Treatment of Unresectable Colorectal Metastases by Radiofrequency Ablation Combined or Not With Resection, With or Without Neoadjuvant Chemotherapy.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Unresectable Colorectal Metastases by Radiofrequency Ablation Combined or Not With Resection, With or Without Neoadjuvant Chemotherapy. (NCT00210106), a na na study. The primary outcome is Complete Hepatic Response Rate at 3 Months.

2. Clinical Question

The study’s stated hypothesis concerns local control in the liver after radiofrequency ablation, either alone or combined with resection. It also raises whether patients may benefit from preoperative chemotherapy, but the registry record does not describe a randomized comparison of chemotherapy strategies or report a separate estimate for that question.

The primary endpoint was a percentage of participants meeting a defined imaging-based response criterion. The registry record identifies the endpoint and its assessment time, but does not report the observed response percentage or its confidence interval. The clinical question can therefore be described from the record, but the magnitude and precision of the response estimate cannot be assessed from the posted results.

3. Trial Design

This completed study is registered as a single-group study of intraoperative radiofrequency ablation for colorectal liver metastases. The record lists an enrollment of 52 and identifies colorectal cancer as the condition. The study was sponsored by Institut Bergonié. Its recorded start was 2003-06 and primary completion was 2008-12.

The intervention is named Ablathermy and categorized as a device. The described IRFA procedure could be performed with or without resection at laparotomy within 28 days of inclusion. The type of current generator and probes, and the decision about resection, were at the surgeon’s discretion. The record’s summary also describes possible preoperative, or neoadjuvant, chemotherapy. It does not provide a treatment allocation scheme that permits a like-for-like comparison of these choices.

Allocation is recorded as NA, masking as none, and the study model as single-group. The phase is recorded as NA. These entries do not establish a randomized or blinded comparison; no separate control group is described. Accordingly, the design can describe outcomes among participants treated in the study, but cannot by itself isolate the effect of ablation from other care or from differences in treatment decisions.

The stated primary endpoint was complete hepatic response at 3 months. Overall survival and event-free survival are listed as secondary outcomes. The registry record lists 3 outcome measures, but does not provide numerical results for these survival outcomes in the registry record described. It also contains no analysis entries. The primary endpoint’s eligible and evaluable population is narrower than the enrollment figure: it comprises eligible, treated patients with 2 scans available. The number meeting that definition is 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients evaluable for efficacy (completed) : eligible, treated and with 2 scans available

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 Complete Hepatic Response Rate at 3 Months, measured over 3 months.

The primary endpoint is the complete hepatic response (CHR) rate at 3 months, expressed as a percentage of participants. The registry definition requires absence of new hepatic lesions or contrast enhancement at the ablation and resection sites on CT performed at 2 and 3 months. The endpoint therefore focuses on radiographic evidence of disease in the liver and at the treated sites, rather than directly measuring overall survival or symptoms.

An imaging response endpoint can provide an early assessment of local disease status after a procedure. It is used to operationalize the study’s stated interest in hepatic local control. Because this is a percentage endpoint, its interpretation depends on the number of participants meeting the response definition and the number assessed in the relevant population. The record defines that population as eligible, treated participants with 2 scans available.

The registry does not report the CHR percentage, the number of responders, the denominator evaluated, or the stated 95% confidence interval. It therefore does not permit a numerical assessment of the endpoint’s observed level or precision. The endpoint definition and assessment schedule are reported, but the result needed to interpret the response rate is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by distinguishing an outcome definition from an outcome estimate. The registry defines complete hepatic response at 3 months and specifies the imaging findings required. It does not report the resulting percentage or confidence interval. The method used to define an outcome tells readers what was counted; it does not reveal the observed count or rate.

What does a percentage endpoint represent?

In general, a percentage endpoint expresses the number of participants meeting a specified criterion relative to the number assessed in the relevant population. For this study, the stated population is patients evaluable for efficacy: eligible, treated participants with 2 scans available. The denominator is important because it identifies whose outcomes contribute to the reported rate. The enrollment figure of 52 is not necessarily the endpoint denominator, and the registry record does not report the number evaluable for efficacy or the number meeting the response definition.

When participants are not assessed, the response rate can depend on how missing endpoint information is handled. For example, an analysis might define an evaluable population, make assumptions about missing outcomes, or use another prespecified approach. Those choices can change the interpretation of a percentage. The registry record identifies an evaluable population but does not report how many participants met it or describe a broader missing-data strategy. That analysis detail is not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval communicates uncertainty around an estimated quantity. It reflects how compatible the data are with a range of values under the interval’s statistical assumptions. It is not a guarantee that the true value lies within the particular interval, and it does not by itself determine whether an outcome is clinically important. For a percentage endpoint, the interval’s width depends in part on the amount of information available and the statistical method used.

The primary endpoint lists a 95% confidence interval as its dispersion measure, but the interval bounds and the point estimate are not reported in the registry record. As a result, the precision of the response estimate cannot be described. No alternative estimate should be reconstructed without the needed endpoint counts and analysis details.

Why does the design affect inference?

In general, comparisons between treatment groups can help distinguish treatment-associated differences from changes that might occur for other reasons. This record describes a single-group study with allocation recorded as NA; it does not describe a control group. Therefore, the design does not furnish a randomized between-group contrast. An outcome rate in the treated group would be descriptive of that group and would not alone establish the effect attributable to ablation.

The procedural description also allows treatment variation: the surgeon decided whether resection was performed and selected the type of generator and probes. The study summary refers to possible neoadjuvant chemotherapy, but the record does not provide comparative estimates for patients with and without it. In general, treatment decisions made at clinician discretion can be associated with patient or disease characteristics. Without reported comparative analyses and adequate adjustment details, the role of those differences cannot be separated from treatment choices.

How should the planning assumptions be understood?

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They specify that the effect to detect is a stated fraction of the observed effect. In general, such calculations explore the sample size associated with chosen design assumptions; they are not evidence that a trial had a particular probability of detecting an effect after the results were observed. The planning values themselves are not reported in the registry record, and the study is registered as a single-group study rather than a two-arm comparison. Any planning illustration should therefore be interpreted as a hypothetical design exercise, not as observed power or as a feature of the registered study design.

Over-dispersion is a general statistical concern when outcome variability is greater than a model assumes. It can make standard errors too small and confidence intervals too narrow if the model fails to account for that extra variability. The registry record does not report an over-dispersion model or enough analysis detail to determine whether one was considered; the statistical analysis plan is not reported in the registry record.

Finally, the record lists 3 outcome measures and no analysis entries. That does not supply estimates or methods for the primary endpoint, overall survival, or event-free survival. The methods needed to reproduce or fully appraise those analyses are not reported in the registry record. General statistical principles can explain what the endpoint and uncertainty measures mean, but they cannot replace the absent numerical outcomes and analysis specifications.

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("Intraoperative Radiofrequency Ablation (IRFA)")
n      <- c(38)
events <- c(30)
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  Intraoperative Radiofrequency Ablation (IRFA)  38  30  78.9  62.7  90.4  63.7  88.9  63.5  88.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint, complete hepatic response at 3 months, and identifies overall survival and event-free survival as secondary outcomes. It also lists 3 outcome measures. Testing or interpreting several endpoints can raise multiplicity concerns: in general, when many statistical questions are addressed, the chance of at least one apparently notable finding may increase unless the analysis plan accounts for it. The registry record does not report whether multiplicity adjustments were planned or applied, or how any secondary outcomes were to be interpreted.

Missing data are especially relevant to the primary endpoint because the efficacy population is defined as eligible, treated participants with 2 scans available. The record does not state how many participants had the required scans, how many were excluded from that population, or why any scans were unavailable. It also does not report whether participants without complete imaging were included in another analysis or how their outcomes were treated. Those details are not reported in the registry record.

The record lists no analysis entries and does not report a statistical analysis plan. The analysis population for the secondary outcomes, the treatment of missing survival information, censoring rules, and any interim analyses are not reported in the registry record. No assumptions about these choices can be inferred from the endpoint description alone.

These omissions do not establish that a particular method was or was not used; they limit what can be verified from the registry record. In general, clear reporting of endpoint hierarchy, analysis populations, missing-data handling, and multiplicity procedures helps readers understand how much confidence to place in results across multiple outcomes. Here, numerical endpoint results and these analysis details are unavailable, so neither endpoint-specific uncertainty nor the consequences of missingness and multiple outcomes can be assessed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thromboembolic event (2.0%), hepatic infection (2.0%), hepatic failure (2.0%), intra-abdominal hemorrhage (2.0%), sepsis (2.0%).

For the IRFA group, the registry lists 49 at risk for serious adverse events, with 5 affected. It also lists 49 at risk for other adverse events, with 6 affected. The record separately lists 16 deaths. It does not specify the timeframe for the death count in the registry record described, nor explain how deaths relate to the adverse-event counts.

The listed serious-event terms are thromboembolic event, hepatic infection, hepatic failure, intra-abdominal hemorrhage, and sepsis; each is recorded at 2.0%. These are registry entries for selected serious-event terms. The information does not establish whether the categories overlap, whether the list is exhaustive, or how each term was defined and assessed. The percentages should not be converted into event counts without further information.

In general, safety counts and percentages describe events recorded under the study’s reporting approach. Their interpretation depends on definitions, observation time, completeness of ascertainment, and the population at risk. The registry record does not provide all of those details or a comparator group. Thus, the reported counts can be described, but they do not support a comparative estimate of safety or a conclusion about the causes of the reported events.

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

The registry record establishes the clinical question and the intended primary endpoint: complete hepatic response at 3 months, based on specified CT findings at 2 and 3 months. It also describes an IRFA procedure that could be combined with resection, and a study summary that allows for possible neoadjuvant chemotherapy. These details clarify the setting and what investigators sought to measure.

What the record does not establish is the numerical response rate. The primary endpoint estimate, its confidence interval, the response count, and the number of participants evaluable for efficacy are not reported in the registry record. Consequently, the posted information cannot show how often complete response occurred or how precisely it was estimated. The record’s hypothesis about local control is not itself evidence that the endpoint was achieved.

The single-group design also means that a result in treated participants would not, on its own, quantify the difference attributable to the intervention compared with an alternative. The surgeon’s discretion over procedural details and resection, and the mention of possible neoadjuvant chemotherapy, further describe potential variation in care; comparative findings by those choices are not reported in the registry record. Overall survival and event-free survival are listed as secondary outcomes, but their numerical results are not reported.

The safety entries describe selected counts and serious-event terms, but lack the context needed to make a comparative or causal interpretation. The study is completed, yet completion status does not substitute for reporting outcome estimates. The appropriate reading is therefore limited: the record documents a study design, endpoint definition, and some safety information, while leaving the primary clinical result and key analytic details unavailable.

14. Why This Trial Matters Statistically

This study is statistically instructive because it makes the distinction between a clear endpoint definition and a reportable endpoint result especially important. Complete hepatic response is defined using CT findings at specified follow-up times, and the record identifies the population intended for the efficacy assessment. Yet without the estimate, denominator, and confidence interval, readers cannot evaluate the endpoint’s level or precision.

It also illustrates why design labels matter. A single-group study can describe outcomes among participants who received a treatment approach, but it does not create a randomized comparison with an alternative. The registry’s account of surgeon discretion over resection and procedural equipment, alongside possible neoadjuvant chemotherapy, makes it particularly important not to treat a descriptive outcome as a causal treatment effect.

The record also highlights the role of analysis-population reporting. The primary endpoint is defined for participants with 2 scans available, but the number meeting that criterion and the handling of participants without complete imaging are not reported. Those details are necessary to understand what population a response percentage would represent and how missing observations might affect it.

Finally, the registry lists secondary survival outcomes and safety information, but does not provide numerical survival estimates or comprehensive analysis details. The case demonstrates that a completed study and a detailed endpoint description do not necessarily provide enough information for a full statistical appraisal. Transparent reporting of estimates, uncertainty, analysis populations, and methods is essential for readers to judge what the data support.

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 that the primary endpoint’s numerical result is not reported in the registry record. The CHR rate, confidence interval, response count, and efficacy denominator are all unavailable. Without those values, neither the observed response nor its precision can be assessed.

The study is listed as single-group, with allocation recorded as NA and no comparator described. It therefore cannot provide a registered randomized contrast between IRFA and another strategy. The procedural description allows resection and device choices at the surgeon’s discretion, while the summary refers to possible neoadjuvant chemotherapy. The registry record does not report outcome comparisons across those choices or adjusted analyses that could account for differences between participants.

The efficacy population requires eligible, treated participants with 2 scans available, but the record does not report how many participants met this definition or how missing imaging was handled. The statistical analysis plan, analysis methods, and multiplicity approach are not reported in the registry record. Overall survival and event-free survival are listed as secondary outcomes, but numerical results and analysis details for them are not reported.

Safety reporting is also limited in context. Counts are given for serious and other adverse events, along with deaths and selected serious-event terms, but the record does not specify the deaths’ timeframe in the registry record described or establish whether reported event categories overlap. There is no comparator for assessing relative event frequency. The phase is recorded as NA, and the record does not provide further design detail that would resolve these interpretive limitations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treatment of Unresectable Colorectal Metastases by Radiofrequency Ablation Combined or Not With Resection, With or Without Neoadjuvant Chemotherapy. — NCT00210106.
• Registry record last updated 2021-05-18; status last verified 2021-04.
• Results first posted 2021-05-18.
• 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

NCT00210106 is a completed, single-group study sponsored by Institut Bergonié. The registry lists an enrollment of 52, a start of 2003-06, and primary completion in 2008-12. The study concerns colorectal cancer and intraoperative radiofrequency ablation for unresectable colorectal liver metastases, with or without resection; the summary also refers to possible neoadjuvant chemotherapy.

The primary endpoint is complete hepatic response at 3 months, defined by CT findings at 2 and 3 months. The efficacy population is eligible, treated participants with 2 scans available. Overall survival and event-free survival are listed as secondary outcomes. Numerical primary and secondary outcome estimates are not reported in the registry record. Safety entries include serious and other adverse-event counts, a death count, and selected serious-event terms. Allocation is NA, masking is none, phase is NA, and the record contains no analysis entries.