Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases (NCT03391362), a na na study. The primary outcome is Neurologic Mortality.

2. Clinical Question

The central statistical question is descriptive: what percentage of participants in the stereotactic-radiation group experienced neurologic mortality by the specified assessment time, and how precisely is that percentage estimated? The posted record identifies the endpoint and its intended assessment, but it does not include an observed percentage or confidence interval. As a result, the clinical question can be described from the design, but its answer cannot be read from the registered results.

The study also lists outcomes involving all-cause mortality, quality of life, neurocognitive function, daily activities and performance status. These outcomes address different aspects of patient experience and clinical course. Their inclusion does not establish that results are available, and the registry record does not report their findings.

3. Trial Design

The registry describes a single-group study of stereotactic radiation in patients with small cell lung cancer and 1-10 brain metastases. It is not a randomized comparison. The allocation field is listed as NA, masking is listed as none, and the model is single group. Consequently, the registered design does not include a concurrent control arm for direct comparison with whole-brain radiation.

The official title calls the study a phase II trial, while the structured phase field is listed as NA. The discrepancy should be retained rather than resolved by inference: the title uses phase II language, but the structured phase value is not reported in the registry record. Enrollment is listed as 100. The study start date is 2018-02-23, the primary completion date is 2024-04-10, and the status is active, not recruiting.

The intervention is stereotactic radiation. The study summary describes focused radiation targeting individual tumors rather than the surrounding brain and contrasts this approach with whole-brain radiation as the broader clinical context. The arm description states that stereotactic radiation begins within 14 days of the MRI used for radiation planning. It also gives lesion-size-specific treatment descriptions, but the available description is truncated; further treatment details are not reported in the registry record.

The primary endpoint is neurologic mortality, expressed as a percentage of participants and assessed at 12 months. The registry describes ascertainment through review of study visits and medical records to identify whether death was neurologic or related to systemic progressive disease. Listed secondary outcomes include all-cause mortality, patient-reported quality of life, several neurocognitive measures, ability to complete activities of daily living and performance status.

This design can describe outcomes observed in the treated group, but it cannot by itself separate the association of treatment with outcomes from other influences on those outcomes. No randomized comparator, masking, analysis plan or detailed eligibility criteria are reported in the registry record. The record also lists 19 outcome measures and no analysis entries; it does not provide endpoint estimates or explain how the listed outcomes were analyzed.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Neurologic Mortality, measured over 12 months.

The primary endpoint is neurologic mortality, defined as a percentage of participants and assessed at 12 months. The registry says the endpoint is assessed by reviewing study visits and medical records to determine the cause of death, distinguishing neurologic death from death due to systemic progressive disease. The endpoint therefore concerns a specific cause-of-death category, rather than death from any cause.

This distinction is useful because deaths related to neurologic disease and deaths related to systemic progression represent different clinical events. A cause-specific endpoint can focus the assessment on the outcome relevant to the study question, while all-cause mortality captures death regardless of attributed cause. The registry lists all-cause mortality separately as a secondary outcome.

For an endpoint expressed as a percentage, the estimate would represent the proportion of the analyzed participants who meet the endpoint definition during the stated assessment period. Its interpretation depends on clear cause-of-death classification, appropriate follow-up, and a denominator that is defined consistently. The registry record does not report the observed percentage, the confidence interval, the number with neurologic mortality, or the analysis population used for this endpoint.

The registry identifies a 95% confidence interval as the dispersion measure for the primary endpoint. Such an interval communicates the statistical uncertainty around an estimated percentage; it does not describe the range of individual outcomes. Without the endpoint estimate and interval, the precision of the study's primary finding cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is registered as a single-group trial, with no masking and no randomized allocation. The primary endpoint is a percentage, and the stated dispersion measure is a 95% confidence interval. The registry record does not report the statistical analysis plan, estimation method, missing-data approach, or analysis population. The explanations below describe general statistical concepts and do not imply that a particular method was used for this study.

What does a percentage estimate represent?

In general, a percentage for a binary endpoint summarizes the proportion of an analyzed group classified as having the event. For this study, the event of interest is neurologic mortality by the specified 12-month assessment, based on the cause-of-death classification described in the registry. The estimate depends on who is included in the denominator and how participants without a recorded outcome are handled. Those details are not reported in the registry record, so the endpoint cannot be reconstructed from the description alone.

How should a confidence interval be read?

In general, a confidence interval gives an interval of values compatible with the data under the statistical method used. A narrower interval indicates greater precision under that method, while a wider interval indicates greater uncertainty. A 95% confidence interval is not a statement that 95% of individual participants fall within the interval, nor is it a guarantee that the interval contains the true value. It describes uncertainty in an estimate, with its interpretation dependent on the method and assumptions.

The registry names a 95% confidence interval but does not report the interval or the method used to calculate it. Without the estimate and interval, readers cannot judge precision or compare the observed result with a clinically meaningful benchmark. The record does not report such a benchmark either.

What does the single-group structure permit?

In general, a single-group study can estimate outcomes among the participants it follows. It does not create the balance between treatment groups that randomization is designed to achieve. If outcomes are compared with an external group, differences could reflect participant characteristics, follow-up, outcome definitions, or other factors rather than the intervention alone. No concurrent comparator is part of the registered design, and the registry record does not report an external comparison analysis.

The sample-size assumptions attached to the registry describe planning illustrations based on an observed effect, with equal allocation between two arms and a normal approximation. These are planning assumptions, not a reported analysis of the single-group trial. The registry record does not report the calculated planning values, the observed effect used for those illustrations, or the trial's own sample-size justification. Such illustrations must not be read as observed power or as evidence about the primary endpoint.

Why does cause-of-death classification matter?

In general, cause-specific mortality requires classifying deaths into categories. The primary endpoint distinguishes neurologic causes from systemic progressive disease, so consistent review of records and rules for resolving uncertain causes can affect the resulting percentage. The registry describes review of study visits and medical records, but the adjudication process, handling of uncertain causes and rules for incomplete records are not reported in the registry record.

All-cause mortality, listed as a secondary outcome, does not depend on assigning a cause of death in the same way. Cause-specific and all-cause outcomes answer different questions and should not be treated as interchangeable. The record does not provide results for either outcome.

What role could over-dispersion play?

In general, over-dispersion means that observed variation is greater than a statistical model expects. It can make standard errors too small if a model assumes less variation than the data contain, leading to confidence intervals that are too narrow. Whether over-dispersion is relevant depends on the outcome structure and chosen model. The registry record does not report the model or diagnostics, so there is no basis for saying that over-dispersion was assessed or affected the analysis.

Can the statistical analysis be evaluated from the record?

The registry lists no analysis entries and does not report an analysis plan, estimation method, adjustment variables, handling of censoring, or missing-data procedure. It also does not state which participants were included in the primary analysis. These omissions prevent an assessment of whether the reported methods, if any, matched the intended endpoint and follow-up. They also prevent independent reproduction of an endpoint estimate. The appropriate conclusion is limited: the endpoint and intended assessment are described, but the analysis and result are not reported in the registry record.

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.

R code and output

arm    <- c("Stereotactic Radiation")
n      <- c(100)
events <- c(11)
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  Stereotactic Radiation  100  11  11.0  5.6  18.8  6.3  18.6  6.3  18.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, including the primary endpoint and outcomes relating to mortality, quality of life, neurocognitive function, activities of daily living and performance status. When several outcomes are assessed, the chance of at least one apparently notable result can increase if each is tested separately without accounting for the family of analyses. In general, multiplicity methods can control this issue, but they may affect the interpretation of estimates and tests. The registry record does not report a multiplicity strategy, outcome hierarchy beyond identifying the primary endpoint, or an adjustment method.

The record lists no analysis entries, so it does not show which outcomes were analyzed or whether any multiplicity approach was applied. The number of listed measures alone does not establish how many statistical tests were performed. Results for secondary outcomes are not reported in the registry record.

Missing data can affect estimates when participants lack an endpoint assessment or when cause of death cannot be classified. In general, conclusions depend on the amount and pattern of missingness and on the assumptions used to handle it. The registry record does not report missing outcome counts, follow-up completeness, censoring rules, imputation, sensitivity analyses, or the handling of uncertain cause of death.

The record also does not specify the primary analysis population. It is therefore not possible to determine which participants contributed to the endpoint denominator or how deviations from the intended follow-up were treated. These are important limits when judging the reliability and reproducibility of an estimated percentage, but no estimate is reported to evaluate.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: systemic disease progression (3.0%), headache (2.0%), radiation necrosis (1.0%), dyspnea (1.0%), seizure (1.0%).

The registry lists safety figures for the stereotactic-radiation group. Serious adverse events are reported for 9 of 100 participants at risk. Other adverse events are reported for 94 of 100 participants at risk. The registry also lists 84 deaths. These are distinct safety entries, and they should not be combined or interpreted as mutually exclusive categories from the information reported.

The serious adverse-event terms with listed percentages are Systemic Disease Progression at 3.0%, Headache at 2.0%, Radiation Necrosis at 1.0%, Dyspnea at 1.0%, Seizure at 1.0%, and Back pain at 1.0%. The registry record does not provide further details about event timing, duration, severity grading, recurrence, or attribution to treatment. The listed terms therefore describe reported events, not proof that stereotactic radiation caused them.

The number at risk is a denominator for the registry's adverse-event reporting, but the record does not describe how those denominators were determined or whether participants had the same length of safety follow-up. The event listings also do not supply a comparison with whole-brain radiation or another control group. These figures can be read as reported safety counts and terms in the treated group, but not as comparative risks or causal estimates.

13. What the Result Does, and Does Not, Mean

The record identifies a study of stereotactic radiation for patients with small cell lung cancer and 1-10 brain metastases. It specifies neurologic mortality at 12 months as the primary endpoint and describes how cause of death is intended to be assessed. It also lists secondary outcomes and safety information. These details explain the study's focus and the kinds of outcomes tracked.

The record does not report the primary endpoint estimate, its 95% confidence interval, or findings for the listed secondary outcomes. It therefore does not establish the observed frequency or precision of neurologic mortality. The absence of a posted result is not evidence that the event did not occur, nor does it indicate a particular direction or size of an effect.

The single-group design is another key limit. It can describe outcomes in the stereotactic-radiation group, but it does not provide a randomized, concurrent comparison with whole-brain radiation. The study summary presents whole-brain radiation as the broader alternative of interest, not as a control arm in this trial. Thus, the registered design cannot by itself show what would have happened to the same population under that alternative.

The safety entries identify reported serious and other adverse events and several event terms. They do not establish causation, and the record does not provide comparative safety results. The listed death count also should not be treated as a count of neurologic deaths: the primary endpoint distinguishes cause of death, while the safety entry is a separate registry figure.

In general, a treatment-effect conclusion requires outcome estimates, a defined analysis and a credible basis for comparison. The registry record does not report those elements for the primary endpoint. The defensible interpretation is therefore limited to the design, intended outcomes and listed safety information; conclusions about comparative effectiveness or causation are not supported by the record.

14. Why This Trial Matters Statistically

This trial raises a statistically important question about a focused radiation approach in a population with small cell lung cancer and 1-10 brain metastases. The study's primary endpoint is cause-specific mortality at 12 months, which requires both follow-up and classification of cause of death. Clear endpoint definitions matter because an overall death outcome and a neurologic-cause outcome describe different events.

The single-group structure makes estimation and causal comparison separate issues. A study may estimate the frequency of an outcome among participants receiving an intervention, but comparison with another treatment requires a suitable reference group and assumptions about comparability. The registered design has no concurrent control arm, so its structure is suited to describing the treated group rather than providing a randomized treatment contrast.

The record also illustrates why outcome registration and outcome reporting are not the same. A primary endpoint and numerous secondary measures are listed, but the registry record contains no analysis entries or endpoint findings. Without estimates, confidence intervals, and an account of the analysis population, readers cannot assess precision, completeness, or the strength of evidence for the study's primary question.

Finally, cause-specific endpoints and safety listings need careful interpretation. Cause attribution may depend on record review, and event counts alone do not establish treatment causation. The registry offers a framework for understanding what was intended to be measured, but outcome data and analytical details are needed before statistical conclusions can be drawn.

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.

Important limitations follow from the registered design and the information recorded. The study is single group and has no concurrent randomized comparator. Accordingly, any outcome description would be specific to the treated participants, and a direct treatment contrast with whole-brain radiation is not available from this design. The summary's mention of whole-brain radiation does not make it a control arm.

The primary endpoint result is not reported in the registry record. The percentage, confidence interval, event count and analysis population are absent, so neither the endpoint magnitude nor its precision can be assessed. The registry also lists no analysis entries and does not report the statistical analysis plan, adjustment strategy, missing-data handling, or rules for incomplete follow-up and uncertain cause of death.

The structured phase field is listed as NA even though the official title describes the study as phase II. This difference is recorded without resolving it. The arm description is truncated, limiting the treatment detail available in the registry record. Additional eligibility criteria and the sample-size justification are not reported.

The listed adverse-event counts and terms lack details about timing, follow-up duration, attribution and event-level overlap. They should not be interpreted as comparative or causal estimates. The registry's sample-size assumptions are described as planning illustrations rather than the trial's own design justification; the calculated planning values and the effect used for those illustrations are not reported.

Together, these gaps restrict interpretation to the registered purpose, design and listed safety entries. They do not allow an independent assessment of the primary endpoint analysis or a comparative evaluation of stereotactic radiation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases — NCT03391362.
• Registry record last updated 2026-09-29; status last verified 2026-03.
• Results first posted 2026-07-14.
• 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.

19. Record Summary

NCT03391362 is a single-group study of stereotactic radiation in patients with small cell lung cancer and 1-10 brain metastases. The official title describes it as phase II, while the structured phase field is NA. Allocation is listed as NA, masking as none, and the study model as single group. Enrollment is listed as 100; status is active, not recruiting.

The primary endpoint is neurologic mortality, expressed as a percentage of participants at 12 months, with cause of death assessed through study visits and medical records. The registry lists secondary outcomes involving mortality, quality of life, neurocognitive function, daily activities and performance status. It also lists safety counts and serious adverse-event terms.

The registry record does not report the primary endpoint result, secondary outcome findings, analysis entries, analysis population, or statistical analysis plan. The single-group design does not include a concurrent control arm. The available record supports a description of the study's intent and structure, but not a conclusion about comparative treatment effects.