Proton Beam Teletherapy for Post-Hysterectomy Cancers of the Uterus and Cervix: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Proton Beam Teletherapy for Post-Hysterectomy Cancers of the Uterus and Cervix (NCT01600040), a na na study. The primary outcome is Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT).

2. Clinical Question

The study is registered as NCT01600040 and is titled Proton Beam Teletherapy for Post-Hysterectomy Cancers of the Uterus and Cervix. Its stated clinical motivation is to examine whether proton radiation can control cancer growth and reduce side effects relative to standard photon radiation. The primary registered outcome, however, is a comparison of dose-volume histograms (DVHs) for proton, 3DCRT, and IMRT plans. The record also lists quality of life and progression-free survival as secondary outcomes. It does not report numerical outcome estimates for those measures, or the numerical dose comparisons. Consequently, the clinical question motivating the study and the primary endpoint actually registered are related but not identical: the primary endpoint describes radiation-dose distributions, while cancer control and patient-reported outcomes are separate questions whose results are not reported in the registry record.

3. Trial Design

This completed study is described as a pilot study of adjuvant proton beam teletherapy for cancers of the uterus and cervix with regional lymph-node metastases after hysterectomy. The registry lists a single study group, with all participants receiving proton radiation therapy. It lists allocation as NA and masking as none; the record does not describe a randomized or masked treatment comparison. The listed phase is NA.

The registry reports enrollment of 22. One participant withdrew consent before study treatment, and the remaining 21 were included in the final analysis. The study start is listed as 2013-08, primary completion as 2022-10-19, and status as completed. The record names Massachusetts General Hospital as sponsor.

The dosimetric comparison uses the structure sets contoured for proton treatment to plan alternative 3DCRT and IMRT plans. The same medical physics team planned those alternatives, and the registry states that 3DCRT and IMRT were not used on study. Thus, the comparison pairs the delivered proton dose with modeled doses for alternative plans; it is not a comparison of groups assigned to receive different treatments. The registry does not report the detailed planning procedures or statistical plan.

The listed primary outcome is a median dose comparison over a 5 years timeframe. Secondary outcomes are quality of life and progression-free survival. Although the record lists five outcome measures, their numerical results are not reported in the registry record. The record lists no analyses. It also does not report a separate clinical control group or a randomization procedure. These design features matter when interpreting what can be concluded: the study describes a dosimetric assessment within a single treatment group, rather than a controlled estimate of comparative clinical outcomes.

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: 22 patients enrolled, 1 of whom withdrew consent prior to study treatment. Remaining 21 patients were included in the final analysis.

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: 22 patients enrolled, and 1 patient withdrew consent prior to study treatment. The other 21 patients were included in the final analyses.

6. Primary Endpoint

The registry lists the primary outcome as Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), measured over 5 years.

The primary outcome is a dosimetric comparison of proton beam treatment with alternative 3DCRT and IMRT plans. It reports median doses, with the 25th and 75th percentile doses, by tissue volume irradiated in mL or percentage irradiated. Dose is measured in grays (Gy). The registered timeframe is 5 years.

A DVH describes how radiation dose is distributed across a contoured tissue structure. Looking at dose across the volume can show whether a plan exposes a larger or smaller portion of a structure to particular dose levels. Reporting the median alongside the 25th and 75th percentiles describes the center and spread of the dose distribution without assuming that its values follow a particular symmetric pattern. This is useful in radiation planning because comparisons can consider how much dose reaches different tissue volumes, rather than relying on a single overall dose value.

The endpoint is a planning and dosimetry comparison, not a direct measure of cancer control, survival, or side effects. The registry’s rationale is that proton radiation delivers less radiation beyond the target area and may spare surrounding normal tissue. The endpoint can address the dose-distribution aspect of that rationale, but it cannot by itself establish a clinical benefit or quantify side effects. The record describes the comparison method but does not report the median doses or percentile values, so the direction and size of any dosimetric differences are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median dose describe?

The median is the central value in an ordered set: half the measurements fall at or below it and half at or above it. For this study, the registered measure is the median dose across specified tissue volumes or percentages. A median can describe a typical point in a dose distribution without being pulled as strongly by unusually high or low values as an arithmetic mean might be. It does not show the full distribution on its own, which is why the registry also specifies the 25th and 75th percentile doses.

The inter-quartile range (IQR) describes the span from the 25th percentile to the 75th percentile. It characterizes the middle portion of the distribution and gives a sense of its spread. A wider IQR indicates more dispersion among the central values; a narrower IQR indicates less. The IQR does not describe the extremes of the distribution. The registry identifies IQR as the dispersion measure and lists the median and percentile doses, but numerical results are not reported in the registry record.

What information does a dose-volume histogram provide?

A dose-volume histogram summarizes the relationship between radiation dose and the volume of a contoured structure receiving that dose. It can be read to understand how dose is distributed across a target or surrounding tissue. A comparison can focus on the dose received by a given tissue volume, or the volume receiving a given dose. This helps characterize a plan beyond a single prescription or average value. It does not, by itself, establish whether a dose difference leads to a difference in tumor control or toxicity.

The registry describes doses by tissue volume irradiated in mL or percentage irradiated. It specifies grays (Gy) as the dose unit, with a gray defined as the absorption of a joule of radiation energy per kilogram of matter. The primary outcome compares proton treatment with 3DCRT and IMRT plans. The alternative plans were generated using the structure sets contoured for proton treatment and were not delivered on study. Therefore the comparison is about planned dose distributions, with the proton dose representing treatment delivered and the other dose distributions representing alternatives.

Why do comparisons of modeled plans need careful interpretation?

Using the same contoured structures for alternative plans supports a dosimetric comparison on a shared anatomical basis. The registry says the same medical physics team planned the alternatives. Even so, these plans are not equivalent to treatment groups observed under different assigned therapies. Clinical outcomes such as progression or side effects arise in people receiving treatment and may depend on factors beyond a plan’s dose distribution. A modeled plan can address what dose would have been delivered under that planning approach, but it cannot supply observed clinical outcomes for that approach.

Because the design is single-group and all participants received proton radiation, there is no randomized allocation to proton, 3DCRT, or IMRT in the study. The allocation field is listed as NA, and masking is listed as none. The registry does not describe a statistical plan for comparing the dose distributions, such as a specified inferential test or a method for accounting for paired measurements. Those details are not reported in the registry record. The presence of two alternative plans does not mean that the study randomized participants among modalities.

What can the record establish about statistical evidence?

The registry describes the summaries to be reported, but lists no analyses and supplies no numerical dose estimates. Without reported estimates, readers cannot assess the observed magnitude or direction of a difference. Without reported uncertainty measures or inferential results, readers cannot assess the precision of the comparison or whether an analysis found evidence against a specified null hypothesis. A median and IQR are descriptive summaries; they do not, by themselves, establish statistical significance.

In general, a confidence interval expresses a range of values compatible with the data under a stated statistical procedure. Its width conveys precision: narrower intervals indicate more precise estimates, while wider intervals indicate greater uncertainty. A confidence interval is not a guarantee that the true value lies within its bounds. The registry record does not report confidence intervals for the primary outcome, so the precision of any dose differences cannot be assessed from that record.

In general, over-dispersion means that observed variability exceeds what a statistical model assumes. If a model ignores over-dispersion, its standard errors can be too small and its uncertainty estimates too optimistic. The registry does not identify a model for the primary dosimetric comparison, and the record does not report whether over-dispersion was assessed. This is a general consideration rather than a claim about the analysis used in this study.

How should planning illustrations be understood?

Any sample-size illustrations associated with the study are planning calculations, not observed results and not observed power. The stated assumptions describe two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the stated calculation uses total events under the Schoenfeld approach; for other outcomes, it expresses the result as participants per arm for 80% power or another specified power level. These are general planning assumptions and do not describe this single-group study’s allocation or prove that its design had a particular power.

Such illustrations depend on the chosen effect size and assumptions. A smaller effect to detect generally requires more information than a larger effect to detect, but no new sample-size calculation or result can be inferred from the registry description alone. The registry does not report its own sample-size justification, and it does not report the detailed statistical plan. The illustrative assumptions should not be mistaken for the study protocol or for evidence that a clinical effect was observed.

What does the analysis population tell readers?

The record reports 22 enrolled, notes that 1 withdrew consent before study treatment, and states that the remaining 21 were included in the final analysis. This identifies the population described as analyzed, but does not fully specify the analysis population for each outcome. The registry does not report whether all measures were available for every participant, how missing measurements were handled, or whether analyses used different populations for different outcomes. Those details are not reported in the registry record.

These distinctions are important because descriptive estimates depend on which observations are included. Missingness can affect an estimate if the unavailable measurements differ systematically from the available ones. This is a general statistical concern, not a finding about the participants in this study. Since the record does not describe missing-data methods, it is not possible to determine whether the analysis used imputation, complete-case methods, or another approach.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary dosimetric outcome and also lists quality of life and progression-free survival as secondary outcomes. The primary comparison itself includes proton treatment and alternative 3DCRT and IMRT plans, with dose summaries across tissue volumes or percentages. When several outcomes, dose measures, or comparisons are examined, the chance of finding an apparently notable result by chance can increase. Statistical methods sometimes address this multiplicity through prespecified testing hierarchies or adjustments. The registry record does not report whether any such approach was planned or used.

The record lists five outcome measures and no analyses. It does not report a statistical analysis plan, hypothesis-testing procedures, confidence intervals, multiplicity adjustments, or criteria for selecting which results to emphasize. These details are not reported in the registry record. The listed timeframe for the primary outcome is 5 years, but the record does not explain how outcome timing or repeated measurements were handled in an analysis.

For missing data, the record states that 1 participant withdrew consent before treatment and that the remaining 21 were included in the final analysis. It does not report the reason for withdrawal, whether outcome data were missing for participants in the final analysis, or how any missing measurements were handled. It also does not specify whether the analysis population was defined differently for the primary and secondary outcomes. No assumptions about these issues can be made from the record.

The registry record therefore gives a basic account of enrollment and final analysis inclusion, but not enough detail to evaluate multiplicity control or missing-data procedures. These omissions do not establish that any particular method was or was not used outside the registry record; they mean the relevant methods are not reported there.

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 non-serious adverse event terms

For the Proton Radiation Therapy group, the registry records 21 participants at risk for serious adverse events and 0 in the serious-adverse-event affected count. It records 21 at risk for other adverse events and 21 in the other-adverse-event affected count. The death count is 0. No serious adverse-event terms are listed.

These are registry counts, not a comparative safety estimate. Since the study has a single treatment group and no concurrent group receiving 3DCRT or IMRT, the counts cannot show how these outcomes compare with those treatments. The record does not provide numerical details about the kinds, timing, duration, or severity of the other adverse events. The count of participants affected by other adverse events should not be interpreted as the number of separate events, because that event total is not reported in the registry record.

The safety figures also do not establish that an event was caused by treatment. They describe what the registry records in its adverse-event categories. The record does not report further details about adverse-event collection or attribution. Accordingly, the figures are best read as descriptive counts for the study group, with important context and comparison information not reported.

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

The study’s registered primary outcome asks a focused dosimetric question: how the dose distribution for proton treatment compares with alternative 3DCRT and IMRT plans based on the same contoured structure sets. The registry explains that proton treatment was delivered, whereas the alternative modalities were planned rather than used on study. This makes the comparison relevant to planning and dose distribution, but distinct from a clinical trial in which participants receive different treatments and their outcomes are compared.

The record does not report the numerical median doses, percentile doses, or numerical comparisons. It therefore does not allow readers to determine which plan had a lower dose for a particular structure, or the size and precision of any difference. The registry also lists quality of life and progression-free survival as secondary outcomes but does not report numerical findings for them. No conclusion about cancer control, survival, quality of life, or side effects can be drawn from the registry record’s outcome information.

The stated rationale is that proton radiation delivers less radiation beyond the target area and may reduce side effects relative to photon radiation. That rationale is not itself a result. A dose-volume comparison could describe the radiation distribution, but a dosimetric difference alone would not establish a difference in clinical outcomes. The record’s single-group design also offers no randomized comparison of clinical outcomes across modalities.

The enrollment and analysis information provides context for the study population: 22 enrolled, 1 withdrew before study treatment, and 21 were included in the final analysis. The record does not report detailed missing-data methods or a statistical plan. The appropriate interpretation is therefore limited to the registered design, outcome definitions, and adverse-event counts that are stated. Numerical efficacy and dosimetry findings are not reported in the registry record, so their magnitude and precision cannot be assessed.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it separates a treatment-planning comparison from a randomized clinical comparison. Proton treatment was delivered to the study group, while the 3DCRT and IMRT alternatives were planned using the proton-treatment structure sets. This allows a comparison framed around dose distributions, but it does not create observed outcome groups treated with each modality. The distinction affects what the estimates can mean.

The primary endpoint uses medians and percentile doses to describe distributions across tissue volumes. This approach recognizes that radiation exposure varies within contoured structures and that a single average may not capture that pattern. The IQR describes spread in the central portion of the dose distribution. Such summaries can be useful for dosimetric assessment, while still falling short of evidence about clinical outcomes.

The registry also illustrates why a completed study and a stated analysis population do not guarantee that numerical results are available in the record. The record reports enrollment and final analysis inclusion, lists outcome measures, and describes the primary comparison, but lists no analyses and does not report numerical primary or secondary outcome results. Consequently, readers cannot evaluate the size, direction, or precision of the dose comparisons from the registry record.

Finally, the design and reporting details shape the scope of inference. The single-group treatment design does not provide a randomized clinical comparison, and the registry does not report its statistical plan, multiplicity methods, or missing-data procedures. Sample-size illustrations based on observed effects are planning aids, not observed power and not a substitute for the study’s analysis. Taken together, the record supports a clear description of the question and design, while leaving the main numerical outcome findings unavailable for statistical assessment.

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 direct limitation for interpretation is that the registry record does not report numerical results for the primary dosimetric outcome. Although it specifies median and percentile dose summaries and describes the planning comparison, it provides no values from which the direction, magnitude, or precision of dose differences can be evaluated. Numerical results for the listed quality-of-life and progression-free-survival outcomes are also not reported in the registry record.

The design is single-group: participants received proton radiation, while the 3DCRT and IMRT plans were alternatives that were not used on study. These modeled plans do not provide observed clinical outcomes under those modalities. The registry does not describe a randomized comparison or a concurrent control group, so comparative conclusions about clinical outcomes cannot be established from this design description.

The record reports 22 enrolled, 1 withdrawal before treatment, and 21 included in the final analysis. It does not report the reason for withdrawal, how missing data were handled, or whether each outcome was available for all participants in the final analysis. It also does not report a statistical analysis plan, methods for multiplicity, inferential tests, or uncertainty estimates. These omissions make it difficult to evaluate the analysis choices and precision from the registry record.

The study is labeled a pilot study, but the registry record does not report its sample-size justification. Planning illustrations based on an observed effect are not a substitute for that information and should not be interpreted as observed power. The listed adverse-event counts are descriptive and have no treatment comparator; details about event types and attribution are not reported. These limitations concern what can be concluded from the registry record and do not establish what analyses or data may exist outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Proton Beam Teletherapy for Post-Hysterectomy Cancers of the Uterus and Cervix — NCT01600040.
• Registry record last updated 2024-10-29; status last verified 2024-10.
• Results first posted 2024-10-29.
• 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

NCT01600040 is a completed, single-group pilot study of adjuvant proton beam teletherapy for post-hysterectomy uterine and cervical cancers with regional lymph-node metastases. The registry lists 22 enrolled; 1 withdrew consent before study treatment, and the remaining 21 were included in the final analysis. Proton radiation was delivered on study. Alternative 3DCRT and IMRT plans were created for dosimetric comparison but were not used on study.

The primary outcome compares median and percentile dose distributions by tissue volume or percentage irradiated, with dose measured in Gy and a registered timeframe of 5 years. Quality of life and progression-free survival are listed as secondary outcomes. The record lists no analyses and does not report numerical outcome results. Safety records include 0 in the serious-adverse-event affected count, 21 in the other-adverse-event affected count, and 0 deaths. The registry does not report a statistical plan or missing-data methods.