Hypofractionated Radiation Therapy or Standard Radiation Therapy in Treating Patients With Ductal Breast Carcinoma In Situ or Early Invasive Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hypofractionated Radiation Therapy or Standard Radiation Therapy in Treating Patients With Ductal Breast Carcinoma In Situ or Early Invasive Breast Cancer (NCT01266642), a randomized phase 2 study. The primary outcome is Number of Participants With Scores of Either <2.5 or >=2.5 on the Breast Cancer Treatment Outcome Scale (BCTOS) Cosmesis.

2. Clinical Question

This is a question about a patient-relevant cosmetic outcome following two schedules of whole-breast irradiation. The schedules differ in the approximate duration specified in the arm descriptions. The registry record also lists panel physicians rated cosmesis as a secondary outcome, but it does not report its results.

In general, a randomized comparison is intended to assess outcomes across the groups as assigned, rather than to compare participants selected after treatment. The registry record identifies the primary endpoint population as intent to treat, but does not report how many participants contributed endpoint data, how missing scores were handled, or whether any additional population was analyzed.

3. Trial Design

The registry describes a randomized, parallel-group phase II trial with no masking. Its title identifies a comparison of hypofractionated whole-breast irradiation (HF-WBI) and conventionally fractionated whole-breast irradiation (CF-WBI) among patients with ductal carcinoma in situ or early invasive breast cancer. Enrollment is listed as 301. The sponsor is M.D. Anderson Cancer Center.

The HF-WBI arm description specifies external-beam radiation therapy 5 days a week for approximately 3 weeks. The CF-WBI arm description specifies external-beam radiation therapy 5 days a week for approximately 5 weeks. The record lists external-beam radiation therapy and whole-breast irradiation among the interventions, as well as laboratory biomarker analysis, quality-of-life assessment, and questionnaire administration. The record does not describe how assignment was generated or concealed, or whether allocation was stratified.

The listed study start is 2011-02-08, and the listed primary completion date is 2020-11-30. The current status is active, not recruiting. That status and the listed completion date do not, by themselves, establish that all follow-up or analyses are complete. The phase II designation and the randomized design describe the trial, but the registry record does not provide a protocol-level account of its statistical plan.

The primary endpoint is the number of participants in the intent-to-treat population with BCTOS cosmesis scores in the stated categories, assessed 3 years after completing radiation therapy. The record identifies 2 outcome measures and lists panel physicians rated cosmesis as a secondary outcome. It does not give a group comparison, an effect estimate, a confidence interval, or a p-value for the primary endpoint. The registry record therefore describes the design and intended assessment, but not the comparative endpoint result.

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: Of the 301 participants enrolled, 287 were fully eligible and were randomized to protocol, 13 were excluded (8) Insurance would not cover protocol therapy, (4) withdrew consent and (1) became ineligible due to finding of other primary cancer on simulation CT. 1 participant was registered twice.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat population (all participants assigned to CF-WBI or HF-WBI).

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 Number of Participants With Scores of Either <2.5 or >=2.5 on the Breast Cancer Treatment Outcome Scale (BCTOS) Cosmesis, measured over 3 years after completing radiation therapy.

The primary endpoint concerns the number of participants with BCTOS cosmesis scores in the categories identified in the endpoint title: scores <2.5 or scores >=2.5. The endpoint description states that the scale ranges from 1 to 4 and that scores of 2.5 or more indicate adverse cosmetic outcomes. The assessment timeframe is 3 years after completing radiation therapy, and the stated population is all participants assigned to CF-WBI or HF-WBI.

Cosmesis is a measure of appearance-related outcome, distinct from tumor control or survival. In general, such an endpoint can describe how participants assess or are assessed on an outcome that matters beyond the treatment schedule itself. The registry also lists panel physicians rated cosmesis as a secondary outcome, but does not explain how that assessment relates to the participant score or provide its results.

The record gives no counts by score category or arm, and no statistical comparison. It is therefore not possible to describe the observed distribution, the size or direction of a group difference, or its precision. The record does not report how scores were treated if they were unavailable at the assessment time.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry record supports a limited description of the intended comparison. The trial is randomized, has a parallel-group model, and is unmasked. It is identified as phase II. The record does not report the allocation sequence method, allocation concealment, or a detailed statistical analysis plan. Those omissions matter because a design label does not specify how every aspect of conduct or analysis was implemented.

What does randomization contribute?

In general, randomization assigns participants to groups using a chance-based process. If implemented as intended, it can reduce systematic differences between groups at assignment, including differences that are not measured. It does not guarantee that groups are identical, and it does not remove the need to report participant flow, outcome completeness, and analysis methods. The registry record identifies the trial as randomized but does not give enough detail to evaluate the assignment process.

The parallel-group model means the record describes participants assigned to one of the two schedules: HF-WBI or CF-WBI. The arm descriptions specify external-beam radiation therapy 5 days a week for approximately 3 weeks or approximately 5 weeks, respectively. The record states that masking was none. It does not describe whether outcome assessors were masked separately from participants or clinical staff.

How should the primary endpoint be read?

The stated primary outcome is a count of participants with BCTOS cosmesis scores in the categories identified in the title. The description says scores range from 1 to 4 and scores of 2.5 or more indicate adverse cosmetic outcomes. The timeframe is 3 years after completing radiation therapy. The stated population is intent to treat: all participants assigned to either group. This identifies the intended population and assessment, but does not specify the statistical test, effect measure, or handling of missing scores.

For a binary endpoint, a common analysis compares the proportion of participants meeting the event definition in each group. In general, an effect estimate describes the contrast, while a confidence interval indicates the precision of that estimate under the model used. Other approaches can adjust for prespecified covariates or account for design features, but whether any such approach was planned or used is not reported in the registry record. No primary endpoint counts or analysis results are posted, so no method can be matched to an observed result.

What does the record say about planning?

The record describes sample-size calculations as planning illustrations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are prospective planning tools: they ask what sample size might be needed under specified assumptions. They are not observed power, and they do not establish the trial’s actual design rationale. The record does not report the trial’s own sample-size justification, nor does it identify the effect estimate used for the planning illustration in the information.

In general, a sample-size calculation depends on assumptions about the outcome, the target effect, variability or event frequency, significance level, and desired power. If those assumptions differ from the observed data or the analysis ultimately used, the calculation may not describe the precision achieved. The registry record lists enrollment as 301, but without endpoint results and complete analysis details that enrollment count cannot establish the precision of the cosmesis comparison.

What can be inferred from the posted analyses?

The record lists 0 analyses. That means no statistical analysis result is available in the registry record for interpretation. It does not establish whether analyses were conducted elsewhere, nor does it establish the reasons results are absent. The record also lists 2 outcome measures, but the available information does not provide a full results set for those outcomes.

General statistical interpretation should separate an estimate, its uncertainty, and the assumptions that produced it. An estimate alone does not establish clinical importance; a p-value alone does not describe magnitude or precision. For a count-based binary endpoint, it is also important to know the event definition, the denominator, and how missing outcomes were handled. These items are not fully reported for the primary endpoint. There is therefore no basis to reconstruct or recalculate its comparison.

The record’s adverse-event entries should not be treated as an analysis of the primary endpoint. They provide counts for serious events, deaths, and other adverse events, but not a comparative model or detailed event descriptions. In general, adverse-event counts need context about ascertainment, follow-up, seriousness criteria, and attribution before they can be interpreted as evidence about differences between groups.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies the BCTOS cosmesis outcome as primary and panel physicians rated cosmesis as secondary. It reports 2 outcome measures, but does not describe a strategy for controlling multiplicity, such as designating a hierarchy among outcomes or adjusting statistical thresholds when making multiple comparisons. Whether such a strategy was specified elsewhere is not reported in the registry record.

Multiplicity matters in general when several outcomes, time points, or comparisons are examined. The more statistical questions considered, the greater the chance that some findings may appear noteworthy by chance alone if no suitable approach is used. This general concern cannot be quantified for this trial from the registry record, which lists 0 analyses and gives no endpoint p-values or result estimates.

The primary population is described as intent to treat, including all participants assigned to CF-WBI or HF-WBI. The record does not state how many participants had BCTOS scores available at 3 years after completing radiation therapy, how many were missing, or how missing scores were handled. It also does not report whether participants were analyzed according to assigned group regardless of treatment received, although that is the usual meaning of an intent-to-treat analysis in general. The record’s population label alone does not establish which procedures were applied.

Missing outcome data can affect both the estimate and its precision, particularly when availability differs between groups or relates to the outcome. In general, an analysis should make clear which participants contribute data and what assumptions are made about missing values. Those details, along with any sensitivity analyses, are not reported in the registry record. The completeness and robustness of the primary endpoint analysis therefore cannot be assessed.

11. 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 non-serious adverse event terms

The registry lists serious adverse-event entries separately for CF-WBI and HF-WBI. For CF-WBI, 149 participants are listed at risk and 0 are listed as affected by a serious event; deaths are listed as 0. For HF-WBI, 138 participants are listed at risk and 0 are listed as affected by a serious event; deaths are listed as 1. These are posted counts, not a causal assessment or a statistical comparison.

For other adverse events, the record lists 149 at risk and 149 affected in CF-WBI, and 138 at risk and 138 affected in HF-WBI. The label “other” does not identify the individual events or explain their severity, duration, or relationship to treatment. The record does not report the event definitions, ascertainment method, follow-up window, or attribution criteria needed to interpret these entries in detail.

In general, adverse-event counts are most informative when their definitions and observation periods are clear and when the analysis accounts for exposure and follow-up. A count of affected participants does not by itself establish that an event was caused by treatment. The registry entries should therefore be read as descriptive record fields, not as evidence that the schedules differ in safety.

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

The registry record documents a randomized phase II comparison of HF-WBI and CF-WBI for ductal carcinoma in situ and early invasive breast cancer. It identifies a primary cosmesis endpoint based on BCTOS scores, assessed 3 years after completing radiation therapy, and defines scores of 2.5 or more as adverse cosmetic outcomes. It also identifies the intent-to-treat population and lists panel physicians rated cosmesis as a secondary outcome.

Those design details explain what the trial was intended to compare. They do not establish what the comparison found. The record lists 0 analyses and does not post primary endpoint counts, a group effect estimate, a confidence interval, or a p-value. As a result, the direction, size, and precision of any difference in cosmesis are not reported in the registry record. Nor can the record show whether the observed data, if analyzed, would be compatible with a range of possible effects.

In general, an absence of a posted result is not evidence that the groups had the same outcomes. Conversely, a trial’s randomization and planned endpoint do not establish that one schedule produced a better outcome. Conclusions about equivalence or non-inferiority would require appropriate prespecified margins and analyses; those are not reported in the registry record.

The adverse-event fields also require restraint. Their counts describe what the registry records, but do not provide the details needed to assess event types, timing, attribution, or comparative risk. The listed enrollment cannot replace outcome denominators or missing-data information for the primary endpoint. The record supports a description of the question and design, not a conclusion about treatment effects or clinical choices.

13. Why This Trial Matters Statistically

This trial is statistically notable as a randomized comparison of two whole-breast irradiation schedules with different treatment durations specified in the arm descriptions. Its primary outcome is not simply a count of any event: it is based on a cosmesis score, with a stated threshold for identifying adverse cosmetic outcomes. That makes clarity about the score definition, follow-up, and denominator important for interpreting a group comparison.

The record also illustrates the distinction between an outcome being registered and an outcome having an interpretable result. It describes the endpoint, its timeframe, and the intent-to-treat population, but lists no analyses. Without group counts and uncertainty estimates, readers cannot judge either the magnitude or precision of a comparative effect. In general, this distinction prevents a planned question from being mistaken for an answered question.

The listed secondary outcome of panel physicians rated cosmesis raises a further general statistical issue: different assessment methods can provide related but not identical information. To interpret them together, readers would need the measurement details, analysis plan, and results. These details are not reported in the registry record.

Finally, the adverse-event fields emphasize why event definitions and context matter. Counts without details about event types, observation, or attribution should not be treated as comparative evidence. The record is useful for locating the trial’s design and intended outcome, while its lack of posted analyses limits what can be learned from the registered results.

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 this trial from the registry record is the absence of posted analyses. No primary endpoint counts, between-group estimate, confidence interval, or p-value are reported. The record therefore does not support an assessment of the observed cosmesis outcome or its statistical precision.

The endpoint description identifies BCTOS score categories and the assessment timeframe, but the record does not explain the statistical method, report group-specific denominators at follow-up, or state how missing scores were handled. Although the stated population is intent to treat, the record does not provide participant flow or explain implementation of that analysis population.

Design information is also limited. The trial is identified as randomized and unmasked, but the randomization sequence, concealment procedures, and any stratification are not reported in the registry record. The record does not say whether outcome assessment was masked independently of the overall masking designation. It also does not report a multiplicity plan or a detailed sample-size justification.

The safety entries lack supporting detail on event definitions, event types, timing, attribution, and ascertainment. The status is active, not recruiting, while a primary completion date is listed; the registry information does not resolve the completeness of follow-up or analyses. These limitations restrict interpretation to the trial’s registered design, endpoint definitions, and descriptive safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Hypofractionated Radiation Therapy or Standard Radiation Therapy in Treating Patients With Ductal Breast Carcinoma In Situ or Early Invasive Breast Cancer — NCT01266642.
• Registry record last updated 2026-08-17; status last verified 2026-08.
• Results first posted 2021-11-19.
• 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

NCT01266642 is a randomized, parallel-group, unmasked phase II trial sponsored by M.D. Anderson Cancer Center. It compares HF-WBI, described as external-beam radiation therapy 5 days a week for approximately 3 weeks, with CF-WBI, described as external-beam radiation therapy 5 days a week for approximately 5 weeks. Listed enrollment is 301, and the status is active, not recruiting.

The primary endpoint is the number of participants in the intent-to-treat population with BCTOS cosmesis scores in the stated categories, assessed 3 years after completing radiation therapy. The record lists panel physicians rated cosmesis as a secondary outcome. It lists 0 analyses, so comparative results for the primary endpoint are not reported in the registry record. The serious and other adverse-event entries are descriptive counts without the context needed for a detailed comparison.