Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer (NCT03345420), a na phase 2 study. The primary outcome is Percentages of Participants by EORTC Breast Cosmetic Rating Score at 24 Months Post-radiation Therapy.

2. Clinical Question

In clinical terms, the study was designed to describe cosmetic ratings after the specified radiotherapy course. It also listed secondary outcomes covering quality of life, radiation complications, recurrence, and cost-effectiveness. These are outcomes of interest, not evidence of treatment effects by themselves. The registry record does not report results for those secondary outcomes. Without reported outcome values or a comparison group, the record cannot establish how the observed ratings compare with ratings under another treatment schedule.

3. Trial Design

This was a phase II trial sponsored by the University of Utah. It used a single-group model with no masking and no randomized allocation. The registry record lists 102 enrolled participants and marks the study as completed. It gives a start date of 2017-12-12 and a primary completion date of 2022-08-30. The record does not describe a parallel control arm; therefore, the treatment group cannot be contrasted with a randomized concurrent group in this study.

Participants underwent hypofractionated radiation therapy after breast-conserving surgery. The treatment description specifies 9 fractions over 2 weeks, beginning within 12 weeks after surgery. The registry summary frames the study around early-stage breast cancer, with conditions spanning stage 0 through stage IIB and both in-situ and invasive breast carcinoma. More detailed eligibility criteria, such as restrictions on age or other clinical characteristics, are not reported in the registry record.

The primary outcome was a participant count by EORTC Breast Cosmetic Rating score at up to 24 months after radiotherapy. Images were assessed by three reviewers, described as unbiased, including a radiation oncologist, surgeon, and nurse. The primary endpoint description states that images from 78 participants were available and of sufficient quality for review. The reasons images from other enrolled participants were unavailable or unsuitable are not reported in the registry record.

The record lists six outcome measures and no analysis entries. It names secondary outcomes for Breast-Q quality-of-life scores at 6 months and 24 months after radiotherapy, acute and late radiation complications assessed with CTCAE 4.0, local and local-regional recurrence, and cost-effectiveness relative to standard fractionation. The results for these outcomes are not reported in the registry record. The protocol’s analysis methods, including any prespecified handling of missing observations or adjustment for covariates, are 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: Of 102 total enrolled participants, images from 78 participants at this timepoint were available and of sufficient quality to be reviewed and scored by the 3 unbiased reviewers.

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 Percentages of Participants by EORTC Breast Cosmetic Rating Score at 24 Months Post-radiation Therapy, measured over Up to 24 months post radiation therapy (RT).

The primary endpoint is the count of participants in each EORTC Breast Cosmetic Rating category at 24 months after radiotherapy. The rating uses digital photographs to compare the treated breast with the untreated breast. Reviewers assess features including breast size and shape, areola or nipple location, surgical-scar appearance, skin pigmentation, telangiectasia, and an overall cosmetic rating. The four-point scale runs from 0, excellent or no difference, through 1, good or small difference, and 2, fair or moderate difference, to 3, poor or large difference.

This endpoint offers a structured way to describe cosmetic appearance rather than relying only on an unstructured impression. The photographic method and review by three people from different clinical professions are intended to provide an assessment based on visible features. The registry description says the method is blinded, but does not specify the blinding procedures or how reviewers’ assessments were combined into participant-level categories.

The endpoint is a count, not a continuous measurement such as a mean score. Counts can show how many reviewed participants fell into each category, but need a clear denominator and do not by themselves explain why a rating occurred. The registry record reports that 78 participants’ images were suitable for review, but does not report the rating counts. It also does not report confidence intervals or other estimates of uncertainty for those counts. Thus, the endpoint is defined, while its observed distribution and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is expressed as counts of participants in cosmetic-rating categories. A count answers how many participants were assigned to a category; it is not an average rating and does not describe the distance between categories. The four levels are ordered from excellent or no difference to poor or large difference. That ordering is clinically interpretable, but a count in one category does not show the specific feature that influenced a reviewer’s overall assessment.

What does the photographic rating capture?

The EORTC Breast Cosmetic Rating method compares the radiated breast with the contralateral untreated breast using digital photographs. The described features include size, shape, areola or nipple location, surgical scar, pigmentation, telangiectasia, and a global cosmetic score. A structured scale can make assessments more consistent than an informal description, while still requiring judgment by reviewers. The registry describes the method as blinded and says three reviewers assessed images, but does not report details of the blinding process, reviewer agreement, or how individual assessments were combined.

In general, agreement among reviewers matters when an endpoint involves visual judgment. If reviewers assign different categories to the same images, the reported count may depend on the method used to reconcile or combine their ratings. The registry record does not report an agreement statistic or a reconciliation procedure. This does not show that reviewer disagreement occurred; it means the record does not provide information to evaluate it.

Why does the denominator matter?

The endpoint description states that images from 78 participants were available and of sufficient quality for review, out of 102 enrolled participants. The rating counts, if reported, would need to be read in relation to the participants actually assessed. In general, an endpoint estimate based on participants with available images can be biased if image availability is related to outcome or participant characteristics. The registry record does not report reasons for unavailable or unsuitable images, a comparison of assessed and unassessed participants, or an imputation method. Therefore, the direction or size of any potential bias cannot be determined from this information.

General statistical practice distinguishes missing outcome data from an outcome that was assessed and rated. An unavailable image is not evidence of a particular cosmetic category. Assigning a category to participants without a valid image would require a stated method and assumptions. No such method is reported in the registry record. A count among reviewed images should therefore not be assumed to represent every enrolled participant.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with an estimate under a statistical model and its assumptions. It helps show how much uncertainty surrounds an estimate; it does not guarantee that the true value lies in the interval. For participant counts or proportions, uncertainty depends in part on the number assessed and the observed distribution across categories. No confidence intervals for the primary endpoint are reported in the registry record. No numerical uncertainty estimate can therefore be interpreted from the posted results.

Counts are also distinct from comparisons. In a single-group study, a category count describes the observed group. A treatment contrast would require a comparator and an appropriate analysis. This study has no randomized comparator, so its design does not estimate a randomized difference between the nine-fraction schedule and another schedule. Even a precise description of outcomes in the treated group would not by itself establish the outcome that would have occurred for those same participants under a different treatment.

What do the planning assumptions mean?

The record includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. These are assumptions for planning illustrations, not evidence that the trial used a two-arm design. The study itself is listed as single-group, and the record does not report a trial-specific sample-size justification or statistical analysis plan. The observed effect used for the planning illustration is not reported in the registry record, and no illustration values are reported in the registry record.

In general, a sample-size calculation asks how many participants would be needed under specified assumptions to detect a target effect at a chosen significance level and power. A planning illustration is conditional on its assumptions; it is not a description of the number of events or outcomes actually observed. It is also not “observed power,” which is not a substitute for reporting an estimate and its uncertainty. Because the registry record does not report the calculated planning values or the primary outcome counts, no conclusion about achieved precision or power can be drawn.

What can the event counts establish?

For adverse events, a count is the number of participants recorded with an event in the specified group. Such counts need context about definitions, observation windows, severity, and attribution. The registry reports 4 participants with serious adverse events among 102 at risk, and 102 participants with other adverse events among 102 at risk. It reports no deaths. The record does not provide enough detail in this summary to infer that events were caused by treatment or to characterize the clinical importance of every event. The serious-event term percentages are reported as registry values and should not be added or treated as mutually exclusive categories without further information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary cosmetic-rating outcome and secondary outcomes for quality of life, radiation complications, recurrence, and cost-effectiveness. The record does not report an analysis plan identifying which outcomes or timepoints were primary for statistical testing beyond the named primary outcome. It also does not report whether adjustments for multiple comparisons were planned. When many outcomes or timepoints are examined, the chance of at least one apparently notable result can increase; in general, a prespecified analysis plan helps readers understand how such findings should be interpreted. The record does not provide enough information to assess multiplicity handling.

The registry record lists no analysis entries. Results for the primary endpoint and the named secondary outcomes are not reported in the registry record. Therefore, there are no reported hypothesis tests, effect estimates, or confidence intervals to assess, and no basis for identifying which outcomes were statistically emphasized.

For the primary endpoint, images from 78 participants were available and sufficiently clear for review, while total enrollment was 102. The record does not report why other participants lacked suitable images, how missing endpoint information was handled, or whether the assessed group differed from those without reviewed images. It does not report imputation, sensitivity analyses, or an analysis population definition beyond the endpoint’s description of available images. These omissions prevent assessment of how missing outcome information may affect the endpoint’s representativeness.

The registry record also does not report whether participants were analyzed according to a prespecified population, whether all enrolled participants completed the treatment course, or how deviations from the treatment schedule were handled. Those details are not reported in the registry record. Without them, analysis populations and missing-data assumptions cannot be reconstructed from the posted information.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: breast infection (2.0%), enterocolitis (1.0%), dysphasia (1.0%), myasthenia gravis (1.0%), hypoalbuminemia (1.0%).

The registry lists 102 participants at risk for serious adverse events and reports that 4 were affected; it lists 102 at risk for other adverse events and reports that 102 were affected. It also reports 0 deaths. These figures describe participant counts in the treatment group, not event rates compared with another arm. Because the study is single-group, there is no randomized safety comparison in this record.

The listed serious adverse-event terms include Breast infection at 2.0%, and Enterocolitis, Dysphasia, Myasthenia Gravis, Hypoalbuminemia, and Generalized muscle weakness at 1.0% each. These are reported term percentages. The record does not explain whether terms overlap within participants, whether they represent all serious events, or how event attribution was assessed. They should not be summed to produce a total.

In general, adverse-event counts do not establish causation. An event occurring during a study is not necessarily caused by its intervention, and interpretation depends on definitions, follow-up, severity, and clinical context. The registry summary does not report detailed event timing, duration, individual severity, or attribution. The “other” adverse-event count should not be assumed to mean a particular severity category because that definition is not reported in the registry record. These figures describe what the record lists, but do not establish a comparative safety profile.

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

The record documents a phase II, single-group investigation of hypofractionated radiation therapy in participants with stage 0-IIB breast cancer. Its treatment description specifies 9 fractions over 2 weeks within 12 weeks after breast-conserving surgery. The primary endpoint is a structured photographic assessment of breast cosmesis at 24 months, with ratings assigned across four ordered categories. Images from 78 participants were considered suitable for review by three reviewers.

Those design and endpoint details explain what the investigators intended to assess, but they do not show the resulting cosmetic-rating distribution. The registry record does not report counts by rating category, confidence intervals, or analyses of the primary endpoint. It therefore does not establish the observed level of cosmetic outcomes or their statistical precision. Completion status and enrollment alone cannot be used as substitutes for outcome results.

The study also cannot establish a randomized treatment difference. It has no concurrent control group, so outcomes among its participants cannot be directly contrasted with outcomes under standard fractionation within the trial. The record names cost-effectiveness relative to standard fractionation as a secondary outcome, but does not report that analysis. The other named secondary outcomes likewise have no results reported in the registry record.

The safety summary records serious and other adverse events in the treatment group and reports no deaths. These counts are descriptive. They do not by themselves show whether an event was caused by radiotherapy, whether the event burden differs from another treatment, or how results would compare in a different population. The brief summary’s general rationale for hypofractionation should not be mistaken for a result from this study.

In general, clinical interpretation depends on outcome estimates, uncertainty, missing-data information, and the design’s ability to support comparisons. Here, the registry entry establishes the planned treatment and outcome framework and gives limited enrollment and safety information. It does not provide the primary or secondary efficacy results needed to assess the observed outcomes. No conclusion that the treatment works or does not work follows from the information reported.

13. Why This Trial Matters Statistically

This trial raises several statistical issues that are common in clinical research. First, its primary outcome is based on photographic judgments. A defined rating system and several reviewers provide a structured approach, while the result can still depend on reviewer assessment and on how multiple ratings are combined. The registry describes the scale and reviewers, but does not report agreement or aggregation methods. Those details are useful for judging reproducibility.

Second, the endpoint applies to participants with images suitable for review. The record reports 78 such participants out of 102 enrolled. This highlights why analysis denominators and missing outcome information matter: an outcome among assessed participants may not describe all enrolled participants if the two groups differ. The registry record does not explain image availability or report an analysis of participants without reviewed images.

Third, the single-group design places a limit on causal interpretation. It can describe outcomes in the treated group, but cannot produce a randomized comparison against another fractionation schedule. A treatment effect is a contrast, and the record does not contain a concurrent comparison group or a reported comparative analysis.

Finally, the registry lists multiple clinical outcome areas, but does not report their analyses or outcome values. Clearly reporting prespecified outcomes, estimates, uncertainty, analysis populations, and missing-data handling is important for distinguishing a defined research question from an answer supported by data. In this record, the endpoint definition and design are clear enough to explain what was to be assessed, but the absence of outcome results prevents statistical evaluation of the primary question.

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 central limitation of the registry record for interpreting this trial is that it defines the primary endpoint without reporting the rating counts. The record therefore cannot show the observed cosmetic outcome distribution or its precision. It also lists no analysis entries, and results for the named secondary outcomes are not reported in the registry record.

The primary assessment relied on images available and sufficiently clear for review from 78 participants, rather than all 102 enrolled participants. The registry does not report the reasons for unavailable or unsuitable images, whether the reviewed participants differed from others, or how missing endpoint data were handled. The extent and direction of any resulting selection bias cannot be determined from the record.

The study is single-group and non-randomized, so it has no concurrent control arm for estimating a treatment contrast. The record does not report a trial-specific sample-size justification, a detailed statistical analysis plan, or methods for addressing multiplicity. It also does not report how the three reviewers’ judgments were combined or any measure of their agreement. These details are not reported in the registry record and should not be inferred.

The adverse-event summary is limited to participant counts, selected serious-event terms, and deaths. It does not provide detailed timing, attribution, or individual event descriptions. The registry record therefore cannot establish which events were caused by treatment or support comparison with another treatment group. These limitations concern what can be concluded from the posted record; they do not establish that the unreported analyses or details were absent from other study materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer — NCT03345420.
• Registry record last updated 2025-12-30; status last verified 2025-12.
• Results first posted 2024-02-06.
• 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.

18. Record Summary

NCT03345420 is a completed phase II, single-group study sponsored by the University of Utah. It enrolled 102 participants with stage 0-IIB breast cancer and evaluated hypofractionated radiation therapy delivered as 9 fractions over 2 weeks within 12 weeks after breast-conserving surgery. The primary endpoint was participant counts by EORTC Breast Cosmetic Rating category at 24 months after radiotherapy. Images from 78 participants were available and suitable for review by three reviewers.

The registry record lists six outcome measures and no analysis entries. It does not report the primary rating counts or results for the named secondary outcomes. The safety summary reports 4 participants with serious adverse events, 102 with other adverse events, and 0 deaths. Because the study has no randomized comparator and the outcome analyses are not reported, the record describes the design and selected counts but does not establish comparative treatment effects.