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 Temozolomide and Radiation Therapy in Treating Patients With Gliomas (NCT00114140), a na phase 2 study. The primary outcome is Survival and Progression-free Survival by O(6)-Methylguanine-DNA Methyltransferase (MGMT) Methylation Status.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00114140 |
| Phase | Phase 2 |
| Condition | Brain and Central Nervous System Tumors |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 136 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Radiation Therapy Oncology Group |
| Results posted | Yes |
2. Clinical Question
Population
Eligible patients with low-grade gliomas and O(6)-methylguanine-DNA methyltransferase (MGMT) status. The registry record describes the population as patients with brain and central nervous system tumors, and its primary outcome concerns survival and progression-free survival by MGMT methylation status. It does not report the number of eligible patients in each MGMT status category or the status distribution among those enrolled.
Intervention
Temozolomide given daily with concurrent radiation therapy, followed by temozolomide. The record describes this as a temozolomide-based chemoradiotherapy regimen. It does not provide further dosing details in the outcome information available for interpretation.
Comparator
There is no separate comparison group in the registry record. The study is listed as single group, with allocation recorded as not applicable and no masking. Comparisons by MGMT methylation status are subgroup comparisons within the treated population, not comparisons against an untreated or alternative-treatment control group.
Primary question
How are survival and progression-free survival, measured from registration, described among eligible patients according to MGMT methylation status? The primary outcome specifies median estimates and 95% confidence intervals, with a timeframe of registration to 3 years. The numerical estimates and confidence intervals are not reported in the registry record, so the magnitude and precision of the observed times cannot be assessed from that record.
This is a descriptive question about outcomes in a treated group, with attention to a tumor marker. It is not a randomized test of the regimen against another treatment. A difference between MGMT status groups, if reported, would describe an association within this study population; by itself, it would not establish that methylation status caused a difference in outcome or that the regimen caused the observed survival times.
3. Trial Design
The registry record describes a completed phase II study of temozolomide and radiation therapy for patients with high-risk low-grade gliomas. The study title identifies a temozolomide-based chemoradiotherapy regimen. The record lists one treatment group: daily temozolomide with concurrent radiation therapy, followed by temozolomide. Enrollment is recorded as 136. That registry enrollment figure does not establish how many participants contributed to each outcome analysis; analysis-specific participant counts are not reported in the registry record.
The design is listed as single group, allocation as not applicable, and masking as none. There is therefore no randomized control group for a like-for-like treatment comparison. Outcomes by MGMT methylation status are the focus of the primary measure, but the record does not report the numbers in each status group or the statistical comparison between them. The sponsor is the Radiation Therapy Oncology Group. The recorded start is 2005-01, primary completion is 2013-02, and study status is completed.
The registry lists five outcome measures and three analyses. Those counts alone do not identify the full set of prespecified hypotheses, analysis populations, or any correction for multiple testing. Such details are not reported in the registry record. The record does not report a sample-size justification, a target event count, interim analyses, or a complete statistical analysis plan. These omissions mean the design can be characterized from its listed features, but the rationale for its enrollment and the planned handling of all analyses cannot be reconstructed.
The main design distinction for interpretation is the lack of a concurrent control group. A single-group study can describe survival and progression-free survival after the regimen and can examine patterns across MGMT categories. It cannot, on its own, separate outcomes associated with treatment from outcomes that might have occurred under another treatment or without the regimen. This design feature limits causal interpretation irrespective of the precision of any within-study estimate.
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 | Temozolomide + Radiation Therapy (RT) |
|---|---|
| STARTED | 136 |
| COMPLETED | 129 |
| NOT COMPLETED | 7 |
Reasons for not completing this period:
| Reason | Temozolomide + Radiation Therapy (RT) |
|---|---|
| Protocol Violation | 7 |
Analysis population for the primary outcome, as defined in the registry: Eligible patients
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: Eligible patients
| Characteristic | Unit | Temozolomide + Radiation Therapy (RT) |
|---|---|---|
| Participants analysed | 129 | |
| Age, Continuous | years | 49 (20 to 76) |
| Sex: Female, Male: Female | Participants | 54 |
| Sex: Female, Male: Male | Participants | 75 |
6. Primary Endpoint
The registry lists the primary outcome as Survival and Progression-free Survival by O(6)-Methylguanine-DNA Methyltransferase (MGMT) Methylation Status, measured over Registration to 3 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | years |
| Endpoint classification | Time-to-Event Analysis |
The primary outcome is titled survival and progression-free survival by MGMT methylation status. Survival is defined as the time from registration to death from any cause. Progression-free survival concerns time until disease progression or death, although the registry description gives the detailed criteria for progression rather than a separate full definition of the combined event. It defines progressive disease as a 25% or > increase in the cross-sectional area of enhancing or non-enhancing tumor on consecutive MRI scans, or any new area of tumor. Under exceptional circumstances, progression may be declared without an increase in tumor size based on clinical deterioration, including increasing steroid doses or worsening Karnofsky Performance Status or Neurologic Function Score.
The measure is reported as a median with a 95% confidence interval over the timeframe from registration to 3 years. For a time-to-event outcome, the median is the point in the estimated event-time distribution at which half the distribution has experienced the event and half has not. It can describe the timing of an event without requiring every participant to have experienced it, provided the data support estimating that point. The Kaplan-Meier method is specified for estimating survival and progression-free survival; patients last known to be alive are censored at their date of last contact.
Time-to-event measures are useful when follow-up length varies or some participants have not experienced the event by their last observation. The actual medians and confidence intervals are not reported in the registry record, so their values and precision cannot be interpreted from that record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically relevant time-to-event question: survival and progression-free survival by MGMT methylation status among eligible patients treated with temozolomide and radiation therapy. It specifies Kaplan-Meier estimation, median outcomes, and 95% confidence intervals. However, the numerical primary outcome estimates are not reported in the registry record. Without those values, it is not possible to describe the observed median survival or progression-free survival, compare the estimates across MGMT categories, or assess the width of their confidence intervals.
A confidence interval communicates uncertainty around an estimated quantity under the analysis used. A narrower interval indicates greater statistical precision than a wider interval, but precision is not the same as freedom from bias or proof of a causal effect. The record names 95% confidence intervals but does not include their endpoints. Consequently, no conclusion about precision, overlap, or statistical evidence for a difference between MGMT categories can be drawn from the listed outcome description alone.
The registry record does not report a numerical hazard ratio or a numerical test of a difference by methylation status. A hazard ratio, when reported, compares event rates over follow-up under the model used; it is not itself a median time or an absolute difference in survival. Without a reported estimate and its uncertainty, a direction or magnitude of association cannot be stated. Nor can the primary outcome title alone establish that any subgroup difference was observed.
The single-group design is central to interpretation. Outcomes after treatment can be described, and patient subgroups can be compared, but there is no concurrent randomized control group to distinguish the regimen's effect from other influences on outcome. Subgroup differences may reflect characteristics associated with MGMT status or other differences between participants. The record does not report enough information to assess adjustment for such factors. Thus, even if subgroup-specific estimates were available elsewhere, they would not by themselves establish a causal effect of methylation status or of treatment.
The recorded enrollment is 136, but the registry record does not report analysis-specific sample sizes, event counts for the primary outcome, or the distribution of follow-up. Enrollment is not interchangeable with the number contributing information to a particular time-to-event estimate. Censoring is part of the stated Kaplan-Meier approach, but the frequency and pattern of censoring are not reported. Those details matter because estimates can become less stable when few participants remain under observation at later times, and informative loss to follow-up can affect interpretation.
The primary outcome timeframe is registration to 3 years. The endpoint description does not supply numerical results within that timeframe. Therefore, the most defensible conclusion from this registry record is about what the study set out to estimate and how it said it would estimate it, not about the size or direction of a clinical outcome. The reported safety entries are separate descriptive information and do not fill the gap in the primary efficacy estimates.
9. Statistical Methods Explained
The registry record describes a time-to-event analysis using Kaplan-Meier estimates. The method is designed for outcomes measured as time from a defined starting point until an event, while allowing some participants' event times to remain unknown because observation ends before the event is seen. In this study, registration is the stated time origin for survival, and death from any cause is the event. The record also specifies progression-free survival and gives criteria for progressive disease.
What does Kaplan-Meier estimation do?
Kaplan-Meier estimation builds an estimate of the proportion of participants who remain free of the event over time. Each observed event changes the estimate, while a participant who has no event by the last known observation is censored at that time. Censoring means that the participant's event time is not known beyond the last contact; it does not mean that the participant experienced the event at that point. The registry record states that patients last known to be alive are censored at the date of last contact.
The method relies on assumptions about censoring. In general, Kaplan-Meier estimates are most straightforward to interpret when the reasons observation ends do not make the unobserved event experience systematically different from that of people who continue to be followed, after accounting for the analysis. The registry record does not report the amount or pattern of censoring, reasons for loss to follow-up, or checks of this assumption. Those omissions prevent an assessment of how much the estimates depend on censoring.
What does a median time-to-event estimate mean?
A median event time is a summary of the estimated event-time distribution, not the average follow-up time and not a guarantee about an individual participant's outcome. It identifies the point at which the estimated event-free proportion reaches the median threshold. Estimating it requires enough information in the observed data for the estimated curve to reach that point. If that condition is not met, a median may be difficult or impossible to estimate. The registry record lists the median as the parameter but does not include its value or clarify whether every subgroup median was estimable.
The 95% confidence interval represents statistical uncertainty around the estimated median, subject to the analysis assumptions. It is not a range containing 95% of individual participants' event times. A wide interval signals limited precision, while a narrow interval signals greater precision. The registry record specifies confidence intervals but does not report their limits. It is therefore not possible to judge precision or compare uncertainty across MGMT methylation categories.
Why are time-to-event methods used?
Participants may have different lengths of observation, and some may not experience the event during the period in which they are followed. Methods that account for censoring can use the observed time without treating every participant as if they had a known event time. This is useful for survival and progression-free survival, where event timing and incomplete follow-up are integral to the data. It does not remove the need to report follow-up and censoring patterns or to consider whether censoring is informative.
How should progression be understood?
The registry definition includes an imaging criterion: a 25% or > increase in cross-sectional area of enhancing or non-enhancing tumor on consecutive MRI scans, or a new area of tumor. It also allows a progression determination under exceptional circumstances based on clinical deterioration without an increase in tumor size. The examples include the need for increasing doses of steroid or worsening Karnofsky Performance Status or Neurologic Function Score. This definition combines imaging and specified clinical considerations. The record does not report how often the exceptional criterion was applied or whether progression assessments were independently reviewed.
Progression-free survival combines disease progression and death as time-to-event information, but the record's wording does not provide a separate full operational definition of the composite event. The exact numerical results for this outcome are not reported. The endpoint title and method therefore describe the intended analysis, not its observed magnitude.
What can subgroup comparisons establish?
The primary outcome is organized by MGMT methylation status. Comparing estimated curves or medians across categories can describe how outcomes differ within the enrolled study group. Such comparisons are not randomized: participants are not assigned to MGMT status. An observed association can be influenced by other differences between groups, and the registry record does not report whether covariate adjustment was used. Without numerical estimates, uncertainty intervals, and details of the analysis, neither the size nor statistical evidence of a subgroup difference can be evaluated.
A hazard ratio, if reported, would summarize a relative event rate over follow-up under a specified model. It would answer a different statistical question from a median. The registry record does not report a numerical hazard ratio for the primary outcome, so no relative event-rate comparison can be described. General statistical interpretation should keep the estimand in view: medians concern a point on the event-time distribution, while hazard ratios concern relative rates over time.
What does the planning illustration mean?
Sample-size illustrations based on an observed effect are planning scenarios, not observed trial findings and not evidence of the study's achieved power. In general, such illustrations ask how much information a future study might need to detect an effect of a specified fraction of an observed effect under stated assumptions. The record's planning description specifies a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. For time-to-event outcomes, it describes total events using the Schoenfeld approach; other planning displays are described in terms of participants per arm for 80% power or other stated power levels.
These assumptions describe an illustrative future comparison, not this single-group study's design. The record does not report the numerical planning outputs in the information available for interpretation. They should not be read as observed participant counts, observed event counts, or a retrospective claim about power. The registry record also does not report a sample-size justification from the trial's original design, so the illustration cannot be treated as that justification.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists five outcome measures and three analyses. Multiple outcomes or analyses can create multiple opportunities to identify a result that appears statistically notable by chance. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory analyses can help readers understand how multiplicity was handled. Such a procedure is not reported in the registry record. The counts of measures and analyses do not reveal which comparisons were confirmatory, whether outcomes were related, or whether any adjustment was used.
The primary outcome is described as survival and progression-free survival by MGMT methylation status. The record does not report the numerical estimates, confidence intervals, analysis-specific participant counts, or event counts. It also does not report a full statistical analysis plan, definitions of analysis populations, or whether analyses were conducted according to an intention-to-treat principle. The enrollment figure of 136 should not be assumed to be the number included in every analysis.
The record specifies censoring of patients last known to be alive at their date of last contact. This describes one aspect of handling incomplete time-to-event information. It does not explain missing MGMT status, missing imaging assessments, missed visits, or other forms of incomplete data. Those details are not reported in the registry record. The extent and possible consequences of missingness therefore cannot be assessed.
Because subgroup comparisons are not randomized, differences in group composition may also affect estimates. The record does not report covariate adjustment or sensitivity analyses. These gaps do not establish that the analyses were inappropriate; they limit what can be verified from the registry record. A careful reading distinguishes what is stated about the endpoint and censoring from unreported decisions about multiplicity, missing data, and analysis populations.
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 |
|---|---|---|---|
| Temozolomide + Radiation Therapy (RT) | 37 | 129 | 28.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Temozolomide + Radiation Therapy (RT) | 129 of 129 |
Most frequent serious adverse event terms
| Event term | Organ system | Temozolomide + Radiation Therapy (RT) |
|---|---|---|
| Convulsions NOS | Nervous system disorders | 13 of 129 |
| Platelet count decreased | Investigations | 8 of 129 |
| Fatigue | General disorders | 6 of 129 |
| Neutrophil count | Investigations | 3 of 129 |
| Thrombosis | Vascular disorders | 3 of 129 |
| Abdominal pain NOS | Gastrointestinal disorders | 2 of 129 |
| Infection - Other: | Infections and infestations | 2 of 129 |
| Leukopenia NOS | Investigations | 2 of 129 |
| Dehydration | Metabolism and nutrition disorders | 2 of 129 |
| Hyponatremia | Metabolism and nutrition disorders | 2 of 129 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Temozolomide + Radiation Therapy (RT) |
|---|---|---|
| Fatigue | General disorders | 115 of 129 |
| Nausea | Gastrointestinal disorders | 96 of 129 |
| Alopecia | Skin and subcutaneous tissue disorders | 88 of 129 |
| Headache | Nervous system disorders | 76 of 129 |
| Leukopenia NOS | Investigations | 67 of 129 |
| Constipation | Gastrointestinal disorders | 61 of 129 |
| Platelet count decreased | Investigations | 58 of 129 |
| Lymphopenia | Investigations | 57 of 129 |
| Anorexia | Metabolism and nutrition disorders | 57 of 129 |
| Vomiting NOS | Gastrointestinal disorders | 55 of 129 |
Serious events with the highest arm-level rate: convulsions nos (10.1%), platelet count decreased (6.2%), fatigue (4.7%), neutrophil count (2.3%), thrombosis (2.3%).
The registry record lists a single treatment group, Temozolomide + Radiation Therapy (RT). For serious adverse events, 129 participants are listed as at risk and 37 as affected. For other adverse events, 129 are listed as at risk and 129 as affected. The record does not provide a death count; that field is not reported in the registry record.
The listed serious adverse-event terms and percentages are Convulsions NOS, 10.1%; Platelet count decreased, 6.2%; Fatigue, 4.7%; Neutrophil count, 2.3%; Thrombosis, 2.3%; and Abdominal pain NOS, 1.6%. These are the terms identified among the top serious terms in the record. The record does not provide the full event listing or specify the denominator underlying each term percentage, so the percentages should be read as registry-listed values rather than recalculated from the at-risk or affected counts.
Serious adverse-event counts and other adverse-event counts are distinct registry summaries. The affected count does not necessarily represent the number of events, since a participant can experience more than one event; the record does not clarify event-level counting in this summary. The figures are descriptive for this single treatment group. With no control group, they cannot establish how frequently these events would occur under another treatment or without the regimen. They also do not, by themselves, establish causation.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed phase II study of a temozolomide-based regimen with radiation therapy in patients with low-grade gliomas. It identifies survival and progression-free survival by MGMT methylation status as the primary outcome, specifies a time origin and progression criteria, and names Kaplan-Meier estimation and 95% confidence intervals. Those details clarify what the study set out to measure.
The record does not report the numerical primary outcome estimates or confidence intervals. It therefore does not support a statement about the observed median survival, median progression-free survival, the direction or size of differences across MGMT categories, or the precision of those estimates. The outcome title is not a result. Nor does the completed status of the study supply the missing outcome values.
Even with numerical subgroup results, this single-group design would support description of outcomes in the enrolled population more directly than a causal claim about treatment. There is no randomized comparator. Differences by MGMT status would be associations within the treated group, potentially influenced by other differences between participants. A comparison against an external benchmark would require details not reported in the registry record and would not substitute for a concurrent randomized comparison.
The serious adverse-event entries provide descriptive safety information for the listed group, including affected counts and selected event terms with percentages. They do not give a controlled comparison, a complete account of all adverse events, or a basis to attribute each event to treatment. The registry record also does not report the death count in its safety summary.
The main conclusion is therefore about the scope and limits of the available record: it identifies the regimen, design, endpoint definitions, and analysis method, but lacks the numerical primary results needed to judge outcome magnitude or uncertainty. It cannot establish treatment benefit, lack of benefit, or comparative safety. The planning assumptions are illustrations for hypothetical future studies, not observed power or a substitute for the trial's missing estimates.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of how design determines what a result can mean. The primary outcome concerns time to an event, and the registry record names Kaplan-Meier estimation, median times, and confidence intervals. Those choices reflect the fact that participants can have different observation times and that some event times may be censored. Interpreting such outcomes requires attention not only to the chosen estimator but also to the amount and pattern of follow-up.
Its single-group design also illustrates the difference between describing outcomes and estimating comparative effects. A treatment cohort can provide information about outcomes observed during follow-up. It cannot provide the same protection against confounding as a randomized comparison. Analyses by MGMT methylation status can describe variation in outcome, but status is not assigned by the study, and the registry record does not report adjustments that might address group differences.
Completeness of reporting is part of statistical interpretation. The registry record supplies endpoint definitions and the intended form of the estimate, but not the numerical primary results, their confidence intervals, subgroup counts, or event counts. Without those, readers cannot assess effect size, precision, or the evidence for a difference. Stating clearly what is unavailable is more informative than inferring a result from a title or from the fact that the study is completed.
The record also distinguishes study outcomes from planning illustrations. Assumptions about a future two-arm comparison do not change the original single-group design and do not constitute observed power. This is a useful reminder that planning scenarios and trial results answer different questions. The trial matters statistically because its design and reporting show why estimand, comparator, uncertainty, and transparent outcome values must be considered together.
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 immediate limitation of the registry record is that it does not report the numerical primary outcome estimates or their 95% confidence intervals. Without them, the observed survival and progression-free survival cannot be summarized, and the precision of the estimates cannot be assessed. The record also does not report the numerical results for the analyses by MGMT methylation status, the number of participants in each status group, or the event counts for those analyses.
The design has no separate control group. This limits causal interpretation of outcomes after treatment and prevents a direct randomized comparison with another regimen or usual care. Within-study comparisons by MGMT status are observational subgroup comparisons. The record does not report whether potential confounding was addressed through adjustment or sensitivity analysis.
Although the registry defines censoring at last contact for patients known to be alive, it does not report follow-up distributions, numbers censored, reasons for loss to follow-up, or assessments of censoring assumptions. It also does not report how missing MGMT status or incomplete progression assessments were handled. The analysis population for each outcome is not reported, so enrollment cannot be treated as the analysis denominator.
The record lists five outcome measures and three analyses but does not report a multiplicity strategy or a full statistical analysis plan. It does not report whether progression assessments were independently reviewed or how often the exceptional clinical-deterioration criterion was used. The safety summary gives selected serious-event terms and percentages, but not a full event listing or a reported death count. These limitations describe gaps in the registry record and do not establish what may be available in other study documents.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Temozolomide and Radiation Therapy in Treating Patients With Gliomas — NCT00114140.
- Registry record last updated 2024-07-08; status last verified 2022-05.
- Results first posted 2017-11-06.
- 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
The registry record describes a completed phase II, single-group study of daily temozolomide with concurrent radiation therapy followed by temozolomide in patients with low-grade gliomas. Enrollment is recorded as 136; the recorded start is 2005-01 and primary completion is 2013-02.
The primary outcome concerns survival and progression-free survival by MGMT methylation status, with medians and 95% confidence intervals from registration to 3 years. The record specifies Kaplan-Meier estimation and defines survival from registration to death from any cause. Numerical primary outcome estimates, confidence intervals, subgroup counts, and analysis-specific event counts are not reported in the registry record.
There is no randomized comparator. The record lists serious adverse-event counts and selected serious-event terms, but its safety summary does not report a death count. It lists five outcome measures and three analyses, without reporting a multiplicity procedure or full statistical analysis plan.