Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Cancer of the Vulva: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Cancer of the Vulva (NCT00068406), a na phase 2 study. The primary outcome is Complete Clinical and Pathologic Response.

2. Clinical Question

3. Trial Design

This completed phase II trial studied a treatment sequence for locally advanced squamous cell carcinoma of the vulva: radiation therapy with concurrent cisplatin, followed by surgery. The registry lists 61 participants as enrolled and describes a single treatment group. Allocation is recorded as NA, and masking as none; no randomized comparator is described.

The regimen description specifies three-dimensional conformal radiation therapy and cisplatin. Radiotherapy was given daily on days 1-5, with cisplatin administered intravenously over 30 minutes on day 1. Treatment was repeated weekly for approximately 6.5 weeks, for a total of 32 radiotherapy fractions, in the absence of unacceptable toxicity. The description indicates that surgery was planned six to eight weeks after chemoradiation, although the remaining text of that description is incomplete in the registry record. The record does not report cisplatin dose or other treatment-delivery details beyond those stated.

The primary outcome population is described as eligible and treated patients. This definition does not establish how many participants actually contributed to the response analysis, and that analysis population size is not reported in the registry record. The record lists two outcome measures and zero analyses. It identifies complete clinical and pathologic response as the primary measure, but does not report a response percentage or confidence interval. The other outcome measure is not detailed in the available registry information.

The trial began in 2005-01, had primary completion in 2010-12, and is listed as completed. A single-group phase II design can describe outcomes observed among treated participants, but it cannot by itself separate treatment effects from other explanations for those outcomes. Without a concurrent comparator, differences from other treatment approaches cannot be estimated as randomized treatment effects.

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: Eligible and treated patients

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: Eligible and treated patients

6. Primary Endpoint

The registry lists the primary outcome as Complete Clinical and Pathologic Response, measured over Seven weeks after initiating treatment for clinical response and up to fifteen weeks for assessment of pathologic response..

The primary endpoint is the percentage of eligible and treated participants with a complete clinical and pathologic response. The registry definition combines two observations: disappearance of all gross tumor during chemoradiation and no residual tumor in the surgical specimen. The clinical assessment was scheduled seven weeks after initiating treatment, while pathologic response was assessed up to fifteen weeks.

Using a combined clinical and pathologic definition ties the response measure to both the observed tumor during treatment and the tissue removed at surgery. The clinical component captures whether gross tumor remains apparent; the pathologic component assesses whether tumor is present in the surgical specimen. In general, a clearly defined binary endpoint makes it possible to report the proportion of participants meeting the specified response criterion.

The registry lists the endpoint unit as percentage of participants and the dispersion measure as a 90% confidence interval. A confidence interval communicates uncertainty around an estimated response percentage; it does not guarantee that the true percentage lies within its limits. However, neither the response estimate nor its interval is reported in the registry record. The endpoint definition and assessment timing are available, but the outcome magnitude and its statistical precision cannot be evaluated from the registry results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting a clinical trial begins with the design and the quantity the analysis is meant to estimate. This is a phase II, single-group study. In general, a single-group design estimates outcomes among participants receiving the study regimen. It does not create a direct randomized comparison with an alternative regimen, because no separate control group is listed. The registry reports allocation as NA and masking as none. The meaning of a result must therefore remain descriptive rather than comparative.

What does a percentage endpoint represent?

The primary endpoint is a binary response measure: each eligible and treated participant either meets the defined complete clinical and pathologic response criterion or does not. In general, the percentage is the number meeting the criterion relative to the number assessed in the relevant analysis population. Here, the registry states that the population is eligible and treated patients, but does not report the actual analysis denominator or the number meeting the criterion. No percentage can be reconstructed from the enrollment total alone.

The endpoint definition requires disappearance of all gross tumor during chemoradiation and no residual tumor in the surgical specimen. These criteria make clear what counts as a response, but a definition by itself is not an outcome result. The timing is also specified: clinical response was assessed seven weeks after initiating treatment, and pathologic response up to fifteen weeks. The registry does not explain how timing deviations or missing assessments were addressed.

How should a confidence interval be read?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity. For a response percentage, a wider interval indicates less precision and a narrower interval indicates greater precision, subject to the analysis method and its assumptions. The registry identifies a 90% confidence interval as the dispersion measure for the primary endpoint. It does not report the point estimate or either interval limit, so the precision of the response estimate cannot be evaluated. A confidence interval is not a measure of clinical importance and, on its own, does not establish a treatment effect.

For a binary outcome, the uncertainty depends in part on the number of participants contributing to the estimate and the observed response pattern. General statistical methods may use different interval procedures, especially when sample sizes or event counts are limited. The registry does not report which procedure was used, whether the interval was adjusted, or whether the analysis accounted for any other features of the data. These details are not reported in the registry record and should not be inferred from the stated confidence level alone.

What can the analysis population tell us?

The primary population is described as eligible and treated patients. In general, an analysis population defines which participants contribute to a particular estimate. Different choices can yield different estimates when participants are excluded, do not receive the intended treatment, or lack an endpoint assessment. The registry does not report how many participants met the primary analysis definition, whether any enrolled participants were excluded, or how missing outcome assessments were treated. Enrollment of 61 is not a substitute for a reported analysis denominator.

The registry lists zero analyses. This means the statistical results needed to assess the primary endpoint are not posted in the record described. It does not establish that no analyses were performed outside the registry, nor does it establish why results are absent. No analysis plan, model, or method for handling incomplete data is reported in the registry record.

Why is the single-group design important?

In general, random allocation to a concurrent control group helps make treatment groups comparable in expectation and supports estimation of a between-group treatment contrast. This trial has no listed control group. Consequently, a response percentage, if reported, would describe the observed response in the treated group. It could not show how that percentage compares with an outcome under another treatment, and it would not alone establish that the regimen caused the observed outcomes.

The absence of a control group also affects interpretation of safety. The serious adverse event counts describe events recorded among participants receiving the regimen. They do not show whether those events occurred more or less often than they would have with another treatment or without the study regimen. Comparisons with external figures would require information and assumptions not reported in the registry record.

How do planning calculations differ from trial results?

In general, sample-size planning uses assumptions about an effect, variability, significance level, allocation, and desired power to illustrate the number of participants that might be needed for a future study. Such calculations are planning tools, not observed outcomes. The planning description associated with this trial states a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. It explicitly describes the planning illustration as based on the observed effect, not as the trial’s own design.

Those planning assumptions do not change the actual design described in the registry: this is a single-group trial, not a two-arm randomized study. Sample-size illustrations should therefore not be interpreted as observed power or as evidence that the trial was designed with the illustrated two-arm assumptions. The registry does not report the trial’s sample-size justification. No numerical planning estimates are stated in the registry information, so none can be interpreted as trial results.

In general, over-dispersion matters when observed variation is greater than a statistical model expects. If ignored, standard errors may be too small and confidence intervals too narrow. The registry record does not identify an over-dispersion model or report a model-based analysis for the primary binary endpoint. This concept is relevant to statistical interpretation generally, but there is no basis for saying it affected this trial’s reported results.

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("Cisplatin + Radiation, Then Surgery")
n      <- c(58)
events <- c(29)
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  Cisplatin + Radiation, Then Surgery  58  29  50.0  36.6  63.4  37.5  62.5  37.5  62.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures but provides detail for only the primary complete clinical and pathologic response measure in the information available. It lists zero analyses. The second outcome’s definition, result, and analysis are not reported in the registry record.

Multiplicity arises in general when several hypotheses, endpoints, time points, or subgroup comparisons are tested. With multiple tests, the chance of at least one apparently positive result can increase unless the analysis plan accounts for the testing structure. The registry does not report a multiplicity adjustment, a hierarchy of tests beyond identifying the primary measure, or an analysis plan. It is therefore not possible to determine whether or how multiplicity was addressed.

Missing-data handling is also not reported in the registry record. The endpoint requires clinical assessment and a surgical specimen, but the record does not state how participants without either assessment were classified, whether assessments were incomplete, or whether any imputation or sensitivity analysis was used. The size of the primary analysis population is not reported. The registry’s description of eligible and treated patients identifies the intended population but does not resolve those questions.

The primary estimate and its stated 90% confidence interval are absent, as are analysis details such as the interval procedure and any adjustments. These omissions limit assessment of both statistical precision and robustness. They should be read as unavailable information, not as evidence that missing data, multiple testing, or analytic choices did or did not affect the result.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thrombosis embolism (3.4%), wound infectious (3.4%), anemia (1.7%), neutropenia (1.7%), ischemia/cardiac infarction (1.7%).

The registry reports serious adverse events for the treatment group, with 58 participants at risk and 17 affected. It also lists 58 participants at risk and 58 affected for other adverse events. These are separate registry entries; the record does not clarify whether participants could appear in both categories, and the counts should not be added together.

The listed serious event terms and percentages are thrombosis embolism, 3.4%; wound infectious, 3.4%; anemia, 1.7%; neutropenia, 1.7%; ischemia/cardiac infarction, 1.7%; and vomiting, 1.7%. The record presents these as serious adverse event terms, but does not provide further detail about severity grading, event duration, timing, or whether events were considered related to treatment. The term-specific percentages should not be treated as evidence of comparative risk.

The death entry is null, so deaths are not reported in the registry record. These safety figures describe reports in a single treatment group. Without a control group, they cannot show whether an event was more or less common than under another approach, and they do not establish that treatment caused an event.

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

The registry record establishes that a phase II, single-group trial evaluated radiation therapy with weekly cisplatin followed by surgery in patients with locally advanced vulvar cancer. It defines a complete clinical and pathologic response and gives the planned timing of the clinical and pathologic assessments. It also reports selected safety counts and event terms.

It does not report the primary response percentage or its 90% confidence interval. Therefore, the posted registry information cannot establish how many participants met the response definition or how precisely that proportion was estimated. The absence of the result should not be interpreted as a result of zero responses, nor as evidence of a particular response rate.

Even if a response estimate were available, the single-group design would describe outcomes among treated participants rather than estimate a randomized difference from a control treatment. The trial cannot, from the design described, determine what the same participants’ outcomes would have been under an alternative regimen. The results also cannot establish comparative safety in the absence of a control group.

The safety entry reports serious adverse events in 17 of 58 participants at risk and lists event-specific percentages. These figures provide a description of reported safety events, but not a causal attribution or comparison. The registry record does not report deaths in the available entry, and that should be understood as missing registry information rather than proof that no deaths occurred.

Overall, the record supports a careful account of the treatment sequence, endpoint definition, design, and some safety reporting. It does not support a quantitative conclusion about the primary response result, its statistical precision, or comparative effectiveness. Those distinctions matter: a trial’s design and outcome definition explain what was studied, but they do not replace the missing outcome estimate.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a clearly described response endpoint and the absence of a posted primary estimate. The registry defines complete clinical and pathologic response, gives separate assessment timing for its clinical and pathologic components, and identifies a 90% confidence interval as the dispersion measure. Yet the response percentage and interval are not reported in the registry record. This leaves the principal outcome’s magnitude and precision unknown from the registry information.

The single-group design is also central to interpretation. It can describe outcomes among participants receiving chemoradiation followed by surgery, but it does not provide a concurrent randomized comparison. Statistical reporting cannot overcome that design limitation: an estimate within one group is not the same as an estimated difference between treatments.

The record also illustrates why enrollment and analysis denominators should be kept distinct. It reports 61 enrolled participants, describes the primary population as eligible and treated patients, and gives a safety denominator of 58. These figures refer to different aspects of the record; the primary endpoint analysis denominator is not reported. Without it, readers cannot judge how much information contributed to the response estimate, even if that estimate were available.

Finally, the sample-size description is explicitly a planning illustration based on the observed effect, rather than the trial’s design. The stated planning assumptions should not be confused with a trial analysis or interpreted as observed power. In combination, these points make the record a useful example of how design, endpoint definition, analysis population, precision, and result availability each shape what can be concluded.

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 statistical interpretation is that the registry record does not report the primary response estimate or its 90% confidence interval. It lists zero analyses, so neither the response magnitude nor its precision can be assessed. The second listed outcome measure is not described in the available information.

The analysis denominator for the primary endpoint is not reported. Although enrollment is 61 and the primary population is described as eligible and treated patients, the number meeting that definition and the number with endpoint assessments are not stated. The safety denominator of 58 is not a substitute for the primary endpoint denominator. The record does not explain how missing clinical assessments, missing surgical specimens, or exclusions were handled.

The design has no listed control group and no random allocation. As a result, the trial cannot estimate a randomized contrast against another treatment. Any reported outcome would have to be interpreted as an outcome observed in the study group, with no direct internal comparison to establish what would have happened under an alternative approach.

Details of the statistical analysis plan are not reported in the registry record. This includes the confidence-interval procedure, any adjusted analyses, multiplicity handling, and the treatment of missing data. The sample-size justification for the trial is also not reported. The listed planning assumptions describe an illustration, not the study design.

The safety information is limited to counts and selected event terms. The record does not provide further details on event timing, duration, grading, treatment relationship, or comparative rates. Its death entry is null, so deaths are not reported in the registry record. The treatment description is also incomplete after the phrase concerning surgery six to eight weeks after chemoradiation, limiting what can be stated about the full protocol.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Cancer of the Vulva — NCT00068406.
• Registry record last updated 2017-11-20; status last verified 2011-10.
• Results first posted 2017-10-17.
• 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.

19. Record Summary

NCT00068406 is a completed phase II, single-group trial of radiation therapy with weekly cisplatin followed by surgery for locally advanced vulvar cancer. The registry reports enrollment of 61 participants and identifies eligible and treated patients as the primary endpoint population. The primary outcome is complete clinical and pathologic response, assessed clinically seven weeks after treatment initiation and pathologically up to fifteen weeks.

The record does not report the primary response percentage, its 90% confidence interval, or the size of the endpoint analysis population. It lists zero analyses and does not describe the second outcome measure in the available information. Safety reporting lists serious adverse events in 17 of 58 participants at risk and selected event-specific percentages. The single-group design does not provide a randomized comparison, so the available information cannot establish comparative treatment effects.