A Study for Image-Guided Radiation Therapy in Pediatric Brain Tumors and Side Effects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study for Image-Guided Radiation Therapy in Pediatric Brain Tumors and Side Effects (NCT00187226), a non-randomized phase 2 study. The primary outcome is Local Tumor Control.

2. Clinical Question

3. Trial Design

This was a phase II, non-randomized, single-group study with no masking. The registry lists enrollment of 361 and status as completed. The listed sponsor was St. Jude Children's Research Hospital. The study start is recorded as 1997-06, and primary completion as 2005-03-31.

The study included pediatric CNS tumor diagnoses. The registry describes Stratum 1 as ependymoma, craniopharyngioma, and low-grade glioma, and Stratum 2 as high-grade glioma. In the adverse-event listings, groups are also distinguished by diagnosis and clinical target volume margin: 1cm for several diagnoses and 2cm for high-grade glioma and low-grade glioma. The record does not provide a detailed account of how participants were assigned to these groups or how the treatment margin was selected.

The study description states an interest in limiting the volume of normal tissue treated and examining disease control in relation to standard radiation therapy. That objective does not establish that the registry contains a concurrent control group. With a single-group, non-randomized design, comparisons among diagnoses or margin groups are not randomized treatment comparisons. Differences across those groups could reflect differences in the patients or tumors as well as differences in treatment.

The registry lists two radiation therapy procedures, but further procedural details are not reported in the registry record. The number of outcome measures is listed as 1, while no analysis records are listed. Specific eligibility criteria, allocation procedures, masking procedures beyond the stated absence of masking, and protocol deviations 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Patients with Ependymoma, Craniopharyngioma, Low-grade Glioma, and High-grade Glioma were analyzed by diagnosis.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Local Tumor Control, measured over 12 months after the enrollment of the last therapeutic patient.

The primary endpoint was local tumor control, expressed as a proportion of patients. The registry defines local failure as tumor progression within the volume that received the prescribed dose of irradiation. Brain and spine MRI after radiation therapy was used to assess tumor status. The imaging schedule was every 3-4 months during the first three years and then every 6 months through five years.

This endpoint addresses whether disease progression occurred at the treated site, a clinically relevant distinction when a treatment approach aims to limit the volume of normal tissue receiving radiation. The registry’s stated timeframe for the endpoint was 12 months after the enrollment of the last therapeutic patient. That timeframe should not be confused with the full imaging schedule, which extended through five years.

The endpoint is recorded with a 95% confidence interval, but no control proportion or interval estimate is reported in the registry record. The record also does not provide diagnosis-specific event counts or explain how MRI assessments were adjudicated. Thus, the endpoint definition and assessment schedule are available, but the posted information does not establish the observed degree of local tumor control.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies local tumor control as a patient proportion and records a 95% confidence interval as the dispersion measure. It also identifies the endpoint parameterization as LOG MEAN. The estimation procedure, transformation details, and any method used to obtain the interval are not reported in the registry record. No numerical estimate or interval endpoints are posted, so the precision of the primary result cannot be assessed.

What does a confidence interval describe?

In general, a confidence interval expresses uncertainty around an estimate. A narrower interval indicates greater statistical precision than a wider interval, while neither an interval nor its width establishes that an effect is clinically important. The interval is useful only alongside a clearly defined estimate, analysis population, and method. Here, the registry names a 95% confidence interval but does not report its limits or the corresponding local-control estimate.

How should the proportion endpoint be understood?

In general, a proportion summarizes the share of an analyzed group meeting a defined outcome. For this study, the intended outcome concerns local tumor control, with local failure defined as progression within the prescribed radiation volume. To interpret a proportion, readers need to know which patients were included, how missing or unevaluable scans were handled, and the period over which outcome status was assessed. The assessment schedule and stated endpoint timeframe are recorded, but the analysis denominator and missing-data approach are not reported in the registry record.

What does the recorded parameterization establish?

The registry records LOG MEAN as the endpoint parameterization. That label alone does not specify the full statistical model, the estimate on the original proportion scale, or how the confidence interval was constructed. Those details are not reported in the registry record. It would therefore be inappropriate to infer a specific link function, adjustment set, or model-fitting procedure from the label alone.

Why does the design affect statistical interpretation?

In general, random assignment can help make treatment groups comparable at baseline, while a single-group design lacks that randomized contrast. This study is recorded as non-randomized and single-group. Its diagnosis and margin categories can describe outcomes within those groups, but differences between them would not automatically isolate a treatment effect. The registry does not report an adjusted comparative analysis or a control-group estimate.

For a non-randomized study, interpretation can also depend on how participants entered the study, the distribution of tumor diagnoses, and differences in prognosis or follow-up. These details are not reported in the registry record. The fact that patients were analyzed by diagnosis indicates that diagnosis was relevant to reporting, but does not reveal whether any other factors were adjusted for.

What do the planning assumptions mean?

The planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers an effect to detect expressed as a fraction of the observed effect. These are assumptions for hypothetical planning calculations, not evidence of the trial’s own design rationale. In particular, equal allocation between two arms does not match the registry’s description of a single-group, non-randomized study. The registry does not report its sample-size justification, the effect size used in its original planning, or an intended power target.

In general, a sample-size calculation estimates how many observations might be needed under specified assumptions. Changing the assumed effect, variability, allocation, or analysis method can change the resulting planning estimate. A calculation based on an observed effect is especially dependent on that effect estimate, and it should not be read as observed power. Since the primary effect estimate is not reported in the registry record, the assumptions do not establish the precision or detectability of the study’s actual results.

Why can over-dispersion matter in general?

For outcomes modeled as counts or proportions, over-dispersion means that observed variability exceeds what a chosen model assumes. If not accounted for, uncertainty estimates can be too small. This is a general statistical consideration, not a method reported for this trial. The registry does not describe an over-dispersion assessment or a model that would allow readers to determine whether it was relevant.

The number of analysis records is listed as 0. That means the registry record does not supply analysis-level estimates, confidence limits, or test results for interpretation. It does not establish that no analyses were performed outside the registry; their details are simply not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and identifies local tumor control as the primary endpoint. It does not report a multiplicity strategy, such as how statistical error would be handled across multiple endpoints, diagnosis groups, timepoints, or other analyses. It also does not report a complete statistical analysis plan. With no analysis records listed, readers cannot determine which analyses were prespecified or whether additional analyses were performed.

The record says local tumor control was analyzed by diagnosis, and the study also sought to examine neurological, endocrine, and cognitive function. The registry does not provide results or analysis details for those functional outcomes. It is not reported in the registry record whether they were secondary endpoints, how they were measured, or how repeated assessments were analyzed. Without this information, the scope of multiplicity cannot be fully assessed.

Missing-data procedures are not reported in the registry record. In particular, the record does not explain how missing MRI assessments, incomplete follow-up, or participants without an evaluable endpoint were handled. It does not report whether analyses used all enrolled participants, only participants with available outcome assessments, or another defined analysis population. Although enrollment is listed as 361, the number contributing to the primary endpoint is not reported.

Interim analyses and stopping rules are also not reported in the registry record. The absence of those details does not establish whether such procedures were or were not used; it limits what can be concluded from the registry entry. A sample-size justification, including its assumptions and intended power, is not reported in the registry record.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cns ischemia (3.6%), death (3.6%), hemorrhage (2.9%), pulmonary (1.1%).

The adverse-event listings separate serious events and other events, and organize counts by diagnosis and clinical target volume margin. For the 1cm margin groups, the serious-event counts are 1 among 88 at risk for ependymoma, 0 among 49 for low-grade glioma, 2 among 28 for craniopharyngioma, and 0 among 2 for other diagnoses. For the 2cm margin groups, the counts are 1 among 34 at risk for high-grade glioma and 0 among 1 for low-grade glioma. These are group-specific counts, not comparisons between randomized treatments.

The registry lists CNS Ischemia (3.6%), Death (3.6%), Hemorrhage (2.9%), and Pulmonary (1.1%) among the top serious terms. The group-level deaths field contains no reported count. The registry does not state the observation period or explain whether a participant could have multiple events, so the term percentages should not be combined or interpreted as a complete participant-level risk estimate. Small group sizes also mean that counts alone give limited information about how precisely event frequencies are estimated.

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

The registry record establishes that a phase II study examined image-guided radiation therapy for pediatric CNS tumors, with local tumor control as its primary endpoint. It also records a schedule for MRI assessment, a definition of local failure, and adverse-event counts for several diagnosis and margin groups. Those details help readers understand what outcomes the study intended to assess and how the primary endpoint was defined.

The record does not report a local-control estimate, a confidence interval, or diagnosis-specific endpoint results. It therefore does not show how often local control was achieved or how precisely that quantity was estimated. The stated objective of evaluating whether limited-volume conformal treatment could achieve disease control similar to standard radiation therapy is a study question, not a result. The registry’s single-group, non-randomized design also does not provide a randomized control comparison.

The posted safety counts and selected adverse-event terms describe reported events, but do not provide a complete comparative safety assessment. The record does not specify an observation period, detailed event ascertainment procedures, or whether participants could experience multiple events. A listed event count should not be interpreted as proof that treatment caused the event, and the absence of a listed event in a small group does not establish that no such event occurred outside the recorded data.

More broadly, an endpoint definition and a completed study status do not substitute for posted outcome estimates. The registry record supports description of the study’s design and reported safety entries, but it does not provide enough primary-outcome information to judge the magnitude or precision of local tumor control.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly specified endpoint is only one part of interpreting clinical research. The registry defines local tumor control through MRI assessment and a location-specific definition of failure. That specificity gives the outcome a connection to the treatment strategy, which aimed to limit the volume of normal tissue surrounding the tumor or tumor bed that received radiation. At the same time, the numerical outcome estimate and its uncertainty are not reported in the registry record, leaving the central statistical result unavailable.

The design also illustrates the distinction between a research objective and a comparison supported by study structure. The stated interest in disease control relative to standard radiation therapy does not make the study a randomized comparison. The registry describes a non-randomized, single-group study, and no like-for-like control group is reported. This makes it important to avoid treating differences among diagnosis or margin categories as if they were randomized treatment effects.

Finally, the record shows why safety counts need context. The adverse-event listings identify groups, at-risk counts, and affected counts, but do not provide all the information needed to estimate or compare event risks. Follow-up duration, event overlap, and analysis populations are not reported. The study is therefore a useful example of how design, endpoint definition, uncertainty, and reporting completeness all shape the conclusions that can be drawn from a registry entry.

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 main limitation for statistical interpretation is that the registry does not report the primary local-control estimate or its 95% confidence interval. The record also does not provide local-failure counts or diagnosis-specific endpoint denominators. This prevents assessment of the magnitude and precision of the primary outcome, despite the endpoint definition and imaging schedule being described.

The study is recorded as non-randomized and single-group. A control group, allocation process, or comparative estimate is not reported in the registry record. The stated comparison with standard radiation therapy is therefore an objective in the study description, not evidence of a posted controlled comparison. Differences across diagnosis or margin groups may reflect group composition and other factors that are not documented.

The registry does not report the analysis population, handling of missing MRI data, statistical model details, adjustment for potential confounders, or multiplicity procedures. It also does not report interim analyses, stopping rules, or the study’s sample-size justification. The total enrollment cannot resolve these issues because the number contributing to each endpoint analysis is not reported.

Safety interpretation is limited by the absence of a stated event observation period and detailed ascertainment methods. The record does not explain whether individuals could contribute multiple events, and the deaths field has no reported group-level count despite Death appearing among the listed serious terms. These limitations restrict what can be inferred from the posted counts and percentages.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study for Image-Guided Radiation Therapy in Pediatric Brain Tumors and Side Effects — NCT00187226.
• Registry record last updated 2023-05-31; status last verified 2023-05.
• Results first posted 2012-08-20.
• 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.

18. Record Summary

The registry describes a completed phase II, non-randomized, single-group study of image-guided radiation therapy for pediatric CNS tumors, with enrollment of 361. Its stated goals included assessing local tumor control and examining neurological, endocrine, and cognitive effects. Local tumor control was defined using MRI, with local failure based on progression within the prescribed radiation volume.

The record lists one outcome measure and no analysis records. It does not report the primary local-control estimate, its confidence interval, or diagnosis-specific endpoint results. Adverse-event counts are reported for diagnosis and margin groups, alongside selected serious-event terms, but the event observation period and several analysis details are not reported in the registry record. The design and posted information support a description of the study, but not a randomized comparison with standard radiation therapy.