Curcumin for the Prevention of Radiation-induced Dermatitis in Breast Cancer Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Curcumin for the Prevention of Radiation-induced Dermatitis in Breast Cancer Patients (NCT01042938), a randomized phase 2 study. The primary outcome is Severity of Dermatitis in Radiation Treatment Site in Breast Cancer Patients.

2. Clinical Question

The clinical question focuses on skin reactions during radiotherapy, rather than on cancer control or longer-term outcomes. The registry describes radiation dermatitis as a concern because it can affect quality of life and may lead to premature interruption of radiation treatment. Those statements give context for studying a preventive approach; they are not outcomes measured by the primary comparison.

3. Trial Design

This was a phase 2, randomized, parallel-group trial comparing Curcumin C3 Complex with placebo in people with breast cancer receiving postoperative radiotherapy. The registry lists 35 participants as enrolled and identifies the study as completed. The sponsor was the University of Rochester. The recorded study start was 2008-01, and primary completion was 2010-09.

The registry classifies allocation as randomized and masking as quadruple. The brief summary describes the study as randomized, double-blind, and placebo-controlled. Both groups took four capsules three times daily throughout the prescribed radiation course, described as approximately 4-7 weeks. The listed curcumin dose was 2.0 grams per administration; the placebo regimen was described with the same capsule count and stated mass.

The primary analysis used the highest Radiation Dermatitis Severity score recorded at the end of treatment for each participant. The registry says that all 30 participants who fully completed the trial were included in all analyses. The difference between the enrolled total and the number described as completing is not explained in the registry record; reasons for non-completion and any details about participants not included in the analyses are not reported in the registry record.

The registry identifies three secondary outcomes: moist desquamation, redness, and pain at the radiation treatment site. It also describes repeated-measure analyses of dermatitis severity over time in each arm, but the specific repeated-measure results are not reported in the registry record. The original statistical plan, including its sample-size justification, is 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: We used all 30 participants that fully completed the trial in all of our analyses.

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 Severity of Dermatitis in Radiation Treatment Site in Breast Cancer Patients, measured over 4-7 weeks (prescribed course of radiation).

The primary endpoint was severity of dermatitis at the radiation treatment site in breast cancer patients. Severity was measured with the Radiation Dermatitis Severity scale, which ranges from 0.0 to 4.0 in increments of 0.5. The registry describes the scale as a revised form of the NIH Common Toxicity Criteria intended to account for color and subtle texture changes in skin.

For the primary analysis, the value for each participant was the worst dermatitis score, meaning the highest score, at the end of treatment. The comparison was between the group mean scores for curcumin and placebo. The endpoint therefore summarizes the most severe recorded skin reaction during the treatment course, rather than an average across all assessments over time. The registry also says repeated-measure analyses were performed to examine severity over time, but does not report their results.

A mean can describe the group’s overall score, while the standard deviation describes how spread out individual scores are around that mean. Because the scale has a stated range and fixed increments, the group mean is a summary of scores on that scale; it does not mean every participant had a score equal to the group average.

This endpoint was relevant to the stated study aim of assessing prevention of acute radiation-induced dermatitis during postoperative radiotherapy. The registry’s rationale notes that radiation-related skin effects can be consequential during treatment. The primary endpoint does not, by itself, measure quality of life, treatment interruption, or cancer control.

7. Results Posted in the Registry

• Curcumin C3 Complex: mean 2.60 versus 3.40 on control; difference -0.80 (95% CI -1.39 to -0.21), standardized effect d = -1.01; z-test p = 0.008.

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.

Moist Desquamation at Radiation Treatment Site

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Curcumin C3 Complex: 28.6% (4/14) versus 87.5% (14/16) on control; risk difference -58.9 percentage points (95% CI -87.6 to -30.2), risk ratio 0.33 (0.14–0.76); unadjusted two-proportion z-test p = 0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Curcumin C3 Complex than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Redness at Radiation Treatment Site

• 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:
  • Curcumin C3 Complex: mean 4.52 versus 6.06 on control; difference -1.54 (95% CI -3.56 to 0.48), standardized effect d = -0.55; z-test p = 0.135.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Curcumin C3 Complex and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover different aspects of skin reaction at the radiation treatment site: moist desquamation, redness, and pain. The posted numerical results include a lower count of moist desquamation in the curcumin group than in the placebo group, and a lower mean redness score in the curcumin group. The registry names pain as a secondary outcome, but its results are not reported in the registry record.

This broad pattern is directionally consistent with the primary comparison, which also has a lower mean dermatitis severity score in the curcumin group. However, the outcomes measure different features and use different scales or data types. Agreement in direction does not make them interchangeable or establish that they reflect one single underlying effect. The primary result remains the designated main comparison; secondary findings are supporting context rather than independent confirmation.

The reported secondary analyses use different methods: Fisher Exact for moist desquamation and ANOVA for redness. The registry does not report a multiplicity adjustment or explain whether these analyses were prespecified in a statistical plan. When multiple outcomes are tested, unadjusted results carry less weight because they do not account for the increased opportunity to obtain a small p-value across several comparisons. Secondary results can help describe the pattern of outcomes, but they should not be interpreted as if each were the sole, prespecified test.

Not all secondary results are fully reported. In particular, the registry lists pain but does not provide its result, and it describes repeated-measure analyses of dermatitis over time without reporting those results. Missing result details limit assessment of the complete secondary-outcome pattern. The record also does not describe how missing observations for these endpoints were handled.

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

• Moist Desquamation at Radiation Treatment Site
• Redness at Radiation Treatment Site
• Pain at Radiation Treatment Site

9. Statistical Interpretation

10. Statistical Methods Explained

The primary comparison concerns a continuous outcome: the mean of the worst end-of-treatment dermatitis scores in each randomized group. A mean difference expresses how far apart those group averages are, with the comparison calculated as curcumin minus placebo. A negative estimate in this direction means that the curcumin group’s average score was lower. This is a description of the direction of the observed contrast, not a judgment about clinical importance.

What does the pooled-variance t-test assess?

The registry reports a standard pooled variances t-test for the final values. In general, a t-test assesses whether an observed difference between group means is compatible with a null hypothesis of no difference, while accounting for sampling variation. The pooled-variance version combines information about variability in the two groups under an assumption that their underlying variances can be treated as equal for this calculation. The registry does not report whether that assumption was checked or whether other model assumptions were assessed.

The posted comparison also gives group standard deviations. These describe variation among participants’ scores within each arm. The standard deviation is distinct from the standard error, which describes the uncertainty in an estimated mean. The posted standard errors for the two group means are 0.266 for curcumin and 0.139 for placebo. They are ingredients in the uncertainty around the group means, not measures of the range of individual scores.

How should the confidence interval and p-value be read?

A confidence interval gives a range of estimates compatible with the data and the method used, at the stated confidence level. It is not a range containing a known proportion of individual participant scores. For the primary comparison, the registry reports a 95% confidence interval for the mean difference, and the unadjusted re-calculation also gives a 95% interval. The interval describes uncertainty around the estimated group contrast. A p-value measures how incompatible the observed data are with a specified null hypothesis, given the test’s assumptions; it is not the probability that the null hypothesis is true.

The registry’s primary test is described as a pooled-variance t-test. The re-calculation is an unadjusted comparison formed from the posted summary statistics. It is useful as a consistency check, but it cannot recover analyses that require participant-level data or adjustment variables. The registry’s reported analysis remains the trial’s own analysis.

Why do outcome types matter?

The primary endpoint is continuous because each participant has a score on the Radiation Dermatitis Severity scale, and the primary comparison uses group means. The secondary moist-desquamation endpoint is a count of participants with the outcome, so it is binary at the participant level. A Fisher Exact test is reported for that comparison. In general, an exact test is suited to comparing categorical outcomes when the observed counts are small; it evaluates the pattern of counts under a no-association hypothesis without relying on a large-sample approximation in the same way as some other tests.

Redness is reported as a mean on a 0.0 to 20.0 scale and was analyzed with ANOVA according to the registry. In general, analysis of variance compares means across groups. With two groups, its basic question concerns whether the group means differ, although the registry does not give enough detail to describe any additional ANOVA structure.

What does unadjusted mean?

An unadjusted estimate compares the groups without adjustment for other variables or for multiple outcome testing. The primary re-calculation uses the posted arm-level means, standard deviations, and sample sizes. The registry reports its own pooled-variance analysis. No covariate adjustment is described in the posted primary result, and any fuller prespecified adjustment plan is not reported in the registry record.

Unadjusted p-values and intervals do not account for the fact that several outcomes or analyses may be examined. If many tests are considered, the chance of at least one apparently unusual result can increase. Whether a multiplicity correction was planned or used is not reported in the registry record. This matters particularly when interpreting secondary outcomes, which should not automatically be given the same evidential weight as the designated primary endpoint.

Why can variability affect an analysis?

In general, greater variability among individual observations makes a group mean less precise when the sample size is unchanged. For count outcomes, over-dispersion means that the observed variation is greater than a model would expect under its assumptions; ignoring it can make uncertainty appear too small. The posted primary analysis is a t-test for a continuous score, not a count model, and there is no reported over-dispersion analysis for this endpoint. These concepts are general statistical considerations, not claims about an unreported diagnostic in this trial.

11. Confidence Intervals and Precision

The primary estimate is a mean difference of -0.8 units, with a 95% confidence interval from -1.387 to -0.213 in the unadjusted re-calculation. The interval lies on the negative side of zero, so the estimates compatible with that calculation favor a lower mean score in the curcumin group. The registry’s own interval is -1.369 to -0.229. Both intervals convey uncertainty about the group contrast; neither describes the spread of individual scores.

The two intervals are similar but not identical because the registry’s reported analysis and the simple re-calculation use their respective reported values and methods. The registry result is the study’s own analysis. Precision is limited by the fact that the primary analysis included 30 completers, split between groups of 14 and 16 participants. The confidence interval expresses that uncertainty more informatively than a p-value alone, because it gives a range of plausible effect estimates on the original score scale.

For the primary mean difference, zero represents no difference between the group means. The interval’s exclusion of zero is consistent with the reported p-value of 0.008 from the registry’s analysis and the unadjusted re-calculated p-value of 0.008. Statistical evidence of a difference does not by itself establish whether the observed score contrast is clinically important. The registry record does not state a threshold for a clinically important difference, and it does not report a separate interpretation of the interval in those terms.

Confidence intervals depend on the analysis method and its assumptions. The registry identifies a pooled-variance t-test, but does not report diagnostics for its assumptions. In addition, the analysis population is described as participants who fully completed the trial; the implications of excluding anyone who did not complete are not quantified in the record. These considerations limit how much can be inferred about precision beyond the posted estimate and interval.

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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row considers an effect to detect equal to the stated fraction of the observed effect. The figures for these comparisons are participants per arm, not total events.

The 80% power column gives the planned number of participants per arm under those assumptions for a design with an 80% chance of detecting the specified effect if that effect is the true one. The 90% power column gives the corresponding per-arm number for a design with a 90% chance. Power is a property of a hypothetical study design under stated assumptions; it is not a measure of whether a result is true.

Rows planning for a smaller fraction of the observed effect require more participants per arm than rows planning for the full observed effect. That is expected: a smaller group difference is harder to distinguish from sampling variation, so more information is generally needed to detect it at the same significance level and power. These calculations are illustrations based on the observed result and should not be read as the original trial’s sample-size justification. The original design assumptions are not reported in the registry record.

This is not observed power. The illustrations do not change the number of people who took part in the trial and do not indicate the probability that the observed treatment effect is real. They show how hypothetical participant requirements vary with the effect size and selected power target under the stated planning assumptions.

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 = -0.800; pooled standard deviation σ = 0.789.
2. n = 2 × (1.96 + 0.842)² × 0.789² / -0.800² = 15.3, rounded up to 16 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 <- -0.8                      # observed difference in means
sigma <- 0.789398686161996                     # 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(1042938)
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 = 16 (80% power), 21 (90% power)
 75% of observed effect: n per arm = 28 (80% power), 37 (90% power)
 50% of observed effect: n per arm = 62 (80% power), 82 (90% power)
power.t.test: 16.3 
Simulated power at n = 16 per arm: 0.791 (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. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a standard pooled variances t-test of final values. It gives a mean difference of -0.799, a 95% confidence interval from -1.369 to -0.229, and p = 0.008. The unadjusted re-calculation from the posted arm summaries gives a mean difference of -0.8, a 95% confidence interval from -1.387 to -0.213, and p = 0.008.

The estimates and inferential results are close. There is no material discrepancy flagged between the sponsor’s analysis and the simple re-calculation. The sponsor’s analysis should be treated as the trial’s own reported result; the re-calculation is a transparent, unadjusted check using summary information, rather than a substitute for a participant-level analysis or the sponsor’s stated test.

The registry does not report additional details about covariate adjustment, diagnostics, or a fuller analysis plan. Consequently, the comparison should be described using the method and result that are actually posted, without assuming that unreported procedures were conducted.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes, and reports seven analyses in total. It does not report whether the analyses were organized into a hierarchy, whether any secondary tests were considered confirmatory, or whether a multiplicity adjustment was planned or applied. A statistical plan describing these decisions is not reported in the registry record.

Multiplicity matters because repeated testing across outcomes, time points, or analysis choices can increase the chance of at least one result appearing statistically notable by chance. An unadjusted p-value addresses its own comparison under its test assumptions; it does not account for the full set of tests unless that adjustment is built into the method. This is one reason the designated primary result generally carries more weight than several secondary findings, especially when the plan for those secondary analyses is unavailable.

The registry says that all 30 participants who fully completed the trial were included in all analyses. It does not state that the analyses followed an intention-to-treat approach, and the record does not explain the status of the enrolled participants not included among the 30 completers. Reasons for non-completion, missing-data patterns, imputation procedures, and sensitivity analyses are not reported in the registry record. It is therefore not possible to assess from the posted information whether missingness could have affected the estimates.

The record gives the randomized, parallel design and masking classification, but the original statistical analysis plan and the trial’s own sample-size justification are not reported. It also does not report whether interim analyses were planned or conducted. These omissions should not be filled by assumption: the available interpretation is limited to the analyses and participant population described in the registry record.

16. 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.

The registry reports zero serious adverse events among the 14 participants at risk in the curcumin group and among the 16 participants at risk in the placebo group. It also reports zero other adverse events among the 14 and 16 participants at risk, respectively. No serious adverse event terms are listed. These counts describe the safety information posted for the recorded groups; they do not establish that no unrecorded events occurred.

Death counts are not reported in the registry record. The adverse-event figures should be read alongside the small analyzed groups and the trial’s duration, which was the prescribed radiation course described as 4-7 weeks. The registry record does not provide further details about event definitions, timing, severity grading, or how adverse events were collected. The counts therefore describe what is posted, but do not provide a complete basis for evaluating safety beyond those recorded figures.

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

The primary result shows a lower mean worst end-of-treatment dermatitis score in the curcumin group than in the placebo group among the participants included in the analyses. The sponsor’s reported analysis and the unadjusted re-calculation both indicate a group difference, and their confidence intervals convey the uncertainty around its size. This is the statistical finding supported by the posted primary outcome.

That finding does not, by itself, establish how the score difference would matter to an individual, since the registry does not report a threshold for clinical importance. It does not show that every participant assigned to curcumin had a lower score than every participant assigned to placebo. Group means summarize the groups; individual responses can vary.

The result also does not establish effects on quality of life, radiotherapy interruption, or cancer control. Although the registry discusses these issues as context for the study, they are not reported as measured primary outcomes in the posted results. The primary endpoint captures worst dermatitis severity at the end of treatment, not the full course of symptoms or longer-term skin effects.

The study was a pilot and the primary analysis included 30 participants who fully completed the trial. The registry does not report the reasons that the analyzed number was lower than the enrolled number, the original sample-size justification, or missing-data sensitivity analyses. These limits affect how confidently the result can be generalized or interpreted beyond the population and period described in this record.

Overall, the posted results support a statistical difference in the primary score comparison in this trial. They do not answer every question about the intervention, and they should not be treated as medical advice or as a definitive conclusion about outcomes not measured or not reported.

18. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can be interpreted through an outcome scale, a mean difference, a confidence interval, and a test result. The primary endpoint is defined in concrete terms: the highest dermatitis severity score at the end of the radiation course. Clear endpoint definition matters because it distinguishes the primary comparison from assessments over time and from other skin outcomes.

It also illustrates why effect estimates and confidence intervals add information beyond a p-value. The estimated mean difference gives the contrast on the scale used to assess dermatitis, while the interval shows the uncertainty around that estimate. The p-value alone would not describe the range of effect sizes compatible with the data.

The trial’s small analyzed population makes precision and analysis-population details especially important. The registry says that 30 completers were used, but does not explain the status of the remaining enrolled participants or report missing-data analyses. Transparent reporting of these details helps readers assess how the analyzed population relates to randomization and how robust the result may be.

The record also highlights the distinction between a primary endpoint and multiple secondary outcomes. A consistent pattern can be informative, but unadjusted secondary tests do not carry the same weight as the designated primary analysis, particularly when multiplicity plans and some results are not reported. The planning illustrations likewise show how hypothetical sample requirements depend on the effect size and power target; they are not evidence that the original study had those design assumptions.

19. 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 analysis was limited to 30 participants who fully completed the trial, while the registry records 35 enrolled. The record does not explain what happened to participants not included among the completers, why they did not complete, or whether their outcomes were available. The stated analysis population therefore cannot be assumed to include every randomized participant.

The trial is identified as a pilot and the analyzed groups were small: 14 participants assigned to curcumin and 16 assigned to placebo. The confidence interval communicates uncertainty in the primary estimate, but the registry does not report a prespecified threshold for clinical importance. Nor does it report the trial’s original sample-size justification, so the planning illustrations based on the observed result should not be mistaken for the study’s own design rationale.

The registry describes repeated-measure analyses of dermatitis severity over time, but does not report their results. It lists pain as a secondary outcome without posting a result. Details of missing-data handling, multiplicity procedures, interim analyses, and the complete statistical analysis plan are not reported in the registry record. These gaps limit evaluation of the full analysis strategy and secondary-outcome pattern.

The primary endpoint concerns the worst score at the end of treatment and does not, by itself, describe symptoms throughout the course or longer-term effects. The registry discusses quality of life, treatment interruption, and cancer control as context, but does not report them as outcomes in these results. Safety reporting is also limited to the posted event counts; death counts are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Curcumin for the Prevention of Radiation-induced Dermatitis in Breast Cancer Patients — NCT01042938.
• Registry record last updated 2012-06-25; status last verified 2012-06.
• Results first posted 2012-06-20.
• 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.

23. Record Summary

This completed phase 2 randomized, parallel-group trial compared Curcumin C3 Complex with placebo during postoperative breast radiotherapy. The University of Rochester was the sponsor. The record lists 35 enrolled participants, with primary completion in 2010-09, and states that analyses included 30 participants who fully completed the trial.

The primary endpoint was the mean worst Radiation Dermatitis Severity score at the end of the radiation course. The sponsor reported a mean difference of -0.799, with a 95% confidence interval from -1.369 to -0.229 and p = 0.008. The unadjusted re-calculation is close to the sponsor’s result. The registry also lists moist desquamation, redness, and pain as secondary outcomes, although pain results are not reported.

Reasons for non-completion, missing-data procedures, multiplicity plans, the original sample-size justification, and the results of repeated-measure analyses are not reported in the registry record.