Proton Therapy for Early Stage Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Proton Therapy for Early Stage Breast Cancer (NCT00614172), a na na study. The primary outcome is Ipsilateral Breast Tumor Recurrence-free Survival.

2. Clinical Question

3. Trial Design

This is a completed, single-group trial of proton radiotherapy for early-stage breast cancer following lumpectomy. The registry lists the study title as Proton Therapy for Early Stage Breast Cancer and the official title as Phase II Trial of Lumpectomy and Partial Breast Proton Therapy for Early Stage Breast Cancer. Although the official title includes Phase II, the registry’s phase field is listed as NA. The sponsor is Loma Linda University.

The registry lists enrollment as 50. It describes one intervention, proton radiation therapy, and one arm, Proton Radiotherapy. The arm description states that participants received a two week course of proton radiotherapy to the breast. Masking is listed as NONE, and allocation is listed as NA. The record therefore does not describe a randomized comparison or a like-for-like control group.

The study start is recorded as 2004-02, primary completion as 2020-05-12, and status as COMPLETED. The primary endpoint concerns ipsilateral breast tumor recurrence-free survival. Overall Survival is listed as a secondary outcome. The record names two outcome measures but lists zero analyses. It does not report the primary endpoint estimate, its confidence interval, an overall survival result, or an analysis population.

Without a concurrent comparator, the study can describe outcomes recorded among participants in the proton radiotherapy group, but it cannot estimate a randomized treatment contrast. The registry record does not report additional design details such as eligibility criteria, the planned statistical analysis, or the method used to handle follow-up. Those details should not be inferred from the title or the endpoint label.

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.

Population: Females with invasive nonlobular carcinoma greater or less than 3 cm

6. Primary Endpoint

The registry lists the primary outcome as Ipsilateral Breast Tumor Recurrence-free Survival, measured over Up to 5 years post-treatment completion, average of 48 months.

The primary endpoint is Ipsilateral Breast Tumor Recurrence-free Survival, measured as a percentage of patients. Its description defines the endpoint in terms of lack of tumor recurrence in the treated breast, assessed by imaging and physical exam. The stated timeframe is up to 5 years post-treatment completion, average of 48 months.

This endpoint focuses on recurrence in the treated breast rather than on all possible outcomes. It is distinct from Overall Survival, which the registry lists as a secondary outcome. The name includes the word survival, but the endpoint description posted in the registry is specifically about lack of tumor recurrence; a separate definition of how deaths or other events affect this endpoint is not reported in the registry record.

In general, a recurrence-free endpoint can summarize whether recurrence has been observed during a specified follow-up period. Reporting the percentage together with a confidence interval would communicate both the estimated outcome and its statistical uncertainty. The registry identifies 95% Confidence Interval as the dispersion measure, but does not report the endpoint percentage or confidence interval. The number of participants with evaluable follow-up, the handling of incomplete follow-up, and the precise calculation method are also not reported in the registry record.

Because the endpoint result is absent, the available record does not establish the observed recurrence-free percentage or how precisely it was estimated. The endpoint definition and timeframe clarify what was intended to be measured, but they are not a substitute for an outcome estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as a binary percentage: the kind meaning is percentage of participants with an event. The endpoint title and description frame the outcome as lack of tumor recurrence in the treated breast. The record names 95% Confidence Interval as the dispersion measure, but gives no endpoint percentage or interval estimate. The method used to derive that interval is not reported in the registry record.

What does a confidence interval communicate?

In general, a confidence interval describes uncertainty around an estimated quantity under a statistical procedure. It is not a guarantee that the true value lies within the interval, nor does it describe the range of individual participant outcomes. A narrower interval generally indicates greater statistical precision, while a wider interval indicates more uncertainty. Here, the registry record identifies the intended interval type but does not report its bounds, so its width and the precision of the endpoint estimate cannot be assessed.

How should the endpoint timeframe be read?

The stated timeframe is up to 5 years post-treatment completion, average of 48 months. This supplies a follow-up context for the endpoint, but it does not specify how the percentage was calculated when participants had different follow-up durations. For example, a simple proportion and a time-to-event estimate can use follow-up information differently. The registry record does not report which calculation was used, nor does it state how censoring, incomplete follow-up, or events occurring after the recorded follow-up were handled. The endpoint result and its analysis method are therefore not recoverable from the record.

What does the single-group design allow?

In general, a single-group study can describe outcomes observed in the treated group. A randomized comparison is needed to estimate a treatment contrast while using random assignment to balance groups on average. This trial is listed as SINGLE GROUP, with allocation NA, and the record does not identify a concurrent control group. It therefore does not provide a randomized estimate comparing proton radiotherapy with another treatment. The absence of masking, listed as NONE, is another design feature; the registry does not report what assessment safeguards, if any, were used for the primary endpoint.

What is over-dispersion, and does it apply?

In general, over-dispersion arises when outcome variation is greater than a statistical model assumes. It can affect uncertainty estimates when a model relies on a particular variance structure. The registry record does not report a model, an over-dispersion assessment, or a statistical analysis for this endpoint. It would therefore be inappropriate to claim that over-dispersion was tested or corrected in this trial. The concept matters when interpreting methods, but its use in this analysis is not reported in the registry record.

How should planning illustrations be interpreted?

In general, a sample-size calculation is a planning exercise under stated assumptions, not a measure of what a completed trial actually achieved. The planning description associated with this record specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Those assumptions describe a hypothetical two-arm planning illustration, not the single-group design recorded for this trial. Any sample sizes derived under those assumptions would be planning illustrations, not observed power, and should not be interpreted as the trial’s actual enrollment or evidence of an outcome. The record does not report the trial’s own sample-size justification or design assumptions.

The planning description also distinguishes the type of quantity used for time-to-event calculations from those used for other outcomes. That distinction does not establish that a time-to-event analysis was conducted for this trial. The registry names a recurrence-free endpoint and an average follow-up, but does not report the analysis method. The distinction between a percentage endpoint and a time-to-event analysis should therefore remain explicit rather than inferred from the endpoint’s use of the word survival.

Finally, a p-value, effect estimate, adjusted analysis, or inferential conclusion cannot be reconstructed from the registry entries in this record. No endpoint result or listed analysis is available. General statistical concepts can explain how such results would ordinarily be read, but they cannot fill in results that the registry does not report.

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("Partial Breast Radiotherapy With Proton Beam")
n      <- c(50)
events <- c(46)
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  Partial Breast Radiotherapy With Proton Beam  50  46  92.0  80.8  97.8  81.2  96.8  81.1  96.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and names Ipsilateral Breast Tumor Recurrence-free Survival as the primary endpoint. Overall Survival is listed as a secondary outcome. The record does not report a multiplicity strategy, such as whether or how the interpretation of multiple outcomes was adjusted. It also does not report a hierarchy of testing or an analysis plan specifying which outcomes were intended for confirmatory inference. The effect of multiplicity on statistical interpretation is therefore not reported in the registry record.

The registry lists zero analyses. This means that no analysis entries appear in the record; it does not establish that no analysis was performed elsewhere. No primary endpoint estimate, confidence interval, p-value, or overall survival result is reported in the registry record.

The enrollment field lists 50, but the number included in an endpoint analysis is not reported in the registry record. The analysis population, exclusions, and reasons for any exclusions are also not reported. The record does not describe missing outcome data, loss to follow-up, censoring, imputation, or sensitivity analyses. These omissions limit assessment of whether the reported enrollment corresponds to the participants contributing information to each outcome.

The primary outcome’s stated timeframe is up to 5 years post-treatment completion, average of 48 months. That description alone does not explain whether every participant was observed for the same duration or how incomplete follow-up was addressed. In general, missingness and differing follow-up can affect both an estimated percentage and its uncertainty. Without an analysis population and missing-data methods, the endpoint estimate cannot be evaluated for these issues. No approach to multiplicity or missing data should be assumed from the registry’s outcome labels alone.

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

Serious events with the highest arm-level rate: grade 1 - 2 acute skin toxicity (60.0%), telangiectasia (26.0%), distant metatastatic disease (6.0%), isolated axillary occurence (2.0%), events leading to death (2.0%).

The registry’s Proton Radiotherapy safety entry lists 50 participants at risk for serious events, with 49 affected, and 50 at risk for other events, with 0 affected. It also lists 2 deaths. These are registry fields; the record does not explain their operational definitions, event-level timing, or whether every entry is attributable to treatment. The figures should be read as reported counts, not as a causal assessment.

The listed serious-event terms include Grade 1 - 2 Acute Skin Toxicity at 60.0%, Telangiectasia at 26.0%, Distant metatastatic disease at 6.0%, Isolated axillary occurence at 2.0%, Events Leading to Death at 2.0%, and Esopageal Carcinoma at 2.0%. These are the terms and percentages recorded; the registry does not provide further detail about overlap between terms, duration, or individual event narratives. The terms and their percentages should not be added together, since the record does not state that they represent mutually exclusive categories.

The entry reports counts of affected participants, not necessarily the total number of event episodes. Seriousness and severity are also distinct concepts; the record names Grade 1 - 2 for one term but does not provide a full severity distribution. Further clinical context and attribution are not reported in the registry record.

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

The registry record documents a completed single-group study of proton radiotherapy following lumpectomy for early-stage breast cancer. It identifies recurrence-free survival in the treated breast as the primary endpoint, describes how recurrence was assessed, and gives the stated follow-up timeframe. These details clarify the clinical question and the intended outcome.

The record does not report the primary endpoint result or its 95% Confidence Interval. It therefore does not show the observed percentage of patients without recurrence, or how precisely that percentage was estimated. Overall Survival is listed as a secondary outcome, but its result is not reported in the registry record. The record also lists zero analyses, and does not state how the endpoint was calculated or how missing follow-up was handled.

The single-group design is important to what can be concluded. Without a concurrent comparator, outcomes in the proton radiotherapy group cannot establish how those outcomes compare with another treatment within this trial. The record does not report random allocation or a control arm, and the sample-size planning description is a hypothetical illustration rather than a trial-specific comparison. It does not supply a treatment-effect estimate.

The safety entries provide counts and selected event terms, but do not establish causality or provide the detailed timing, event narratives, and attribution needed for a fuller safety interpretation. They should be read as registry-recorded information, with the limits of the available descriptions in mind.

In general, a clinical trial result is best interpreted by combining the outcome estimate, its uncertainty, the design, the analysis population, and the handling of follow-up. Several of those elements are not reported in the registry record. The appropriate interpretation is consequently limited: the record describes the study and selected safety entries, but does not provide the primary efficacy result needed to characterize the observed endpoint or a comparator-based treatment contrast.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary question concerns a percentage endpoint with a stated follow-up period, while the design is single-group. The distinction between describing an outcome and estimating a comparative treatment effect is central. A single-group outcome can describe what was recorded among participants in that group, but it cannot supply a randomized contrast with another treatment when no concurrent comparator is reported.

The endpoint label includes survival, while its description focuses on lack of tumor recurrence in the treated breast. The registry also lists Overall Survival separately as a secondary outcome. Keeping those outcomes distinct matters because they address different questions. The record’s description identifies the intended recurrence assessment, but does not provide the result or the method used to calculate it.

Precision is also important. The registry names a 95% Confidence Interval as the dispersion measure, but does not report the interval. Without an estimate and its uncertainty, readers cannot assess the statistical precision of the primary outcome. The listed enrollment does not replace an analysis population or a reported endpoint result.

Finally, this record illustrates why design-specific planning assumptions must be kept separate from the completed trial’s reported evidence. The sample-size description refers to a two-arm planning illustration, whereas the recorded trial is single-group. Such illustrations are not observed power and do not turn a single-group study into a comparative design. The registry’s absent outcome analyses and missingness details further limit what can be inferred. These distinctions help prevent a study description, planning assumptions, or safety entries from being mistaken for an unreported efficacy result.

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 primary limitation for interpretation is that the registry record does not report the primary endpoint result, although it identifies the endpoint and its 95% Confidence Interval as the intended dispersion measure. Without an estimate and interval, neither the observed recurrence-free percentage nor its precision can be assessed. The record lists zero analyses.

The study is recorded as single-group, with allocation NA and masking NONE. No concurrent comparator is reported, so the registry does not provide a like-for-like treatment comparison. The record also does not report eligibility criteria, the endpoint analysis population, the calculation method, or an analysis plan. Those details cannot be inferred from the title or the listed enrollment.

Follow-up is described as up to 5 years post-treatment completion, average of 48 months, but the distribution of follow-up and the handling of incomplete observation are not reported in the registry record. Missing-data procedures, censoring methods, and sensitivity analyses are also not reported. The listed enrollment of 50 does not establish how many participants contributed to the primary endpoint analysis.

Overall Survival is listed as a secondary outcome but no result is reported. The record names two outcome measures without describing a multiplicity strategy. The safety section contains selected counts and terms, but does not report event-level narratives, timing, or attribution. Finally, the planning assumptions describe an illustrative two-arm calculation, not the recorded single-group design or a trial-specific sample-size justification. These limitations restrict interpretation to the study description and the posted registry entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Proton Therapy for Early Stage Breast Cancer — NCT00614172.
• Registry record last updated 2023-09-21; status last verified 2023-08.
• Results first posted 2023-09-21.
• 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, single-group trial sponsored by Loma Linda University, studying proton radiotherapy after lumpectomy for early-stage breast cancer. The intervention is a two week course of proton radiotherapy to the breast. Enrollment is listed as 50; the study start is recorded as 2004-02 and primary completion as 2020-05-12.

The primary endpoint is Ipsilateral Breast Tumor Recurrence-free Survival, defined by lack of tumor recurrence in the treated breast assessed by imaging and physical exam, with a timeframe of up to 5 years post-treatment completion, average of 48 months. Overall Survival is listed as a secondary outcome. The primary endpoint estimate, its confidence interval, and the secondary outcome result are not reported in the registry record. The record lists zero analyses.

Safety entries include affected counts, deaths, and selected serious-event terms. The study has no reported concurrent comparator, so the registry does not provide a randomized treatment contrast. Analysis populations, endpoint calculation details, and missing-data methods are not reported in the registry record.