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 Proton/Photon Rt - Benign Meningiomas(P92-13) (NCT02947984), a randomized phase 3 study. The primary outcome is Progression Free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02947984 |
| Phase | Phase 3 |
| Condition | Benign Meningioma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 44 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
The study asks whether a higher radiation dose changes progression-free survival for people with benign meningiomas that have recurred after surgery or could not be completely removed. The comparison is between standard treatment, 55.8 CGE, and higher-dose treatment, 63.0 CGE. The registry record describes the purpose as evaluating whether the higher dose decreases the likelihood of tumor regrowth compared with standard radiation doses.
Population
Participants with benign meningiomas that had recurred after previous surgery or had not been completely excised. The primary outcome description also refers to the entire cohort and radiation-indication subgroups.
Intervention
Higher-dose radiation: 63 CGE in 35 treatments of 1.8 CGE, given once a day for five days of each week.
Comparator
Standard radiation: 55.8 CGE in 31 treatments of 1.8 CGE, given once a day for five days each week.
Primary question
What is progression-free survival at 5, 10, and 15 years, measured from the start of radiation therapy, and how does it vary across the treatment groups and radiation-indication subgroups?
The primary endpoint includes time until death or radiologic progression, with follow-up otherwise censored for participants who remain alive and progression-free. The registry record does not report the numerical progression-free survival results for either treatment group at the specified time points. It therefore does not allow a direct description of the observed primary-outcome contrast.
3. Trial Design
This is a randomized, phase 3, parallel-group trial sponsored by Massachusetts General Hospital. The registry record lists an enrollment of 44 and describes two radiation groups: standard treatment and higher-dose treatment. The adverse-event record lists 22 participants at risk in each group. The study is marked completed.
The standard-treatment arm received 55.8 CGE over 31 daily treatments of 1.8 CGE, given five days each week. The higher-dose arm received 63 CGE over 35 daily treatments of 1.8 CGE, also given five days each week. These are the treatment schedules recorded for the comparison; other details of treatment delivery are not reported in the registry record.
Masking is listed as none. The record does not describe a masked outcome-assessment procedure, and details of the randomization sequence or allocation concealment are not reported in the registry record. These omissions mean that the allocation methods cannot be assessed from the available description; they do not establish that a particular procedure was or was not used.
The study started in 1999-03, and primary completion is listed as 2016-09. Progression-free survival is specified at 5, 10, and 15 years. The registry record also lists acute toxicities, late toxicities, and local failure rate as secondary outcomes. Detailed protocols for follow-up, treatment adherence, and the conduct of outcome assessments 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
| Stage | Standard Treatment | Higher Dose Treatment |
|---|---|---|
| STARTED | 22 | 22 |
| COMPLETED | 22 | 22 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Progression free survival in the entire cohort and by radiation indication sub-groups
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 | Standard Treatment | Higher Dose Treatment | Total |
|---|---|---|---|---|
| Participants analysed | 22 | 22 | 44 | |
| Age, Continuous | years | 61 (31 to 77) | 50.5 (38 to 76) | 55.5 (31 to 76) |
| Sex: Female, Male: Female | Participants | 14 | 15 | 29 |
| Sex: Female, Male: Male | Participants | 8 | 7 | 15 |
| Region of Enrollment: United States | participants | 22 | 22 | 44 |
| Tumor Location: Sphenoid wing | Tumors | 7 | 8 | 15 |
| Tumor Location: Cavernous sinus | Tumors | 3 | 8 | 11 |
| Tumor Location: Sella/Parasella | Tumors | 6 | 2 | 8 |
| Tumor Location: Cerebellar pontine angle | Tumors | 3 | 1 | 4 |
| Tumor Location: Clival/prepontine space | Tumors | 3 | 1 | 4 |
| Tumor Location: Olfactory groove | Tumors | 1 | 0 | 1 |
| Tumor Location: Optic canal | Tumors | 0 | 1 | 1 |
| Tumor Location: Tentorium | Tumors | 0 | 1 | 1 |
| Smoking Status: Smoker | Participants | 9 | 13 | 22 |
| Smoking Status: Non-smoker | Participants | 11 | 6 | 17 |
| Smoking Status: Unknown | Participants | 2 | 3 | 5 |
| Co-morbidities: Hypertension | participants | 3 | 6 | 9 |
| Co-morbidities: Diabetes mellitus | participants | 0 | 4 | 4 |
| Co-morbidities: Hyperlipidemia | participants | 1 | 0 | 1 |
| Co-morbidities: Coronary artery disease | participants | 1 | 0 | 1 |
| Co-morbidities: One or more of the above | participants | 4 | 6 | 10 |
| Radiation Indication: Sub-Total Resection, postoperative | Participants | 11 | 12 | 23 |
| Radiation Indication: Recurrent Disease | Participants | 11 | 10 | 21 |
| Gross Tumor Volume | Cubic Centimeters | 39.7 (5.6 to 243) | 13.2 (3 to 313) | 26.5 (3 to 313) |
| Clinical Target Volume | Cubic Centimeters | 49 (9 to 464) | 28 (6.5 to 150.7) | 38.5 (6.5 to 464) |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival, measured over 5, 10, 15 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants surviving |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is progression-free survival, measured from the starting date of radiation therapy. An event is defined as either death or radiologic progression. Participants who remain alive without radiologic progression are censored at their last follow-up for progression-free survival. The outcome is specified at 5, 10, and 15 years, with results described as percentages of participants surviving.
Progression-free survival is useful in a trial focused on tumor control because it reflects the time until a clinically relevant event rather than only whether an event occurred by a single cutoff. Including death in the endpoint means that it captures more than radiologic tumor progression alone. The endpoint definition also makes clear that a participant without a recorded event may contribute follow-up time and then be censored; censoring is not itself a progression or death event.
In general, survival estimates depend on the timing of events and the follow-up available for participants. A confidence interval communicates uncertainty around an estimate, rather than identifying a range in which every participant's outcome lies. The registry record specifies a 95% confidence interval for the primary outcome, but the numerical estimates and intervals at the listed time points are not reported in the registry record. Thus, the endpoint can be described, but the size and precision of the observed treatment-group results cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison of standard-dose and higher-dose radiation and defines progression-free survival as the primary endpoint. It does not report progression-free survival estimates for either arm at 5, 10, or 15 years, or the corresponding confidence intervals. As a result, the posted results do not establish the direction or magnitude of the primary-outcome contrast, nor how precisely that contrast is estimated. No conclusion about comparative tumor control can be drawn from the primary outcome information recorded.
The record does include adverse-event counts. For Standard Treatment, 6 participants are listed as affected by serious adverse events, with 22 at risk; for Higher Dose Treatment, 0 are listed as affected, with 22 at risk. The record lists 22 participants at risk for other adverse events and 22 affected in each arm. These are descriptive counts, not estimates of the causal effect of dose. The record does not provide the event definitions, observation period, event-level details, or an analysis accounting for follow-up. The count of deaths is 14 for Standard Treatment and 5 for Higher Dose Treatment. Their causes and timing, and whether they correspond to the primary endpoint during the specified follow-up, are not reported in the registry record.
The serious-event terms listed include Neuromotor deficit and Vision loss, each at 9.1%, and Endocrine deficit and Cerebral edema, each at 4.5%. The record does not specify the denominator or whether these percentages refer to the whole cohort or an arm. They should therefore be read as registry-listed descriptive percentages, not as arm-specific risks or as a comparison between doses.
The primary outcome is described as analyzed by intention to treat. In general, this approach analyzes participants in their randomized groups, regardless of treatment received, and aims to preserve the benefits of random allocation. The registry record does not report enough detail to determine how this principle was implemented for each analysis. It also does not report a statistical comparison, adjusted effect estimate, or multiplicity procedure for the primary outcome. Without those results, statistical significance and the practical size of any treatment difference cannot be assessed.
The record's mention of radiation-indication subgroups means that the primary endpoint was intended to be considered across those subgroups, but their definitions and numerical estimates are not reported in the registry record. Subgroup patterns, even when available, generally require cautious interpretation because estimates may be less precise and comparisons can be affected by multiple testing. No subgroup conclusion can be drawn from the information recorded.
9. Statistical Methods Explained
The registry describes randomized allocation, no masking, and a parallel-group design. Randomization is intended, in general, to distribute both measured and unmeasured prognostic factors between treatment groups, supporting a fair comparison. It does not guarantee identical groups, especially in a study of limited size. The registry record does not describe how the random sequence was generated, whether allocation was concealed, or what procedures were used to preserve the assigned groups.
How should progression-free survival be understood?
Progression-free survival is a time-to-event outcome. For this trial, the clock starts at the beginning of radiation therapy, and the event is the earlier of death or radiologic progression. A participant who has neither event contributes follow-up until the last assessment at which they are known to be alive and progression-free; the record describes that point as the censoring time. Censoring allows incomplete follow-up to be represented without treating the last contact as an event. In general, valid survival estimation relies on assumptions about the relationship between censoring and future event risk. The registry record does not report diagnostic checks or sensitivity analyses for those assumptions.
The endpoint is specified at 5, 10, and 15 years. Each time-specific estimate would describe progression-free survival at that follow-up horizon, rather than the average experience over the entire period. The record specifies a 95% confidence interval. In general, a confidence interval expresses the statistical uncertainty associated with an estimate under the method used; it is not a range containing a fixed proportion of individual outcomes. The numerical estimates, confidence limits, and methods used to calculate them are not reported in the registry record.
What does intention to treat imply?
The outcome description says that progression-free survival is analyzed by intention to treat. In general, this means that participants are analyzed according to their randomized assignment, even if treatment received differs from the assigned regimen or treatment is discontinued. Preserving randomized assignment can reduce bias introduced by decisions made after randomization. The record does not explain how deviations, incomplete outcome records, or participants without follow-up were handled in practice. It also does not report a separate per-protocol or as-treated analysis.
How should the adverse-event counts be read?
The adverse-event record gives counts at risk and counts affected for serious and other adverse events in each arm. In general, such counts are straightforward descriptions, but they do not account for how long participants were followed or how often events could occur unless the analysis specifically incorporates those features. The registry record does not specify whether the figures represent participants with at least one event, individual events, or a particular follow-up interval. It lists 6 serious-event-affected participants and 0 in the two treatment groups, and lists 22 affected by other adverse events in each. No inferential comparison or uncertainty interval for these figures is reported in the registry record. The figures should not be interpreted as evidence that treatment assignment caused or prevented an event.
The listed serious-event terms have percentages, but the record does not state their denominator, arm assignment, or event-counting convention. Without that context, they cannot be compared directly with the arm-level serious-event counts. The recorded death counts are also descriptive; causes, timing, and analysis methods are not reported.
What can be learned from planning assumptions?
The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It specifies that the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the planning approach gives a total number of events; for other outcomes, it gives participants per arm. These are planning assumptions, not the trial's original design justification and not observed power. The registry record does not report the trial's own sample-size justification. It also does not provide numerical planning outputs in the information available for this analysis. In general, planning calculations depend on assumptions about the effect and analysis; they do not establish that a study had a particular probability of detecting an effect after the study is complete.
The record describes several outcome time points, radiation-indication subgroups, and secondary outcomes. In general, examining multiple outcomes or subgroups can increase the chance of a misleading positive result if testing is not planned and interpreted appropriately. Adjustment methods and a prespecified testing hierarchy are not reported in the registry record. The detailed statistical analysis plan, software, model specifications, and procedures for checking model assumptions are also not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is specified at 5, 10, and 15 years, and the outcome description also refers to the entire cohort and radiation-indication subgroups. The registry lists acute toxicities, late toxicities, and local failure rate as secondary outcomes. Considering several follow-up times, subgroups, and outcomes raises a general multiplicity issue: the more comparisons explored, the greater the opportunity for chance patterns to appear. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which comparisons were designated as confirmatory.
The primary outcome description states that progression-free survival is analyzed by intention to treat and that participants without progression who remain alive are censored at their last follow-up. It does not describe how missing assessments, loss to follow-up, or other incomplete records were handled. The reasons for censoring and the amount of follow-up by treatment group are not reported in the registry record. In general, censoring is distinct from missing data, though incomplete follow-up can affect the information available for estimating survival.
The registry record does not report the analysis population for the adverse-event figures, the handling of treatment discontinuation, or whether participants were analyzed according to randomized assignment for those outcomes. It also does not report sensitivity analyses for missing outcome data. These omissions limit assessment of whether analysis choices could have influenced the estimates. They do not show that the analyses were inappropriate; they mean the relevant procedures cannot be evaluated from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Standard Treatment | 6 | 22 | 27.3% |
| Higher Dose Treatment | 0 | 22 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Standard Treatment | 14 of 22 |
| Higher Dose Treatment | 5 of 22 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Standard Treatment | 22 of 22 |
| Higher Dose Treatment | 22 of 22 |
Most frequent serious adverse event terms
| Event term | Organ system | Standard Treatment | Higher Dose Treatment |
|---|---|---|---|
| Neuromotor deficit | Nervous system disorders | 2 of 22 | 0 of 22 |
| Vision loss | Eye disorders | 2 of 22 | 0 of 22 |
| Endocrine deficit | Endocrine disorders | 1 of 22 | 0 of 22 |
| Cerebral edema | General disorders | 1 of 22 | 0 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Standard Treatment | Higher Dose Treatment |
|---|---|---|---|
| Skin changes | Skin and subcutaneous tissue disorders | 17 of 22 | 19 of 22 |
| Fatigue | General disorders | 16 of 22 | 13 of 22 |
| Alopecia | Skin and subcutaneous tissue disorders | 7 of 22 | 13 of 22 |
| Headache | Nervous system disorders | 8 of 22 | 11 of 22 |
| Nausea | Gastrointestinal disorders | 9 of 22 | 8 of 22 |
| Neurocog deficit | Nervous system disorders | 8 of 22 | 9 of 22 |
| Endocrine deficit | Endocrine disorders | 6 of 22 | 11 of 22 |
| Hearing loss | Ear and labyrinth disorders | 7 of 22 | 6 of 22 |
| Eye, other | Eye disorders | 5 of 22 | 7 of 22 |
| Facial weakness | Musculoskeletal and connective tissue disorders | 6 of 22 | 4 of 22 |
Serious events with the highest arm-level rate: neuromotor deficit (9.1%), vision loss (9.1%), endocrine deficit (4.5%), cerebral edema (4.5%).
The adverse-event record lists 22 participants at risk in each treatment group. Serious adverse events affected 6 participants in Standard Treatment and 0 in Higher Dose Treatment. Other adverse events affected 22 participants in each group. These figures are counts, not adjusted comparisons, and the registry record does not report uncertainty intervals or statistical tests for them.
The record also lists deaths: 14 in Standard Treatment and 5 in Higher Dose Treatment. It does not report their causes, timing, relationship to treatment, or whether these counts refer to a particular analysis period. Death is also part of the primary progression-free survival definition, but the available information does not connect the death counts to the primary-outcome estimates.
Neuromotor deficit and Vision loss are listed at 9.1% each; Endocrine deficit and Cerebral edema are listed at 4.5% each. The denominator, treatment-group attribution, and event-counting rules for these percentages are not reported in the registry record. They cannot be used to infer arm-specific risks or to compare doses. In general, adverse-event counts require context about definitions, follow-up, and ascertainment before they can support a comparative interpretation. The record does not provide that context in sufficient detail.
12. What the Result Does, and Does Not, Mean
The registry record establishes the study question and describes a randomized comparison of 55.8 CGE with 63.0 CGE radiation in people with recurrent or incompletely excised benign meningiomas. It defines progression-free survival, gives its follow-up times, and lists safety outcomes. It also reports descriptive adverse-event counts and selected serious-event terms.
However, the numerical primary-outcome estimates and confidence intervals at 5, 10, and 15 years are not reported in the registry record. The record therefore cannot show whether progression-free survival differed between groups, how large any difference was, or how precisely it was estimated. A treatment schedule and a study objective are not substitutes for outcome results.
The adverse-event figures also have important limits. The counts do not establish that a treatment caused an event or that one dose is safer than the other. Details about event definitions, follow-up duration, causes of death, and the denominator for the listed percentages are not reported. These descriptive figures should not be treated as a complete account of harms or as a causal comparison.
In general, a randomized design can support causal interpretation when allocation and follow-up are appropriately implemented and analyses are adequately reported. The registry description does not contain enough information to assess several of those features, including allocation procedures, missing-data handling, and multiplicity. This absence of detail is not evidence that a procedure was not used. It limits what can be concluded from the record itself.
The most defensible interpretation is therefore bounded: the registry records a randomized, open-label, parallel-group dose comparison and defines the outcomes of interest, but it does not provide the primary results needed to assess the comparative progression-free survival finding. No conclusion about treatment benefit or lack of benefit follows from the missing estimates.
13. Why This Trial Matters Statistically
This study is statistically notable because it frames radiation dose as a randomized comparison and defines a time-to-event primary outcome. The endpoint includes both radiologic progression and death, with censoring for participants who remain alive and progression-free at their last follow-up. That definition matters because it determines which events count toward progression-free survival and how incomplete observation is represented.
The specified follow-up times extend to 15 years. In general, long-term survival outcomes depend on event timing and continued follow-up, and estimates later in follow-up can be affected by how much information remains. The registry record does not report follow-up completeness or the numerical estimates, so the precision and stability of results at those horizons cannot be evaluated.
The study also illustrates why a result needs more than an endpoint definition and treatment schedule to be interpretable. Numerical estimates, confidence intervals, analysis details, and transparent handling of censoring and missing data are necessary to understand the strength of evidence. The registry record specifies a 95% confidence interval but does not report its values for the primary outcome.
Finally, the record lists several secondary outcomes, subgroup analyses, and adverse-event measures. These require clear definitions and analysis procedures to distinguish exploratory patterns from confirmatory comparisons. The available record leaves those procedures unreported. The statistical importance of the trial therefore lies in its question and design, while the record's limitations prevent a statistical assessment of its central efficacy result.
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 primary outcome is described, but its numerical results at 5, 10, and 15 years are not reported in the registry record. Confidence intervals, treatment-group comparisons, and subgroup estimates are likewise not reported. This prevents assessment of the magnitude, direction, and precision of the primary finding.
Allocation is listed as randomized and masking as none, but the randomization method, concealment procedures, and outcome-assessment procedures are not reported. The record also does not describe adherence, treatment deviations, or how these were handled analytically. Although intention-to-treat analysis is stated for progression-free survival, implementation details are not reported.
Important survival-analysis details are missing, including follow-up completeness, numbers censored, and checks or sensitivity analyses concerning censoring. The record does not describe the methods used to calculate progression-free survival estimates or confidence intervals. It does not report how incomplete records or missing assessments were handled.
Safety reporting is limited by the absence of event definitions, follow-up period, causes and timing of death, and an explanation of the denominators for the serious-event percentages. The record does not specify whether the adverse-event counts represent participants with events or individual event occurrences. It also does not provide inferential safety comparisons.
Finally, outcome multiplicity and subgroup interpretation cannot be evaluated because a testing hierarchy and adjustment procedures are not reported in the registry record. These limitations concern what the record allows readers to assess; they do not establish that unreported procedures were absent or that the trial was conducted improperly.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Proton/Photon Rt - Benign Meningiomas(P92-13) — NCT02947984.
- Registry record last updated 2017-06-14; status last verified 2017-05.
- Results first posted 2017-06-14.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT02947984 is a completed randomized phase 3 parallel-group study sponsored by Massachusetts General Hospital. It compares standard radiation, 55.8 CGE, with higher-dose radiation, 63.0 CGE, for recurrent or incompletely excised benign meningiomas. The record lists enrollment of 44, no masking, a start date of 1999-03, and primary completion in 2016-09.
The primary outcome is progression-free survival from the start of radiation therapy, with death or radiologic progression counted as an event and otherwise censoring at last follow-up for participants who remain alive and progression-free. Results are specified at 5, 10, and 15 years, but numerical primary-outcome estimates are not reported in the registry record. Secondary outcomes include acute toxicities, late toxicities, and local failure rate. Adverse-event counts and selected serious-event terms are listed, but important definitions and analysis details are not reported.