Individualized Stereotactic Body Radiotherapy of Liver Metastases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Individualized Stereotactic Body Radiotherapy of Liver Metastases (NCT01239381), a na na study. The primary outcome is Local Control Rate.

2. Clinical Question

3. Trial Design

This was a completed, single-group study of stereotactic body radiotherapy using proton radiation for liver metastases. The registry lists the phase as NA, allocation as NA, and masking as none. The intervention group is named SBRT-Proton, and its description identifies proton radiation as the means of delivering stereotactic body radiotherapy. No separate control group is described, so the study is not a randomized comparison and its treatment group should not be interpreted as a like-for-like control comparison.

The record reports 92 participants enrolled. The primary endpoint description identifies the analysis population as the 90 participants who started study treatment. It does not explain why these counts differ, or describe the characteristics of participants who enrolled but did not start treatment. Eligibility criteria, recruitment details, treatment delivery details, and any individualized dosing or planning procedure are not reported in the registry record.

The record lists a start date of 2010-10-05, a primary completion date of 2016-01-01, and a status of completed. Those dates describe the registry record’s trial timeline; they do not provide the follow-up duration for each participant. The listed secondary outcomes include median follow-up time, median overall survival, median progression-free survival, local-control outcomes, and outcomes among participants with colorectal cancer. Their numerical results are not reported in the registry record.

The record does not report a statistical analysis plan, a sample-size justification, or the details of any planned interim analyses. The posted planning illustrations are not the trial’s design rationale. In particular, illustrations based on an assumed two-arm comparison do not turn this single-group study into a controlled comparison or establish a confirmatory study design.

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:

Analysis population for the primary outcome, as defined in the registry: The 90 participants that started study treatment

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: Patients that were registered but did not start study therapy were not included in the analysis.

6. Primary Endpoint

The registry lists the primary outcome as Local Control Rate, measured over 1 year.

The primary endpoint is the percentage of participants with local control at the primary tumor site at 1 year. The endpoint description specifies the 90 participants who started study treatment as the population. Local control was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), with complete response, partial response, or stable disease counted as local control.

As defined in the record, complete response means disappearance of the entire lesion with no additional evidence of disease. Partial response requires at least a 30% decrease in the sum of the longest diameter of the primary lesion, using the baseline sum as the reference. Stable disease means neither sufficient shrinkage to qualify as partial response nor sufficient increase to qualify as progressive disease, using the smallest sum of longest diameters since treatment started as the reference.

A percentage endpoint provides a concise description of how many participants in the defined population met the specified response-based criterion at the stated assessment time. It is useful for describing local tumor status, but its interpretation depends on the response definitions, timing, and population used. The numerical percentage, its uncertainty, and the handling of participants without an assessable 1-year evaluation are not reported in the registry record. The endpoint definition alone therefore does not establish the observed local-control result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary classification at the participant level: a participant either meets the stated local-control definition at the 1-year assessment or does not. The outcome is then expressed as a percentage of the specified analysis population. The registry defines that population as the 90 participants who started study treatment. This description establishes the intended denominator, but it does not establish whether every participant had an evaluable assessment or whether the reported denominator was modified in an analysis.

What does the endpoint classify?

The record uses RECIST categories to define local control. Complete response, partial response, and stable disease count as local control. The definitions depend on lesion measurements and changes from a reference measurement over time. This makes the endpoint a rule-based classification rather than a direct measurement of a tumor’s biological state. Consistent assessment timing, measurement practice, and application of the criteria matter because they determine how participants are classified. The registry record does not report details about assessment procedures, independent review, or how ambiguous or unavailable assessments were resolved.

What would a percentage estimate tell a reader?

In general, a percentage summarizes the fraction of the analysis population meeting a defined outcome. It is a descriptive estimate for the group assessed under the study conditions. A confidence interval, when reported, describes statistical uncertainty around an estimate under the assumptions of the method used; it does not account for every possible source of bias or uncertainty. No primary endpoint percentage or confidence interval is reported in the registry record, so neither the observed proportion nor its statistical precision can be interpreted from the posted results.

What is the role of the study design?

The study is recorded as single-group, with no separate comparator. A single-group estimate can characterize outcomes in participants receiving the study intervention, if those results are reported, but it does not estimate a randomized contrast against another group. Differences between observed outcomes and expectations from other settings would not, by themselves, establish a treatment effect. Differences in participant characteristics, assessment, follow-up, or other factors could affect a comparison across settings. The registry record does not report a controlled comparison or a causal-effect analysis.

What can be inferred from the analysis entries?

The record lists 0 analyses. It does not report a statistical analysis plan, a model for the primary endpoint, an interval-estimation method, or any adjustments for covariates. These details are not reported in the registry record. It would therefore be inappropriate to attribute a particular analytical method to the investigators or to assume that an unadjusted proportion, a time-to-event method, or another approach was used for the primary endpoint.

The record names secondary outcomes that include median follow-up time, median overall survival, median progression-free survival, and local-control outcomes at other time points. Time-to-event outcomes generally require attention to both event times and censoring: a participant may stop contributing observed follow-up before the event of interest is recorded. A median time-to-event estimate, when reported, depends on the observed event and censoring information and the analysis method. The registry record does not report numerical secondary results, event counts for those outcomes, or methods for handling censoring. These general considerations do not identify the method used in this study.

How should planning illustrations be read?

General sample-size planning asks how much information a study would need to detect a specified effect under selected assumptions. The posted planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. These are planning illustrations, not a reported design justification for this single-group trial. They do not describe the study’s actual allocation, which is recorded as NA, and they should not be read as observed power. The numerical planning outputs and the study’s own sample-size justification are not reported in the registry record.

Over-dispersion is a general issue for some outcome models when observed variability exceeds what a model assumes. In those settings, standard errors and intervals can be too narrow if the extra variability is ignored. The registry record does not report a model for the primary endpoint or evidence that over-dispersion was assessed, so it is not possible to say whether this issue applied to the analysis. This general point does not imply that any particular model was used.

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("SBRT-Proton")
n      <- c(90)
events <- c(69)
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  SBRT-Proton  90  69  76.7  66.6  84.9  66.9  84.2  66.9  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record names multiple secondary outcomes in addition to the primary local-control endpoint. When several outcomes are tested, the chance of at least one apparently notable result can increase if each is assessed separately without adjustment. General approaches include prespecifying one primary question, using a defined hierarchy, or adjusting interpretation for multiple testing. The registry record does not report a multiplicity strategy, a testing hierarchy, or statistical analyses for these outcomes. Because the secondary numerical results are not reported, their findings and any multiplicity implications cannot be assessed.

The primary endpoint population is stated as the 90 participants who started treatment, while enrollment is reported as 92. The registry record does not explain the difference. It also does not report the number with an evaluable 1-year assessment, the amount or pattern of missing outcome data, or a method for handling missing assessments. A participant without an assessment cannot automatically be assumed to have either local control or lack of local control; the analysis rule would need to be stated to understand the resulting estimate.

The analysis population is described only for the primary endpoint as participants who started study treatment. The record does not report whether the analysis followed an intention-to-treat principle, how any exclusions were made, or whether secondary endpoints used the same population. It does not report sensitivity analyses for missing data or alternative analysis populations. These details are not reported in the registry record, so the robustness of any outcome analysis cannot be evaluated from the posted results.

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

For the SBRT-Proton group, the registry record reports 0 participants with a serious adverse event among 90 at risk. It reports 86 participants with other adverse events among 90 at risk, and 1 death. These entries should be read as distinct registry counts, not as interchangeable summaries of the same outcome. The record lists no serious adverse event terms.

The counts describe the entries recorded for this group; they do not provide details about event type, severity grading beyond the serious-event classification, timing, duration, recurrence, or relationship to treatment. The cause and timing of the reported death are not reported in the registry record. The record also does not explain whether the safety follow-up period was the same for every participant or how event collection was conducted.

A zero count in a registry entry means that no affected participants are recorded in that entry; it does not establish that no event could occur or resolve uncertainty about how events were captured. Similarly, the count for other adverse events should not be read as a measure of seriousness. These safety figures are descriptive and do not provide a comparative estimate because the study has no separate control group.

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

The registry record describes a study of proton stereotactic body radiotherapy for liver metastases and defines a 1-year local-control endpoint based on RECIST categories. It also records a single treatment group, 92 enrolled participants, and 90 participants who started treatment and form the stated primary endpoint population. These features explain what was studied and how the primary outcome was intended to be classified.

The record does not report the numerical local-control result, a confidence interval, or numerical results for the listed secondary outcomes. Thus, it does not allow a reader to determine the observed primary outcome value or how precisely it was estimated. The absence of a posted estimate is not itself evidence that local control was high or low, or that a particular effect was present or absent.

The single-group design also limits what can be concluded about cause and effect. Even if an outcome estimate were available, without a separate comparator it would describe outcomes among participants in this group rather than establish how outcomes would differ under another approach. The record does not report a randomized treatment contrast.

The safety entries report no participants with a serious adverse event in the listed group, along with counts for other adverse events and deaths. Those entries do not include enough detail to characterize the event types, timing, or causal relationships. Nor do they permit a comparative safety assessment.

Accordingly, the registry record supports a description of the study design, population counts, outcome definitions, and selected safety counts. It does not support a conclusion about the magnitude, precision, or comparative effect of the intervention on local control, survival, or other clinical outcomes. Those conclusions require outcome results and methods that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a clearly defined primary endpoint and the absence of a numerical primary result in the registry record. The endpoint specifies a time point, a population, and response categories for determining local control. Those details are important because they establish what the study intended to measure. Without the result and its uncertainty, however, the definition cannot answer how often participants met the criterion.

The single-group structure is another central statistical feature. It makes the study a setting for describing outcomes in the treated group, rather than estimating a randomized difference between treatment strategies. This distinction is essential when interpreting any observed outcome: a within-group result and a comparative treatment effect are different statistical quantities.

The population counts also matter. Enrollment is 92, while the primary endpoint description refers to the 90 participants who started treatment. The registry does not explain the difference or report how missing endpoint assessments were handled. Those details are relevant to understanding which participants contribute to an estimate and how broadly it might apply to the enrolled group.

Finally, the list of secondary outcomes illustrates why registry entries must be distinguished from results. Outcome names establish that an outcome was listed, but they do not provide its estimate, uncertainty, or analysis. The record names survival and additional local-control outcomes but does not report their numerical results. Keeping these distinctions clear prevents endpoint definitions, planning assumptions, and safety counts from being mistaken for evidence about unreported clinical outcomes.

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.

Several trial-specific details needed to interpret the study are not reported in the registry record. Eligibility criteria beyond the listed conditions, the radiation dose and schedule, treatment-planning details, and the meaning of individualization are not described in the available record. The intervention name establishes proton SBRT, but does not specify how treatment was tailored or delivered across participants.

The record reports 92 enrolled participants and identifies 90 treatment starters for the primary endpoint, without explaining the difference. It does not report the number with an evaluable local-control assessment at 1 year or how missing assessments were treated. As a result, the intended endpoint population is identifiable, but the completeness and handling of outcome data cannot be evaluated.

No numerical primary or secondary outcome results are reported. The record also does not report confidence intervals, statistical models, covariate adjustment, multiplicity procedures, or an analysis plan. The number and types of serious adverse events beyond the affected-participant count are not listed; causes and timing for the reported death are not reported in the registry record.

The single-group design has no separate comparator, which limits comparative interpretation independently of the missing numerical results. The record does not report a sample-size justification or details of interim analyses. These gaps constrain assessment of both the analysis and the strength of any conclusions that might otherwise be drawn from the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Individualized Stereotactic Body Radiotherapy of Liver Metastases — NCT01239381.
• Registry record last updated 2025-09-30; status last verified 2025-09.
• Results first posted 2017-07-13.
• 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 record identifies a completed, single-group study of proton stereotactic body radiotherapy for liver metastases. It reports 92 enrolled participants and defines the primary endpoint population as the 90 participants who started treatment. The primary endpoint is the percentage with local control at the primary tumor site at 1 year, assessed using RECIST response categories.

The numerical primary endpoint result and listed secondary outcome results are not reported in the registry record. The record lists no analyses and does not describe a statistical analysis plan or missing-data approach. Safety entries report 0 participants with a serious adverse event among 90 at risk, 86 with other adverse events among 90 at risk, and 1 death. The single-group design provides no separate control comparison.