Post-operative Radiation With IMRT in the Management of Stage IIB-III Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Post-operative Radiation With IMRT in the Management of Stage IIB-III Breast Cancer (NCT00508352), a na na study. The primary outcome is Acute Radiation Effects (Less Than 90 Days Post Treatment).

2. Clinical Question

The registry summary frames the study as a feasibility investigation of a radiation technique intended to reduce radiation-induced toxicity relative to conventional techniques. That stated aim is not itself evidence that toxicity was reduced. To evaluate the aim, readers would need outcome results, a clear definition of how effects were assessed, and an appropriate basis for interpreting the observed frequency. The registry record does not report a comparative group or detailed primary-endpoint results.

3. Trial Design

This is a single-group feasibility study of post-operative locoregional irradiation using helical tomotherapy IMRT in stage IIb-III breast cancer. The registry record lists enrollment of 30 and identifies Ottawa Hospital Research Institute as the sponsor. The study is marked completed; the recorded start is 2007-01 and the recorded primary completion is 2009-10. Phase is listed as NA.

The intervention is described as helical tomotherapy IMRT, with 50 Gy delivered in 25 fractions and daily treatment. Masking is listed as none. Allocation is NA, consistent with the registry's single-group model. There is no active or usual-care comparison arm in the posted design, so outcomes cannot be read as a direct treatment contrast.

The feasibility framing matters. A feasibility study can describe whether a treatment approach was carried out and can examine outcomes observed among participants, but the label alone does not establish what criteria defined feasibility or whether those criteria were met. Such criteria are not reported in the registry record. The record also does not report a protocol-level sample-size justification or a statistical analysis plan.

Two secondary outcomes are listed: rate of local recurrence and rate of regional recurrence. The registry record lists four outcome measures, but does not report analyses. The primary outcome concerns acute radiation effects less than 90 days post treatment. The available registry information therefore identifies the questions and treatment approach, but does not supply a full account of outcome estimates, follow-up, or analytic methods.

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 Acute Radiation Effects (Less Than 90 Days Post Treatment), measured over less than 90 days post treatment.

The primary endpoint is described as acute radiation effects less than 90 days post treatment, with the outcome defined as grade 3 or higher radiation effects during that timeframe. Its unit is participants, and its measure is a count of participants with an event. In practical terms, this endpoint is intended to capture the occurrence of relatively severe acute radiation effects in the period specified by the registry.

Acute toxicity endpoints are useful in treatment studies because they focus on harms that arise during or soon after treatment, rather than on later recurrence outcomes. A threshold such as grade 3 or higher also distinguishes more severe effects from lower-grade effects, although the registry record does not include the grading criteria or describe how assessments were made.

The registry record does not report the observed result for this primary endpoint. The adverse-event summary lists participants with serious adverse events and other adverse events, but those categories should not be treated as the primary endpoint result: the posted information does not establish that they use the same definition, assessment window, or grading threshold. Without a reported endpoint count and its assessment details, the frequency of grade 3 or higher acute radiation effects cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

This study is listed as a single-group feasibility study. Statistical interpretation therefore begins with a distinction between describing an observed group and estimating a treatment contrast. In a randomized comparison, an outcome difference between assigned groups can be interpreted in light of the random allocation, subject to the study's conduct and analysis. In a single-group study, there is no concurrent randomized group to provide that contrast. A count in the treated group describes what was recorded among those participants; it does not establish what would have occurred under another treatment.

What does a participant count express?

A count of participants with an event is an absolute description of the number recorded as meeting an outcome definition. For the primary endpoint, the event is specified as grade 3 or higher radiation effects less than 90 days post treatment. The registry record does not report the count for that endpoint. Counts are most interpretable when their event definition, observation window, and assessed population are clear. Here, the endpoint title and description identify a timeframe and severity threshold, but grading procedures and the endpoint result are not reported in the registry record.

The safety summary also uses participant counts. It lists serious adverse events, other adverse events, and deaths separately. These labels do not by themselves establish whether events are treatment-related, whether categories overlap, or whether they cover the same period. A count in one category should not be combined with or substituted for a count in another unless the record defines how they relate.

Why does the absence of a comparator matter?

Without a comparison group, there is no between-group estimate of relative effect. Descriptive outcomes can be useful for documenting experience with a treatment approach, but they do not control for differences in disease characteristics, concurrent care, follow-up, or how outcomes are assessed. Historical results may be discussed in a study rationale, but a rationale is not a concurrent control and does not create a statistically controlled comparison. The registry summary refers to conventional radiation in its background, but does not report a conventional-radiation arm in this study.

Randomization is one method for making groups comparable on average, including on factors that may not be measured. This study is not listed as randomized: allocation is NA and the model is single group. Masking is listed as none. The registry record does not describe blinded outcome assessment or other procedures that might limit assessment bias.

How should planning illustrations be understood?

The stated sample-size assumptions describe illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. These are planning illustrations, not the trial's own design justification, and any sample sizes generated under them are not observed power. Power is a design-stage probability tied to assumptions about an effect, variability, significance level, and analysis. It cannot be inferred after the fact by treating a realized result as proof that a study was adequately powered.

In this study, the single-group design also differs from the two-arm setup described for the illustrations. The planning assumptions should not be read as a description of the actual trial allocation. The registry record does not report a protocol-based sample-size rationale, the assumptions used by investigators at design, or a detailed statistical plan. Consequently, the illustrations cannot establish the study's intended precision or whether its enrollment was adequate for a particular objective.

What do significance tests and confidence intervals usually add?

In general, a significance test assesses how compatible data are with a specified null model, under the assumptions of the analysis. A p-value does not measure the probability that a treatment works, and it does not convey the size or clinical importance of an effect. A confidence interval gives a range of values compatible with the data and method at a stated confidence level. Its width communicates precision: wider intervals indicate less precise estimation, while narrower intervals indicate greater precision. Neither can repair confounding or the absence of a comparator.

No analyses are reported for this registry entry, and no p-values or confidence intervals for the listed outcomes are reported in the registry record. The general interpretation of these statistical tools therefore does not imply that they were used or that a specific inferential result exists for this study.

What does over-dispersion mean in general?

For count outcomes, a statistical model may assume a particular amount of variability. Over-dispersion occurs when observed variation is greater than the model assumes. If it is ignored, standard errors may be too small and intervals or tests may appear more decisive than warranted. Whether over-dispersion is relevant depends on the outcome structure and model. The registry record does not report a count model or analysis plan, so it is not possible to determine whether this issue arose or how it was handled.

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("Helical Tomotherapy")
n      <- c(30)
events <- c(0)
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  Helical Tomotherapy  30  0  0.0  0.0  11.6  0.0  11.4  0.1  11.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and two secondary outcomes: rate of local recurrence and rate of regional recurrence. It also lists four outcome measures, but does not report analyses. The record does not describe a multiplicity plan, such as whether the secondary outcomes were intended to be exploratory or whether any adjustment would be used when interpreting several tests. This matters because repeated testing can increase the chance of finding at least one apparently notable result even when no underlying effect exists. Without reported analyses, there are no posted test results to assess for this issue.

Missing-data handling is not reported in the registry record. The entry does not explain whether all enrolled participants contributed to each outcome, how incomplete follow-up was handled, or how participants without an assessment in the stated acute-effects timeframe were treated analytically. These details are important because counts can be difficult to interpret if outcome availability differs across participants or endpoints.

The analysis population is also not reported in the registry record. The record does not specify whether outcome summaries were based on all enrolled participants, those who began treatment, those who completed treatment, or another defined population. No assumptions about missing outcomes or analysis sets should be inferred from the enrollment figure alone.

The registry lists 30 enrolled, but does not report an outcome-specific denominator or analysis population for the primary endpoint. As a result, the completeness and scope of the posted safety counts cannot be fully evaluated. The absence of an analysis description also means that adjustment for baseline characteristics, follow-up differences, or other factors cannot 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

Serious events with the highest arm-level rate: distant recurrent disease (16.7%).

The registry safety summary for the Helical Tomotherapy group lists 5 participants with serious adverse events, 0 with other adverse events, and 6 deaths. It also lists Distant Recurrent Disease as a serious adverse-event term at 16.7%. These are distinct entries in the safety summary and should be read as recorded, rather than treated as interchangeable measures.

The record does not report whether the serious events or deaths were considered related to treatment, when they occurred, or whether the categories overlap. It does not describe the time period used for the safety summary or explain how events were collected. The listing of a death does not establish that it was caused by treatment, and the serious adverse-event term does not establish a treatment relationship.

The figure of 0 for other adverse events does not mean that no adverse effects occurred: the separate serious-event category is nonzero, and the registry does not explain the relationship between the categories. Nor should the safety summary be used as the primary acute-radiation-effects result. That endpoint is defined by grade 3 or higher radiation effects less than 90 days post treatment, and its observed result is not reported in the registry record.

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

The registry record documents a completed single-group feasibility study of post-operative helical tomotherapy IMRT for stage IIb-III breast cancer. The intervention description specifies 50 Gy in 25 fractions with daily treatment. The primary endpoint is defined around grade 3 or higher radiation effects less than 90 days post treatment, and recurrence outcomes are also listed.

Those details describe the study question and treatment approach, but they do not establish that the intended feasibility objective was achieved. The registry record does not report the primary endpoint result, recurrence rates, or analyses. The posted safety summary provides counts and a listed serious-event term, but does not give attribution or timing. It cannot show whether an event was caused by the intervention or whether a treatment-related risk differed from another approach.

The single-group design also limits what can be concluded about comparative effects. Even if an outcome estimate were available, an observed frequency in the treated group would not by itself tell readers what the frequency would have been under conventional radiation or another treatment. Differences in patient characteristics, other care, outcome assessment, and follow-up could influence an uncontrolled observation.

Accordingly, the record supports a description of the planned intervention and registered outcomes, alongside a limited safety summary. It does not support a conclusion that HT-IMRT reduced toxicity, improved locoregional control, or changed survival relative to conventional techniques. The background rationale describes those aims, not trial results. Nor does the registry information establish the precision of the primary outcome estimate, because that estimate is not reported. The result is a sparse registry account, not a complete basis for evaluating effectiveness or safety.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why design and outcome reporting must be considered together. A feasibility study can document an approach and describe observed events, but a single-group design does not provide a randomized comparison. The study's focus on post-operative locoregional irradiation and acute radiation effects is clear; the evidence needed to assess the stated toxicity objective is not present in the registry record.

The endpoint definition illustrates the importance of specifying severity and timing. Grade 3 or higher radiation effects less than 90 days post treatment identifies a particular acute outcome, rather than all possible adverse events or later events. Yet an endpoint definition alone is not a result. Without its observed count and assessment details, readers cannot judge the frequency or precision of that outcome.

The safety entries also show why event categories need context. Serious adverse events, other adverse events, deaths, and a named serious-event term are listed, but the record does not explain attribution, timing, overlap, or collection methods. These omissions constrain interpretation even when counts are present.

Finally, planning illustrations should be kept separate from the actual study design. The stated assumptions involve equal allocation between two arms, while this study is listed as single group. Illustrative sample sizes are not observed power and do not substitute for the investigators' design rationale. The registry record does not report that rationale or an analysis plan. Together, these features make the study useful for teaching careful distinctions between feasibility aims, descriptive safety reporting, comparative evidence, and statistical precision.

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.

Several trial-specific limitations affect interpretation. The registry lists a single group and no comparator, so outcomes cannot establish a relative effect against conventional radiation or another treatment. Allocation is NA and masking is none. The record does not describe blinding of outcome assessment, so the possibility and handling of assessment bias cannot be evaluated.

The primary endpoint result is not reported in the registry record. Although the endpoint identifies grade 3 or higher radiation effects and a timeframe of less than 90 days post treatment, the record does not describe grading procedures, assessment frequency, or completeness of ascertainment. The listed serious-event counts are not a substitute for that endpoint.

Local and regional recurrence are listed as secondary outcomes, but their results and follow-up duration are not reported in the registry record. The entry also does not report analyses, confidence intervals, or other measures of uncertainty. It is therefore not possible to assess precision, missing-outcome effects, or whether the intended outcome assessments were completed.

The safety summary lacks reported attribution and event timing. The relationship among the serious-event, other-event, and death categories is not explained. In addition, the registry record does not report an analysis population, missing-data methods, multiplicity approach, or protocol-based sample-size justification. These gaps limit assessment of both outcome reliability and the study's planned inferential goals. The background rationale and feasibility label do not resolve these limitations or establish that the intended aims were met.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Post-operative Radiation With IMRT in the Management of Stage IIB-III Breast Cancer — NCT00508352.
• Registry record last updated 2025-06-13; status last verified 2025-05.
• Results first posted 2025-06-13.
• 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

NCT00508352 is a completed single-group feasibility study sponsored by Ottawa Hospital Research Institute. It enrolled 30 and studied post-operative locoregional helical tomotherapy IMRT for stage IIb-III breast cancer. The intervention is described as 50 Gy in 25 fractions, daily treatment; phase is listed as NA, allocation as NA, and masking as none.

The primary endpoint concerns grade 3 or higher acute radiation effects less than 90 days post treatment. Local and regional recurrence are listed as secondary outcomes. The registry record does not report analyses or the primary endpoint result. The safety summary lists 5 participants with serious adverse events, 0 with other adverse events, 6 deaths, and Distant Recurrent Disease at 16.7% as a serious-event term. Attribution and timing are not reported in the registry record.