TheraSphere for the Treatment of Liver Metastases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for TheraSphere for the Treatment of Liver Metastases (NCT00511862), a non-randomized phase 2 study. The primary outcome is Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST).

2. Clinical Question

The study also names overall survival as a secondary outcome and describes safety as an objective. These aims do not create a controlled comparison: without a separate comparator group, the trial is descriptive rather than a randomized test of treatment against another approach. The registry record reports enrollment of 151, but that enrollment figure should not be mistaken for the primary endpoint analysis population. The endpoint description specifies that participants needed at least one treatment and images that could be evaluated by RECIST. A numerical result for that endpoint, and the number included in its analysis, are not reported in the registry record.

3. Trial Design

This was a phase 2, open-label, non-randomized, single-group trial of TheraSphere for liver metastases. The registry lists Boston Scientific Corporation as the sponsor and records the study status as completed. The recorded study start is 2007-01, and primary completion is recorded as 2011-03. Enrollment is listed as 151.

The intervention is yttrium 90 glass microspheres, described in the arm information as TheraSphere at 120 Gy +/- 10%. The single group was stratified by disease type: colorectal cancer, neuroendocrine cancer, and non-colorectal/non-neuroendocrine cancer. Stratification describes how participants were categorized; it does not make the trial randomized or provide an untreated control.

Because the trial was open label, masking is listed as none. The registry does not describe a blinded assessment process. Its primary endpoint is hepatic progression-free survival according to RECIST, with the endpoint population defined as patients who received at least one TheraSphere treatment and had images evaluable by RECIST. The endpoint timeframe begins on the date of first treatment and ends at the date of first documented progression; the record also states median patient follow-up of 30 months.

The study description says it evaluates liver progression-free survival and safety in patients with metastatic liver disease that could not be treated or was progressing after systemic or other liver-directed therapies. Overall survival is listed as a secondary outcome. The registry record does not report a comparator arm, a randomization procedure, masking, or numerical efficacy results. Additional protocol details, including the rationale for the enrollment target and the statistical analysis plan, 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.

Before assignment: Patients were assigned to groups on the basis of type of primary cancer - colorectal cancer; neuroendocrine cancer or non-colorectal/non-neuroendocrine. Subjects who unable to receive TheraSphere (target dose 120 Gy) due to vascular shunting to the lungs or GI tract were not enrolled in the study and did not receive yttrium 90 glass microspheres.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Patients receiving at least one TheraSphere treatment with images evaluable by RECIST

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: Subjects treated with TheraSphere were enrolled and assigned to groups based on their primary cancer type. The total population and each subgroup population was analyzed for safety, progression and survival endpoints. In the neuroendocrine group, a median overall survival was not achieved so a post-hoc analysis of 2 year survival was performed.

6. Primary Endpoint

The registry lists the primary outcome as Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST), measured over From the date of first treatment until date of first documented progression; median patient follow-up 30 months.

Hepatic progression-free survival measures the time from the first TheraSphere treatment until hepatic progression is determined. The registry defines progression using RECIST version 1.0 and gives a liver-specific rule for this trial: hepatic progression is an increase of at least 20% in the sum of the longest diameters of target hepatic lesions. The description also includes progression of existing non-target lesions or appearance of new lesions in its general RECIST definition.

The endpoint is a time-to-event measure. Its median would describe the time by which half of the endpoint population had experienced the defined event, subject to the study’s analysis and follow-up. The registry identifies the summary measure as a median and the uncertainty measure as a 95% confidence interval. However, neither the median nor its confidence interval is reported in the registry record.

General statistical context: a liver-specific progression endpoint can focus attention on disease behavior in the treated organ, rather than treating progression elsewhere as equivalent to hepatic progression. That focus depends on consistent lesion assessment and the stated criteria. The registry says that a maximum of 5 target lesions per organ are assessed. It also specifies that the primary endpoint population must have evaluable images. The details of how image evaluability, censoring, or assessment timing were handled are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median time-to-event measure mean?

General statistical explanation: a time-to-event endpoint records how long it takes for a defined event to occur. For this trial, the defined event is hepatic progression, and the clock begins at the first TheraSphere treatment. A median is a summary of the event-time distribution: it marks the point at which the estimated event-free proportion reaches its midpoint. It does not mean that every participant experiences progression at that time. The registry names the median as its primary summary, but does not report the estimate.

Time-to-event analyses can use information from participants who have not experienced the event by the end of their observed follow-up. Such observations are commonly treated as censored at their last known assessment, rather than as if the event had occurred then. This approach requires assumptions about follow-up and censoring. The registry record does not report the censoring rules, the number censored, or the analytical method used to estimate the median.

What does the confidence interval add?

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the method used. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. It does not describe the range containing every participant’s event time. The registry identifies a 95% confidence interval for the median hepatic progression-free survival, but does not report its endpoints. Precision therefore cannot be assessed from the registry information.

How is progression defined?

The primary endpoint uses RECIST version 1.0. The registry’s general description defines progression as at least 20% increase in the sum of the longest diameter of target lesions, using the smallest sum recorded since treatment started as the reference; it also includes unequivocal progression of an existing non-target lesion or appearance of new lesions. For assessing a non-systemic local therapy, the trial specifies hepatic progression as at least 20% increase in the sum of the longest diameter of target hepatic lesions. A maximum of 5 target lesions per organ are assessed.

General statistical explanation: standardizing the event definition helps make outcome assessments more consistent. It does not eliminate judgment in identifying lesions or deciding whether changes meet the criteria. The registry says images must be evaluable by RECIST for inclusion in the primary endpoint population. It does not report details of image review, adjudication, assessor training, or handling of unevaluable scans.

What can a single-group design estimate?

General statistical explanation: a single-group study can describe outcomes among participants who received the intervention, subject to the defined analysis population and follow-up. Without a concurrent control group, it cannot separate the intervention’s contribution from other influences on outcomes. Non-randomized allocation also means that treatment assignment does not provide the balance that randomization is intended to support. In this trial, the registry records a single-group model, non-randomized allocation, and no masking. It does not report a comparative hazard ratio.

What do the planning assumptions mean?

General statistical explanation: a sample-size calculation is a planning exercise based on assumptions about the effect to detect, the significance threshold, allocation, and statistical method. It is not an observed trial result or a measure of the trial’s achieved power. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of the observed effect. Those are planning assumptions, not the design recorded for this single-group trial. The registry does not report the trial’s own sample-size justification.

The planning description states that time-to-event calculations use the total number of events under the Schoenfeld approach, while other calculations use participants per arm. These conventions describe how planning quantities are expressed; they do not supply an observed event count or an efficacy result for this trial. Planning illustrations should not be interpreted as observed power, and no such power estimate is reported in the registry record.

What does the registry report about analysis?

The registry lists 3 outcome measures and 0 analyses. The primary endpoint is identified as a median with a 95% confidence interval, but the numerical estimate and interval are not reported in the registry record. The analysis population is described for the primary endpoint as patients with at least one treatment and RECIST-evaluable images. The record does not report the number analyzed, the statistical software, the estimation procedure, or sensitivity analyses. These omissions limit the ability to reproduce or fully evaluate the endpoint analysis from the registry information alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, identifies hepatic progression-free survival as primary, and names overall survival as a secondary outcome. It also reports 0 analyses. The registry record does not report whether the study used a multiplicity adjustment, a testing hierarchy, or another approach to account for examining multiple outcomes. No p-values or numerical efficacy analyses are reported in the registry record.

General statistical explanation: when several outcomes or comparisons are examined, the chance of a nominally unusual result can increase if each is interpreted without accounting for the set of tests. Prespecifying a primary endpoint and describing how secondary outcomes will be interpreted can help readers understand the intended inferential emphasis. The registry identifies a primary endpoint, but details of any multiplicity strategy are not reported in the registry record.

The primary endpoint population is defined as patients who received at least one TheraSphere treatment and had images evaluable by RECIST. The registry does not report how many participants met that definition or how missing or unevaluable images were handled. It also does not report missing-data methods, reasons for missing assessments, censoring rules, or sensitivity analyses. Enrollment should therefore not be assumed to equal the analysis population for the primary endpoint.

Beyond the endpoint-specific population description, the analysis populations used for safety or other outcomes are not reported in the registry record. The record does not specify whether any participants were excluded from particular analyses or how those exclusions were handled. Without these details, the completeness of outcome follow-up and the robustness of estimates to missing data cannot be assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: abdominal or epigastric pain (3.3%), death (1.3%), gi ulcer (1.3%), liver dysfunction/failure (1.3%), nausea (1.3%).

The registry lists 151 participants at risk for serious adverse events and reports 21 affected. It also lists 151 at risk for other adverse events and reports 139 affected. These are separate registry categories; the record does not establish that the categories are mutually exclusive, so the counts should not be combined. They are descriptive safety figures, not comparisons with another group.

The registry’s serious-term list includes abdominal or epigastric pain at 3.3%, and death, GI ulcer, liver dysfunction/failure, nausea, and obstruction at 1.3% each. These percentages are reported as serious terms. A separate count for deaths is not reported in the registry record, so the listed death term should not be treated as a complete mortality summary. The record does not give event timing, duration, participant-level overlap among terms, or attribution details in this summary.

General statistical explanation: an affected-participant count and an event-term percentage may describe different aspects of safety reporting. Multiple terms can be recorded for a participant, and the same term can involve repeated events, depending on the reporting rules. Those details are not reported in the registry record. The counts can therefore be read as the safety information the registry reports, but not as a complete account of event patterns or comparative risk.

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

The registry record establishes that this was a completed, open-label, single-group phase 2 trial of TheraSphere for liver metastases. It documents the intervention, the intended dose range, the disease categories, the primary endpoint definition, and selected safety counts. It also identifies overall survival as a secondary outcome. These registry entries describe the study’s scope; they do not establish a treatment effect.

The primary endpoint is clinically focused on hepatic progression and is defined using RECIST-based criteria. However, the registry does not report the median hepatic progression-free survival or its 95% confidence interval. Without that estimate, readers cannot determine the observed time-to-event summary or its statistical precision from this registry entry. A numerical overall survival result is also not reported.

The single-group design means the registry information cannot provide a randomized comparison against another treatment or usual care. General statistical context: outcomes observed after treatment can reflect the intervention as well as participant characteristics, disease course, follow-up, and other care. A comparator group and an appropriate design are needed to make a stronger comparative interpretation. The registry does not report a comparative effect estimate.

The serious and other adverse-event counts describe reported events in the trial group. They do not, on their own, establish whether events were caused by treatment or how the reported frequency compares with another option. The registry’s summary does not provide event timing, overlap, or a separate deaths count.

Accordingly, the posted registry information supports a description of the trial design, endpoint criteria, and selected safety reporting. It does not support a conclusion about the size, direction, or certainty of an efficacy effect, nor a comparative safety conclusion. Additional numerical outcome results and analysis details are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a clearly named endpoint and a reported endpoint result. The registry defines hepatic progression-free survival in terms of time from first treatment to hepatic progression, specifies a RECIST-based assessment framework, and identifies a median with a 95% confidence interval as the intended summary. Yet the numerical estimate and interval are not reported in the registry record. Readers therefore have a defined outcome but cannot assess its observed value or precision from this record.

It also demonstrates why study design shapes statistical interpretation. The trial is recorded as non-randomized and single group, with no masking. Such a design can describe outcomes among treated participants, but does not provide a concurrent randomized comparator for estimating a treatment contrast. Stratification by disease type organizes the group by cancer category; it does not replace randomization or create a control group.

The safety information offers another practical lesson: affected-participant counts, event terms, and percentages need to be interpreted in light of their denominators and reporting definitions. The registry reports separate serious and other adverse-event categories, but does not report whether participants overlap between categories or among terms. Nor does the summary give event timing or attribution details. Those limits matter when using registry safety data for descriptive interpretation.

Finally, the record lists overall survival as a secondary outcome, but does not report its numerical result, and lists 0 analyses. A registry entry can document design and intended measures without supplying the information needed for a full statistical appraisal. Distinguishing reported details from absent results is essential to avoid turning an endpoint label or study completion status into evidence of a particular outcome.

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 main limitation for interpreting efficacy is that the registry record does not report the primary endpoint estimate or its 95% confidence interval. It also does not report numerical overall survival results, a hazard ratio, or other comparative efficacy estimates. Although the registry identifies 3 outcome measures, it lists 0 analyses. The outcome definitions alone do not reveal what values were observed.

The single-group, non-randomized design has no concurrent control group. Consequently, the record cannot support a randomized treatment comparison. Open-label conduct and the absence of masking are recorded, but the registry does not describe whether endpoint assessments were independently reviewed or otherwise protected from assessment bias.

The primary endpoint population requires at least one treatment and images evaluable by RECIST, but the number of participants in that population is not reported in the registry record. The record also does not report event counts, censoring rules, missing-image handling, reasons for exclusions, or sensitivity analyses. These omissions limit assessment of completeness and robustness.

The safety summary reports affected-participant counts and selected serious terms, but does not provide event timing, duration, attribution, participant-level overlap, or a separate deaths count. The registry record does not report a statistical analysis plan, multiplicity procedures, or the trial’s sample-size justification. These are limitations of the information available in the registry record, not evidence that particular procedures were or were not used outside the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: TheraSphere for the Treatment of Liver Metastases — NCT00511862.
• Registry record last updated 2021-05-13; status last verified 2021-04.
• Results first posted 2014-05-23.
• 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

NCT00511862 is recorded as a completed phase 2, open-label, non-randomized, single-group trial sponsored by Boston Scientific Corporation. The registry lists enrollment of 151, a study start of 2007-01, and primary completion of 2011-03. The intervention is yttrium 90 glass microspheres, described as TheraSphere at 120 Gy +/- 10%, with groups stratified by disease type.

The primary outcome is median hepatic progression-free survival according to RECIST, with a 95% confidence interval specified. Its population is patients with at least one treatment and RECIST-evaluable images. Overall survival is listed as a secondary outcome. Numerical efficacy results and the primary endpoint estimate are not reported in the registry record. The safety summary reports 21 affected by serious adverse events and 139 affected by other adverse events, with 151 at risk in each category.