population. The primary endpoint description specifies that response was assessed in 21 eligible and treated patients. The registry lists an enrollment of 26, but does not report how those enrolled relate to the endpoint population.
Intervention
The intervention combined orally administered temozolomide with whole-brain radiation therapy. The registry rationale describes the combination as a way to investigate whether temozolomide might make tumor cells more sensitive to radiation; that rationale is not itself evidence of an observed treatment effect.
Comparator
There was no separate control group. The study is recorded as single group, with allocation listed as not applicable and masking listed as none. Consequently, the registry record does not describe a randomized, like-for-like comparison between treatment groups.
Primary question
The primary question was how many eligible and treated patients had an intracranial response, defined as complete response or partial response under the stated RECIST-based criteria. The response outcome was assessed using brain MRI, alongside corticosteroid dose and neurologic examination criteria. The registry record does not report the number who responded, so the primary result cannot be quantified from that record.
3. Trial Design
This was a phase II study of temozolomide and radiation therapy in patients with brain metastasis from non-small cell lung cancer. The registry describes a single-group model and lists enrollment as 26. The intervention combined oral temozolomide with whole-brain radiation therapy. Allocation is listed as not applicable, and masking as none; there is no separate control arm described. The record is marked completed.
The study began on 2005-12-20, and primary completion is recorded as 2008-08. The primary endpoint was the number of patients with intracranial response. Its assessment population is described as 21 eligible and treated patients, distinct from the enrollment figure. The registry does not explain the relationship between these two figures, so no particular reason for the difference should be inferred.
Three secondary outcomes are listed: 1-year neurologic (central nervous system) progression-free rate, time to non-CNS (systemic) progression, and overall survival time. The registry lists four outcome measures in total. It does not provide numerical results for the primary endpoint or the secondary outcomes in the record.
A single-group design can describe outcomes observed among people who received the intervention, but it does not by itself estimate how those outcomes would differ under a separate alternative treatment or no treatment. Without a concurrent control group, differences attributable to treatment cannot be separated from other explanations, such as the course of disease or differences in patient characteristics. This limitation is important when interpreting any outcome count from this study.
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.
Overall Study
| Stage | Temozolamide and Radiation |
|---|---|
| STARTED | 26 |
| Began Protocol Therapy | 25 |
| Eligible and Treated | 21 |
| COMPLETED | 2 |
| NOT COMPLETED | 24 |
Reasons for not completing this period:
| Reason | Temozolamide and Radiation |
|---|---|
| Adverse Event | 3 |
| Withdrawal by Subject | 6 |
| Death | 2 |
| Lack of Efficacy | 7 |
| other disease | 1 |
| Not started protocol therapy | 1 |
| Ineligible | 4 |
Analysis population for the primary outcome, as defined in the registry: Eligible and treated patients
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 | Temozolamide and Radiation |
|---|---|---|
| Participants analysed | 21 | |
| Age, Continuous | years | 61 (40 to 85) |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 12 |
| Region of Enrollment: United States | participants | 21 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients With Intracranial Response, measured over assessed every cycle while on treatment, then every 3 months for 2 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of patients with intracranial response. The registry defines response as complete response plus partial response, assessed by brain MRI under RECIST. Complete response requires disappearance of the clinically detectable brain metastasis or metastases being followed, while the patient is off corticosteroids, together with a stable or improving neurologic examination. Partial response requires a reduction of 50% or more in the sum of the products of maximal cross-sections on MRI, with a stable or decreasing corticosteroid dose and a stable or improving neurologic examination.
These criteria combine imaging with clinical context. The MRI measurement captures change in the lesions being followed; the corticosteroid and neurologic examination conditions help specify what counts as a response rather than interpreting imaging in isolation. This is a general feature of composite response definitions: the endpoint is determined by meeting the stated criteria, not simply by a change on one measurement.
Response was assessed every cycle while patients were on treatment and then every 3 months for 2 years. The endpoint population is described as 21 eligible and treated patients. Although the registry names the endpoint and its assessment rules, it does not report the response count or proportion. Therefore, the extent or precision of the observed response cannot be described from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a phase II, single-group study and names intracranial response as its primary endpoint. It also specifies the response criteria and assessment schedule. It does not report the number of patients with complete or partial response. As a result, the central outcome cannot be summarized as a response count, and no estimate of the response rate or its precision can be stated from the registry record.
The distinction between enrollment and endpoint population matters. Enrollment is recorded as 26, while the primary endpoint description says response was assessed in 21 eligible and treated patients. The registry does not explain the relationship between these figures. It would therefore be inappropriate to assume why the populations differ or to use one as the denominator for the other without further information.
For a binary endpoint, an estimate describes how many participants experienced an event—in this case, meeting the response definition. A confidence interval, when reported, communicates uncertainty around an estimate: it gives a range of values compatible with the data and the method used to calculate the interval. It is not a guarantee that the true value lies in that particular range. Here, the registry record does not report the response estimate or an interval, so neither the magnitude nor the statistical precision of the primary result can be assessed.
The single-group design also limits interpretation. Even if the response count were available, an outcome observed after treatment would not establish what would have happened to comparable patients under a different treatment or without the combination. That counterfactual comparison requires a suitable comparator and a design that supports the comparison. The registry lists no separate control group and no randomized comparison.
The registry lists three secondary outcomes—neurologic progression-free rate at 1 year, time to non-CNS progression, and overall survival time—but does not report their numerical results. It lists four outcome measures overall and zero analyses. That listing is not a substitute for outcome estimates, definitions beyond those recorded, or statistical comparisons. In particular, no p-value, confidence interval, or treatment-effect estimate is reported for the primary endpoint in the registry record.
The registry entries therefore support a description of the study question, design, endpoint definition, and selected safety counts. They do not support a claim about the size of the intracranial response, the benefit or lack of benefit of the intervention, or the comparative effect of treatment. General statistical interpretation should remain separate from the unreported trial results.
9. Statistical Methods Explained
Statistical methods concern how outcomes are defined, summarized, and interpreted. For this study, the registry identifies a count-based primary endpoint: the number of patients with intracranial response. The endpoint is binary at the patient level, because each eligible and treated patient either meets the complete or partial response criteria or does not. The registry record does not report the response count or an inferential analysis of that endpoint.
What does a binary endpoint describe?
In general, a binary endpoint records whether a defined event occurred for each participant. A count of participants with the event is directly interpretable, while a rate or proportion relates that count to a specified population. The denominator is essential: a response count among all enrolled participants can differ in meaning from a count among eligible and treated participants. This record identifies 26 enrolled participants and states that response was assessed in 21 eligible and treated patients, but does not reconcile those populations. No response denominator should be substituted or reconstructed from that information.
The criteria also define the event being counted. Here, response means complete response or partial response under the stated RECIST-based brain MRI criteria. The definition includes MRI findings, corticosteroid conditions, and neurologic examination status. This detail matters because changing the criteria can change which observations count as response. The registry states that assessments occurred every cycle while on treatment and then every 3 months for 2 years; it does not report patient-level assessment data or the response result.
What would uncertainty measures mean?
As a general statistical concept, a confidence interval describes uncertainty in an estimate under a specified statistical method. A narrow interval usually indicates greater precision than a wide interval, while neither interval width nor the estimate alone resolves limitations in study design. For a single-group response endpoint, an interval could describe uncertainty around the observed response proportion, but it would not create a control-group comparison. No response estimate or confidence interval is reported in the registry record.
A p-value, in general, measures how incompatible observed data are with a specified statistical hypothesis under the assumptions of a test. It does not measure the probability that a treatment works, and it does not state the size or clinical importance of an effect. The registry lists zero analyses, and no p-value is reported for the primary endpoint. There is consequently no reported hypothesis test to interpret.
How does the design shape the analysis?
A single-group study summarizes outcomes among participants receiving the study intervention. It cannot directly estimate a contrast against a concurrent control group because no such group is described. Random allocation, when used in a comparative trial, can help balance known and unknown prognostic factors across groups on average. This study is recorded as single group, with allocation not applicable and masking none, so a randomized treatment contrast is not available. The design can still describe observed outcomes, but those descriptions should not be treated as causal comparisons.
Blinding or masking can reduce some kinds of influence on outcome assessment or reporting. The registry lists masking as none. The primary endpoint uses imaging as well as clinical criteria, but the record does not report procedures for independent or blinded review. Those procedures are not reported in the registry record and should not be assumed.
What does the planning illustration represent?
General sample-size planning asks how many participants might be needed to detect a specified effect under chosen assumptions. The stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it describes effects as fractions of the observed effect. For time-to-event outcomes, it specifies a total number of events, while other outcomes use participants per arm. These are planning conventions, not a description of the trial’s single-group design. The record does not report numerical planning estimates or the trial’s own sample-size justification. Such illustrations are not observed power and do not indicate the probability that the study detected an effect.
The observed effect on which a planning illustration is based would need to be available to interpret the resulting target. The primary response result is not reported in the registry record, and no numerical planning estimates are given in the information available. It is therefore not possible to describe a particular target number or assess whether the enrollment met a planned target. A planning illustration should not be mistaken for a retrospective measure of how informative the actual study was.
Why are the analysis population and outcome timing important?
Analysis populations define which participants contribute to a given result. The primary endpoint description names eligible and treated patients, whereas enrollment is recorded separately. The record does not report a full accounting of exclusions, treatment discontinuations, or missing assessments. Without those details, the handling of participants who lacked an evaluable scan or did not complete follow-up cannot be determined.
Repeated assessment over time can yield multiple measurements per participant, but the primary endpoint is stated as a patient count, not a model of repeated measurements. The registry does not describe how assessments at different visits were combined, beyond defining response and giving the schedule. The statistical plan, including any prespecified modeling, covariate adjustment, interim analyses, or method for handling missing outcome data, is not reported in the registry record. These absent details limit assessment of how the endpoint was analyzed, rather than changing what the endpoint definition says.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Temozolamide and Radiation | 21 | 3 | 14.3% | 3.0% to 36.3% | 5.0% to 34.6% | 5.2% to 34.9% |
R code and output
arm <- c("Temozolamide and Radiation")
n <- c(21)
events <- c(3)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Temozolamide and Radiation 21 3 14.3 3.0 36.3 5.0 34.6 5.2 34.911. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures: the primary intracranial response endpoint and three secondary outcomes. Examining multiple outcomes can raise a general multiplicity issue: when several statistical tests are performed, the chance of at least one apparently noteworthy result can increase if each is interpreted without accounting for the collection of tests. The registry lists zero analyses and reports no p-values or outcome estimates here, so there is no reported set of tests or adjustment procedure to evaluate. Whether multiplicity was addressed in the study’s statistical plan is not reported in the registry record.
The primary endpoint is defined for 21 eligible and treated patients, while enrollment is listed as 26. The record does not state how missing scans, unevaluable assessments, withdrawals, or other missing outcome data were handled. It does not report whether participants were analyzed according to an intention-to-treat principle, in an evaluable population, or under another rule. The endpoint description identifies the population used for assessment, but it is not a complete account of all analysis populations.
These omissions matter because the choice of population and treatment of missing outcomes can affect a binary result. For example, excluding participants without an assessment can produce a different summary from a rule that includes all enrolled participants. This is a general methodological consideration, not a claim about what occurred in this study. No missing-data method, sensitivity analysis, or population reconciliation is reported in the registry record.
12. 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 |
|---|---|---|---|
| Temozolamide and Radiation | 10 | 25 | 40.0% |
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 |
|---|---|
| Temozolamide and Radiation | 21 of 25 |
Most frequent serious adverse event terms
| Event term | Organ system | Temozolamide and Radiation |
|---|---|---|
| Fatigue | General disorders | 5 of 25 |
| Constipation | Gastrointestinal disorders | 2 of 25 |
| Dehydration | Metabolism and nutrition disorders | 2 of 25 |
| Nausea | Gastrointestinal disorders | 2 of 25 |
| Hyperglycemia | Metabolism and nutrition disorders | 2 of 25 |
| Nonneuropathic lower extr muscle weak | Musculoskeletal and connective tissue disorders | 2 of 25 |
| Dizziness | Nervous system disorders | 2 of 25 |
| Anemia | Blood and lymphatic system disorders | 1 of 25 |
| Thrombocytopenia | Investigations | 1 of 25 |
| Muco/stomatitis by exam,oral cavity | Gastrointestinal disorders | 1 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Temozolamide and Radiation |
|---|---|---|
| Fatigue | General disorders | 13 of 25 |
| Anemia | Blood and lymphatic system disorders | 11 of 25 |
| Alopecia | Skin and subcutaneous tissue disorders | 9 of 25 |
| Thrombocytopenia | Investigations | 8 of 25 |
| Nausea | Gastrointestinal disorders | 8 of 25 |
| Constipation | Gastrointestinal disorders | 6 of 25 |
| ALT Increased | Hepatobiliary disorders | 6 of 25 |
| Vomiting | Gastrointestinal disorders | 5 of 25 |
| Head/headache | Nervous system disorders | 5 of 25 |
| Leukopenia | Investigations | 4 of 25 |
Serious events with the highest arm-level rate: fatigue (20.0%), constipation (8.0%), dehydration (8.0%), nausea (8.0%), hyperglycemia (8.0%).
The registry’s safety listing identifies a group titled “Temozolamide and Radiation” and records 25 participants at risk for the serious-event figure, with 10 affected. It also records 25 at risk for other adverse events, with 21 affected. These are counts in the posted safety data, not comparative estimates: the study is single group and has no separate control arm described. The registry record does not explain the relationship between the safety population of 25 and the enrollment of 26.
The most frequently listed serious adverse event terms and percentages are Fatigue, 20.0%; Constipation, 8.0%; Dehydration, 8.0%; Nausea, 8.0%; Hyperglycemia, 8.0%; and Nonneuropathic lower extr muscle weak, 8.0%. The record does not give further detail in this listing about event grade, timing, recurrence, or whether an individual experienced more than one term. The percentages should be read as posted, without inferring a denominator or recalculating counts from them.
Safety counts describe events recorded in the study population; by themselves, they do not establish that treatment caused an event or enable comparison with another intervention. The registry does not report a death count for this group. Further details on adverse-event definitions and collection procedures are not reported in the registry record.
13. What the Result Does, and Does Not, Mean
The registry record establishes that a phase II, single-group study evaluated oral temozolomide with whole-brain radiation therapy in patients with brain metastasis from non-small cell lung cancer. It specifies an intracranial response endpoint, defines complete and partial response using MRI and clinical criteria, and gives a schedule for assessment. It also lists secondary outcomes and selected safety counts.
What the record does not establish is the observed primary response result. It does not report how many eligible and treated patients had complete or partial response, nor does it report an estimate of response precision. The listed safety figures do not fill that gap: adverse events and tumor response are different outcomes. The absence of the response result in the registry record should not be interpreted as evidence that no patients responded.
The single-group design limits what can be concluded even if an outcome count is available. A treated-group outcome is not a direct estimate of what would have happened to similar patients under a different approach. No randomized comparison or separate control group is described. Therefore, the study description alone cannot establish that the intervention caused an observed outcome or quantify its comparative effect.
In general, a study result should be interpreted using its endpoint definition, analysis population, uncertainty, and design. Here, the endpoint definition and the stated assessment population are available, but the numerical response result, uncertainty measures, analysis details, and missing-data handling are not reported in the registry record. The record also does not provide numerical results for the listed secondary outcomes. These limits prevent a conclusion about the magnitude or precision of the study’s clinical outcomes from the information recorded.
The appropriate statistical reading is therefore bounded: the registry describes what investigators set out to assess and reports selected safety counts, but it does not provide the primary efficacy result needed to characterize intracranial response. It neither supports a claim of benefit nor supports a claim of no benefit. Any stronger interpretation would require outcome information and analysis details not reported in the registry record.
14. Why This Trial Matters Statistically
This trial illustrates why a clear endpoint definition is central to clinical research. “Intracranial response” is not left as an informal judgment: the registry specifies complete and partial response criteria based on brain MRI, corticosteroid status or dose, and neurologic examination. Such criteria make the intended event more explicit and show that response is not determined by imaging change alone.
It also illustrates the importance of matching the analysis population to the question. Enrollment is recorded as 26, while the endpoint description refers to 21 eligible and treated patients. Without an explanation of that relationship, a reader cannot confidently select a denominator or assess how participant eligibility and treatment status shaped the endpoint population. Clear accounting of screened, enrolled, treated, and analyzed participants is important for interpreting a count-based result.
The single-group design is another useful statistical teaching point. It can describe outcomes in the group receiving the intervention, but it does not provide a direct control-group contrast. This distinction prevents an observed outcome from being mistaken for a treatment effect. A comparator and a design supporting valid comparison are needed to estimate how outcomes differ between treatment strategies.
Finally, the record demonstrates that a defined outcome is not the same as a reported result. The primary measure and its assessment schedule are present, but the number of responses and measures of uncertainty are not. Outcome definitions, analysis methods, population accounting, and numerical results all contribute to a complete statistical interpretation; no single one can stand in for the others.
15. 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 principal limitation for interpreting efficacy is that the registry record does not report the primary intracranial response count or an estimate of its precision. The endpoint criteria and assessment schedule are described, but the numerical result is absent. The listed secondary outcomes also have no numerical results in the record.
The design is single group, with no separate control arm described. Accordingly, the study cannot provide a randomized comparison of the combination against another treatment. Any outcome observed among treated participants would need to be interpreted as an outcome in that group, not as a causal treatment contrast.
The record lists enrollment as 26 and identifies 21 eligible and treated patients for the response assessment, but does not explain the relationship. Safety data list 25 participants at risk. The registry record does not give a participant flow accounting or explain how the populations differ. The handling of missing assessments and the analysis population rules beyond the stated eligible and treated group are not reported in the registry record.
The record also does not report a statistical analysis plan, sample-size justification, interim analysis procedures, multiplicity approach, or methods for missing data. It lists zero analyses. Masking is listed as none, and the record does not describe whether response assessments were independently reviewed. These details should not be inferred.
Safety reporting is limited to the listed counts and serious-event terms with percentages. Further information about event grade, timing, recurrence, attribution, and ascertainment is not reported in the registry record. These limitations constrain how fully outcomes can be assessed; they do not establish that an unreported method or result was absent from all study materials.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Temozolomide and Radiation Therapy in Treating Patients With Brain Metastasis Secondary to Non-Small Cell Lung Cancer — NCT00080938.
- Registry record last updated 2023-06-29; status last verified 2023-06.
- Results first posted 2011-09-27.
- 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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19. Record Summary
This completed phase II study evaluated oral temozolomide with whole-brain radiation therapy in patients with brain metastasis from non-small cell lung cancer. It is recorded as single group, with allocation not applicable and masking none. Enrollment is listed as 26. The primary endpoint was the number of patients with intracranial response, assessed by brain MRI and specified clinical criteria in 21 eligible and treated patients.
The registry lists three secondary outcomes: 1-year neurologic progression-free rate, time to non-CNS progression, and overall survival time. It reports selected safety counts for a group of 25 participants at risk and lists serious adverse event terms with percentages. The primary response result, secondary outcome estimates, uncertainty measures, and detailed analysis methods are not reported in the registry record.