Radiation Therapy and Cisplatin With or Without Amifostine for Patients With Stage IIIB or IVA Cervical Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Radiation Therapy and Cisplatin With or Without Amifostine for Patients With Stage IIIB or IVA Cervical Cancer (NCT00012012), a non-randomized phase 1, phase 2 study. The primary outcome is Rate of Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia).

2. Clinical Question

3. Trial Design

This was a phase I/II study of radiation therapy and cisplatin, with or without amifostine, for patients with stage IIIB or stage IVA cervical cancer. The record describes extended-field external beam radiation to the para-aortic region and pelvis, intracavitary brachytherapy, and concurrent weekly cisplatin in both regimens. Amifostine trihydrate was included in one regimen. The trial was non-randomized and unmasked, and its registry model is listed as single group. Those design features matter when interpreting the two regimen descriptions: the record does not establish that patients were assigned by chance or that the groups were intended as directly comparable controls.

The enrollment is listed as 45. The record lists the trial as starting in 2001-08, reaching primary completion in 2007-09, and having completed status. The sponsor is the Radiation Therapy Oncology Group. The primary outcome description says the first part was intended to determine acute grade 3/4 toxicity, excluding grade 3 leukopenia, as a starting point for the second part of the study. It does not give further detail about the transition between parts, allocation procedures, or analysis plan.

Two adverse-event groups are listed: Radiation Therapy Plus Cisplatin and Radiation Therapy Plus Cisplatin & Amifostine. Their at-risk counts are 26 and 15, respectively. The reason these counts differ from each other or from total enrollment is not reported in the registry record. Pelvic tumor control and distant metastases are listed as secondary outcomes, but their results 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All eligible 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: All eligible patients.

6. Primary Endpoint

The registry lists the primary outcome as Rate of Acute Grade 3/4 Toxicity (Excluding Grade 3 Leukopenia), measured over From start of treatment to 90 days.

The primary endpoint is the rate of acute grade 3/4 toxicity, excluding grade 3 leukopenia, among all eligible patients. Its stated timeframe runs from start of treatment to 90 days. The outcome is expressed as a percentage of participants, so it is intended to describe how many eligible participants experienced the specified level of acute toxicity during that period. The registry description says the endpoint was chosen to assess feasibility and tolerance of extended-field external radiotherapy to the pelvis and para-aortic region and intracavitary irradiation combined with weekly cisplatin.

Excluding grade 3 leukopenia narrows the endpoint definition: that toxicity category at that grade is not counted within the stated primary outcome. This definition must be kept in mind when comparing the endpoint with broader toxicity summaries, which may include different events or severity categories. The registry record does not report the number of participants meeting the endpoint, its percentage, or its confidence interval. It also does not report the endpoint result separately for the two described regimens.

As general statistical context, a prespecified toxicity endpoint can provide a structured way to describe short-term treatment tolerability. A percentage gives an event frequency within the analysis population, while a confidence interval conveys uncertainty around that estimate. Neither the estimate nor its interval is available in the registry record, so the primary endpoint cannot be quantified from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a percentage endpoint: the proportion of eligible participants with acute grade 3/4 toxicity, excluding grade 3 leukopenia, during the period from start of treatment to 90 days. It names a 95% confidence interval as the dispersion measure. However, no endpoint estimate or interval is reported in the registry record. The posted information therefore identifies the intended type of analysis without giving its numerical result.

What a percentage endpoint describes

As general statistical context, a participant-level percentage summarizes how frequently a defined event occurred in a specified group over a specified period. It depends on the event definition, the participants included, and whether event status is known for those participants. Here, the event definition excludes grade 3 leukopenia and focuses on acute grade 3/4 toxicity. A broader count of adverse events or a different severity threshold would answer a different question.

The denominator is important. The primary outcome description names all eligible patients, but the actual number included in the endpoint analysis is not reported in the registry record. Total enrollment is 45, while the adverse-event groups list 26 and 15 participants at risk. The registry does not establish that these counts are the denominator for the primary outcome. They should therefore be kept distinct from the unreported primary analysis population.

How to understand the confidence interval

As general statistical context, a confidence interval expresses uncertainty around an estimated quantity. It gives a range of values compatible with the data and the statistical procedure used; it is not a guarantee that the true value lies in that specific interval. An interval’s width reflects both the amount of information and the variability of the data. In a participant-percentage analysis, fewer observed participants can make an estimate less precise, though the actual precision also depends on the event count and the analysis method.

The registry names a 95% confidence interval for the primary outcome but does not post its limits. There is consequently no interval width to interpret and no basis for describing the estimate as precise or imprecise. The endpoint’s confidence level alone does not reveal the observed toxicity frequency.

Design and comparison

The allocation is listed as non-randomized, masking as none, and the model as single group. At the same time, two regimens are described, and adverse-event counts are listed for two groups. This combination should be reported as it appears rather than resolved by assumption. The registry does not explain how the groups were formed, whether the regimen descriptions correspond exactly to the adverse-event groups, or how the two-part study was operationalized beyond saying that the first part was intended to provide a starting point for the second part.

As general statistical context, random allocation can help balance measured and unmeasured factors between groups. Without randomization, baseline or treatment-related differences can affect an observed contrast. In this record, no randomized comparison is described; accordingly, the two groups do not support a causal comparison on the information available. The registry also does not report adjustment methods or other procedures that might address group differences.

Adverse-event counts and event terms

The safety record distinguishes participants at risk from participants affected, with counts listed for serious adverse events and other adverse events. These are participant counts, not a measure of the number of separate event episodes. The serious-event terms listed include nausea, vomiting NOS, hyponatremia, diarrhea NOS, hypokalemia, and packed red blood cell transfusion. The record gives percentages alongside these terms but does not identify a denominator or group attribution for each term in the information available. They should not be treated as group-specific rates unless that attribution is reported.

As general statistical context, serious adverse events and a toxicity endpoint defined by grade are related but not interchangeable classifications. A serious event may be classified using criteria that differ from the endpoint’s grade-based definition. The registry does not provide enough detail to map individual serious-event terms to the primary endpoint or determine whether an event met its exact criteria.

Planning calculations versus trial results

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such illustrations are planning scenarios, not observed power and not evidence that the original trial used those assumptions. The registry does not report a sample-size justification or the trial’s own statistical plan. It also does not report the primary effect estimate needed to interpret calculations based on that effect. No planning values are stated in the registry record.

As general statistical context, a sample-size calculation depends on assumptions about the target effect, variability or event frequency, significance threshold, power, and allocation. Changing an assumption changes the planning result. A planning calculation does not show what the trial observed, and it cannot make a missing endpoint estimate available. The sample-size illustrations should therefore be read as hypothetical planning exercises rather than evidence about the trial’s findings.

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("Radiation Therapy Plus Cisplatin")
n      <- c(26)
events <- c(21)
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  Radiation Therapy Plus Cisplatin  26  21  80.8  60.6  93.4  62.1  91.5  61.9  91.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes: pelvic tumor control and distant metastases. It does not report results for these outcomes, and it lists no outcome analyses. The multiplicity strategy—such as whether or how the analysis accounted for assessing more than one outcome—is not reported in the registry record. Without results and an analysis plan, it is not possible to assess how multiple outcome testing was handled or whether any reported statistical claims were adjusted.

Missing-data procedures are also not reported in the registry record. The record does not describe how participants with incomplete follow-up, unavailable toxicity assessments, or other missing endpoint information were handled. It does not state whether all eligible patients had outcome status determined through the 90-day timeframe. The number included in the primary analysis is not reported.

The primary endpoint description specifies all eligible patients as the population of interest, but this does not establish the actual analysis population or how eligibility was applied in the results. There is no reported intention-to-treat analysis, per-protocol analysis, or other named analysis population. The total enrollment of 45 and the adverse-event at-risk counts do not resolve this absence because the registry does not state that those counts form the primary endpoint denominator.

As general statistical context, missing outcome data can affect both the estimated event frequency and its uncertainty, particularly when the chance of missingness is related to health status or treatment. A transparent report usually describes how much information is missing and the assumptions used to address it. Those details are not reported in the registry record, so the potential impact of missing data cannot be assessed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (33.3%), vomiting nos (26.7%), hyponatremia (26.7%), diarrhea nos (23.1%), hypokalemia (23.1%).

The adverse-event record lists two groups. For Radiation Therapy Plus Cisplatin, 26 participants were at risk for serious adverse events and 20 were affected; 26 were at risk for other adverse events and 26 were affected. For Radiation Therapy Plus Cisplatin & Amifostine, the corresponding counts are 15 at risk and 12 affected by serious adverse events, and 15 at risk and 15 affected by other adverse events. These are counts of participants, not counts of event episodes.

The record also lists serious adverse-event terms with percentages: nausea, 33.3%; vomiting NOS, 26.7%; hyponatremia, 26.7%; diarrhea NOS, 23.1%; hypokalemia, 23.1%; and packed red blood cell transfusion, 20.0%. The denominator and attribution of these term percentages are not reported in the registry record, so they should not be assigned to a particular regimen or treated as rates for the entire enrolled population.

These safety summaries do not provide the primary endpoint result. They use serious and other adverse-event categories, whereas the primary endpoint is specifically acute grade 3/4 toxicity excluding grade 3 leukopenia. The record does not report deaths, and the reason for the difference between at-risk counts is not reported. Because allocation was non-randomized, the group counts do not establish that one regimen caused more or fewer adverse events than the other.

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

The registry record establishes that a phase I/II study examined extended-field external beam radiation, intracavitary brachytherapy, and weekly cisplatin, with one regimen also including amifostine trihydrate. It identifies a primary endpoint intended to measure acute grade 3/4 toxicity excluding grade 3 leukopenia through 90 days from treatment start. It also lists adverse-event counts for two treatment groups and names pelvic tumor control and distant metastases as secondary outcomes.

It does not report the primary endpoint rate, its confidence interval, or results for the secondary outcomes. Therefore, the posted information cannot show the observed frequency or precision of the primary toxicity outcome. Nor can it establish the comparative effect of adding amifostine. The non-randomized allocation and single-group model listing further mean that the two regimen descriptions should not be interpreted as a randomized, like-for-like comparison.

The adverse-event counts do show how many participants in each listed group were recorded as affected by serious or other adverse events. They do not, by themselves, identify the primary endpoint rate, explain the clinical importance of each event, or establish that treatment caused an event. The serious-event terms and their listed percentages also lack reported denominator and group attribution in the registry record.

As general statistical context, the meaning of a trial result depends on the outcome definition, analysis population, study design, and uncertainty around estimates. A result that is not reported cannot be inferred from the design description or from other safety counts. The absence of posted results is not evidence for either a favorable or unfavorable outcome. The registry record supports a limited account of what was planned and which safety counts were posted, but it does not support a quantified conclusion about toxicity or tumor control.

14. Why This Trial Matters Statistically

This trial illustrates why the distinction between a defined endpoint and a reported result is essential. The record gives a specific primary toxicity measure, including a grade threshold, an exclusion for grade 3 leukopenia, and a timeframe from treatment start to 90 days. Those details define what an eventual estimate would represent. Yet the record does not report the estimate or its 95% confidence interval, leaving the main statistical question unanswered in the posted results.

It also highlights the importance of reading the design labels together. Two regimen descriptions and two adverse-event groups appear, but allocation is non-randomized and the registry model is listed as single group. A contrast between group counts is not automatically a treatment effect. Without random allocation and without reported methods for addressing group differences, a causal interpretation is not supported by the record.

The different counts at risk also underscore why denominators need to be explicit. Enrollment is listed as 45, while the two adverse-event groups list 26 and 15 participants at risk. The record does not explain how these populations relate to the eligible-patient primary endpoint population. No conclusion about exclusion, dropout, or analysis inclusion should be inferred from these numbers alone.

As general statistical context, a report is most useful when it connects the clinical question to the analysis population, estimate, uncertainty, and missing-data handling. This record provides part of the question and selected safety counts, but not the details needed to evaluate the primary estimate or its precision. That distinction is important for statistical interpretation, regardless of the treatment setting.

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.

Several limitations specific to the registry record constrain interpretation. The primary outcome is described, but its event count, percentage, and 95% confidence interval are not reported. The record also lists no outcome analyses. As a result, the primary toxicity question cannot be answered quantitatively from the posted results, and the listed secondary outcomes cannot be evaluated.

The design information is not fully aligned: allocation is non-randomized, the model is single group, and two regimens and two adverse-event groups are described. The registry record does not explain the relationship among these features or how participants entered the two groups. The at-risk counts are 26 and 15, while total enrollment is 45; the reasons for the different counts are not reported. The number included in the primary endpoint analysis is also not reported.

The record does not provide baseline characteristics, detail on treatment delivery, the duration or completeness of follow-up beyond the primary endpoint timeframe, or methods for handling missing outcomes. It does not describe an analysis plan, multiplicity handling, or an adjustment strategy for non-randomized group differences. These omissions prevent assessment of comparability, potential bias, and the robustness of any group contrast.

Safety information is limited to participant counts and listed event terms. The registry does not report deaths, and it does not specify the denominators or group attribution for the percentages associated with serious-event terms. The serious-event counts do not necessarily correspond to the grade-based primary endpoint. These limitations apply to what is reported in the registry record and do not establish what may have been reported elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Radiation Therapy and Cisplatin With or Without Amifostine for Patients With Stage IIIB or IVA Cervical Cancer — NCT00012012.
• Registry record last updated 2015-01-07; status last verified 2014-12.
• Results first posted 2015-01-07.
• 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

This completed phase I/II study, sponsored by the Radiation Therapy Oncology Group, enrolled 45 participants and examined extended-field radiation and cisplatin regimens with or without amifostine for stage IIIB or stage IVA cervical cancer. The primary outcome was acute grade 3/4 toxicity excluding grade 3 leukopenia, assessed from start of treatment to 90 days. The registry record describes non-randomized allocation and a single-group model, while also listing two regimen descriptions and two adverse-event groups.

The registry lists serious and other adverse-event counts and names pelvic tumor control and distant metastases as secondary outcomes. It does not report the primary endpoint estimate or confidence interval, secondary outcome results, or outcome analyses. Missing-data methods, the primary analysis population count, and the relationship between enrollment and adverse-event group counts are not reported in the registry record.