Prone Breath Hold Technique to Decrease Cardiac and Pulmonary Doses in Women Receiving Left Breast Radiotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prone Breath Hold Technique to Decrease Cardiac and Pulmonary Doses in Women Receiving Left Breast Radiotherapy (NCT02379988), a na na study. The primary outcome is The Radiation Dose in Gy to the Heart and Lung Using Two Radiation Techniques..

2. Clinical Question

In statistical terms, this is a within-participant dosimetric comparison: each participant contributes a plan based on each scan condition. That pairing can account for some differences between people because the two plan measurements come from the same person. It does not, by itself, establish how the technique would compare across different clinical settings, nor does it show a patient outcome. The stated aim was to examine whether adding inspiratory hold could decrease radiation dose received by the heart and lung for women treated for left-sided breast cancer. The registry labels the study a pilot and describes feasibility as part of its primary endpoints. However, it does not report a numerical feasibility measure or a feasibility result. The posted information therefore defines the comparison and its clinical rationale, but does not establish the size or direction of a dose difference.

3. Trial Design

This was a completed pilot study with a single-group model and no masking. The registry lists allocation as NA and enrollment as 15. It records the study start as 2014-11-06, primary completion as 2016-07-03, and status as COMPLETED. The sponsor was the University of Arizona. The phase is recorded as NA.

Although the study has one group, the dose comparison is paired at the plan level. Each participant was to have two radiation plans generated: one using the free-breathing CT scan and one using the inspiratory gated breath-hold CT scan. The registry says both scans were performed on Treatment Day 1. This is not a randomized comparison between treatment groups, and the registry itself cautions that the listed arms are not a like-for-like control comparison. The two plans are alternative dosimetric representations for the same participant, not evidence that participants were assigned to receive one technique or the other.

The intervention entry is named “Verify radiation dose to heart and lung” and is classified as radiation. Its description specifies standard-of-care CT simulation plus an additional breath-hold CT. The record does not provide further details about treatment delivery, how plans were selected for clinical use, or whether either plan was delivered to participants. Those details are not reported in the registry record.

The primary endpoint record gives a mean continuous measure with standard deviation as the stated dispersion, measured in Gy. Its description says paired differences were computed for heart, LAD, and left lung doses, with associated 95% confidence intervals, and that a Wilcoxon paired signed rank test was used because the distributions were described as non-normal. The registry record does not include the values for those analyses. No separate randomized arm contrast or masked assessment is described. Further details of the protocol, analysis population, and conduct 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.

Before assignment: One patient who consented was deemed not eligible as she could not tolerate prone positioning

Overall Study

Reasons for not completing this period:

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 The Radiation Dose in Gy to the Heart and Lung Using Two Radiation Techniques., measured over Treatment Day 1 (both pFB and pDIBH scans were done on the same day).

The primary endpoint is titled as radiation dose in Gy to the heart and lung using two radiation techniques. It is a continuous dosimetric outcome: the reported measure is a mean, with standard deviation identified as the dispersion. The comparison is based on plans generated from the participant’s free-breathing and inspiratory gated breath-hold scans. The endpoint description also identifies heart, LAD, and left lung dose differences.

Dose is used in this study as a direct measure of the radiation exposure planned for organs of interest. Comparing the plans can quantify how the dosimetric estimates differ under the two scan conditions. Because the plans are paired within participants, the analysis can focus on each participant’s contrast rather than treating the two sets of plans as independent samples. This is relevant to the study’s stated aim of assessing whether the additional breath-hold approach could reduce cardiac and pulmonary doses.

The endpoint does not, on its own, measure a clinical event, symptoms, tumor control, or long-term health outcome. A plan-based dose difference should be interpreted as a dosimetric finding, not as direct evidence about those outcomes. The registry record does not report the observed mean doses, mean paired differences, standard deviations, confidence interval limits, or test result. Consequently, the magnitude, direction, and precision of the dose comparison cannot be described from the registry information available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous, expressed in Gy, and described using a mean and standard deviation. The registry’s primary endpoint description says that differences between the two plans were evaluated for heart, LAD, and left lung radiation doses. It further says that the mean difference and an associated 95% confidence interval were computed, while the Wilcoxon paired signed rank test was used and listed as the primary analysis because the distributions were non-normal. The numerical results from those analyses are not reported in the registry record.

Why use paired measurements?

General statistical explanation: in a paired design, two measurements are linked because they come from the same participant. The analysis can form a within-person contrast, such as the difference between that participant’s values under the two planning conditions. This is distinct from comparing two independent groups of people. When measurements from one person tend to resemble each other, pairing can remove some between-person variability from the comparison and make the within-person contrast more informative.

Pairing depends on having both measurements for a participant, and on matching them correctly. If one plan measurement is missing, that participant may not contribute to an analysis requiring a complete pair, unless a different method is used. The registry record does not report how many complete pairs were available for each dose endpoint, how missing paired measurements were handled, or whether every enrolled participant contributed to the analysis.

What does the Wilcoxon paired signed rank test assess?

General statistical explanation: the Wilcoxon paired signed rank test is a nonparametric method for paired data. It uses the direction and rank ordering of nonzero within-pair differences to assess whether those differences are centered around zero under its assumptions. It does not require the paired differences to follow a normal distribution in the way a paired t-test does. The registry says this test was selected because of non-normal distributions. It does not report which diagnostic assessment established non-normality, how many differences were available, or whether any additional assumptions were evaluated.

The test’s p-value, if reported, would address compatibility between the observed paired data and a specified null hypothesis under the test’s assumptions. A p-value would not quantify the size of a dose difference or the probability that a hypothesis is true. The registry does not report the p-value or the test statistic. For interpretation, an effect estimate and its uncertainty would also be important; the record says a 95% confidence interval was computed but does not give its limits.

How should a confidence interval be read?

General statistical explanation: a confidence interval describes uncertainty around an estimated quantity under the method used to construct it. A 95% confidence interval is generated by a procedure intended to cover the target quantity in 95% of repeated samples when its assumptions hold. It is not a guarantee that a particular interval contains the true value, nor does it state the probability that a treatment effect is clinically important. The registry indicates that 95% confidence intervals accompanied mean differences, but their values are not reported in the registry record. Therefore their width and the precision of the estimates cannot be assessed.

The endpoint description identifies a mean difference and a Wilcoxon paired signed rank test. These summarize data in different ways: a mean difference describes the average numerical contrast, whereas the signed rank test uses the ranks and signs of paired differences. When a distribution is non-normal or contains extreme values, a mean may be influenced by the magnitude of those values, while a rank-based test emphasizes ordering. The record does not explain how the confidence intervals were calculated or whether they were designed to align with the signed rank test.

What cannot be inferred from this analysis description?

General statistical explanation: a test choice and confidence level do not reveal an outcome. To interpret the study’s result, the estimates, uncertainty intervals, and test results must be available, along with information about the analyzed participants. Here, the registry record documents the planned dose comparison and the selected primary test, but it does not report those numerical results. It also does not report a sample-size justification, analysis details beyond the stated paired test, or whether there were interim analyses. Such details should not be inferred from the pilot label or enrollment count.

Because the data arise from alternative plans for the same participants, this is a dosimetric comparison rather than a randomized clinical-outcome trial. In general, that design can address how the plan estimates differ in the studied participants, but it cannot by itself establish an effect on later clinical outcomes. The registry does not report whether either plan was delivered, and no clinical outcome comparison is described in the primary endpoint record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint title concerning heart and lung dose using two techniques and describes paired differences for heart, LAD, and left lung. It also lists secondary outcomes concerning cardiac and lung dose reduction, heart mean dose based on breast volume, and LAD dose reduction. The registry records four outcome measures and eight analyses. These entries indicate that more than one measurement or analysis was included, but the record does not report how the analyses were grouped or which were confirmatory.

Multiplicity arises in general when several endpoints, comparisons, or analyses are tested. If each is interpreted as an independent opportunity to declare a finding, the chance of at least one false-positive result can increase. Statistical approaches can address this in different ways, but the registry record does not report a multiplicity adjustment, a hierarchy among endpoints, or a prespecified strategy for interpreting multiple tests. It would not be appropriate to assume that an adjustment was or was not used beyond what the record states.

The registry describes a paired nonparametric test as the primary analysis and says confidence intervals were computed. It does not report whether an analysis plan specified these methods before data review, or whether other analyses were performed. Interim analyses are not reported in the registry record.

Missing-data handling and the analysis population are also not described. The study records enrollment of 15, while the safety group lists 14 participants at risk; the reason for this difference is not reported. These counts do not establish how many participants had paired dose plans available for each endpoint. The registry does not state how incomplete scans, unavailable dose measurements, or other missing data were handled, nor does it identify an intention-to-treat or per-protocol population. As a result, the amount and potential influence of missing endpoint information cannot be assessed from the registry record.

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.

The safety entry lists 14 participants at risk in the group named “Verify Radiation Dose to Heart and Lung.” It records 0 participants with serious adverse events, 0 with other adverse events, and 0 deaths. No serious adverse event terms are listed. These are the counts recorded for this safety entry; the registry does not provide further event descriptions or a safety follow-up period in the information available.

These figures should be read as recorded counts, not as proof that no adverse events could occur or as a complete assessment of safety. The entry does not describe how events were collected, how long participants were followed for safety, or whether events were sought systematically. The registry lists enrollment of 15, while 14 are shown as at risk in the safety group. The reason for the difference is not reported in the registry record, so the safety denominator should not be replaced with the enrollment count.

The study is a pilot dosimetric comparison, and its listed primary outcome concerns planned radiation dose rather than adverse events. The zero counts therefore do not answer the primary dose question. They also cannot be interpreted as a comparison of adverse-event rates between techniques: the registry describes one group and paired plans, not randomized treatment groups. The safety figures are limited to the recorded counts and do not establish comparative safety or exclude unrecorded events.

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

The study addresses a specific planning question: how heart and lung dose estimates compare between plans based on free-breathing and inspiratory gated breath-hold CT scans in women receiving left breast radiotherapy. Its within-participant structure means the intended comparison uses two plans per participant rather than separate groups of people. The registry also identifies heart, LAD, and left lung dose differences as part of the analysis description.

What the record does not establish is the actual result of that comparison. It does not report the numerical dose estimates, paired differences, confidence interval limits, or test result. The stated goal of decreasing dose should not be read as evidence that the dose was decreased. Without the results, neither the direction nor magnitude of the observed differences can be determined, and their precision cannot be judged.

Even if a dose difference were reported, a plan-based dose comparison would answer a dosimetric question, not directly establish a difference in symptoms, long-term health, tumor control, or other clinical outcomes. Those outcomes are not the primary endpoint described in the record. Whether either plan was ultimately delivered is not reported in the registry record.

The design also limits the scope of interpretation. This is a pilot with a single-group model, allocation listed as NA, and no masking. The paired plans can support a within-participant comparison of dose estimates, but they do not constitute random assignment to clinical treatment strategies. Further, the registry does not report eligibility details, participant characteristics, complete-pair counts, handling of missing measurements, or a sample-size justification.

The appropriate conclusion is therefore bounded: the registry documents a completed pilot study designed to compare dosimetric plans and identifies a paired nonparametric analysis. It does not provide the numerical findings required to characterize the result. The recorded safety counts are zero for serious events, other events, and deaths among 14 at risk, but that entry is not a randomized safety comparison and does not resolve the primary endpoint question.

13. Why This Trial Matters Statistically

This study is statistically notable for using two plan estimates from each participant rather than comparing unrelated groups. In general, a paired design can focus on within-person differences and reduce the influence of characteristics that remain stable across the two measurements. The registry specifies that the free-breathing and inspiratory gated breath-hold scans were obtained on the same day, and that two plans were generated for each participant.

The study also illustrates why the analysis method should be read together with the design and the outcome scale. Radiation dose is a continuous quantity, and the registry describes mean differences with 95% confidence intervals. It names the Wilcoxon paired signed rank test as the primary analysis because the distributions were described as non-normal. Those details identify the intended statistical approach, but without the estimates and test results they cannot tell readers what was observed.

The pilot context matters when judging what the record can establish. Enrollment was 15, and the study was described as evaluating feasibility as well as dosimetric endpoints. However, numerical feasibility results and a sample-size justification are not reported in the registry record. The study should not be treated as a definitive randomized comparison: the model is single-group, allocation is NA, and the comparison concerns alternative plans for participants.

Finally, the record provides a useful distinction between a statistical endpoint and a clinical outcome. Comparing organ dose estimates can address a planning question, while downstream clinical effects are separate questions. The posted registry information documents the intended dose comparison but not its numerical outcome. That makes transparent reporting of paired estimates, uncertainty, analysis populations, and missing-data handling especially important for interpreting this pilot.

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 most immediate limitation is that the registry record does not report the numerical primary outcome results. Although it describes mean dose differences, 95% confidence intervals, and a Wilcoxon paired signed rank test, it gives no dose values, difference estimates, interval limits, test statistic, or p-value. The direction, magnitude, and precision of the comparison therefore cannot be evaluated from the record.

The study is a pilot with enrollment of 15 and a single-group model. The allocation field is NA and masking is NONE. The comparison is between plans generated from two scan conditions for each participant, not a randomized comparison of clinical treatment groups. This design is suited to a within-participant dosimetric comparison as described, but does not establish effects on clinical outcomes or comparative treatment outcomes.

The registry’s safety group lists 14 participants at risk, whereas the enrollment count is 15. The reason for this difference is not reported. The number of participants with usable paired dose data for each outcome is also not reported, so the analyzed sample and completeness of paired measurements cannot be established.

Other relevant details are absent from the registry record: eligibility criteria beyond the stated population, participant characteristics, missing-data methods, analysis population, sample-size justification, multiplicity strategy, and interim analyses. The record names feasibility as an endpoint but gives no numerical feasibility result or definition. It also does not say whether either plan was delivered. These omissions restrict assessment of generalizability, robustness, and the relationship between planned dose and actual clinical care.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Prone Breath Hold Technique to Decrease Cardiac and Pulmonary Doses in Women Receiving Left Breast Radiotherapy — NCT02379988.
• Registry record last updated 2023-05-17; status last verified 2023-04.
• Results first posted 2023-05-17.
• 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

NCT02379988 is a completed pilot study sponsored by the University of Arizona. The registry records a single-group model, no masking, allocation NA, and enrollment of 15. The study concerns women with left-sided breast cancer receiving radiotherapy and compares plans based on free-breathing and inspiratory gated breath-hold CT scans.

The primary endpoint concerns mean radiation dose in Gy to the heart and lung. The description identifies paired differences for heart, LAD, and left lung, 95% confidence intervals, and a Wilcoxon paired signed rank test. Numerical outcome results are not reported in the registry record. The safety entry records 0 serious adverse events, 0 other adverse events, and 0 deaths among 14 participants at risk. Further details about analyzed pairs, missing data, and feasibility results are not reported.