Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors (NCT01177007), a na phase 2 study. The primary outcome is Time to Progression (TTP) of the Treated Lesion(s) According to RECIST Criteria.

2. Clinical Question

This structure makes the central question descriptive: what outcomes and safety information were recorded after TheraSphere treatment in the enrolled study group? It does not set up a direct treatment-versus-control estimate. Without a comparison group, the study cannot isolate how much of an observed outcome is attributable to treatment rather than the underlying disease, prior therapies, subsequent care, or other factors. The registry record does not give numerical results for the alternative progression-free survival outcome, so the size and precision of that outcome cannot be described from this record.

The stated population is clinically selected by prior treatment history: participants had liver metastases and had failed or could not tolerate other systemic or liver-directed therapies. That description defines the intended context of the study, but the registry record does not provide further participant characteristics with which to assess who was represented. The clinical question therefore concerns this selected group and this treatment setting, rather than all people with liver metastases or a comparison of treatment options.

3. Trial Design

The registry record describes a prospective, open-label Phase 2 trial of intra-arterial Yttrium-90 glass microspheres, named TheraSphere. Its design is single-group, allocation is listed as not applicable, and masking is listed as none. The record lists an enrollment of 50 and identifies Yale University as the sponsor. The study status is completed; its listed start is 2010-09 and primary completion is 2014-08.

In a prospective study, outcome information is followed after entry according to the study's planned schedule. Here, the brief summary says participants would be followed for time to progression, safety, and overall survival after treatment. It also describes treatment at doses of 120 ± 10% Gy. The registered timeframe for the primary time-to-progression outcome was evaluation 4 weeks following each procedure and at 2-3 month intervals thereafter. The registry record says this particular primary outcome was not assessed, however, and that progression-free survival based on RECIST and EASL criteria was assessed and reported instead.

Because this is a single-group study, its results would describe outcomes among treated participants rather than estimate a randomized contrast against another treatment or usual care. Open-label means masking was not used, as the record indicates; the record does not explain any procedures for limiting assessment bias. There is no like-for-like control comparison to support a causal treatment-effect estimate.

The registry lists secondary outcomes covering time to progression of treated lesions, tumor response by RECIST v1.0 and EASL criteria, overall survival, the overall survival rate at 2 Years, safety graded by CTCAE Version 3.0, and mean radiation dose delivered to the total liver. It reports 9 outcome measures and 0 analyses. The registry record does not report the protocol's statistical plan, eligibility details beyond the brief population description, or the numerical results for the alternative progression-free survival outcome.

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: These data were not collected. See outcome measure #2.

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 Time to Progression (TTP) of the Treated Lesion(s) According to RECIST Criteria, measured over Evaluated 4 weeks following each TheraSpheres procedure, and at 2-3 month intervals thereafter..

The registered primary endpoint was time to progression of treated lesions according to RECIST criteria. Time-to-progression endpoints describe the interval from a defined starting point until disease progression is identified under specified assessment rules. The registry timeframe says evaluation was to occur 4 weeks following each TheraSpheres procedure, then at 2-3 month intervals thereafter. The record does not specify a time origin for this endpoint beyond that assessment schedule.

In general, a time-to-event measure can retain information about when an event occurs, rather than reducing follow-up to a single status at one selected visit. It is commonly used when the timing of progression matters and participants may have different follow-up durations. Such analyses require clear event definitions and handling of participants whose event is not observed during follow-up. The registry record does not report those analysis details for the registered endpoint.

Crucially, the registry record says the specified primary outcome was not assessed and that its data were not collected. Instead, it says progression-free survival based on RECIST and EASL criteria was assessed and reported. The record does not provide numerical estimates, event counts, confidence intervals, or other results for that alternative outcome. Thus, the registered endpoint's definition and intended schedule can be described, but its outcome cannot be interpreted as an observed result in this record. The reason for the endpoint change and the associated analysis plan 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?

In general, a single-group study follows participants who receive the intervention and describes their outcomes. It can document what happened in the study group, subject to the completeness and quality of the measurements. It does not directly estimate a contrast with an untreated or alternative-treatment group. A randomized comparison is designed to make groups comparable, on average, with respect to both measured and unmeasured prognostic factors. That design feature is absent: the registry labels the model single-group, allocation not applicable, and masking none. Consequently, an outcome observed after treatment cannot by itself identify the treatment's causal effect.

This distinction is not a judgment that descriptive findings are uninformative. It specifies the question they can address. They can describe outcomes and safety observations in this enrolled group, while leaving open how those outcomes compare with another course of care. The registry record does not provide a control-group estimate or a causal analysis.

What is a time-to-event endpoint?

In general, time-to-event methods analyze the time until an event such as progression or death. The approach can use information from participants whose event is observed and participants whose event has not been observed by the end of their available follow-up. Those without an observed event are commonly treated as censored at a defined point; censoring is not the same as experiencing the event. Valid interpretation depends on the event definition, the time origin, follow-up, and assumptions about censoring.

The registered primary endpoint was time to progression of treated lesions under RECIST criteria, with evaluations scheduled 4 weeks after each procedure and at 2-3 month intervals thereafter. The record says this endpoint was not assessed and its data were not collected. It says progression-free survival under RECIST and EASL criteria was assessed and reported instead. The event definitions, time origin, censoring rules, and numerical analysis for that alternative outcome are not reported in the registry record.

Why do assessment rules matter?

In general, response criteria give a structured way to classify changes in tumors using defined measurements and rules. Consistent criteria can make assessments more reproducible and help readers understand what counted as response or progression. RECIST and EASL are both named in the registry outcomes, but the record does not give the detailed assessment procedures or explain how assessments were conducted in an open-label setting. It also does not provide numerical response findings in the registry record relevant to this account. Naming a criterion alone does not provide an outcome estimate.

Open-label status means participants and study personnel were not masked according to the registry. In general, knowledge of treatment can affect reporting, clinical management, or subjective judgments, depending on the outcome and the process used to assess it. The extent of any such influence cannot be determined from the design label alone. The registry record does not describe blinded image review or other safeguards, so their use should not be assumed.

How should uncertainty be understood?

In general, an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval reflects sampling variability under an analysis model; it does not account automatically for bias, missing information, or design limitations. A small sample may yield imprecise estimates, but sample size alone is not enough to quantify precision. For time-to-event outcomes, the number and timing of events and the follow-up pattern are also important. No numerical progression-free survival estimate, interval, or event count is reported in the registry entries, so its precision cannot be assessed.

The record lists 0 analyses. That is a registry-record feature, not evidence that no analysis was performed outside the record. The statistical methods used for the reported progression-free survival outcome are not reported in the registry record. There is no basis to infer whether a particular model, adjustment, or sensitivity analysis was used.

What does the planning illustration represent?

In general, sample-size planning asks how many participants or events might be needed to detect a specified effect under chosen assumptions. A planning calculation is not an observed trial result, and it does not show that a completed study had a particular probability of detecting an effect. The registry describes its illustration as using 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 the observed effect. For time-to-event outcomes, the illustration is described as giving the total number of events; other illustrations are described in participants per arm.

These are planning assumptions, not a description of the actual design: this study is single-group, not a two-arm randomized comparison. The registry explicitly describes the illustration as not the trial's own design. The numerical planning outputs and the observed effect used to derive them are not present in the registry record for this explanation, so no sample-size value or effect can be interpreted. These illustrations should not be called observed power.

What can the registry record establish?

The registry record establishes its listed design labels, stated outcome schedule, description of the primary-outcome substitution, and the safety entries included in the record. It does not provide enough information to reconstruct a statistical analysis or to estimate efficacy from the alternative progression-free survival outcome. General statistical principles can clarify what the methods would mean, but they cannot replace missing estimates, analysis details, or participant-level information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes, including response assessed by RECIST and EASL criteria, time to progression, overall survival, an overall survival rate at 2 Years, safety, and mean radiation dose delivered to the total liver. Considering multiple outcomes raises a general interpretive issue: the more outcomes or analyses examined, the more opportunities there may be for chance findings. In general, a statistical plan may specify a primary outcome, testing order, or adjustment for multiple comparisons. The registry record does not report such a plan or any multiplicity adjustment.

The registered primary time-to-progression outcome was not assessed, according to the record. The record says progression-free survival based on RECIST and EASL criteria was assessed and reported instead. It does not explain why the outcome changed, whether this change was specified before analysis, or how the replacement outcome was handled within any testing strategy. Those details are not reported in the registry record and should not be inferred.

The record gives 0 analyses, but this does not establish that no analyses were conducted; it means that analyses are not listed in the registry information represented. Numerical results for the alternative progression-free survival outcome, analysis populations, missing-data handling, exclusions, and follow-up completeness are not reported in the registry record. In general, missing outcomes can affect estimates when the probability of being missing is related to a participant's outcome or prognosis. Assessing that possibility requires information about missingness and analysis choices that is not available in this record.

The registry's description of a sample-size planning illustration does not supply a trial-specific statistical plan or explain the analysis population. No assumptions about interim analyses, stopping rules, or imputation methods can be made; those details 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (disease progression) (8.0%), abdominal pain (4.0%), brain surgery for metastatic disease (2.0%), allergic reaction (2.0%), renal failure (2.0%).

The registry lists serious adverse events for the TheraSphere group, with 50 at risk and 14 affected. It separately lists 50 at risk and 48 affected for other adverse events, and records 4 deaths. These are registry entries with different event categories; they should not be combined or treated as interchangeable. The record also lists serious adverse event terms with percentages: Death (disease progression), 8.0%; Abdominal pain, 4.0%; Brain surgery for metastatic disease, 2.0%; Allergic reaction, 2.0%; Renal failure, 2.0%; and Failure to thrive, 2.0%.

These figures describe what the registry records, not a comparison with another treatment. In general, an adverse event is an event occurring during a study, while determining whether it was caused by a treatment requires further assessment. The registry entries do not establish causality for each event. The record does not report event timing, duration, recurrence, participant-level overlap across terms, or an attribution assessment. The listed death term specifically includes disease progression, but the record does not provide enough detail to interpret all deaths or to substitute these entries for an overall-survival analysis. The event counts and percentages should therefore be read as safety reporting, not as a controlled estimate of risk or proof of cause.

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

The registry record describes a Phase 2, prospective, open-label, single-group study of TheraSphere in patients with liver metastases from solid tumors who had failed or were intolerant to other systemic or liver-directed therapies. It documents the intended treatment and follow-up context and includes safety entries. It also makes clear that the registered primary time-to-progression outcome according to RECIST was not assessed. Instead, progression-free survival based on RECIST and EASL criteria was assessed and reported.

That substitution is important for interpretation, but the registry entries do not include numerical results for the alternative outcome. No estimate, event count, confidence interval, or analysis detail is available to describe its magnitude or precision. The record therefore does not support a quantitative statement about progression-free survival in this study.

Even if numerical outcomes were available, a single-group design would describe the course observed among treated participants rather than establish what treatment caused. Without a comparator, outcomes cannot be separated from the effects of underlying disease, prior therapies, participant selection, or other factors. This is a design limitation, not a claim that the observed clinical course had any particular direction.

The safety entries provide information about adverse events recorded in the registry, including serious events and deaths. They do not by themselves prove that treatment caused the events, and they do not allow a comparison of safety against another treatment. The record does not report enough detail about attribution, timing, or overlap among listed events for those questions.

The statistical planning illustration is not an observed finding and is not the trial's own design. The record does not provide the trial's statistical plan, sample-size justification, or the numerical planning outputs in the registry record used for this account. The appropriate conclusion is therefore bounded: the registry describes a treated group, a primary-outcome assessment that was not performed, an alternative outcome that was assessed and reported without numerical details in this record, and safety entries that require non-causal interpretation.

13. Why This Trial Matters Statistically

This trial is statistically notable because the registered primary endpoint and the outcome described as assessed are not the same. The primary endpoint was time to progression of treated lesions according to RECIST criteria, yet the registry says that outcome was not assessed and its data were not collected. Instead, progression-free survival based on RECIST and EASL criteria was assessed and reported. Recognizing that distinction prevents the registered endpoint from being mistaken for an observed result and draws attention to the need for transparent reporting when an outcome changes.

The record also illustrates the limits of interpreting single-group clinical evidence. A study can describe outcomes in a treated group, but without a comparator it cannot directly estimate how those outcomes differ from what would have occurred under another treatment or without treatment. Statistical precision and causal identification are separate issues: even a precise descriptive estimate would not by itself resolve the lack of a control group.

The registered outcomes span progression, tumor response, survival, safety, and radiation dose. In general, a collection of outcomes can answer different questions, but readers need a prespecified analysis strategy to understand which findings are primary and how multiple results are interpreted. That strategy is not reported in the registry record. The record lists 0 analyses and does not include numerical efficacy estimates for the alternative progression-free survival outcome, limiting the quantitative conclusions that can be drawn.

Finally, safety counts and listed event terms are meaningful as registry reporting, but they are not comparative causal estimates. Separating event description from attribution is essential when a study has no control group and when the record lacks event-level detail. Together, these features make this study useful for discussing endpoint reporting, design-based limits on causal inference, and the distinction between registered outcomes, assessed outcomes, and interpretable results.

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.

Several limitations specific to this record constrain interpretation. First, the registered primary outcome, time to progression of treated lesions according to RECIST, was not assessed, and its data were not collected. The record identifies progression-free survival based on RECIST and EASL criteria as assessed and reported instead, but does not give numerical results or explain the change. Its timing, analysis details, and relationship to the registered primary question are therefore unclear from the registry record.

Second, the study is single-group, open-label, and has no randomized comparator. Outcomes cannot be interpreted as a controlled treatment effect. Open-label status may also matter for assessment processes, but the registry record does not describe whether outcome assessments were independently reviewed or otherwise protected from knowledge of treatment.

Third, the record does not report the statistical analysis plan, sample-size justification, analysis populations, missing-data methods, or follow-up completeness. It lists 0 analyses, but that registry entry does not establish whether analyses took place outside the registry record. The numerical efficacy results, estimates of uncertainty, and event counts for the alternative progression-free survival outcome are not reported in the registry record.

Finally, the safety information is limited to listed counts and event terms with percentages. The record does not provide timing, duration, attribution, or details about whether the same participant appears under multiple event terms. The listed safety information cannot support a comparative risk estimate or a causal conclusion. Participant characteristics beyond the stated disease and prior-treatment context are also not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors — NCT01177007.
• Registry record last updated 2017-08-28; status last verified 2017-07.
• Results first posted 2017-08-28.
• 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 describes a completed, prospective, open-label Phase 2 single-group study of intra-arterial Yttrium-90 glass microspheres, named TheraSphere, for patients with liver metastases from solid tumors who had failed or were intolerant to other systemic or liver-directed therapies. It lists an enrollment of 50, Yale University as sponsor, and treatment doses of 120 ± 10% Gy.

The registered primary time-to-progression outcome according to RECIST was not assessed; the record says progression-free survival based on RECIST and EASL criteria was assessed and reported instead. Numerical results for that alternative outcome are not reported in the registry entries. The record lists secondary outcomes across response, progression, survival, safety, and radiation dose, and reports 0 analyses. Serious and other adverse event entries are present, but they do not constitute a controlled comparison or establish causation. The single-group design, absent primary endpoint assessment, and missing numerical efficacy details limit the conclusions that can be drawn.