Proton Radiation Therapy for Invasive Breast Cancer Following Mastectomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Proton Radiation Therapy for Invasive Breast Cancer Following Mastectomy (NCT01340495), a na na study. The primary outcome is Number of Participants With Grade 3 or Higher Radiation Pneumonitis or Any Grade 4 Adverse Event.

2. Clinical Question

This question combines a specific pulmonary toxicity threshold with a broader severe-adverse-event criterion. A participant meeting either part of the endpoint would count toward the primary outcome. The endpoint is a safety and feasibility measure; it is not, by itself, a comparison of proton radiation with another radiation approach. The registry also lists secondary outcomes covering acute and late skin toxicity, radiation pneumonitis, cosmetic outcomes and satisfaction, breast reconstruction, cardiac effects, unplanned additional surgery, and progression-free survival. Values for those outcomes are not reported in the registry record.

3. Trial Design

The registry describes NCT01340495 as a completed pilot study of proton radiation therapy for invasive breast cancer following mastectomy. The recorded enrollment was 70, and the study status is completed. The registry lists a start date of 2011-06 and a primary completion date of 2017-04. The phase is listed as NA.

This was a single-group study. Allocation is listed as NA, and masking as none. The intervention arm is Proton Radiation, described as radiation therapy with a proton beam. The registry summary describes proton delivery using 3D conformal proton radiation or scanned beam/IMPT. No control arm is recorded, so outcomes cannot be read as a direct estimate of the difference between proton radiation and conventional radiation, another proton technique, or no radiation.

The study’s stated purpose was to assess feasibility based on the occurrence of the specified serious toxicity endpoint. Its registry description discusses the rationale that proton radiation may spare surrounding tissues, but that rationale is not itself evidence of a comparative treatment effect. The primary endpoint was assessed from the start of treatment until 3 months after treatment ended; the registry gives a median treatment duration of 6 weeks.

One participant withdrew before treatment began and was not included in the analysis population. The registry does not report the final analysis denominator for the primary outcome, the number who completed follow-up, or whether other participants had missing endpoint information. Those details matter when interpreting an event count, particularly for an endpoint assessed after treatment. The registry does not report a randomized design, a control group, or a masking procedure beyond listing masking as none.

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: One participant withdrew from the trial before the start of treatment and was not included in the analysis population.

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 Grade 3 or Higher Radiation Pneumonitis or Any Grade 4 Adverse Event, measured over From the start of treatment until 3 months after the end of treatment, median duration of treatment of 6 weeks.

The primary endpoint is the number of participants with grade 3 or higher radiation pneumonitis or any grade 4 adverse event. It is recorded as a count of participants. The observation window begins at treatment start and extends until 3 months after treatment ends; the registry reports a median treatment duration of 6 weeks.

The endpoint was chosen to address feasibility in terms of serious toxicity. It combines a threshold for radiation pneumonitis with a broad criterion for any grade 4 adverse event. The logical connection is “or”: a participant who meets either criterion would qualify. Counting participants rather than events focuses the measure on how many people experienced a qualifying outcome, rather than how many separate episodes occurred.

General statistical context: a binary endpoint distinguishes participants who meet its definition from those who do not. A count can describe the observed burden in the analysis population, but interpreting it also requires knowing the denominator and how completely the endpoint was assessed. For this trial, the primary endpoint’s outcome count and analysis denominator are not reported in the registry record. Consequently, the stated endpoint definition and timeframe can be described, but the primary result cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry records a binary clinical outcome as a count of participants: the primary measure is how many participants experienced either qualifying radiation pneumonitis or any grade 4 adverse event. The event definition is a composite. A composite combines multiple criteria into one endpoint; a participant qualifies if at least one criterion is met. In this case, the first criterion is grade 3 or higher radiation pneumonitis, and the second is any grade 4 adverse event. The endpoint title and description identify the event threshold and the assessment period.

General statistical context: for a binary outcome, each participant is classified according to whether the event definition was met. A count is interpretable alongside its denominator. A count without a denominator does not show how frequently the event occurred in the analysis population, while a denominator without complete outcome ascertainment may also be insufficient. The registry notes that one participant withdrew before treatment and was not included in the analysis population, but does not report the primary endpoint count or the complete analysis denominator. No primary endpoint proportion can therefore be read from the registry record.

General statistical context: a confidence interval expresses the uncertainty around an estimate under a statistical model. It is not a guarantee that the true value lies within the interval, and its width depends on the amount and pattern of information as well as the method used. No confidence interval for the primary endpoint is reported in the registry record. Nor does the record identify an interval method for that endpoint. It is therefore not possible to assess the endpoint’s precision from the available registry information.

The outcome window is important to the interpretation. The registry says assessment ran from the start of treatment until 3 months after the end of treatment and gives a median treatment duration of 6 weeks. Participants must be observed over the relevant period for the event count to reflect the endpoint as defined. Follow-up completeness, the handling of participants whose follow-up ended early, and the timing of any qualifying events are not reported in the registry record. These missing details cannot be filled in by assuming that all participants had complete follow-up.

General statistical context: over-dispersion is a concern when count data vary more than a chosen model expects. It can lead a model to understate uncertainty if the extra variability is ignored. The primary measure in this study is described as a count of participants meeting a binary event definition, not as a recurrent-event count or a rate model. The registry does not report a model for over-dispersion or a model-based analysis of the primary endpoint. There is no basis in the record to infer that such a model was used.

The design is single-group, with no control group and no randomized allocation. That means a count in the proton radiation group is a descriptive result for that group. General statistical context: comparative analyses need a defined contrast between groups, and interpretation depends on how those groups were formed and how relevant differences were handled. Since this registry record has no like-for-like control comparison, it cannot provide a randomized estimate of the effect of proton radiation relative to another approach. The registry does not report an adjusted comparative analysis.

The record lists zero analyses. This does not specify how investigators handled the primary endpoint or whether a statistical test was planned or conducted elsewhere. A statistical analysis plan, method for confidence intervals, interim analysis approach, and adjustment strategy are not reported in the registry record. It would be inappropriate to infer a particular model or testing procedure from the endpoint name or the fact that the study was completed.

A planning illustration based on an observed effect is distinct from an analysis of this trial’s results. The stated assumptions for that illustration are a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. The record says time-to-event illustrations use the total number of events, while other illustrations use participants per arm. These are planning assumptions, not the study’s recorded design: the trial itself is single-group, and its allocation is listed as NA. Any resulting arm-size figure is a planning quantity, not observed power and not evidence that the trial had that probability of detecting an effect. The registry does not report a sample-size justification for the trial itself.

General statistical context: power is a design property calculated under specified assumptions, not a measure of whether a study’s findings are true. Planning calculations depend on the assumed effect, variability or event frequency, analysis method, and target error rates. A planning illustration using an observed effect is especially different from a prospective justification because the observed effect is not independent of the data that produced it. The registry record does not state that the stated illustration assumptions were used to design or conduct this pilot study.

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("Proton Radiation")
n      <- c(69)
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  Proton Radiation  69  0  0.0  0.0  5.2  0.0  5.3  0.0  5.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine secondary outcome measures in addition to the primary endpoint. These cover acute skin toxicities, radiation pneumonitis, late skin toxicity, cosmetic outcome and satisfaction, breast reconstruction toxicity and additional surgery, early cardiac effects, and progression-free survival. The record does not report numerical results for these secondary measures.

When a study evaluates multiple outcomes, there can be multiple opportunities to observe an apparently notable result. General statistical context: a multiplicity strategy specifies how the interpretation or testing of several outcomes is handled, for example by identifying a primary outcome or adjusting inference across tests. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or adjustment procedures. It also does not report interim analyses or stopping rules. No particular approach should be assumed.

The analysis population description notes that one participant withdrew before treatment began and was not included in the analysis population. The record does not give the primary endpoint analysis denominator, identify whether participants were analyzed under any other population definition, or state how missing outcome data were handled. It does not report imputation, sensitivity analyses, or follow-up completeness. The documented withdrawal is not enough to determine whether there were other missing data after treatment began.

General statistical context: missing outcomes can affect both the estimated event frequency and its uncertainty, depending on why the information is missing and how missing participants differ from those assessed. A complete-case result, an imputed result, and a sensitivity analysis can answer different questions. Since the analysis methods and outcome completeness are not reported in the registry record, these possibilities cannot be distinguished. The primary endpoint result itself is also not reported, so the consequences of any missing data cannot be evaluated from the registry information.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: surgical and medical procedures - other, specify (18.6%), musculoskeletal and connective tissue disorders - other, specify (10.0%), dermatitis radiation (2.9%), fibrosis deep connective tissue (1.4%), seroma (1.4%).

The registry’s serious-adverse-event summary for Proton Radiation lists 20 affected participants among 70 at risk. The other-event summary lists 70 affected among 70 at risk, and the deaths field is 0. These are the group-level figures recorded in the adverse-event summary; they should not be mistaken for the primary endpoint result.

The registry also lists serious-event terms with reported percentages: Surgical and medical procedures - Other, specify, 18.6%; Musculoskeletal and connective tissue disorders - Other, specify, 10.0%; Dermatitis radiation, 2.9%; Fibrosis deep connective tissue, 1.4%; Seroma, 1.4%; and Skin infection, 1.4%. These entries are terms and percentages, not a complete account of each participant’s clinical course. The record does not explain the overlap between terms, give the underlying participant counts for each term, or state whether each term was judged related to proton radiation.

General statistical context: adverse-event summaries describe what was recorded, not necessarily what was caused by an intervention. The serious-event summary also does not identify how many participants met the primary composite endpoint, which has its own definition and observation window. The registry does not report the primary endpoint count or its analysis denominator, so the serious-event figures cannot substitute for that missing result. These summaries should be read as descriptive safety entries, not as a controlled comparison.

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

The registry record establishes that a completed pilot study evaluated proton radiation after mastectomy for invasive breast cancer. It specifies a primary feasibility endpoint based on grade 3 or higher radiation pneumonitis or any grade 4 adverse event, observed from treatment start through 3 months after treatment ended. It also records one participant who withdrew before treatment and was excluded from the analysis population, along with group-level adverse-event summaries.

What the record does not establish is the number of participants who met the primary endpoint. The result and denominator for that outcome are not reported in the registry record. Consequently, the primary endpoint’s observed frequency and precision cannot be assessed from these registry entries. The listed serious-adverse-event figures provide a separate safety summary, but they do not supply the missing primary outcome count.

The single-group design also limits what can be concluded. An observed event count in one group does not show how that count would compare with another radiation approach or with a different treatment strategy. There is no randomized comparator in the registry record, so the study cannot establish a comparative effect. The registry’s description of the rationale for proton radiation is not a substitute for comparative outcome evidence.

General statistical context: a feasibility endpoint can indicate whether a treatment approach was evaluated against a prespecified safety-related criterion, but interpretation requires the actual outcome, denominator, and analysis method. Those details are not reported for the primary endpoint. The study’s completion status does not by itself imply that the endpoint was met, nor does it show that every planned outcome was analyzed or reported.

The appropriate reading is therefore bounded: the record describes the trial’s design, intervention, event definitions, follow-up window, and some adverse-event summaries, while leaving the primary endpoint result and secondary outcome values unreported. It does not establish that proton radiation works or does not work, and it does not support a claim that it is safer or less safe than another treatment.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary question is framed as a participant-level safety and feasibility endpoint, yet the registry record does not report the count needed to answer that question. The endpoint definition is specific, and its assessment window is stated, but without the outcome count and analysis denominator neither the observed frequency nor its precision can be evaluated. A clear endpoint definition is necessary for interpretation; it is not sufficient without a result.

The study also illustrates the distinction between a single-group description and a comparative treatment estimate. The registry identifies one proton radiation group and no control group. A single-group result can describe recorded outcomes among that group, but it cannot isolate how outcomes would differ under another approach. That distinction remains important even when a treatment has a plausible rationale or when the registry includes several safety measures.

The adverse-event summary and primary endpoint should not be conflated. The serious-event group summary reports 20 affected participants among 70 at risk, while the primary endpoint concerns a defined combination of event criteria and has no reported result. Those are not interchangeable measures. The record also shows why event labels, denominators, and assessment windows need to be read together rather than treating all safety summaries as the same outcome.

Finally, planning calculations are not observed trial performance. The stated sample-size illustration uses assumptions that include equal allocation between two hypothetical arms, while the actual study is recorded as single-group. Such calculations can illustrate the scale of a hypothetical design under assumptions, but they do not demonstrate that this pilot was designed with those assumptions or had a particular observed power. These distinctions help keep descriptive evidence, comparative inference, and planning mathematics separate.

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 main trial-specific limitation in interpreting the primary question is that the registry record does not report the primary endpoint result. It also does not give the endpoint analysis denominator, despite noting that one participant withdrew before treatment began and was excluded from the analysis population. The registry therefore does not allow calculation or assessment of the primary event frequency or its precision.

The single-group design has no recorded control arm, and allocation is listed as NA. As a result, outcomes cannot be compared with a concurrent control under randomization. The record also lists masking as none. It does not provide details of how outcome assessment was conducted or whether assessors were independent, so no further statement about ascertainment procedures can be made.

Follow-up is described as extending until 3 months after treatment ended, with a median treatment duration of 6 weeks. The record does not report individual follow-up completeness, the number of participants assessed at each time point, or the handling of participants with incomplete observation. The primary endpoint’s outcome count is absent, and the listed secondary outcomes do not have reported result values.

The registry lists adverse-event summaries, but does not report how event terms overlap, whether the listed terms were attributed to treatment, or the details of event ascertainment. It also does not report a statistical analysis plan, a sample-size justification for the trial, missing-data methods, interim analyses, or a multiplicity strategy. Those omissions prevent a more detailed assessment of the analysis approach and its safeguards against uncertainty or selective emphasis.

These limitations are specific to what is recorded for this study. They do not show that the underlying trial lacked procedures or analyses; they mean that those details are not reported in the registry record. The design and reporting information available is insufficient to draw a comparative conclusion or to quantify the primary feasibility endpoint.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Proton Radiation Therapy for Invasive Breast Cancer Following Mastectomy — NCT01340495.
• Registry record last updated 2026-07-20; status last verified 2026-06.
• Results first posted 2018-04-20.
• 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

NCT01340495 is recorded as a completed pilot study of proton radiation therapy for invasive breast cancer following mastectomy. The registry lists enrollment of 70, a start date of 2011-06, and a primary completion date of 2017-04. The phase is NA. The study used a single-group design, with allocation listed as NA and masking as none.

The primary endpoint was the number of participants with grade 3 or higher radiation pneumonitis or any grade 4 adverse event during the period from treatment start until 3 months after treatment ended. Median treatment duration was 6 weeks. One participant withdrew before treatment and was not included in the analysis population.

The primary endpoint result and values for the listed secondary outcomes are not reported in the registry record. The adverse-event summary lists 20 serious-event participants among 70 at risk, 70 other-event participants among 70 at risk, and 0 deaths. With no control group and no reported primary result, the record supports a description of the trial and its recorded safety summaries but not a comparative treatment conclusion.