Low-Dose Radiation Therapy to the Whole Liver With Gemcitabine and Cisplatin in IHC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Low-Dose Radiation Therapy to the Whole Liver With Gemcitabine and Cisplatin in IHC (NCT02254681), a na phase 2 study. The primary outcome is Number of Participants With Radiographic Disease Response After Combination Low-dose Radiotherapy and Gemcitabine-cisplatin..

2. Clinical Question

3. Trial Design

This was a phase 2, single-group study of combined low-dose fractionated radiotherapy and gemcitabine-cisplatin for locally advanced mass-forming intrahepatic cholangiocarcinoma. The registry lists enrollment of 6 and identifies the study status as terminated. The start date is recorded as 2014-09 and primary completion as 2016-09.

Because there was one treatment group and no randomized allocation, the design can describe outcomes observed among the enrolled participants, but it cannot isolate the effect of the combination from other explanations using a concurrent control comparison. In a single-group study, observed outcomes can be useful for describing what happened in the treated group. They do not, by themselves, establish what would have happened to comparable participants under another approach.

The treatment description specifies four three-week cycles. Gemcitabine and cisplatin were scheduled on days one and eight of each cycle. Whole liver and portal lymph node basin low-dose radiotherapy was scheduled on days one, two, eight, and nine of each cycle. These are the regimen details in the record; it does not report participant-level adherence, dose modifications, or how many participants completed each cycle.

The study was unmasked, and its allocation is listed as not applicable. No masking procedure or comparator arm is described. The record states that a decision was made to close the study due to futility of the regimen in the first 6 subjects, as well as lack of funding to complete the study. It does not report a formal stopping boundary, a prespecified futility rule, or a separate analysis supporting that decision.

The record identifies one primary radiographic response outcome and several secondary outcomes covering surgical complications, histologic response, background liver injury, intrahepatic recurrence, and intrahepatic progression. The endpoint definitions and results are not all present in the available record. In particular, no primary response count or inferential analysis is reported, so the design description should not be mistaken for a complete account of the study's findings.

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: decision was made to close the study due to the futility of the regimen in the first 6 subjects, as well as the lack of funding to complete the 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 Number of Participants With Radiographic Disease Response After Combination Low-dose Radiotherapy and Gemcitabine-cisplatin., measured over 16 weeks after treatment start.

The primary endpoint was the number of participants with radiographic disease response after the combination treatment, assessed 16 weeks after treatment start. The record says that response was assessed by CT or MRI under RECIST v1.1 for target lesions. Complete response was defined as disappearance of all target lesions. Partial response was defined as at least a 30% decrease in the sum of the longest diameters of target lesions. Progressive disease was defined as at least a 20% increase in the sum of target-lesion diameters, using the smallest sum observed on study as the reference; that reference could be the baseline sum if it was the smallest.

Radiographic response is used to describe changes in measurable disease on imaging. Standardized criteria help make those classifications more consistent across participants and studies. A count of participants meeting a response category is a clinically interpretable summary, while the underlying categories preserve distinctions between response, progression, and other outcomes. The record does not state how stable disease was handled in the primary endpoint or give the number of participants in any response category.

The registry record does not report the primary endpoint result. It therefore does not establish how many participants had complete response, partial response, progressive disease, or another classification at the assessment time. The closure statement mentions futility in the first 6 subjects, but does not give the response data, a numerical threshold, or the analysis behind that characterization. The endpoint definition alone cannot fill in those missing results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase 2 study with a binary-style primary outcome expressed as a count of participants with radiographic response. The endpoint used RECIST v1.1 categories based on CT or MRI assessment of target lesions at 16 weeks after treatment start. The record does not give a primary response count, an effect estimate, or an inferential analysis. These absences limit what can be explained about the study's actual statistical findings.

What does a response count tell us?

A count records how many participants met an outcome definition. For a binary outcome, each participant is classified according to whether the specified event occurred. Here, the endpoint title refers to participants with radiographic disease response, while the RECIST description distinguishes complete response, partial response, and progressive disease. The record does not state how non-response categories were combined for the primary analysis, nor does it report the count in any category. It would therefore be inappropriate to reconstruct a response total from the closure statement.

A count is often accompanied by a proportion and a measure of uncertainty. General explanation: the proportion summarizes the observed frequency in the study group, while a confidence interval conveys uncertainty about the underlying response frequency under a specified statistical model. With few observations, estimates are especially sensitive to the outcome of each participant and confidence intervals tend to be broad. No response proportion or confidence interval appears in the registry entries, so neither the magnitude nor precision of the primary response result can be assessed.

Why does the single-group design matter?

The record identifies a single group and no comparator. General explanation: an uncontrolled study can report what occurred among those who received the regimen, but it lacks a concurrent group to show what outcomes would have occurred under an alternative approach. Changes in disease status cannot be attributed to the treatment combination solely from a before-and-after or single-group description. This is a design limitation, not a calculation that can be repaired by applying a different statistical test to the same data.

The regimen combines chemotherapy and radiotherapy. In a single-group design, the observed outcomes would pertain to the combination as used in that group; the design would not separate the contribution of one component from the other. The registry does not report adherence, treatment completion, or participant-level exposure, which also prevents a detailed account of how the scheduled regimen was delivered.

What can be inferred from the closure statement?

The record reports that the study was closed because of futility in the first 6 subjects and lack of funding. General explanation: a futility assessment asks whether continuing a study is unlikely to meet its objective, according to a chosen criterion. A credible interpretation depends on the criterion, timing, data available, and statistical method used. The registry does not report those details, nor does it report interim analyses or the primary outcome data underlying the decision. The closure statement should consequently be reported as written, without assuming a particular rule or reconstructing an analysis.

The record lists no analyses. This means there are no analysis results in the posted details to interpret; it does not establish what analyses may have been considered internally. The statistical plan, handling of analysis populations, and any adjustment for multiple outcomes are not reported in the registry record.

How should the planning illustrations be read?

The sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. For non-time-to-event outcomes, the illustrations are expressed as participants per arm for 80% power or another stated power level; time-to-event illustrations use total events. These are planning illustrations, not observed power and not the trial's reported sample-size justification.

Those assumptions describe a hypothetical two-arm calculation, whereas this study is listed as single-group with allocation not applicable. The illustration should therefore not be interpreted as the actual design or enrollment plan for this trial. The registry does not report the trial's own sample-size justification, target effect, or stopping rule. The displayed planning values, if consulted, answer a hypothetical planning question rather than adding an efficacy result to the record.

Why does uncertainty matter?

General explanation: an estimate is more informative when readers can see both its value and its precision. A confidence interval is one way to express that precision, but it does not remove limitations in the design or data. Statistical significance, if reported, would not by itself establish clinical importance, and a non-significant result would not prove that an effect is absent. In this record, no primary estimate, confidence interval, or test result is reported, so these distinctions cannot be applied to an observed efficacy result.

The main statistical reading is therefore restrained: the registry gives an endpoint definition and a reason for early closure, but not the primary outcome data or analysis needed to quantify response. General statistical principles can explain how such data might ordinarily be summarized, but they cannot replace results that are not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the radiographic response endpoint as primary and names secondary outcomes concerning post-operative complications, histologic disease response, background liver injury, intrahepatic recurrence, and intrahepatic progression. It also states that there were 7 outcome measures overall. The listed details name 5 secondary outcomes in addition to the primary endpoint; the identities and definitions of any remaining outcome measures are not reported in the registry record.

General explanation: testing or interpreting many outcomes creates a multiplicity issue. When several outcomes are examined, the chance of at least one apparently notable finding can increase unless the analysis plan accounts for the number and relationship of the tests. The registry record does not report a multiplicity adjustment, a hierarchy for secondary endpoints, or a detailed statistical analysis plan. It is not possible to determine from the listed outcomes whether or how multiplicity was handled.

The record does not describe missing outcome data, withdrawals, or the population included in any efficacy analysis. It does not report whether every enrolled participant had imaging at the 16-week assessment, how unavailable scans were handled, or whether any participants were excluded from an analysis. These details are important because missing outcome information can affect both the estimate and its interpretation.

Likewise, the registry does not specify an intention-to-treat population, a per-protocol population, or another analysis population. These are not interchangeable: the population definition sets out which participants contribute to a particular estimate. Without that information and without outcome counts, readers cannot reconstruct the primary analysis. The study's statistical plan, missing-data methods, and analysis populations are not reported in the registry record.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cholelithiasis (16.7%).

The treatment group safety summary lists 6 participants at risk for serious adverse events and 1 serious adverse-event-affected participant. It lists 6 participants at risk for other adverse events and 6 affected. The record also reports 3 deaths. These are counts in a group of 6, not rates from a comparative safety analysis.

The top serious adverse-event term is cholelithiasis, listed at 16.7%. The registry entries do not state how this term relates to the serious-event count, whether events were considered related to treatment, or when they occurred. They also do not describe the causes or timing of the deaths. The figures should therefore be read as reported safety summaries, not as evidence that the treatment caused a particular event or death.

General explanation: adverse-event summaries depend on how events are defined, collected, graded, and attributed. A count of affected participants does not show the full pattern of event severity, duration, recurrence, or clinical context. In a single-group study without a comparator, the record cannot show whether an event was more or less common than it would have been under another approach. The available safety figures are limited by the small enrolled group and the absence of further event-level detail.

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

This record documents a phase 2, single-group study of low-dose radiotherapy combined with gemcitabine and cisplatin for locally advanced mass-forming intrahepatic cholangiocarcinoma. It describes the scheduled regimen, identifies radiographic response at 16 weeks as the primary endpoint, and reports selected safety counts. It also records that the study was terminated after a decision citing futility in the first 6 subjects and lack of funding to complete the study.

What it does not show is the primary response result. The registry record contains no count of complete responses, partial responses, or progressive disease, and no estimate of response frequency or precision. The closure rationale is not accompanied by the underlying outcome data or the statistical criterion used. Accordingly, this record cannot quantify the treatment's observed efficacy or support a precise conclusion about the primary endpoint.

The design also limits the kinds of comparisons that can be made. With one treatment group and no randomized comparator, the registry cannot estimate a treatment difference against another intervention or control. The combination design cannot separate the contribution of radiotherapy from the contribution of chemotherapy. These are limits of the available design and record, rather than evidence for or against either component.

The safety summaries give counts of adverse-event-affected participants and deaths, but lack event timing, attribution, causes of death, and a comparison group. They describe reported events; they do not establish causation. The small enrollment also means that the listed safety counts provide only a limited description of what occurred in this group.

In general, a trial result is best understood by considering the outcome definition, observed estimate, uncertainty, analysis population, and design together. Here, several of those elements are absent from the registry entries. The findings that can be stated are therefore limited to the study's design, its listed outcomes, its recorded closure reason, and its posted safety counts. Any stronger claim about response or comparative effects would require results not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically instructive because its registry record separates several things that are easy to conflate: a defined endpoint, a stated reason for stopping, and a numerical result. The primary endpoint is clearly described using RECIST v1.1, but its participant count and response categories are not reported. The closure statement refers to futility, but the decision rule and supporting analysis are also not reported. An endpoint definition and a futility label do not substitute for the data needed to estimate response.

The single-group design is another important feature. It can describe outcomes within the treated group, but it does not create a randomized comparison. This distinction matters even when an outcome is objectively assessed by imaging: standardized measurement can improve consistency of classification, but it cannot supply a control group or resolve the causes of observed changes.

The listed enrollment of 6 also illustrates why precision matters. General explanation: estimates based on few participants can be strongly affected by each participant's outcome, and uncertainty is often wide. Since the primary result and its uncertainty are not reported, readers cannot judge the size or precision of any observed response from this record.

Finally, planning calculations should be kept distinct from trial findings. The sample-size illustrations use stated hypothetical assumptions and should be read as planning exercises, not as observed power or as the study's own design justification. The record does not report the rationale for the trial's sample size. Keeping these distinctions clear helps prevent a planning table, a stopping rationale, or a safety count from being misread as a complete efficacy analysis.

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 available record has substantial limits for interpreting the primary outcome. It defines radiographic response and its assessment time, but does not report the number of participants with response or the distribution across RECIST categories. It also gives no confidence interval, test result, or other estimate of uncertainty. The record's futility statement does not identify the response data or decision threshold behind that description.

Enrollment was 6, and the study had a single group. The small group limits how precisely outcomes can be described, while the absence of a comparator prevents a randomized estimate of differences between treatments. The combination regimen also means that the design cannot distinguish the effects of its separate components.

The registry does not report participant characteristics, treatment adherence, treatment completion, dose modifications, or the number with imaging at the primary assessment. It does not describe missing-data handling or the analysis population. These omissions prevent a detailed assessment of who contributed to an outcome estimate and how incomplete follow-up might have been addressed.

The secondary outcome list includes surgery-related complications, histologic response, liver injury, recurrence, and progression, but results and complete definitions are not present in the available details. The record states 7 outcome measures, while the listed information identifies the primary endpoint and 5 secondary outcomes; any additional outcome identities are not reported. Multiplicity methods and the statistical analysis plan are also not reported.

The safety summary lacks event timing, causes of death, and attribution to treatment. It offers no comparator safety data. Finally, the stated closure due to futility and lack of funding is not accompanied by the protocol-level rationale, stopping criteria, or analysis details. These limitations should frame any reading of the posted results and planning illustrations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Low-Dose Radiation Therapy to the Whole Liver With Gemcitabine and Cisplatin in IHC — NCT02254681.
• Registry record last updated 2018-10-03; status last verified 2018-10.
• Results first posted 2018-10-03.
• 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.

18. Record Summary

The registry record describes a phase 2, unmasked, single-group study of low-dose fractionated radiotherapy with gemcitabine and cisplatin for locally advanced mass-forming intrahepatic cholangiocarcinoma. Enrollment is listed as 6, and the study status is terminated. The primary endpoint was the number of participants with radiographic disease response at 16 weeks after treatment start, assessed using RECIST v1.1.

The record states that the study was closed because of futility in the first 6 subjects and lack of funding. It does not report the primary response count, response categories, or an efficacy analysis. Safety listings include 1 serious adverse-event-affected participant among 6 at risk, 6 participants with other adverse events among 6 at risk, and 3 deaths; cholelithiasis is listed as a serious adverse-event term at 16.7%.

The record does not describe a comparator, analysis population, missing-data method, multiplicity adjustment, or detailed statistical plan. It supports a description of the study and its reported safety counts, but not a numerical estimate of primary efficacy or a controlled treatment comparison.