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 Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation (NCT01288235), a na phase 2 study. The primary outcome is Endocrine Dysfunction.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01288235 |
| Phase | Phase 2 |
| Condition | Brain Tumor, Low Grade Glioma, Astrocytoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 100 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
The study asks whether endocrine dysfunction occurs during follow-up after proton radiotherapy for pediatric brain tumors requiring partial brain irradiation, and estimates its cumulative incidence at 3- and 5-years after treatment. The registry also identifies disease control and cumulative incidence of grade 3+ toxicities and ototoxicity as secondary outcomes. Numerical results for these outcomes are not reported in the registry record.
Population
Patients with brain tumors requiring partial brain irradiation. The listed conditions include brain tumor, low grade glioma, astrocytoma, ependymoma, and ganglioglioma. The record does not report detailed eligibility criteria or an age range.
Intervention
Proton radiotherapy. The study description presents proton treatment as a way to target the tumor or tumor bed while limiting irradiation of normal tissue. That is the stated rationale, not a comparative result from this single-group study.
Comparator
There is no concurrent comparator group: the study is recorded as single-group, with allocation listed as NA. The registry therefore does not provide a like-for-like control comparison with standard radiation or another treatment.
Primary question
What percentage of participants at risk develops endocrine dysfunction by 3- and 5-years following completion of proton radiotherapy? The endpoint is described as cumulative incidence, but its numerical estimates and confidence intervals are not reported in the registry record.
The question is about outcomes after treatment in the enrolled study group. Without a control group, any observed event frequency would describe this group under the study’s follow-up and assessment procedures. It would not, by itself, establish how the frequency compares with another treatment or what would have happened to the same participants under a different approach.
3. Trial Design
This is a phase II, single-group study of proton radiotherapy. The registry lists an enrollment of 100 and identifies Massachusetts General Hospital as the sponsor. The study status is completed; the recorded start is 2011-02 and the primary completion is 2016-09. These registry fields describe the study record and do not establish how many participants completed follow-up or contributed data to each analysis.
The intervention is proton radiotherapy, listed as radiation. The title identifies pediatric brain tumors requiring partial brain irradiation, and the listed conditions include brain tumor, low grade glioma, astrocytoma, ependymoma, and ganglioglioma. Detailed eligibility rules, tumor-specific enrollment counts, treatment schedules, and participant characteristics are not reported in the registry record.
Allocation is listed as NA, masking as none, and the model as single-group. There is no randomized allocation or masked comparison described. Consequently, the design can report outcomes observed among participants receiving the intervention, but it cannot isolate the treatment’s effect from other differences or influences through a concurrent randomized control comparison.
The primary outcome is endocrine dysfunction, expressed as a percentage of participants, with a 95% confidence interval and assessments at 3- and 5-years post radiation treatment. The description identifies the population as participants at risk of developing endocrine dysfunction during follow-up. Disease control, cumulative incidence of grade 3+ toxicities, and cumulative incidence of ototoxicity are listed as secondary outcomes. The registry lists five outcome measures and eleven analyses, but their full analysis specifications and numerical findings are not reported in the registry record.
The study description explains that proton techniques are intended to spare normal tissue while delivering radiation to the tumor or tumor bed. The description also states that proton techniques irradiate 2-3 times less normal tissue than standard radiation. That statement is part of the study rationale; this single-group design does not itself supply a controlled estimate of the difference between proton and standard radiation.
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 | Proton Radiotherapy |
|---|---|
| STARTED | 100 |
| COMPLETED | 100 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Patient population at risk of developing an endocrine dysfunction during follow-up
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 | Proton Radiotherapy |
|---|---|---|
| Participants analysed | 100 | |
| Age, Continuous | years | 8.0 (3.5 to 13.8) |
| Sex: Female, Male: Female | Participants | 49 |
| Sex: Female, Male: Male | Participants | 51 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 80 |
| Race (NIH/OMB): More than one race | Participants | 4 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 13 |
| Region of Enrollment: United States | participants | 100 |
6. Primary Endpoint
The registry lists the primary outcome as Endocrine Dysfunction, measured over 3- and 5- years post radiation treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is endocrine dysfunction, measured as the cumulative incidence of participants who develop the dysfunction at 3- and 5-years following completion of proton radiotherapy. The registry describes the measure as a percentage of participants and specifies a 95% confidence interval. Its stated population is those at risk of developing endocrine dysfunction during follow-up.
Cumulative incidence is useful for describing how often an event arises over a defined follow-up period, rather than reporting only an event count without reference to time. General statistical context: when participants are followed for different lengths of time, a time-specific estimate can give a more relevant account than a simple percentage that ignores follow-up. If events can prevent later observation of the outcome, the choice of method for handling those competing events can also affect the interpretation. The specific calculation and handling of competing events for this endpoint are not reported in the registry record.
Endocrine dysfunction is relevant to the study’s stated long-term outcome focus. However, the registry does not give the operational definition of dysfunction, the assessment procedures, the numerical cumulative-incidence estimates, or the confidence-interval limits. It is therefore not possible from the registry record to describe the size or precision of the endpoint result.
The endpoint describes outcomes after proton treatment in the study group. It is not a direct measure of comparative benefit or harm, because no control group is recorded. The time points and endpoint definition indicate what the study intended to assess, but they do not substitute for numerical results or details of how participants were assessed and included in each analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes the study’s central outcome question but does not report the numerical primary endpoint results. Endocrine dysfunction was to be summarized as cumulative incidence at 3- and 5-years after proton radiotherapy, with a 95% confidence interval. Without the estimates and interval limits, neither the observed frequency nor its statistical precision can be assessed from the registry record. The record also does not report numerical findings for disease control, grade 3+ toxicities, or ototoxicity.
The enrollment is listed as 100, but enrollment is not the same as the analysis population at each time point. The registry does not report how many participants were at risk at the 3- or 5-year assessment, how many developed endocrine dysfunction, how much follow-up was available, or whether any participants were excluded from a particular analysis. It would therefore be inappropriate to treat the enrollment figure as the denominator for an endpoint estimate.
The single-group design is central to interpretation. Any incidence estimate would describe events observed in the treated group under the study’s follow-up procedures. It would not establish a difference from standard radiation or another comparator. The study description gives a rationale for proton treatment, but the registry record does not report a comparative analysis that tests that rationale.
The safety fields report a Proton Radiotherapy group with 100 participants at risk for serious adverse events and 2 affected. For other adverse events, 100 were at risk and 98 were affected. Hypernatremia and lymphocyte count decreased are listed among the leading serious-event terms, each at 1.0%. The record also lists 15 deaths. These counts require careful reading: the registry does not report event timing, duration, severity details beyond the categories shown, relationship to treatment, causes of death, or whether the categories overlap. They should not be used to infer a treatment-related cause.
General statistical context: confidence intervals describe uncertainty around an estimate under the assumptions of the method used. They do not remove design limitations, and a wide or narrow interval does not resolve the lack of a control group. Since the interval values and analysis details are not reported in the registry record, the endpoint’s precision cannot be judged. No conclusion about comparative effectiveness or treatment causality follows from the registry entries alone.
9. Statistical Methods Explained
The primary outcome is recorded as a percentage of participants with an event, and its parameter is described as a number with a 95% confidence interval. The event is endocrine dysfunction, with cumulative-incidence estimates intended for 3- and 5-years after completion of proton radiotherapy. The record does not report the estimates, confidence-interval limits, statistical model, or calculation details.
What does a confidence interval communicate?
General statistical context: a confidence interval presents a range of values compatible with an estimate under a specified statistical procedure and its assumptions. It communicates uncertainty about the estimated quantity; it is not a range containing a fixed percentage of individual participants, nor does it establish causation. For a clinical endpoint, interval width is affected by factors such as the amount of information available and the variability in the observed data. Because the interval limits are not reported in the registry record, the precision of the endocrine dysfunction estimates cannot be evaluated.
Why use cumulative incidence?
General statistical context: cumulative incidence concerns the probability of experiencing an event by a particular time during follow-up. This can be more informative than an un-timed proportion when the question concerns when events occur or when follow-up varies. In settings where another event can prevent the outcome from occurring or being observed, competing risks may matter. The registry records deaths, but does not report whether or how deaths were handled in the primary endpoint analysis. It also does not report the estimator, censoring rules, or assumptions used for the time-to-event calculation.
What does the single-group design allow?
The registry identifies a single-group model with no masking and allocation listed as NA. A single-group outcome summary can describe events among participants receiving proton radiotherapy. It does not provide a randomized contrast with a control group. General statistical context: a comparative treatment effect requires a meaningful comparison, and differences between groups can be interpreted causally only under suitable design and analysis assumptions. Since no like-for-like control group is recorded, the registry cannot establish whether outcomes differ from those under another treatment.
How should the planning illustration be read?
The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes effects to detect as stated fractions of the observed effect. These are assumptions for a planning exercise, not the design of the registered single-group study. They do not report observed power, and the illustration cannot be read as an actual randomized comparison. The registry record does not provide a trial-specific sample-size justification or the details needed to assess how the planning assumptions relate to the completed study.
General statistical context: sample-size planning asks what number of participants would be needed under specified assumptions to detect a chosen effect with a chosen operating characteristic. Such calculations depend on the endpoint, assumed effect, variability or event rate, allocation, and analysis method. They are not evidence that a study achieved a particular power after completion. In this case, the registry does not report the numerical endpoint result needed to interpret an illustration based on the observed effect, nor does it document that the illustration was the trial’s original design calculation.
What analysis details are missing?
The registry lists five outcome measures and eleven analyses, but the precise statistical methods for those analyses are not reported in the registry record. The record does not specify model forms, covariate adjustment, confidence-interval construction, hypothesis tests, missing-data procedures, sensitivity analyses, or how follow-up was handled. These omissions matter because different reasonable methods can produce different estimates, especially for time-specific outcomes and outcomes with incomplete observation. The stated endpoint and confidence-interval format identify the intended kind of summary, but do not fully describe its statistical implementation.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and eleven analyses. This indicates that more than one outcome or analysis is recorded, but the registry does not report the complete analysis plan, the hierarchy of outcomes, or whether any formal adjustment was planned for multiple comparisons. It is also not reported in the registry record whether the analyses were confirmatory, exploratory, or both. Without that information, the chance of false-positive findings across multiple tests cannot be assessed from the record.
The primary endpoint is named as endocrine dysfunction, with cumulative-incidence estimates at 3- and 5-years. It is not reported in the registry record whether one time point was designated as the main inferential test, whether both were treated as co-primary, or how any multiplicity between them was addressed. Numerical estimates and test results are also not reported, so there is no basis for evaluating statistical significance or consistency across time points.
Missing-data and analysis-population details are not reported in the registry record. The record does not say how many participants contributed to each outcome, how incomplete follow-up was handled, what censoring rules were used, or whether participants who did not complete assessments were included in any particular population. Enrollment of 100 alone cannot answer those questions. Deaths are recorded, but their treatment in the endpoint analysis is not described.
General statistical context: multiplicity procedures can control the overall risk of false-positive conclusions when several hypotheses are tested, while missing-data methods can affect both the estimate and its uncertainty. Neither issue can be resolved simply by knowing the number of outcomes or analyses. Interpretation requires the prespecified plan and the actual analysis details, which are not reported in 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 |
|---|---|---|---|
| Proton Radiotherapy | 2 | 100 | 2.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Proton Radiotherapy | 15 of 100 |
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 |
|---|---|
| Proton Radiotherapy | 98 of 100 |
Most frequent serious adverse event terms
| Event term | Organ system | Proton Radiotherapy |
|---|---|---|
| Hypernatremia | Metabolism and nutrition disorders | 1 of 100 |
| Lymphocyte Count Decreased | Investigations | 1 of 100 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Proton Radiotherapy |
|---|---|---|
| Fatigue | General disorders | 84 of 100 |
| Alopecia | Skin and subcutaneous tissue disorders | 75 of 100 |
| Dermatitis radiation | Injury, poisoning and procedural complications | 46 of 100 |
| Nausea | Gastrointestinal disorders | 34 of 100 |
| Headache | Nervous system disorders | 31 of 100 |
| Cognitive disturbance | Nervous system disorders | 28 of 100 |
| Growth hormone abnormal | Investigations | 26 of 100 |
| Anorexia | Metabolism and nutrition disorders | 24 of 100 |
| Endocrine disorders - Other | Endocrine disorders | 22 of 100 |
| Memory impairment | Nervous system disorders | 22 of 100 |
Serious events with the highest arm-level rate: hypernatremia (1.0%), lymphocyte count decreased (1.0%).
The registry reports safety figures for the Proton Radiotherapy group. For serious adverse events, 100 participants were at risk and 2 were affected. For other adverse events, 100 were at risk and 98 were affected. The record lists Hypernatremia and Lymphocyte Count Decreased among the leading serious-event terms, each at 1.0%. It also records 15 deaths.
These are registry safety counts, not a complete description of each event. The record does not report the event dates, duration, clinical details, relationship to proton radiotherapy, or causes of death. It also does not explain whether the serious and other adverse-event categories can overlap or whether the listed event terms refer to unique participants. The 15 deaths should not be assumed to be treatment-related, and the counts do not establish the cause of any event.
General statistical context: adverse-event counts are interpreted in relation to the defined population at risk, the observation period, and how events were collected and classified. Those details are not reported in the registry record. The figures therefore describe what the registry records in its safety fields, but do not on their own measure comparative safety against another treatment or establish causation.
12. What the Result Does, and Does Not, Mean
The study is a completed phase II evaluation of proton radiotherapy in a single group of patients with brain tumors requiring partial brain irradiation. Its primary question concerns the cumulative incidence of endocrine dysfunction at 3- and 5-years after treatment. The registry provides the endpoint definition and confidence-interval format, but numerical estimates and interval limits are not reported in the registry record. As a result, the size and precision of the primary outcome cannot be described.
The registry’s enrollment figure is 100, but it does not establish the number assessed at each follow-up time or the number included in each endpoint analysis. The study’s recorded status as completed also does not supply missing outcome estimates. Disease control, cumulative incidence of grade 3+ toxicities, and cumulative incidence of ototoxicity are listed as secondary outcomes, but numerical findings for them are not reported in the registry record.
The study description gives a reason for examining proton radiotherapy: the technique is intended to deliver radiation to a tumor or tumor bed while sparing normal tissue. That rationale is not itself a clinical result. Because this is a single-group study without a recorded comparator, outcomes among treated participants cannot demonstrate how results compare with standard radiation or another treatment. They also cannot, by themselves, separate treatment effects from patient characteristics, disease course, or other aspects of care.
The safety counts document serious and other adverse events and deaths in the registry fields, but they do not identify causes or treatment relationships. The available information therefore supports a description of the study’s purpose, design, specified endpoints, and recorded safety counts. It does not support a conclusion that proton radiotherapy is more or less effective or safe than another option, or that it caused or prevented a particular outcome.
General statistical context: a clinical result is interpreted through its estimate, precision, design, and analysis population together. The absence of numerical endpoint results and detailed methods limits what can be inferred, regardless of the planned follow-up times or the stated rationale.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary outcome concerns a long-term event after treatment rather than an immediate response. The registry specifies cumulative incidence at 3- and 5-years for endocrine dysfunction. Time-specific outcomes raise questions about how participants are followed, how incomplete observation is handled, and how events that prevent later observation are treated. Those details are essential for understanding an estimate, but are not reported in the registry record.
The single-group design also sets a clear boundary on interpretation. It can describe outcomes among participants who received proton radiotherapy, but it does not offer a concurrent control comparison. That distinction is important because a rationale about sparing normal tissue is not a comparative estimate of clinical outcomes. The study’s design and results must not be conflated.
Precision matters as much as the event estimate. The registry specifies a 95% confidence interval for the primary outcome, but does not report its limits or the estimate itself. Readers therefore cannot determine how much uncertainty surrounds the endpoint or whether the observed data would be compatible with a broad range of event frequencies.
The record also lists several outcome measures and analyses, while omitting details of multiplicity, missing data, and analysis populations. Those omissions make it difficult to assess how outcome selection and analytic decisions shaped the findings. The safety figures similarly need context about timing, event classification, and relationship to treatment.
General statistical context: careful reporting links the research question to the design, estimand, analysis method, and uncertainty. This record identifies the question and some design features, but leaves important results and methods unspecified. Recognizing those boundaries is necessary for a balanced reading of a phase II study.
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 most consequential limitation of the registry record for interpretation is that numerical primary and secondary outcome results are not reported. The primary endpoint specifies cumulative incidence and confidence intervals at 3- and 5-years, but there are no estimates or interval limits with which to judge event frequency or precision. The record also does not give the endpoint’s operational definition or assessment procedures.
The single-group design provides no concurrent comparator. Thus, even if event estimates were available, they would describe the study group rather than quantify a difference from standard radiation or another intervention. The study rationale about targeting tumors while sparing normal tissue should not be treated as evidence of a comparative clinical effect.
Enrollment is listed as 100, but the numbers at risk at each endpoint time, the analysis populations, participant flow, and follow-up completeness are not reported in the registry record. Detailed eligibility criteria, participant characteristics, treatment delivery details, and tumor-specific results are also not reported. These omissions limit the ability to understand which participants the results would represent.
Statistical methods for the cumulative-incidence estimates, handling of deaths and other competing events, censoring, missing observations, confidence intervals, and multiple analyses are not reported. The safety fields do not provide timing, event duration, attribution, or causes of death. These limitations are specific to the information recorded for this study and restrict both the clinical and statistical conclusions that can be drawn.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation — NCT01288235.
- Registry record last updated 2025-06-03; status last verified 2025-06.
- Results first posted 2025-06-03.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT01288235 is a completed phase II, single-group study sponsored by Massachusetts General Hospital. It evaluates proton radiotherapy for pediatric brain tumors requiring partial brain irradiation and lists an enrollment of 100. The recorded start is 2011-02 and the primary completion is 2016-09. Allocation is NA and masking is none.
The primary outcome is cumulative incidence of endocrine dysfunction at 3- and 5-years after proton treatment, expressed as a percentage with a 95% confidence interval. Disease control, cumulative incidence of grade 3+ toxicities, and cumulative incidence of ototoxicity are listed as secondary outcomes. Numerical outcome results and detailed analysis methods are not reported in the registry record.
The safety record lists 2 participants affected by serious adverse events among 100 at risk, 98 affected by other adverse events among 100 at risk, and 15 deaths. Event timing, treatment relationship, causes of death, and safety-analysis details are not reported. The single-group design does not provide a controlled treatment comparison.