Cisplatin + Radiation in SCCHN and Correlation With Oxidative Stress Markers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cisplatin + Radiation in SCCHN and Correlation With Oxidative Stress Markers (NCT02994069), a randomized phase 2 study. The primary outcome is CTCAE Grade 3-5 Cisplatin-related Adverse Event Rate (Percentage).

2. Clinical Question

The trial also examines the relationship between cisplatin toxicity and reactive oxygen species generated by the drug. That biological relationship is part of the stated study purpose, but a result for it is not reported in the registry record. Local control rates and survival are listed as secondary outcomes. The posted numerical secondary summary concerns survival; a numerical local-control result is not reported in the registry record.

The primary outcome is framed as a comparison of toxicity between treatment schedules, rather than as a comparison of tumor response. Because both groups receive radiation, the schedule contrast concerns weekly versus every-3-weeks cisplatin alongside radiation. The registry record does not report eligibility details or a more specific description of the population beyond locally advanced disease and the listed cancer conditions.

3. Trial Design

This is a randomized, phase 2 trial with a parallel-group design and no masking. Participants are assigned to radiation therapy with either cisplatin every 3 weeks or weekly cisplatin. The registry lists an enrollment of 80. The posted primary outcome summaries include 39 participants in the every-3-weeks group and 41 in the weekly group.

The study began on 2017-04-11, has a primary completion date of 2024-09-03, and is listed as active, not recruiting. The record names cisplatin as a drug intervention and XRT as a radiation intervention. It describes standard-of-care radiation to the primary tumor, involved nodal metastasis, and draining nodal basin, alongside one of the cisplatin schedules.

Random assignment is relevant because, in general, it is intended to make treatment groups comparable with respect to factors that could affect outcomes. The record does not describe the randomization procedure, allocation concealment, stratification factors, or any other design details. It also does not report the original sample-size justification or the trial's planned statistical analysis. The absence of masking is recorded, but the record does not explain whether outcome assessment was blinded.

The posted summaries should therefore be read in the context of a randomized, unmasked parallel comparison, while recognizing that several details needed to assess implementation and analysis are not reported in the registry record. The trial status and dates describe the registry entry; they do not, by themselves, establish that every planned analysis or outcome has been completed.

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:

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 CTCAE Grade 3-5 Cisplatin-related Adverse Event Rate (Percentage), measured over 90 days.

The primary endpoint is the percentage of participants in each group who experience at least one cisplatin-related adverse event of grade 3–5 within 90 days of the first treatment. The registry describes it as a cohort-level rate, calculated from the number of participants with one or more qualifying events. It also states that the endpoint is estimated with exact 95% binomial confidence intervals.

This measure focuses on whether a participant experiences a severe or medically important toxicity, rather than counting every event as a separate observation. In general, using the proportion of participants affected makes the outcome interpretable as the share of a treatment group with at least one qualifying event during the specified period. The restriction to events related to cisplatin and the defined follow-up window makes the endpoint more specific than an all-cause count over an unspecified period.

The posted group summaries express the outcome as a mean percentage with a standard deviation. The posted comparison is a mean difference between those group summaries. The registry record does not include per-group confidence limits for the endpoint, although its description says exact binomial intervals were to be estimated. The primary endpoint concerns toxicity; it does not directly measure tumor control, survival, or the proposed oxidative-stress relationship.

7. Results Posted in the Registry

• Weekly Cisplatin + XRT: mean 68.29 versus 74.36 on control; difference -6.07 (95% CI -9.19 to -2.95), standardized effect d = -0.85; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Survival

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Weekly Cisplatin + XRT: mean 517.06 versus 687.50 on control; difference -170.44 (95% CI -176.01 to -164.87), standardized effect d = -13.30; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Weekly Cisplatin + XRT than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists local control rates and survival as secondary outcomes. It contains numerical summaries for survival, but a numerical local-control result is not reported in the registry record. The posted survival comparison is an unadjusted difference in mean days, with the weekly group's mean lower than the every-3-weeks group's mean. This direction differs from the primary toxicity contrast, where the posted weekly-group summary is lower.

The outcomes answer separate questions. The primary endpoint measures the percentage experiencing a severe cisplatin-related adverse event within the defined period. Survival concerns time alive, while local control concerns disease control at the treated site. A pattern across different endpoints cannot be collapsed into a single conclusion about the relative merits of treatment schedules. The oxidative-stress relationship is also part of the study purpose, but its result is not reported in the registry record.

The registry lists zero reported analyses. The displayed survival contrast is unadjusted, and the record does not describe a prespecified statistical method, adjustment for other factors, censoring approach, or multiplicity strategy. In general, when several outcomes are examined, unadjusted tests can produce apparently notable results by chance more often than a single test would. Secondary results also commonly have less confirmatory weight when they are not supported by a stated analysis plan or multiplicity adjustment. These limitations do not erase the numerical summaries, but they make them less definitive than a clearly prespecified and appropriately analyzed primary comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Local Control Rates
• Survival

9. Statistical Interpretation

10. Statistical Methods Explained

A mean is a measure of the central value of a set of observations. For the primary outcome, the registry reports the mean percentage for each group and a standard deviation. In general, the standard deviation describes variation among observations; it is not the uncertainty in the group mean. The primary endpoint is described as a participant-level percentage, but the record does not clarify in detail how the reported means and standard deviations were constructed across participants or cohorts.

What does the mean difference represent?

The posted contrast is weekly cisplatin plus radiation minus cisplatin every 3 weeks plus radiation. The estimate is -6.07 percentage points. A negative value means the weekly-group summary is lower for this measure. The confidence interval runs from -9.195 to -2.945. In general, a mean difference puts the two group summaries on the original outcome scale, which is percentage points. It is not a relative percentage change, and no relative change is calculated in this interpretation.

The comparison is unadjusted: no adjustment for other variables is stated in the posted contrast. The registry record does not report the method used to obtain the comparison, the model specification, or an adjusted analysis. General statistical methods for comparing means may use assumptions about the outcome distribution and sampling variability, but the particular method should not be inferred when it is not described.

How should the confidence interval be read?

In general, a confidence interval gives a range of values compatible with the observed data under the procedure and assumptions used to construct it. It represents uncertainty about a group contrast, not a guarantee about where the true value lies, nor a range of individual participant outcomes. The primary comparison's 95% interval does not include zero. The reported p-value is p < 0.001. In general, a p-value measures how incompatible the observed data are with a specified null hypothesis under the assumed analysis; it is not the probability that the null hypothesis is true, and it does not quantify clinical importance.

The endpoint description specifically mentions exact 95% binomial confidence intervals for each cohort. The posted comparison, however, gives a confidence interval for a mean difference, and the group-level exact interval limits are not listed. The record does not explain the relationship between those stated endpoint intervals and the displayed comparison interval. The two types of intervals answer different questions: group-specific binomial intervals describe uncertainty in each group's proportion, while an interval for a difference describes uncertainty in the contrast between groups.

Why can over-dispersion matter?

General explanation: a binomial model assumes that each participant's outcome can be represented as an affected or not-affected result with a common event probability, conditional on the model. If outcomes vary more than that model expects, the data are over-dispersed. In that situation, standard errors can be too small if the extra variability is ignored, which can make confidence intervals too narrow and p-values too small. A cluster-level or cohort-level percentage can also have a different variability structure from individual binary outcomes. The registry does not report whether over-dispersion was assessed or how it was handled.

The posted survival comparison is also represented as a mean difference in days with standard deviations. Although survival is often analyzed as time-to-event data, the registry's posted summary labels this outcome as continuous and reports mean days. The record does not report a time-to-event model, censoring method, survival curve analysis, or hazard ratio. Those methods should not be assumed from the outcome name alone.

What is and is not documented?

The registry record identifies a randomized, unmasked, parallel design and provides arm summaries and unadjusted comparisons. It lists no reported analyses. Details such as the planned primary model, handling of missing observations, analysis population, covariate adjustment, and multiplicity control are not reported in the registry record. General statistical interpretation must therefore distinguish the numerical contrast from any claim about how the trial's formal analysis was planned or conducted.

The sample-size planning illustration is based on the observed effect and states assumptions of a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. It considers the stated fraction of the observed effect to be detected. These are planning calculations, not the original trial design assumptions, which are not reported in the registry record. For continuous outcomes, the displayed planning quantities are participants per arm. The study's original rationale for its enrollment target cannot be reconstructed from this illustration.

11. Confidence Intervals and Precision

The primary mean-difference estimate is -6.07 percentage points, and its 95% confidence interval extends from -9.195 to -2.945. The interval is entirely below zero and is relatively narrow around the displayed estimate. This conveys the precision of the unadjusted group contrast under the method used to calculate it. It does not address possible bias from missing data, outcome classification, or analysis choices that are not described in the registry record.

A confidence interval is generally more informative than a point estimate alone because it shows a range of contrast values compatible with the data and procedure. The primary interval does not provide the uncertainty for each group separately. Although the endpoint description says exact 95% binomial intervals were estimated for each cohort, their limits are not reported in the registry record. The posted standard deviations describe variability in the group summaries, not confidence limits for the group means.

The survival comparison has a mean difference of -170.4 days and a 95% confidence interval from -176.0 to -164.9. That interval is also narrow around its estimate, but precision alone does not show whether the analysis is appropriate for the underlying survival data. The registry does not report how censoring, incomplete follow-up, or the distribution of survival times was handled.

In general, a narrow interval indicates less sampling uncertainty under the specified method, not certainty that the estimate is unbiased or broadly applicable. The absence of reported analysis details and per-group endpoint intervals limits a fuller assessment of precision.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustration gives the number of participants per arm for the posted continuous comparisons; it does not give a total number of events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the listed fraction of the observed effect. The trial's original sample-size assumptions and justification are not reported in the registry record.

For the primary endpoint, planning for 100% of the observed effect gives 22 participants per arm for 80% power and 30 participants per arm for 90% power. Planning for 75% of the observed effect gives 39 participants per arm for 80% power and 52 participants per arm for 90% power. Planning for 50% of the observed effect gives 87 participants per arm for 80% power and 117 participants per arm for 90% power. In plain terms, the 80% column is the estimated group size under which the stated assumptions would give an 80% chance of detecting the chosen effect if that effect were real; the 90% column uses a higher target chance of detection.

Smaller effects require more participants under these assumptions, as the primary planning figures illustrate. The survival planning figures are 1 participant per arm across the listed effect fractions. That output reflects the unusually large observed mean contrast relative to the posted variability and should not be treated as a practical design recommendation. These planning calculations are not observed power; they are illustrations based on the observed effect and stated assumptions, not evidence about the trial's actual chance of detecting an effect.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -6.070; pooled standard deviation σ = 7.135.
2. n = 2 × (1.96 + 0.842)² × 7.135² / -6.070² = 21.7, rounded up to 22 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -6.06999999999999                      # observed difference in means
sigma <- 7.13496249069256                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2994069)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 22 (80% power), 30 (90% power)
 75% of observed effect: n per arm = 39 (80% power), 52 (90% power)
 50% of observed effect: n per arm = 87 (80% power), 117 (90% power)
power.t.test: 22.7 
Simulated power at n = 22 per arm: 0.786 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes, but it does not report a multiplicity plan. Multiplicity arises when several statistical questions are tested: even if each test is conducted at a conventional threshold, the chance of at least one false-positive finding across a family of tests can increase. General approaches include defining a hierarchy of outcomes or adjusting the inference across tests. No such approach is reported in the registry record, so the unadjusted secondary p-value should not be treated as if it were protected against multiple testing.

The record lists zero reported analyses. It does not specify which participants were included in each analysis, whether the primary analysis followed the randomized assignment, or how participants who did not complete follow-up were handled. Missing-data methods, exclusions, protocol deviations, and the timing of any interim analyses are not reported in the registry record. No assumptions about these matters can be recovered from the summary values alone.

These omissions matter because an analysis may depend on whether observations are missing and why they are missing. In general, if follow-up or outcome recording differs between groups, a comparison of only observed cases may not preserve the balance intended by randomization. The registry does not provide enough information to determine whether this issue arose or how it was addressed.

The same caution applies to analysis populations and outcome adjudication. The record does not describe a modified intention-to-treat or per-protocol population, nor does it explain how cisplatin-relatedness and event grades were assessed. The endpoint definition is stated, but operational procedures for applying it are not reported. These gaps limit the ability to judge the robustness and confirmatory status of the posted comparisons.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: mucositis oral (36.6%), oral pain (31.7%), white blood cell decreased (29.3%), vomiting (28.2%), nausea (25.6%).

The adverse-event summary lists 39 of 39 participants in the every-3-weeks group and 41 of 41 in the weekly group as affected by serious adverse events. It also lists other adverse events for 8 of 39 participants in the every-3-weeks group and 10 of 41 in the weekly group. The registry lists 7 deaths in the every-3-weeks group and 13 in the weekly group. These are counts in the registry summary; the record does not establish that the deaths were caused by treatment.

The listed serious-event terms include oral mucositis, oral pain, decreased white blood cell count, vomiting, nausea, and decreased neutrophil count. The registry gives percentages for these terms, but does not identify an arm-specific breakdown for those percentages in the available summary. Event terms may not represent mutually exclusive participants, because a participant can experience more than one type of event. The record does not provide enough detail to interpret the percentages as counts of distinct individuals or compare the terms between arms.

Serious adverse events, other adverse events, and deaths are distinct summaries and should not be conflated with the primary endpoint, which is restricted to cisplatin-related grade 3–5 events within 90 days.

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

The posted primary data show a lower mean percentage of participants with the defined severe cisplatin-related adverse-event outcome in the weekly group than in the every-3-weeks group. The unadjusted contrast is -6.07 percentage points, with a 95% confidence interval from -9.195 to -2.945 and p < 0.001. This describes the registry summary and its statistical precision under the displayed comparison; it does not establish a complete account of all harms or outcomes.

The randomized design is relevant to comparing treatment schedules, but the registry record does not report important analysis details such as the primary model, missing-data handling, or analysis population. The study is unmasked, and no reported analyses are listed. The result therefore should not be expanded into a claim about every possible toxicity, the oxidative-stress mechanism, or outcomes beyond the specified endpoint and follow-up window.

The secondary survival summary differs in direction from the primary toxicity contrast, while local-control results are not reported in the registry record. The survival summary is reported as mean days, and no time-to-event analysis details are given. The posted summaries do not explain the relationship between outcomes or establish a single overall treatment effect.

In general, statistical evidence about a defined endpoint is not the same as a judgment about the clinical balance of benefits and harms. The record does not provide the detail needed to assess every source of uncertainty, and the observed data alone do not demonstrate why the groups differ. Interpretation should remain limited to the stated measures, comparisons, and follow-up descriptions.

17. Why This Trial Matters Statistically

This trial presents a statistical challenge common in comparative clinical research: the main outcome is a percentage, while the posted group summaries and contrast are expressed as means and standard deviations. Understanding exactly what is averaged, how the endpoint is constructed, and what the comparison estimates is essential to interpreting the result. The registry describes an exact binomial approach for cohort-level intervals, but does not list those interval limits or explain how they relate to the displayed mean-difference comparison.

The design also places several outcome types side by side. Toxicity, survival, local control, and the proposed oxidative-stress relationship are not interchangeable measures. A strong-looking result on one endpoint cannot automatically stand in for the others, particularly when analysis details and multiplicity handling are not reported. The secondary survival summary is expressed as a mean, although time-to-event outcomes can require methods that account for censoring; the registry does not explain its approach.

Finally, the sample-size illustration is based on the observed effect rather than on the trial's original design assumptions. It helps show how assumed effect size and target power influence planning quantities, but cannot explain why the study enrolled its planned number of participants. This distinction is useful when evaluating registry results: displayed estimates, planning illustrations, and a trial's prespecified design rationale are different kinds of evidence.

18. 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 are specific to the information reported for this trial. The endpoint description refers to exact 95% binomial confidence intervals for each group, but the group-specific interval limits are not reported. The posted group values are means with standard deviations for a percentage endpoint, and the registry does not explain the construction of those summaries in enough detail to reconcile them with the endpoint description.

The registry lists no reported analyses and does not describe the primary model, missing-data handling, analysis population, outcome adjudication, or multiplicity strategy. Consequently, the displayed unadjusted p-values and intervals cannot be evaluated against a stated statistical analysis plan. Local control is listed as a secondary outcome, but a numerical result is not reported in the registry record. The stated relationship between toxicity and reactive oxygen species also has no reported result.

Survival is summarized as mean days, but the record does not report how incomplete follow-up, censoring, or time-to-event analysis was handled. The arm-level survival summaries alone cannot clarify those issues. The adverse-event summary includes group-level affected counts and a list of event terms with percentages, but the available record does not give an arm-specific breakdown for those terms or establish causal attribution for deaths.

The record identifies the trial as unmasked but does not explain outcome-assessment procedures. It also does not report detailed eligibility criteria, randomization procedures, or the original sample-size justification. These limits restrict assessment of implementation, generalizability, and the robustness of the comparisons.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Cisplatin + Radiation in SCCHN and Correlation With Oxidative Stress Markers — NCT02994069.
• Registry record last updated 2026-09-25; status last verified 2026-09.
• Results first posted 2025-10-14.
• 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.

22. Record Summary

NCT02994069 is a randomized, unmasked, phase 2 parallel trial comparing weekly with every-3-weeks cisplatin, each given with radiation, in locally advanced squamous cell carcinoma of the head and neck. Enrollment is listed as 80, and the record is active, not recruiting.

The primary endpoint is the percentage of participants with at least one grade 3–5 cisplatin-related adverse event within 90 days. The posted unadjusted mean difference is -6.07 percentage points for weekly versus every-3-weeks treatment, with a 95% confidence interval from -9.195 to -2.945 and p < 0.001. Secondary outcomes include local control and survival; a numerical local-control result is not reported in the registry record. The registry lists no reported analyses, and key details about analysis methods and missing data are not reported.