A Pilot Study of Individualized Adaptive Radiation Therapy for Hepatocellular Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of Individualized Adaptive Radiation Therapy for Hepatocellular Carcinoma (NCT02460835), a na na study. The primary outcome is The Proportion of Patients for Whom the Intended Treatment Was Feasible.

2. Clinical Question

3. Trial Design

This was a completed pilot study of adaptive radiation therapy for hepatocellular carcinoma. The registry lists the study as single-group, with no masking and allocation recorded as NA. It does not identify a randomized control arm or a concurrent comparison treatment. The intervention was radiation therapy, with individualized planning intended to adapt treatment and spare functional liver tissue.

The registry lists an enrollment of 77. The primary-endpoint description separately states that 77 subjects enrolled and 70 were treated. Those counts describe different stages of the study and should not be treated as interchangeable analysis populations. The record does not state which participants were included in a primary-endpoint analysis, nor does it explain why some enrolled participants were not treated.

The primary aim was feasibility, with preliminary estimates of safety and efficacy also described. The feasibility definition concerned successful delivery of full treatment, including the adaptations and perfusion-based planning and replanning. Secondary outcomes listed in the record include median time to progression, change in ALBI scores, incidence of Grade 3 gastrointestinal bleeding toxicities, and overall survival. The registry records 8 outcome measures and 0 analyses, but does not provide outcome results for these measures.

The study is marked completed. Its start date is 2016-01-26 and its primary completion date is 2022-01-20. The record lists phase as NA. The summary states that, if the approach proved promising, the investigators would proceed to a phase II randomized study of standard versus spatially and dosimetrically adapted radiation therapy. The registry record does not establish whether such a later study occurred.

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: 77 subjects enrolled, 70 subjects treated

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 The Proportion of Patients for Whom the Intended Treatment Was Feasible, measured over At end of treatment; up to ~3 months.

The primary endpoint was the proportion of patients for whom the intended treatment was feasible. Feasibility was defined as successful delivery of the full treatment, including all adaptations and, in particular, perfusion-based planning and replanning. The stated assessment time was at the end of treatment; up to ~3 months.

This kind of endpoint asks whether the planned treatment process can be carried out, rather than directly measuring tumor control or survival. That can be important for a pilot study involving specialized imaging and individualized planning: a treatment approach may need to demonstrate that its required steps can be completed before a larger comparative evaluation is considered. This is a general explanation of the role of feasibility endpoints, not a claim about the study’s observed performance.

The registry reports 77 subjects enrolled and 70 treated, but does not report the number meeting the feasibility definition. Without that numerator, an observed feasibility proportion cannot be stated or recalculated. The record also does not report an uncertainty interval for the endpoint. The endpoint definition is therefore available, while its result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study observes participants receiving the study intervention without a concurrent control group. For a binary endpoint such as whether the intended treatment was feasible, a basic descriptive analysis would report how many participants met the definition, the number assessed, and the resulting proportion. That proportion would describe the observed study group. It would not show what would have happened to comparable participants under another treatment.

For this study, the endpoint is defined, and the record reports 77 enrolled and 70 treated. It does not give the number meeting the feasibility definition or identify the denominator used in a reported endpoint analysis. The feasibility proportion cannot be recovered from the enrollment and treatment counts alone. Treating all enrolled participants as successes or failures, or assuming that only treated participants were evaluated, would require an analysis rule that is not reported in the registry record.

How would uncertainty be described?

A confidence interval expresses uncertainty around an estimate. For a binary proportion, an interval would give context for how precisely the observed feasibility rate is estimated, in addition to the point estimate. Its width depends on the data and the method used. These are general statistical principles; the registry record does not report a feasibility estimate or confidence interval, so no interval can be interpreted for this study.

A p-value, when used, addresses compatibility between observed data and a specified statistical model or null hypothesis. It does not measure the size or practical importance of an effect. The record reports 0 analyses and does not provide p-values or a statistical analysis plan. Because the primary aim is feasibility and there is no concurrent comparator, a comparative treatment-effect p-value is not available in the posted results.

What can safety counts tell readers?

Counts of affected participants can describe how many people were recorded in an adverse-event category, while counts of events can describe event occurrences. Those are not necessarily the same quantity: a participant may have more than one event. The registry entries are labeled as participants at risk and participants affected, so they should be read as participant-level entries rather than assumed to be a complete tally of event episodes. The record does not provide details about recurrent events, timing, duration, or attribution for the figures reported.

Comparisons of event proportions across groups can be informative when groups and follow-up are appropriately defined, but this study has no concurrent control group. Its adverse-event entries therefore describe the reported study group and cannot establish whether the observed frequency is higher or lower than it would have been under another approach. A causal interpretation would require more information and a suitable comparison.

What do the planning illustrations represent?

The registry describes planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. It specifies that time-to-event illustrations use a total event count, while other illustrations use participants per arm. These are planning assumptions, not observed trial results. The record does not provide a trial-specific sample-size justification, and the illustrations should not be described as observed power or as the study’s original design plan.

The registry record does not report the numerical values for those planning illustrations in the registry record used for this analysis. No planning count can therefore be stated. More generally, a planning calculation depends on the assumptions chosen, including the effect to detect, significance level, allocation, and statistical model. Changing an assumption changes the required sample size. Such calculations do not show that a study had a particular probability of detecting an effect after the data were observed.

Why does the analysis population matter?

An analysis population specifies which participants contribute to a particular estimate. Enrollment, treatment receipt, and endpoint assessment can define different populations. The registry reports enrollment of 77 and states that 70 subjects were treated, but does not explain the analysis population for feasibility or the secondary outcomes. It also does not report how missing endpoint information was handled. Those details matter because the estimate depends on who is included and how unevaluable participants are treated.

These statistical explanations are general. The posted record does not include enough result-level information to reproduce an endpoint estimate, assess its precision, or evaluate the statistical model used for an outcome 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("Adaptive Radiation Therapy")
n      <- c(77)
events <- c(70)
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  Adaptive Radiation Therapy  77  70  90.9  82.2  96.3  82.4  95.5  82.4  95.5

11. Multiplicity, Missing Data and Analysis Populations

The registry names several secondary outcomes, including median time to progression, change in ALBI scores, incidence of Grade 3 gastrointestinal bleeding toxicities, and overall survival. It also records 8 outcome measures. When a study assesses multiple outcomes, interpreting isolated statistical findings can be difficult because the chance of at least one apparently unusual result may increase as more tests are conducted. Statistical plans may address this through prespecified primary outcomes, adjustment procedures, or a cautious emphasis on estimation. These are general considerations.

The registry record does not report whether multiplicity was considered, whether any adjustment was planned, or which secondary outcomes were designated for formal hypothesis testing. It lists 0 analyses and provides no outcome estimates or p-values. Thus, no claim about multiplicity-adjusted or unadjusted findings can be made.

Missing-data methods are also not reported in the registry record. The difference between 77 enrolled subjects and 70 treated subjects is given, but the record does not explain the reasons for non-treatment or how participants without an endpoint assessment were handled. It does not state whether any outcomes were missing or how missing observations were addressed. The presence or extent of missing outcome data should not be inferred from the enrollment and treatment counts alone.

The primary endpoint description gives enrollment and treatment counts but does not specify an analysis population or provide the number meeting the feasibility definition. The record also does not identify an intention-to-treat, treated, per-protocol, or other analysis set. Those labels have specific meanings and should not be assigned without documentation. As a result, neither the analysis denominator nor the handling of participants who did not receive treatment can be determined from the registry record.

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: acute kidney injury (2.6%), abdominal pain (1.3%), catheter related infection (1.3%), encephalopathy (1.3%), nausea (1.3%).

The registry lists 77 participants at risk for serious adverse events and 6 participants affected. For other adverse events, it lists 77 at risk and 67 affected. It also reports 19 deaths. These figures are descriptive registry entries; they do not provide a comparison with another treatment group.

The serious adverse-event terms with the largest reported percentages are Acute Kidney Injury at 2.6%, and Abdominal Pain, Catheter Related Infection, Encephalopathy, Nausea, and Pleural effusion at 1.3% each. The registry record does not clarify the denominator for these term-specific percentages in the registry record. They should therefore be quoted as the registry lists them, without assuming a denominator or recalculating them.

These entries do not show whether an adverse event was caused by treatment, when it occurred, or whether a participant experienced more than one event. The record does not provide a comparison group or detailed event-level analyses. The 19 deaths should not be attributed to the intervention based on these figures alone; the registry information does not report the relationship between deaths and treatment.

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

The record establishes that this was a completed single-group pilot study of adaptive radiation therapy for hepatocellular carcinoma. It specifies feasibility as the primary endpoint and describes the treatment features relevant to that definition: delivery of the full treatment, including adaptations and perfusion-based planning and replanning. It also reports 77 enrolled and 70 treated subjects, along with some safety counts.

Those details do not establish the observed feasibility rate. The registry does not report how many participants met the primary endpoint, so the treatment’s feasibility cannot be quantified from the posted result information. The status “COMPLETED” describes the study’s registry status; it is not itself evidence that the endpoint was met.

The record also does not report results for the named secondary outcomes. It therefore does not support a conclusion about time to progression, ALBI score change, Grade 3 gastrointestinal bleeding, or overall survival. Nor does it establish a comparative treatment effect, because the design is single-group and no concurrent comparator is listed.

General statistical interpretation distinguishes what a study set out to measure from what its results show. Here, the endpoint definition and design are documented, but the primary result and outcome analyses are not. Safety counts and listed event percentages can be described, while questions of causation, comparative risk, and precision remain unresolved in the registry information.

The study summary frames the work as a pilot intended to assess feasibility and obtain preliminary estimates of safety and efficacy. It says that a phase II randomized study would be considered if the approach proved promising. The registry record does not report whether that condition was met or whether such a later study was undertaken. Accordingly, the available information characterizes the study’s aims and selected registry entries, rather than providing a complete account of its clinical findings.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between feasibility and clinical efficacy. Adaptive radiation therapy involves individualized planning, and the stated primary endpoint focuses on whether the full treatment process could be delivered, including perfusion-based planning and replanning. For an approach with specialized planning requirements, feasibility is a relevant pilot-study question: it concerns whether the intended intervention can be carried out as specified.

But a feasibility endpoint is not a substitute for an efficacy comparison. The single-group design can describe experience among participants receiving the intervention, but it does not provide a concurrent estimate of outcomes under another treatment. That distinction is particularly important when interpreting outcomes such as progression and survival. Without comparative data, differences cannot be attributed to the adaptive approach on the basis of this record.

The registry also illustrates why a clear endpoint definition is not enough for statistical interpretation. To assess feasibility quantitatively, readers need the number meeting the endpoint, the analysis denominator, and an estimate of uncertainty. Although enrollment and treatment counts are reported, the feasibility numerator and result are not. The record’s 0 analyses reinforces that outcome-level interpretation is not available in the posted registry information.

Finally, the study summary’s proposed next step—a randomized study if the pilot approach proved promising—reflects the distinct roles of pilot and comparative studies. A pilot may inform whether a complex intervention can be implemented and may motivate further evaluation. It does not, by itself, establish that the intervention improves outcomes relative to standard treatment. The registry record makes the pilot’s question clear, while leaving its measured feasibility result and preliminary efficacy estimates unreported.

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 main limitation for interpretation is the absence of the primary feasibility result. The registry defines the endpoint but does not report the number of participants who met it, the resulting proportion, or an uncertainty interval. The reported counts of 77 enrolled and 70 treated do not fill that gap.

The study has a single-group design, with no concurrent comparator identified. This limits interpretation to description of the treated study group and does not support a comparative estimate of efficacy or safety. The record does not report outcome analyses for the named secondary outcomes, despite listing them as study measures.

The registry does not describe the analysis population, the handling of participants who were not treated, missing-data procedures, or the methods used to analyze the primary and secondary outcomes. It also does not report an analysis plan or whether multiplicity was addressed. These omissions limit assessment of how the reported counts relate to the endpoint definition and how much uncertainty surrounds any result.

Safety information is limited to participant counts, deaths, and selected serious-event terms with percentages. The record does not provide event timing, duration, attribution, recurrent-event detail, or a concurrent comparison. The term-specific percentage denominators are not clarified in the registry record. These limits prevent stronger interpretation of safety patterns or causal relationships.

The study is identified as a pilot, and the registry lists phase as NA. Its summary describes preliminary safety and efficacy estimates as aims, but those estimates are not reported. The record also does not establish whether the proposed randomized follow-up study occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Pilot Study of Individualized Adaptive Radiation Therapy for Hepatocellular Carcinoma — NCT02460835.
• Registry record last updated 2023-11-15; status last verified 2023-11.
• Results first posted 2023-11-15.
• 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

This completed pilot study evaluated individualized adaptive radiation therapy for hepatocellular carcinoma in a single-group design. The intervention used specialized radiation planning and functional imaging, with an aim of sparing highly functional portions of the liver. The primary endpoint was feasibility, defined as successful delivery of full treatment, including adaptations and perfusion-based planning and replanning.

The registry reports 77 enrolled subjects and 70 treated subjects, but does not report the number meeting the feasibility endpoint or its estimated proportion. It lists secondary outcomes and safety entries, including 6 participants affected by serious adverse events, 67 affected by other adverse events, and 19 deaths. The record lists 8 outcome measures and 0 analyses. No comparative efficacy conclusion is supported by the posted information, and the registry record does not report results for the named secondary outcomes.