Hypofractionated Radiation Therapy in Treating Participants With Breast Cancer Before Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hypofractionated Radiation Therapy in Treating Participants With Breast Cancer Before Surgery (NCT03624478), a na phase 2 study. The primary outcome is Pathologic Complete Response (pCR) Rate Defined as a Residual Tumor Burden of 0-1 in the Surgical Specimen.

2. Clinical Question

3. Trial Design

This was a completed phase II study sponsored by Mayo Clinic. The registry describes it as a pilot/phase II trial of hypofractionated radiotherapy to the whole breast before breast-conserving surgery. Its design is single-group, with no allocation to competing arms and no masking. The registry lists an enrollment of 25; that is the recorded enrollment figure and should not be mistaken for the number included in every endpoint analysis.

The intervention description says radiation was administered daily for 5 days, followed by standard-of-care surgery 4-16 weeks later. The primary endpoint was to be assessed in the surgical specimen. The primary outcome description defines the analysis as the number of participants achieving pathologic complete response divided by the total number of evaluable participants. It also states that, if more than the target number of 22 patients were accrued, additional patients would not be used to evaluate the stopping rule or inform decision making. The record does not explain how that provision was applied to the enrollment figure.

The registry status is completed. It lists a start date of 2018-11-20 and a primary completion date of 2021-06-30. It also lists 15 outcome measures, including adverse events and several disease-control and survival outcomes. The numerical result for the primary endpoint is not reported in the registry record. The record likewise does not provide numerical results for most of the listed secondary outcomes. Without a comparison group, any reported outcome would describe this group under the study conditions rather than establish a comparative treatment effect.

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

Analysis population for the primary outcome, as defined in the registry: If more than the target number of 22 patients are accrued, the additional patients will not be used to evaluate the stopping rule or used in any decision making process.

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 Pathologic Complete Response (pCR) Rate Defined as a Residual Tumor Burden of 0-1 in the Surgical Specimen, measured over up to 2 years.

The primary endpoint is the pathologic complete response rate, defined as residual tumor burden of 0-1 in the surgical specimen. It measures how often this specified response was observed among evaluable participants at definitive surgery. The registry describes the rate as a proportion: successes divided by the total number of evaluable participants. The stated timeframe is up to 2 years.

A surgical pathology endpoint gives a structured assessment of the tumor remaining in the removed tissue after the preoperative treatment. Defining the endpoint by a specified residual tumor burden makes the success criterion explicit, while using the surgical specimen anchors assessment to a clinical event described in the trial record. These are general features of pathology-based endpoints; they do not establish that the endpoint is a surrogate for later outcomes in this trial.

The record says confidence intervals for the true success proportion would be calculated using the approach of Duffy and Santner. A confidence interval expresses the uncertainty around an estimated proportion: a narrower interval indicates greater precision, while a wider interval indicates less precision. Neither the observed response count, estimated proportion, nor confidence interval is reported in the registry record, so the endpoint’s result and precision cannot be evaluated from the recorded details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods described for the primary endpoint focus on estimating a proportion and quantifying uncertainty around it. The record defines a success as pathologic complete response with residual tumor burden of 0-1 in the surgical specimen. The numerator is the number of participants achieving that response, and the denominator is the total number of evaluable participants. This definition makes clear that the denominator may be smaller than the number enrolled if some participants do not have an evaluable specimen or otherwise do not enter the endpoint analysis. The registry does not report the actual numerator or denominator.

What does a confidence interval add?

A point estimate alone gives a single estimated response proportion. A confidence interval adds information about statistical precision by expressing a range of values compatible with the observed data under the method’s assumptions. In general, estimates based on less information tend to be less precise, while more information can support greater precision. A confidence interval is not a guarantee that the true value lies within the calculated range, and it does not correct for limitations such as selection into the evaluable population or lack of a comparison group. The registry specifies the Duffy and Santner approach for the primary endpoint’s confidence intervals, but the interval itself is not reported in the registry record.

Why is the analysis population important?

The endpoint definition uses evaluable participants, rather than simply referring to everyone enrolled. That distinction matters because an endpoint estimate depends on who has usable outcome information and who is included in the denominator. If evaluability is related to participant characteristics, treatment experience, or outcome status, the resulting proportion may not describe all enrolled participants in the same way. These are general considerations; the registry record does not report an evaluable-participant count, reasons for missing endpoint data, or the analysis population used for a primary result.

The primary outcome description also states that if more than the target number of 22 patients were accrued, additional patients would not be used to evaluate the stopping rule or inform decision making. This indicates a planned distinction between the stated target and any additional accrual for that specific purpose. The registry record does not report whether the condition occurred in the analysis set, how the stopping rule operated, or whether a stopping decision was made. It would be inappropriate to infer these details from enrollment alone.

What can a single-group design estimate?

A single-group study can describe the observed outcome proportion among participants meeting its analysis definition. It cannot directly estimate a randomized treatment contrast because there is no concurrent control arm. A comparison with an external benchmark would require a clearly specified benchmark and assumptions about the comparability of populations, outcome definitions, and care settings. Such a benchmark is not reported in the registry record. The absence of a control group also means that an outcome cannot be attributed uniquely to the intervention based on the design alone.

The registry identifies the trial as phase II and lists allocation as not applicable, masking as none, and the model as single-group. These design features help explain the scope of inference: the primary endpoint is a within-group response measure, not a difference between allocated treatments. The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or details about adjustment for other variables. Those methods should not be assumed.

How should planning illustrations be read?

Any sample-size illustrations associated with this trial should be read as planning calculations, not as observed trial results or as evidence of achieved power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. These assumptions describe an illustration, not the single-group trial’s allocation. The record does not report the trial’s own sample-size justification, and the numerical result used as the observed effect is not reported in the registry record.

In general, a planning calculation estimates how much information might be needed to detect a chosen effect under specified assumptions. If the assumed effect is smaller, the calculation will generally require more participants to attain the same target power; this is a general statistical relationship, not a trial result. Such calculations do not tell whether the trial actually had a particular power after data collection. They also cannot repair the lack of a randomized comparison in this design. Any hypothetical two-arm planning scenario should therefore be kept separate from the reported single-group study design.

For time-to-event planning, the registry’s note describes totals of events as the relevant quantity; other illustrations are expressed as participants per arm. These are general distinctions in planning calculations, not observed event counts or actual allocations in this trial. No numerical planning illustration should be interpreted as a count of trial participants or outcomes unless the registry explicitly reports it as such.

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("Treatment (Hypofractionated Radiation Therapy)")
n      <- c(22)
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  Treatment (Hypofractionated Radiation Therapy)  22  0  0.0  0.0  15.4  -0.0  14.9  0.1  14.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary pathologic complete response endpoint and secondary outcomes related to adverse events, disease control, recurrence, and survival. When a study assesses multiple outcomes, the chance of at least one apparently notable result can increase if each outcome is tested without a plan for handling multiplicity. This is a general statistical concern, not a claim that a particular adjustment was or was not applied in this trial.

A multiplicity strategy might define one primary hypothesis, specify which secondary outcomes are confirmatory, or adjust interpretation for multiple tests. The registry record does not report a multiplicity procedure, a hierarchy of hypotheses beyond identifying the primary endpoint, or a statistical analysis plan describing how multiple outcomes were handled. It records 0 analyses. The numerical results for the primary endpoint and most secondary outcomes are not reported in the registry record, so their statistical significance and any adjustment cannot be assessed.

Missing outcome data also matter because the primary endpoint is defined among evaluable participants. If some enrolled participants lack an evaluable surgical specimen, the estimated proportion may depend on who remains in the denominator. The record does not report the number of evaluable participants, missingness, reasons for missing data, or any imputation or sensitivity-analysis approach. It also does not state whether the primary analysis included all enrolled participants or another analysis population. The enrollment figure should not be substituted for an unreported endpoint denominator.

These omissions limit assessment of precision, selection effects, and robustness. They do not show that the analysis was inappropriate; they mean that the relevant methods and outcome details are not reported in the registry record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death nos (4.2%), resp, thoracic, mediastinal - oth spec (4.2%).

The registry’s treatment-group safety entries list 24 participants at risk and 2 affected for serious adverse events. For other adverse events, the corresponding entries are 24 at risk and 22 affected. The registry also lists 2 deaths. These are recorded counts and should be read as safety summaries, not as a complete account of every event or its clinical course.

The leading serious adverse-event terms are “Death NOS” at 4.2% and “Resp, thoracic, mediastinal - Oth spec” at 4.2%. The label “Death NOS” does not specify a cause in the term itself. The record does not report in the registry record whether the deaths were considered related to treatment, nor does it provide enough detail to determine the timing, circumstances, or overlap among event categories. The percentage entries should therefore be treated as registry-reported descriptions, not as causal estimates.

Adverse-event counts can help describe what was recorded during a study, but interpretation depends on definitions, observation periods, completeness of reporting, and the population at risk. The registry record does not report those details fully in the registry record. The safety figures also come from a single-group study, so they do not establish how event rates compare with another treatment or with background risk.

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

The registry record establishes that a completed phase II, single-group trial evaluated hypofractionated radiation therapy to the whole breast before breast-conserving surgery. It specifies a primary endpoint based on residual tumor burden in the surgical specimen and describes how the response proportion and its confidence interval were intended to be estimated. It also records selected adverse-event figures. These are useful details about the study question and measurement approach.

The primary endpoint result is not reported in the registry record. Without its response count, denominator, estimated proportion, and confidence interval, the observed response and its precision cannot be described. The record’s enrollment figure of 25 does not supply the missing endpoint denominator, because the endpoint analysis is defined among evaluable participants and the trial description includes a provision concerning a target of 22 patients.

The design also limits what a result could establish. With no comparison group, a response proportion would describe outcomes in the treated group, not the difference attributable to treatment relative to another strategy. A single-group study can generate evidence about feasibility and observed outcomes, but separating treatment effects from other influences generally requires a suitable comparison and design assumptions. This is a general statistical distinction, not a conclusion about the clinical value of the intervention.

The adverse-event entries document counts and selected terms but do not identify causation. The record does not report numerical findings for most listed secondary outcomes, including recurrence and survival measures. Consequently, the recorded details do not support conclusions about longer-term outcomes or comparative safety. The appropriate interpretation is narrow: the registry describes the study design and planned endpoint, and reports some safety entries, while leaving the primary numerical result and many outcome details unreported.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a preoperative intervention can be evaluated using a pathology-based endpoint. The record defines success by residual tumor burden in a surgical specimen and identifies the evaluable-participant proportion as the estimand of interest. A clear endpoint definition helps readers understand what is being counted and at what point in care it is assessed.

The study also illustrates the importance of matching interpretation to design. Its single-group structure can support description of outcomes among participants receiving the intervention, but it cannot provide a randomized comparison with a different treatment. Keeping that distinction clear prevents a within-group response rate from being mistaken for a comparative effect. The listed enrollment and the endpoint’s evaluable-population denominator are also different concepts, making transparent reporting of analysis populations important.

Precision is another central issue. The registry describes a confidence-interval method for the primary proportion, but the interval and underlying outcome count are not reported in the registry record. Without them, readers cannot assess how uncertain the estimated response would be, even if the point estimate were available. Similarly, the registry’s list of multiple outcomes raises general questions about how outcome families and analyses should be interpreted, while the relevant multiplicity approach is not reported.

Finally, the record distinguishes trial design from planning illustrations. Hypothetical sample-size calculations based on two arms do not change the fact that this study is recorded as single-group. Treating those planning assumptions as actual allocation or observed power would misstate the evidence. Together, these considerations make the trial a useful case for reading endpoint definitions, denominators, confidence intervals, safety counts, and design limitations as connected parts of statistical interpretation.

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 most consequential limitation for interpreting the posted results is that the primary endpoint’s numerical result is not reported in the registry record. The response count, evaluable denominator, estimated proportion, and confidence interval are all needed to describe the observed endpoint and its precision. The listed enrollment of 25 does not establish the endpoint denominator.

The study has no concurrent comparator. This prevents a direct estimate of the difference between the intervention and another treatment strategy and limits causal interpretation of any within-group outcome. The record does not report a statistical analysis plan, sample-size justification, interim-analysis plan, or details about the stopping rule’s implementation. Although the endpoint description mentions a target of 22 and a rule for additional accrual, it does not report how that provision affected the final analysis.

The record lists 15 outcome measures but does not report the numerical results for most of them. It also does not report how missing endpoint data were handled, why participants might have been unevaluable, or which analysis population was used. These details affect assessment of selection, precision, and robustness. The safety entries include counts and selected event terms, but the registry entries available do not establish attribution, timing, or the full context of those events.

These limitations concern what can be concluded from the registry record; they do not establish that unreported procedures were not carried out. Rather, the relevant design and analysis details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Hypofractionated Radiation Therapy in Treating Participants With Breast Cancer Before Surgery — NCT03624478.
• Registry record last updated 2026-05-15; status last verified 2025-11.
• Results first posted 2022-12-15.
• 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 describes a completed phase II, single-group trial of hypofractionated whole-breast radiation therapy before breast-conserving surgery. The treatment description specifies daily radiation for 5 days and surgery 4-16 weeks later. The recorded enrollment is 25.

The primary endpoint is the proportion of evaluable participants with residual tumor burden of 0-1 in the surgical specimen, assessed up to 2 years. The record specifies confidence intervals using the Duffy and Santner approach, but the primary endpoint result and its precision are not reported in the registry record.

Selected safety entries include serious adverse events, other adverse events, deaths, and two leading serious-event terms. The record lists 15 outcome measures, but numerical results for most listed outcomes are not reported. With no comparison group, the study design supports description of outcomes within the treated group, not a direct treatment comparison.