The Utility of 18F-DOPA-PET in the Treatment of Recurrent High-grade Glioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Utility of 18F-DOPA-PET in the Treatment of Recurrent High-grade Glioma (NCT03242824), a na phase 2 study. The primary outcome is Proportion of Participants With Progression-free Survival.

2. Clinical Question

3. Trial Design

This is a phase 2, completed, single-group pilot study listed under the title “The Utility of 18F-DOPA-PET in the Treatment of Recurrent High-grade Glioma.” Its official title identifies it as MC167B, a pilot study investigating the utility of 18F-DOPA-PET in recurrent high-grade glioma. Mayo Clinic is listed as the sponsor. The registry records 21 participants enrolled.

The study plan, as described in the brief summary, was to compare the volumes of 18F-DOPA-PET avidity with contrast enhancement and T2 FLAIR on MRI. Investigators also planned to compare patterns of failure with target volumes, pretreatment MRI changes, and pretreatment 18F-DOPA-PET. These descriptions indicate the imaging and disease-pattern questions the pilot was intended to examine; they do not constitute reported results of those comparisons.

The study has a single group and no masking. Allocation is listed as not applicable. Participants in the described 18F-DOPA PET arm would receive 18FDOPA-PET for radiation treatment planning. The listed interventions include the fluorodopa drug, intensity-modulated radiation therapy, and positron emission tomography. The record does not describe a concurrent control arm, and the study should not be interpreted as a randomized treatment comparison.

The recorded start date is 2017-09-29, primary completion date is 2020-06-16, and status is completed. Completion status describes the registry record, not whether every planned analysis or outcome was reported. The record does not give details of recruitment procedures, eligibility rules, treatment delivery, follow-up completeness, or departures from the original plan. Although historical controls are mentioned in the primary outcome description, details about how they were selected or analyzed 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.

Before assignment: 1 registered patient did not proceed to protocol treatment because they were deemed ineligible.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Participants With Progression-free Survival, measured over up to 3 months.

The primary endpoint is the proportion of participants with progression-free survival, with a timeframe of up to 3 months. The registry describes it as a number and identifies a 95% confidence interval as the measure of dispersion. It says the outcome was measured by reviewing 18F-DOPA-PET and conventional MRI, with historical controls referenced in the description. No observed proportion, confidence interval, or endpoint analysis is reported in the registry record.

In general, a proportion expresses how many participants in a defined group meet an outcome definition. For a progression-free survival endpoint, the definition and the time point matter: readers need to know what counted as progression, how deaths were handled, how participants without complete follow-up were treated, and who was included in the denominator. Those operational details are not reported in the registry record, so the endpoint’s full analysis definition cannot be reconstructed from its name alone.

In general, a confidence interval communicates uncertainty around an estimate. Its width depends on the amount and variability of information contributing to the estimate, as well as the method used. The record specifies a 95% confidence interval but does not post its bounds or identify the calculation method. The endpoint is relevant to the stated imaging and disease-control question, but without the estimate and its uncertainty, its observed result cannot be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What is the primary outcome estimating?

The primary outcome is stated as a proportion of participants with progression-free survival up to 3 months. In general, estimating a proportion requires a numerator, a denominator, and a rule for classifying each participant. The registry record does not give the observed numerator or analysis denominator. It also does not specify the full criteria for progression, how incomplete follow-up was handled, or how participants without an evaluable scan were classified. Consequently, the endpoint label alone does not reveal the exact analysis procedure.

The outcome description says that 18F-DOPA-PET and conventional MRI were reviewed. The brief summary additionally describes planned comparisons of PET avidity volumes with contrast enhancement and T2 FLAIR on MRI, and planned comparisons involving patterns of failure, target volumes, and pretreatment imaging. These statements describe the study’s intended imaging questions. They do not report the analytic definitions, measurement procedures, reader agreement, or results for those comparisons.

What does a confidence interval communicate?

The record identifies a 95% confidence interval as the dispersion measure for the primary outcome, but reports no interval bounds. In general, a confidence interval gives a range of values compatible with an estimate under the specified statistical method and its assumptions. A narrower interval generally indicates greater precision than a wider interval, though precision does not by itself establish clinical importance or eliminate bias. The interval method and the estimate it would accompany are not reported in the registry record, so no precision judgment can be made for this endpoint.

For a proportion, uncertainty is influenced by the amount of outcome information and the distribution of observed outcomes. In general, small datasets can yield less precise estimates, and the choice of interval procedure can matter. This is general statistical context, not a description of a method confirmed for this study. The registry record does not identify an exact, score-based, or other confidence-interval procedure.

How should the design shape interpretation?

The study is listed as a single group, with allocation not applicable and no masking. It does not have a concurrent randomized control group in the registry description. The primary endpoint description refers to historical controls, but details of any historical-control analysis are not reported in the registry record. In general, comparisons with historical data can be sensitive to differences in participant eligibility, disease characteristics, care, follow-up, and outcome assessment. Those differences can complicate interpretation even when an apparent contrast is calculated. The registry information does not show whether or how such issues were addressed.

The sample-size illustrations associated with the study are described as planning illustrations based on an observed effect, rather than as the trial’s own design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These assumptions do not turn this single-group pilot into a two-arm trial, and the illustrations are not observed power. The registry record does not report the trial’s own sample-size justification or a sample-size calculation used for its actual design.

In general, a sample-size planning calculation estimates how much information a proposed design might need under particular assumptions. Its interpretation depends on the endpoint, target effect, analysis method, and allocation being planned. A planning illustration based on an observed effect is a retrospective scenario and does not establish that a study had a given probability of detecting an effect. No claim about achieved power follows from the enrollment count.

What statistical analysis is documented?

The registry lists 0 analyses. It does not identify a model, hypothesis test, estimator, covariate adjustment, handling of repeated imaging, or procedure for any historical-control comparison. The primary endpoint’s dispersion is named as a 95% confidence interval, but that alone does not specify the analysis method. No analysis population is described, and the record does not state whether analyses were intention-to-treat, per-protocol, or based on evaluable participants.

In general, over-dispersion matters when a model assumes a particular level of variability but the data are more variable than that assumption allows; standard errors can then be understated if the extra variability is ignored. This is general statistical context only. The registry record does not report a count model or any over-dispersion assessment, and the primary outcome is described as a proportion rather than a count-rate endpoint.

Without posted estimates, uncertainty intervals, and analysis details, readers cannot reproduce or assess the statistical analysis of the primary endpoint from the registry record. The design and endpoint can be described, but the result and its precision remain unreported.

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("18F-DOPA PET")
n      <- c(20)
events <- c(0)
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  18F-DOPA PET  20  0  0.0  0.0  16.8  0.0  16.1  0.1  16.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and five named secondary outcomes: overall survival; toxicity, rate of grade 3 or higher treatment-related toxicities; change from baseline in the Quality of Life Brief Fatigue Index; re-operative count; and change from baseline in the Quality of Life MDASI-BT. It records 6 outcome measures and 0 analyses. The record does not provide results for these outcomes or say which were analyzed.

In general, assessing many outcomes can increase the chance that at least one result appears noteworthy by chance if each is tested separately. Multiplicity procedures can address that issue, but the choice depends on the research questions and analysis plan. Whether any adjustment was planned or used, how outcome hierarchy was specified, and whether interim analyses were conducted are not reported in the registry record. No multiplicity approach should be inferred from the list of outcomes.

The registry record does not describe missing-data rules, follow-up completeness, exclusions, or analysis populations. It does not say how participants without imaging at the relevant time point, with incomplete questionnaires, or with unavailable outcome information were handled. These are not confirmed instances of missing data; they are details needed to interpret the reported estimates, which are not available in the record.

In general, missingness can affect an estimate when the participants with observed data differ systematically from those without observed data. The implications depend on why information is missing and how the analysis handles it. Since no primary result, denominator, or missing-data method is reported, the effect of missing information cannot be assessed. The registry also does not report whether the analysis population was defined by enrollment, treatment receipt, or endpoint evaluability.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists one 18F-DOPA PET group with 20 participants at risk. It records 0 participants affected in the serious adverse-event category, 20 affected in the other adverse-event category, and 15 deaths. These are the counts as recorded; the enrollment count for the study is 21, and the registry does not explain why the safety group’s at-risk count differs from total enrollment.

The serious adverse-event term list is empty. This means no top serious terms are listed in the record; it does not provide event descriptions or additional detail about ascertainment. The other adverse-event count is not broken down by event type, severity, timing, or participant-level experience in the information.

The death count should not be treated as a treatment-related death count. The registry does not report cause, timing, attribution, or whether deaths occurred during a particular follow-up period. It also does not clarify how death information relates to the primary progression-free survival endpoint. The counts alone do not establish a causal relationship with imaging, radiation, or any other intervention, and they do not describe comparative safety against a concurrent control group.

In general, adverse-event counts are best interpreted with clear definitions, observation periods, denominators, severity criteria, and attribution rules. Those details are not reported in the registry record. The figures are therefore descriptive registry entries, not a complete account of safety or a basis for estimating comparative risk.

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

The registry record identifies a pilot study of 18F-DOPA-PET for radiation treatment planning in recurrent high-grade glioma. It describes a single-group design, enrollment of 21 participants, an imaging-focused study rationale, and a primary endpoint concerning the proportion with progression-free survival up to 3 months. It also records selected adverse-event and death counts. These details establish what the study set out to examine and what counts appear in the record.

They do not establish the observed primary outcome. The registry does not report the proportion with progression-free survival, its 95% confidence interval, or an analysis comparing the result with historical controls. It likewise does not post findings for the imaging-volume comparisons or the named secondary outcomes. Without those results, the magnitude, direction, and precision of the primary endpoint cannot be described from the registry record.

The single-group design also limits what can be concluded from the study description. The mention of historical controls is not enough to judge whether a fair or valid comparison was carried out. Details about the historical cohort and comparative methods are not reported in the registry record. No causal claim about the effect of an intervention can be drawn from the design information alone.

The safety counts are not efficacy results and do not resolve these limitations. They lack details about timing, attribution, and event definitions. In particular, the listed deaths cannot be assumed to be treatment-related or interpreted as a progression-free survival estimate.

In general, a study’s result is interpreted using its outcome definition, analysis population, estimate, uncertainty, and design. Here, the endpoint and design are identifiable, but the primary estimate and statistical analysis are not posted. The record therefore supports a description of the pilot’s aims and recorded counts, not a conclusion about the primary endpoint’s observed value or what the imaging strategy achieved.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a clearly named endpoint and an absent endpoint result. The registry identifies progression-free survival as a proportion measured up to 3 months and specifies a 95% confidence interval as the intended expression of dispersion. Yet neither the proportion nor its interval is reported, and the record lists 0 analyses. Readers can identify the planned question without being able to evaluate its estimate or precision.

The design also matters. A single-group pilot can describe experience and support exploratory investigation, but it does not provide a randomized concurrent contrast. Although historical controls are mentioned, the registry record does not describe them or report a comparative analysis. It is therefore important not to treat the study arm as a direct control comparison or infer a treatment effect from the design label.

The study’s planned imaging comparisons raise additional statistical questions about how PET avidity, MRI findings, target volumes, and patterns of failure were defined and compared. The brief summary outlines those aims, while the registry does not report their analytic methods or results. In general, clear measurement definitions and transparent reporting of estimates are essential for readers to distinguish an imaging association from a validated prediction or a comparative treatment effect.

The record also illustrates why enrollment and safety counts are not substitutes for endpoint reporting. The total enrollment, safety-group counts, and deaths are descriptive items, but they do not reveal the primary endpoint denominator, uncertainty, or handling of follow-up. Statistical interpretation depends on these elements as well as the study’s design. Their absence leaves the central outcome question unanswered in the registry record.

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 available registry information does not report the primary endpoint estimate, its 95% confidence interval, or any analysis results. It lists 0 analyses. This prevents assessment of the observed proportion with progression-free survival up to 3 months, its precision, and whether any comparison with historical controls was performed.

The record describes a single-group, unmasked study with allocation not applicable. It does not identify a concurrent randomized control group. Historical controls are mentioned in the primary outcome description, but their source, eligibility, size, follow-up, outcome definition, and analytic use are not reported in the registry record. The comparability of any historical data cannot therefore be assessed.

Additional design and analysis details are absent: eligibility criteria, the primary endpoint’s operational definition, the analysis denominator, follow-up completeness, handling of missing outcomes, analysis populations, statistical methods, multiplicity procedures, and any interim analyses. The registry record also does not report whether planned imaging comparisons or secondary outcomes were completed or analyzed.

Safety interpretation is limited by the lack of event descriptions, observation periods, severity detail beyond the listed serious category, and attribution. The record lists 20 participants at risk for the safety group despite 21 enrolled, but does not explain that count. It also lists 15 deaths without cause or timing details. These figures cannot be used to reconstruct the primary endpoint or establish an intervention-related outcome.

Finally, the planning illustrations are explicitly not the trial’s own design calculation. The registry record does not report the sample-size justification for the pilot. These limitations concern what is reported; they do not establish that the corresponding procedures or analyses were absent from the study itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Utility of 18F-DOPA-PET in the Treatment of Recurrent High-grade Glioma — NCT03242824.
• Registry record last updated 2023-03-14; status last verified 2023-02.
• Results first posted 2022-07-05.
• 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

The registry describes a completed phase 2 pilot study sponsored by Mayo Clinic, with 21 participants enrolled. The study is single-group, has no masking, and lists allocation as not applicable. It concerns 18F-DOPA-PET for radiation treatment planning in recurrent high-grade glioma.

The primary outcome is the proportion of participants with progression-free survival up to 3 months, assessed by reviewing 18F-DOPA-PET and conventional MRI; historical controls are mentioned. The registry record lists a 95% confidence interval but reports no primary estimate, interval, or analysis. It lists 6 outcome measures and 0 analyses.

The safety entry lists 20 participants at risk, 0 affected by serious adverse events, 20 affected in the other adverse-event category, and 15 deaths. Further event details and the primary result are not reported in the registry record.