Observation or Radiation Therapy in Treating Patients With Grade I, Grade II, or Grade III Meningioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Observation or Radiation Therapy in Treating Patients With Grade I, Grade II, or Grade III Meningioma (NCT00895622), a non-randomized phase 2 study. The primary outcome is Progression-free Survival Rate at 3 Years.

2. Clinical Question

3. Trial Design

This was a phase II, parallel, non-randomized study with no masking. The registry record lists an enrollment of 244 and a completed status. The recorded start was 2009-06, and primary completion was 2016-09. The sponsor was the Radiation Therapy Oncology Group.

Management differed by risk group: the low-risk group received no treatment, the intermediate-risk group received 54 Gy radiotherapy, and the high-risk group received 60 Gy radiotherapy. This structure is important when interpreting any differences among the groups. Since participants were not randomly allocated to a common treatment comparison, risk status and treatment are linked in the design. Group outcomes therefore cannot be read as a direct randomized comparison of observation against radiotherapy.

The record lists MRI-based progression-free survival at 3 years as the primary endpoint. It also lists outcomes concerning acute and late adverse events, overall survival at 3 years, MRI imaging features, tumor dimensions, radiotherapy parameter adherence, and agreement in histopathologic grading and subtyping. The listed outcome measures do not establish that numerical results for each were posted.

The registry record does not report the rationale for the enrollment target, details of participant allocation within risk categories, or a statistical analysis plan beyond the stated primary endpoint method. It also does not report whether interim analyses were planned or conducted. These details should not be inferred from the phase designation or study duration.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Two hundred forty-four patients registered for the first step registration which consisted of central pathology review confirmation of histology. One hundred seventy-eight continued on to the second step registration.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eligible patients who started study treatment and evaluable for 3-year progression-free survival

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: All eligible patients

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival Rate at 3 Years, measured over From registration to 3 years.

The primary endpoint is the progression-free survival rate at 3 years, measured from registration. It summarizes the proportion of eligible patients who started study treatment and were evaluable for the endpoint who had not met the study definition of progression by the specified follow-up point. The registry record says rates were estimated using the binomial method.

Progression was determined by central review of MRI examinations. The definition included an increase in measurable tumor of > 20% in any diameter, or new nodular enhancement when there was no measurable tumor on initial postoperative imaging. When neurologic progression was absent, suspected imaging progression of < 5 mm in maximum diameter needed confirmation on two successive follow-up MRI studies at least 3 months apart. Neurologic progression meant a new or progressive neurologic deficit attributed to the meningioma, with or without measurable tumor growth.

A progression-free survival endpoint combines time-related disease status into a clinically interpretable rate at a defined follow-up point. It is distinct from overall survival: progression can occur without death. The registry record does not report the estimated rate or its 95% confidence interval, so the endpoint’s observed magnitude and precision cannot be assessed from the posted results described in the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is expressed as a percentage of participants, and the registry record states that progression-free survival rates are estimated using the binomial method. In general, a binomial estimate describes the proportion of people in a defined group who meet an outcome definition. Its interpretation depends on the population included in the calculation and how outcome status is determined. Here, the stated endpoint population is eligible patients who started study treatment and were evaluable for 3-year progression-free survival.

The record gives a 95% confidence interval as the measure of dispersion for this endpoint. In general, a confidence interval conveys statistical uncertainty around an estimated quantity, with narrower intervals indicating greater precision under the method’s assumptions. It does not guarantee that the true value lies within the calculated interval, and it does not correct for limitations in study design or outcome ascertainment. Numerical interval limits are not reported in the registry record, so the endpoint’s precision cannot be judged.

The progression criteria combine imaging and neurologic findings. Central review of MRI examinations was used to determine progression. The imaging definition includes an increase in measurable tumor of > 20% in any diameter or new nodular enhancement for patients without measurable tumor on initial postoperative imaging. When neurologic progression is absent, suspected imaging progression of < 5 mm in maximum diameter must be confirmed on two successive follow-up MRI studies at least 3 months apart. Neurologic progression is a new or progressive neurologic deficit attributed to the meningioma, whether or not measurable growth is present.

Central review can promote consistent assessment across institutions by applying common criteria to imaging. Requiring follow-up confirmation for certain suspected imaging changes may also reduce classification based on an unconfirmed finding. These design features describe the endpoint’s ascertainment approach; they do not show how often imaging was missing, how frequently confirmation was possible, or whether assessments were complete. Those details are not reported in the registry record.

The non-randomized, risk-based allocation is central to the statistical interpretation. In a randomized comparison, allocation can balance measured and unmeasured prognostic factors on average. Here, management is assigned by risk group, so the groups are not interchangeable comparison arms. A difference in outcomes across the groups could reflect the underlying risk classification, other participant characteristics, treatment, or several influences together. The registry record does not report an adjusted comparison that would address these concerns.

General statistical principle: over-dispersion occurs when outcome variability is greater than a simple model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not account for the extra variability. The record identifies a binomial method for the primary rate; it does not report an over-dispersion assessment or another method to address it. This general concern should not be taken as evidence that over-dispersion occurred in this study.

The posted information does not state whether the primary estimate was calculated separately for each risk group or for a pooled population, nor does it provide numerical estimates. It also does not describe covariate adjustment, handling of censoring, or an alternative time-to-event analysis for the primary endpoint. Those methods are not reported in the registry record and should not be inferred from the endpoint name alone.

There are no reported recalculated estimates to compare with sponsor analyses. The record does not include sufficient numerical primary-outcome data to reproduce the rate or its confidence interval. If posted sponsor results and simple unadjusted recalculations were ever to differ, the sponsor’s own analysis would take precedence, but no such discrepancy is described in the registry record.

General distinction: sample-size planning calculations address what a study might need under stated assumptions; they do not describe the precision actually achieved or constitute observed power. The registry record does not report the study’s sample-size justification or assumptions. Any such planning information should not be attributed to the trial’s original design unless the registry record states that it was used for that purpose.

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("Low Risk", "Intermidiate Risk", "High Risk")
n      <- c(51, 48, 51)
events <- c(47, 45, 30)
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  Low Risk  51  47  92.2  81.1  97.8  81.5  96.9  81.5  96.8
ARM  Intermidiate Risk  48  45  93.8  82.8  98.7  83.2  97.9  83.1  97.7
ARM  High Risk  51  30  58.8  44.2  72.4  45.2  71.2  45.1  71.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and multiple secondary outcomes, including adverse events, overall survival, MRI characteristics, radiotherapy adherence, and concordance in grading and subtyping. It does not report how statistical testing across these outcomes was handled. In particular, a multiplicity adjustment, a hierarchy of hypotheses, or an interpretation plan for multiple comparisons is not reported in the registry record.

In general, testing multiple outcomes can increase the chance of finding an apparently notable result by chance when each is considered separately. A prespecified testing strategy can help clarify which findings are confirmatory and which are exploratory. No such strategy is described in the registry record, so the secondary outcomes should not be treated as a coordinated set of confirmatory tests.

The record defines the primary endpoint population as eligible patients who started study treatment and were evaluable for 3-year progression-free survival. It does not report how many participants met that definition, how missing or incomplete MRI follow-up was handled, or whether participants with unavailable endpoint status were excluded or otherwise addressed. The approach to missing data is not reported in the registry record.

The record does not specify a broader analysis population, such as an intention-to-treat population, nor does it describe exclusions after enrollment or protocol deviations for the primary analysis. The outcome-specific population description should therefore be read as the only stated definition, not as evidence of a particular missing-data strategy. Without participant flow and analysis details, the impact of incomplete follow-up or exclusions on the estimate cannot be assessed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: seizure (3.8%), central nervous system necrosis (1.9%), gait abnormal (1.9%), pain [other] (1.9%), soft tissue infection [with normal or grade 1-2 anc] (1.9%).

The registry record lists serious adverse events by risk group: 0 of 60 participants in the low-risk group, 1 of 52 in the intermediate-risk group, and 5 of 53 in the high-risk group. It separately lists other adverse events affecting 22 of 60, 47 of 52, and 47 of 53 participants in those groups, respectively. The record also reports deaths of 22, 47, and 47 by group. These are descriptive counts, not evidence that an intervention caused an event or death.

The groups were non-randomized and differed in risk classification and management. They therefore cannot be interpreted as comparable treatment arms for causal safety comparisons. The registry record does not report the event attribution, detailed observation windows, or the precise definition of the other-adverse-event category in the information. The number of participants at risk for the listed categories is stated, but the safety figures alone do not describe exposure duration or all relevant clinical context.

The record lists serious-event terms including seizure at 3.8%, central nervous system necrosis at 1.9%, gait abnormal at 1.9%, pain [other] at 1.9%, soft tissue infection [with normal or Grade 1-2 ANC] at 1.9%, and neurological disorder NOS at 1.9%. These percentages are listed terms; the registry record does not give additional context to establish their timing, attribution, or relationship to treatment.

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

The registry record describes a phase II study that used observation for the low-risk group and radiotherapy for intermediate- and high-risk groups. Its primary endpoint was progression-free survival at 3 years, with MRI-based progression criteria and central review. This conveys the clinical question and the outcome definition, but the numerical primary endpoint result and confidence interval are not reported in the registry record.

As a result, the posted information does not quantify the observed rate of progression-free survival or its precision. It also does not provide a numerical estimate comparing the risk groups. Even if group-specific rates were available, the non-randomized risk-based design would not support treating those differences as a direct causal comparison of observation and radiotherapy. Participants were not assigned at random to comparable treatment options.

The record’s serious adverse-event and other event counts describe what was recorded in each group. They do not establish that treatment caused an event, nor do they establish that an approach prevented one. The risk groups have different management and are not a like-for-like safety comparison. Additional information on attribution, follow-up, and analysis populations is not reported in the registry record.

In general, a confidence interval helps communicate the precision of an estimate, while study design determines how confidently associations can be interpreted. Neither the magnitude nor precision of the primary outcome can be evaluated without the estimate and its interval. The record also does not report a statistical plan addressing multiplicity or missing endpoint data. These absences limit interpretation of both primary and secondary outcomes.

The study record can therefore be used to understand its intended population, risk-based management, and outcome definitions. It cannot, from the information reported, establish how well the groups fared on the primary endpoint or quantify the relative effects of observation and radiotherapy. No clinical recommendation follows from these registry entries alone.

14. Why This Trial Matters Statistically

This study is statistically notable for the way its clinical question and allocation structure differ. The rationale describes observation for low-risk meningioma and radiotherapy for intermediate- and high-risk disease, while the purpose frames these approaches in relation to one another. Yet the study is explicitly non-randomized, and participants receive management according to risk category. That makes it essential to distinguish a descriptive comparison across groups from an estimate of treatment effect.

The primary endpoint also illustrates the importance of defining progression carefully. Central MRI review, a specified imaging threshold, confirmation of certain suspected changes, and a neurologic progression definition all shape which participants count as having progressed. These rules are part of the statistical meaning of the endpoint, not merely technical details.

The registry record lists a 95% confidence interval for the primary rate as the precision measure, but does not report the rate or interval limits. Without those results, the endpoint cannot be assessed for magnitude or precision. The record also names multiple secondary outcomes without reporting a multiplicity strategy or missing-data approach. These gaps matter when deciding how much weight to give any isolated outcome finding.

Finally, safety counts are presented across groups with different risk classifications and treatment. Statistical interpretation requires keeping those design differences in view and avoiding causal claims from descriptive counts. The record is useful for examining endpoint construction and design constraints, while the absence of primary numerical results limits conclusions about observed outcomes.

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 central limitation for interpreting efficacy is that the primary progression-free survival rate and its 95% confidence interval are not reported in the registry record. Although the record defines the endpoint and its assessment criteria, it does not report the numerical outcome needed to assess its magnitude or precision.

The non-randomized allocation is a further limitation. Low-risk participants received no treatment, while the intermediate- and high-risk groups received different radiotherapy doses. The risk categories are therefore tied to management, and group comparisons cannot isolate treatment effects from differences in baseline risk or other participant characteristics.

The registry record does not report the sample-size justification, the detailed statistical analysis plan, interim analysis procedures, or an adjustment strategy for multiple outcomes. It also does not report the handling of missing MRI data, the number evaluable for the primary endpoint, or a fuller account of analysis populations. These details are needed to assess how the planned and observed analyses relate to the endpoint definition.

The listed adverse-event figures lack reported context about attribution and observation windows in the information available in the record. The counts should be treated as descriptive, particularly because the groups are not randomized comparison arms. The record’s completed status does not itself supply the missing outcome estimates or analysis details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Observation or Radiation Therapy in Treating Patients With Grade I, Grade II, or Grade III Meningioma — NCT00895622.
• Registry record last updated 2023-09-08; status last verified 2023-08.
• Results first posted 2018-01-19.
• 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

NCT00895622 is a completed phase II, parallel, non-randomized study sponsored by the Radiation Therapy Oncology Group, with an enrollment of 244. Its recorded start was 2009-06 and primary completion was 2016-09. Low-risk participants received no treatment, intermediate-risk participants received 54 Gy radiotherapy, and high-risk participants received 60 Gy radiotherapy.

The primary endpoint was progression-free survival at 3 years from registration, assessed using central MRI review and specified imaging and neurologic progression criteria. The registry record states that rates were estimated by the binomial method and identifies a 95% confidence interval as the dispersion measure. The numerical primary result and interval are not reported in the registry record.

Because allocation was non-randomized and based on risk groups, the groups are not a like-for-like comparison. The record lists secondary outcomes and adverse-event figures, but the available information does not report a full analysis plan, missing-data methods, or multiplicity strategy.