Study of Hypofractionated Proton Beam Radiation Therapy for Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Hypofractionated Proton Beam Radiation Therapy for Prostate Cancer (NCT00831623), a na na study. The primary outcome is Number of Participants With Late Treatment-Related Toxicity Greater Than or Equal to Grade 3, CTCAE Version 4.0.

2. Clinical Question

These details separate the study's clinical motivation from the evidence its recorded design can directly produce. A single group can describe outcomes observed after the proton schedule, but without a concurrent conventional-fractionation group it cannot, by itself, estimate a between-group treatment effect. The registry's objective refers to similarity with the institutional standard, yet comparative conclusions require an appropriate reference and a defined analysis. Neither a control arm nor comparative results are listed. Accordingly, the most direct question represented by the recorded primary endpoint is how many participants experienced late grade 3 or higher treatment-related toxicity during the stated follow-up, rather than whether the proton schedule was equivalent or noninferior to conventional fractionation.

3. Trial Design

The registry describes a completed, single-group study titled “Study of Hypofractionated Proton Beam Radiation Therapy for Prostate Cancer.” Its official title identifies it as a phase I-II trial of hypofractionated conformal proton beam radiation therapy for favorable-risk prostate cancer. The phase entry itself is listed as NA. Loma Linda University is identified as the sponsor. The recorded start date is 2009-02-17, and primary completion is dated 2019-07-18.

Enrollment is 167. The allocation entry is NA, masking is listed as none, and the model is single group. The arm description identifies proton radiation therapy as the single arm. These design features matter when interpreting the study's stated interest in similarity to conventional fractionation: the registry does not list a randomized allocation or a concurrent conventional-fractionation group. It therefore records an intervention cohort, not a direct comparison between two treatment strategies.

The primary outcome is a count of participants with late treatment-related toxicity of grade 3 or higher under CTCAE version 4.0. The follow-up description says assessment occurs every 6 months after treatment through the trial's duration, with a minimum of 2 years of follow-up and an average of 5 years. The registry also lists a secondary outcome concerning participants with acute and late gastrointestinal or genitourinary grade 2 morbidity. It reports two outcome measures in total, but does not give numerical results for them in the registry record recorded for this analysis.

The registry marks the study completed, but completion status does not itself establish that all planned analyses or outcomes are reported. Statistical analysis details, eligibility criteria, treatment-delivery specifics, and the reasons for the difference between enrollment and the adverse-event risk set 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

Reasons for not completing this period:

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: 8 refused treatment, 158 treated per protocol, 146 at least 2 years since completing treatment, 1 with no follow up data

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Late Treatment-Related Toxicity Greater Than or Equal to Grade 3, CTCAE Version 4.0, measured over Every 6 months after completing treatment through the duration of the trial with a minimum of 2 years follow-up and an average of 5 years.

The primary endpoint counts participants with late treatment-related toxicity of grade 3 or higher according to CTCAE version 4.0. Its unit is participants, so it is a count-based outcome rather than a measure of average toxicity severity or time to first toxicity. The stated assessment schedule is every 6 months after treatment, through the duration of the trial, with a minimum of 2 years of follow-up and an average of 5 years.

This endpoint is relevant to the study's stated safety question: whether serious late treatment-related morbidity can be maintained in a hypofractionated schedule. In general, a threshold-based endpoint can make clinically important events easier to distinguish from lower-grade symptoms, while a participant count communicates how many people crossed that threshold. The endpoint description does not provide a detailed rule for attributing an event to treatment, handling repeated events in one participant, or defining the analysis window for each individual.

Interpreting a count requires attention to how many participants were assessed and for how long. In general, participants with longer observation have more opportunity for a late event to be detected. The registry gives a minimum and average follow-up description, but does not report individual follow-up times or the primary endpoint count. It is therefore not possible from the recorded endpoint information alone to assess the observed frequency of late grade 3 or higher toxicity or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a count of participants meeting a binary event definition: late treatment-related toxicity of grade 3 or higher under CTCAE version 4.0. A binary outcome classifies each assessed participant as either having met the event definition or not having met it. A count then adds the participants with the event. This description does not establish how repeated toxicity events were counted, how treatment attribution was assessed, or how participants without complete follow-up were handled; those details are not reported in the registry record.

What does a participant count tell the reader?

A count is directly interpretable as the number of participants who met the endpoint definition, provided the denominator and analysis population are clear. A count alone does not express the proportion of participants affected, the duration of observation, or the timing of events. In general, a proportion pairs the number with an event with a defined denominator; a time-to-event analysis additionally uses event timing and follow-up information. The primary outcome is listed as a participant count, and the record does not provide its numerical result or a corresponding interval estimate.

The follow-up description calls for assessments every 6 months after treatment through the duration of the trial, with a minimum of 2 years and an average of 5 years. These details indicate that late effects were intended to be observed over time, but they do not give the actual follow-up distribution for participants. In general, variable follow-up can affect the chance that a late event is observed. A simple count does not adjust for such differences unless the analysis explicitly uses follow-up time or another method. The registry does not report such an analysis.

Why does the single-group design matter?

A single-group study can describe outcomes observed after the intervention. It does not include a concurrent group receiving the institutional conventional-fractionation standard. General comparisons with historical experience can be affected by differences in patient eligibility, follow-up, event definitions, care, and data collection. Without details establishing comparability, a difference or similarity to an external benchmark cannot be attributed solely to treatment schedule. The registry's stated goal of achieving similar treatment benefits is therefore not equivalent to a reported statistical demonstration of equivalence.

Randomization, when used, is a general design method for balancing prognostic factors across treatment groups in expectation. This registry lists allocation as NA and describes a single group, so there is no randomized treatment contrast to interpret. Masking is listed as none. The record does not describe additional safeguards for outcome assessment, nor does it report whether outcome assessors were independent of treatment delivery. These limitations concern possible sources of bias in general; the record does not establish that any particular bias occurred.

What can confidence intervals contribute?

In general, a confidence interval conveys the precision of an estimate under a specified statistical model. A narrow interval indicates less sampling uncertainty than a wide interval, while neither interval width nor the point estimate alone resolves design limitations or bias. For a low event count, interval estimates are especially important because the observed count may be compatible with a range of underlying event frequencies. No confidence interval for the primary endpoint is reported in the registry entries, so the precision of that endpoint cannot be evaluated.

The registry entries include a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is set as a stated fraction of the observed effect. Such a calculation is a planning exercise, not a report of the trial's design justification or a measure of observed power. In general, calculations based on an observed effect can be sensitive to uncertainty in that effect. The illustration does not turn this single-group study into a two-arm comparison, and the original protocol's sample-size justification is not reported in the registry record.

Why do event distributions matter?

For binary outcomes, the information available for estimating an event frequency depends on both the number of participants observed and the number of events. In general, sparse events can yield imprecise estimates, and standard approximations may perform poorly when counts are very small. The appropriate method depends on the analysis objective and study design. The registry does not report the primary endpoint event count, confidence interval, hypothesis test, or model. It is not possible to identify the method used for a primary-outcome analysis from the record.

Over-dispersion is a general issue in count-data modeling: observed variation can exceed what a chosen model assumes. It matters when an analysis models counts and relies on a distributional assumption about their variability. The primary endpoint is described as a participant count with a binary event definition, not as a repeated-event count model. The registry does not report a model or diagnostics, so there is no basis to say whether over-dispersion was assessed or relevant to the actual analysis.

More generally, statistical interpretation depends on a prespecified endpoint definition, a clear analysis population, a transparent account of missing observations, and an analysis aligned with the design. The registry identifies the outcome and its follow-up description, but does not report the full statistical plan, analysis population, handling of missing data, or primary numerical result. These gaps prevent readers from reconstructing or independently evaluating the primary analysis.

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("Proton Radiation Therapy")
n      <- c(146)
events <- c(1)
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  Proton Radiation Therapy  146  1  0.7  0.0  3.8  0.1  3.8  0.2  3.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary measure of late treatment-related toxicity of grade 3 or higher, and a secondary measure concerning acute and late gastrointestinal or genitourinary grade 2 morbidity. It does not report numerical results for these outcomes in the registry record for this analysis. The record also lists no analysis entries. Whether other outcomes were examined, and how any analyses were selected for reporting, are not reported in the registry record.

In general, multiplicity arises when several outcomes, time points, subgroups, or statistical tests are considered. The more opportunities there are to identify a result as noteworthy, the more important it is to distinguish prespecified analyses from exploratory ones and to explain any adjustment for multiple testing. This is a general statistical concern, not evidence that a particular multiplicity problem occurred in this trial. The registry does not report a multiplicity strategy or the statistical plan needed to determine how it was handled.

Missing-data methods and analysis populations are also not reported. The registry gives total enrollment of 167 and lists 146 participants at risk in the adverse-event summary, but does not explain the relationship between these counts. No inference should be made about exclusions, withdrawal, incomplete follow-up, or endpoint availability from that difference alone. The record does not state whether all enrolled participants were included in each outcome analysis, how missing assessments were treated, or whether participants were analyzed according to any prespecified population definition.

In general, missing outcomes can affect interpretation if the likelihood of missingness is related to participants' health or outcomes. Reporting the number assessed, reasons for missingness, and analysis choices helps readers judge this risk. Those details, along with a statistical plan and a description of any interim analyses, are not reported in the registry record. Their absence limits evaluation of both multiplicity and the potential influence of incomplete outcome data.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hematuria (0.7%).

The registry's adverse-event summary for proton radiation therapy lists 146 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it also lists 146 participants at risk and 20 affected. The record reports 0 deaths. These are registry adverse-event categories; they are not the numerical result for the primary endpoint of late treatment-related toxicity of grade 3 or higher.

The serious adverse-event summary names hematuria as a top serious term and gives 0.7%. That percentage is reported as recorded; the registry entries do not describe the calculation or clarify further how the term relates to the serious-event count. The terms and categories should therefore be read as registry summaries rather than a complete description of every safety event or its timing.

In general, an adverse-event count needs context: the definition of seriousness, observation period, method of collection, and number of participants actually assessed all affect interpretation. The record supplies the risk-set counts but does not explain how they relate to enrollment of 167. It also does not provide event-level timing, duration, recurrence, or attribution details. Counts alone do not establish that an event was caused by the intervention, and the record does not support a comparative safety assessment because it lists a single study group.

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

The registry record establishes that a completed, single-group study evaluated hypofractionated proton radiation therapy for favorable-risk prostate cancer and identified late treatment-related toxicity of grade 3 or higher as its primary outcome. It also gives the planned follow-up description and an adverse-event summary. These details clarify the question the study was designed to address and the kind of safety information entered in the registry.

However, the numerical result for the primary endpoint is not reported in the registry record. Without that result, readers cannot determine how many participants met the primary toxicity definition, estimate an event frequency, or assess the precision of an estimate. The reported serious and other adverse-event counts are not substitutes: they refer to distinct registry safety categories and do not report the primary endpoint result.

The study's rationale mentions similar treatment benefits to the institutional conventional-fractionation standard. The recorded design does not include a concurrent conventional-fractionation arm, and the registry does not report comparative results. It therefore does not establish that the approaches produced equivalent outcomes, nor does it quantify a difference between them. No equivalence or noninferiority margin is reported. The stated aim should be distinguished from a demonstrated comparative conclusion.

More generally, a completed status does not guarantee that all outcomes, analyses, or details needed for interpretation are present in the registry. The record does not report the analysis population, handling of missing data, statistical methods for the primary outcome, or a confidence interval. Those omissions make it difficult to assess not only the outcome estimate, but also its uncertainty and robustness.

The appropriate conclusion is narrow: the registry describes the design and intended late-toxicity measure, and it records selected adverse-event figures for the proton radiation group. It does not provide enough primary-outcome or comparative information to support a quantitative judgment about late toxicity relative to conventional fractionation. This is a limitation of what the registry record reports, rather than evidence that the study did or did not observe particular unreported outcomes.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its stated clinical objective and recorded design do not answer exactly the same kind of question. The study's rationale refers to similar treatment benefits compared with conventional fractionation, while the registry records a single group receiving proton radiation therapy. A single-arm design can describe outcomes after treatment, but it cannot directly estimate a between-group contrast without a comparator. This distinction is essential when interpreting language about similarity.

The primary endpoint also illustrates the importance of separating an outcome definition from an outcome result. The registry specifies a participant count for late treatment-related toxicity of grade 3 or higher and gives a follow-up description. Yet the numerical primary result and its precision are not reported. A precise endpoint label can improve clarity, but it cannot replace the estimate, denominator, analysis population, and uncertainty needed to understand what was observed.

The adverse-event summary offers some recorded safety information, including 1 serious adverse-event participant among 146 at risk, 20 participants with other adverse events among 146 at risk, 0 deaths, and the listed serious term hematuria at 0.7%. Those figures should be read within their registry categories and not as an indirect primary endpoint result. Their denominator also differs from the enrollment figure of 167, and the record does not explain the relationship.

For biostatisticians and clinical researchers, the record highlights why design, estimand, follow-up, analysis population, and reporting completeness must be considered together. It also shows why a planning calculation based on an observed effect should not be mistaken for the original design rationale or observed power. The registry entries leave several of these details unreported, so interpretation must remain bounded by what is explicitly recorded.

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 most consequential limitation for interpreting efficacy and safety is that the registry record does not report a numerical result for the primary endpoint. The outcome is defined as the number of participants with late treatment-related toxicity of grade 3 or higher, but no primary count, estimate, or interval is available. The record lists two outcome measures and no analysis entries, leaving the numerical findings for those outcomes unreported in the registry record.

The single-group design is a further limitation for the stated interest in comparison with conventional fractionation. There is no concurrent comparator arm in the recorded design. The registry does not report a comparative analysis, equivalence or noninferiority margin, or results for a conventional-fractionation group. As a result, the stated goal of similar treatment benefits cannot be evaluated as a direct treatment contrast from this record.

Other trial-specific details needed to judge interpretation are also absent: eligibility criteria, treatment schedule specifics, the statistical analysis plan, analysis populations, missing-data handling, actual individual follow-up, and the relation between the enrollment count of 167 and the adverse-event risk sets of 146. The record does not report whether all planned analyses were completed or whether interim analyses occurred. These are reporting gaps; they do not establish that any particular procedure was or was not undertaken.

The adverse-event summary is limited to recorded categories and counts. It does not give detailed timing, recurrence, severity distributions beyond the serious/other categories, or treatment attribution for each event. The primary endpoint should not be inferred from those safety figures. Together, the missing outcome result and limited design details prevent a complete assessment of the magnitude and precision of late toxicity or a comparison with conventional fractionation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Hypofractionated Proton Beam Radiation Therapy for Prostate Cancer — NCT00831623.
• Registry record last updated 2023-03-13; status last verified 2023-02.
• Results first posted 2023-03-13.
• 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 identifies a completed single-group study of hypofractionated conformal proton beam radiation therapy for favorable-risk prostate cancer, sponsored by Loma Linda University. Enrollment is 167; allocation is listed as NA, masking as none, and phase as NA. The study's stated rationale concerns similar treatment benefits to the institutional conventional-fractionation standard, but the recorded design has no concurrent comparator arm.

The primary outcome is the count of participants with late treatment-related toxicity of grade 3 or higher under CTCAE version 4.0, with assessment every 6 months after treatment and a stated minimum follow-up of 2 years and average of 5 years. A secondary outcome concerns acute and late gastrointestinal or genitourinary grade 2 morbidity. The primary numerical result and analyses are not reported in the registry record.

The adverse-event summary lists 1 serious adverse-event participant and 20 participants with other adverse events, each category with 146 at risk, 0 deaths, and hematuria at 0.7% among the top serious terms. These figures do not replace the missing primary endpoint result or provide a comparison with conventional fractionation.