Use of a Proliferation Saturation Index to Determine Personalized Radiotherapy for HPV + Oropharyngeal Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of a Proliferation Saturation Index to Determine Personalized Radiotherapy for HPV + Oropharyngeal Cancers (NCT03656133), a na na study. The primary outcome is Percentage of Response at Week 4 of Treatment.

2. Clinical Question

3. Trial Design

The registry record describes a completed, single-group study of personalized radiotherapy fractionation for patients with HPV+ oropharyngeal cancers. The listed intervention is radiotherapy fractionation. Investigators were to use each patient’s proliferation saturation index (PSI) to select conventional fractionation or hyperfractionation, with the aim of improving the likelihood of a rapid response. The response definition is a reduction in tumor volume of at least 32% at 4 weeks.

Allocation is recorded as NA, and masking is listed as none. The record does not describe random assignment or a like-for-like control comparison. It also does not provide the number of participants assigned to each fractionation option, the selection rule linking PSI to treatment, or the treatment details beyond the broad options. Those details are not reported in the registry record.

The registry lists an enrollment of 55 and a status of completed. The listed study dates are 2018-09-26 for start and 2022-03-14 for primary completion. The phase is recorded as NA. These registry entries describe the study record; they do not establish how many participants contributed evaluable data to the primary outcome.

The primary outcome is the percentage of participants meeting the week-4 volume-reduction criterion. A secondary outcome is rate of complete response at 2-3 Months. The record lists 2 outcome measures and 0 analyses. It does not report the observed primary or secondary outcome results, an analysis plan, or how participants with missing assessments were handled.

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

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 Percentage of Response at Week 4 of Treatment, measured over At 4 weeks of treatment.

The primary endpoint is the percentage of participants who meet the study’s definition of response at week 4 of treatment: a reduction in tumor volume of at least 32%. It is a binary outcome at the participant level—each person either meets the criterion or does not—and is then expressed as a percentage of participants. The timeframe is 4 weeks of treatment.

A fixed-time response measure can make an early change in tumor volume explicit and can be compared with a stated response expectation. The registry describes an objective of increasing the response rate to 63%, above an expected 49%. These are the objective and reference stated in the outcome description, not reported observed results. The registry does not give the actual number or percentage meeting the endpoint.

The endpoint captures whether a specified threshold is crossed; it does not describe the size of the volume reduction for every participant. A participant just meeting the threshold and a participant with a larger reduction both count as meeting the criterion. The registry does not report the measurement procedures, how tumor volumes were assessed, or how the endpoint was analyzed. The clinical meaning of a response threshold also depends on its measurement reliability and its relationship to later outcomes; those relationships are not described in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on what outcome was measured, who contributed data, and how the analysis was conducted. The registry identifies a binary percentage endpoint at a fixed time, but leaves important analysis details and the actual result unreported. The concepts below explain how such information is generally interpreted; they do not describe analyses confirmed for this study.

What does a percentage response measure?

For a binary endpoint, each participant is classified according to whether the defined event occurred. In this study, the event is meeting the criterion of at least 32% reduction in tumor volume by week 4. A response percentage is the count meeting the criterion divided by the number assessed for that endpoint, expressed as a percentage. The registry gives neither the response count nor the number assessed, so the observed percentage cannot be reconstructed or checked.

The denominator matters. Enrollment is listed as 55, but some participants could lack an evaluable measurement or be excluded from a particular analysis; whether that happened is not reported in the registry record. It would be inappropriate to assume that the enrollment number is also the primary-outcome denominator. A result is most interpretable when the numerator, denominator, assessment time, and handling of missing observations are stated together.

How should a response estimate be read?

As a general statistical principle, an observed percentage is an estimate of the response frequency in the population represented by the study, not a perfectly precise value. A confidence interval describes the uncertainty around that estimate under the assumptions of the method used. Its width depends on the information in the data and on the analysis approach. No response estimate or interval is reported for this endpoint, so neither the magnitude nor the precision of the study’s primary result can be assessed.

The outcome description names an expected rate of 49% and a target of 63%. Those values state the objective and reference written into the registry; they are not substitutes for an observed estimate. A comparison with a benchmark requires a clear definition of the benchmark, the analysis population, and an appropriate statistical method. The record does not identify the source of the expected rate, say whether a formal test against it was planned, or report a result from such a test.

What can a single-group design establish?

In general, a single-group study can describe outcomes among people receiving the study intervention. Without a concurrent control group, it does not directly compare outcomes under PSI-guided fractionation with outcomes under another strategy in comparable participants. A reference rate can provide context, but differences from that reference may reflect differences in patient characteristics, outcome assessment, follow-up, or other features rather than the intervention alone. The registry does not report enough information to assess how comparable its expected rate is to the study population.

The intervention is described as selecting conventional fractionation or hyperfractionation using an individual PSI. The registry does not report the selection algorithm, the distribution of participants across the options, or an analysis comparing those options. Consequently, the record does not support an estimate of the separate outcome associated with either fractionation option or an assessment of how PSI values influenced treatment selection.

What do the listed planning assumptions mean?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is the stated fraction of the observed effect. These are assumptions for a planning calculation, not evidence that the trial used that design or analysis. The study itself is registered as single-group, and the registry does not report an observed primary effect from which to evaluate the illustration. Any sample-size values in a planning illustration are planning quantities, not observed power and not a post-study probability that the findings are correct.

In general, sample-size planning asks how much information a future study might need to detect an effect under specified assumptions. Changing the assumed effect changes the planning result; the calculation does not demonstrate that the assumed effect is true. Here, the stated planning assumptions do not fill in the missing outcome estimate, analysis plan, or study-specific justification. The protocol’s sample-size justification is not reported in the registry record.

Why do analysis details matter?

For a binary endpoint, the chosen method should match the design and account for how observations were collected. If participants differ substantially in their underlying likelihood of response, a simple pooled proportion may not describe that variation well; modeling choices can affect estimated uncertainty. This is a general consideration, not a finding about this study. The registry does not describe covariate adjustment, a statistical model, handling of clustering or other dependence, or any other inferential procedure.

Assessment timing and completeness also affect interpretation. A fixed week-4 outcome requires a definition of the eligible assessment window and a rule for participants lacking a measurement. The record gives the timeframe but does not report either rule or the amount of missing data. Without those details and the actual endpoint result, statistical precision, robustness, and reproducibility cannot be evaluated from the registry record.

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("Radiotherapy Fractionation")
n      <- c(55)
events <- c(34)
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  Radiotherapy Fractionation  55  34  61.8  47.7  74.6  48.6  73.5  48.5  73.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of percentage response at week 4 and a secondary outcome of complete response at 2-3 Months. It also lists 2 outcome measures and 0 analyses. No statistical analysis plan, hierarchy for testing outcomes, or adjustment for multiple comparisons is reported in the registry record.

Multiplicity is a general concern when several outcomes or analyses are examined: the chance of observing an apparently notable result can increase as more comparisons are considered. Whether this concern applies in a particular way depends on which analyses were planned and reported. Because the registry record does not provide the analysis plan or results, it is not possible to determine whether multiplicity was addressed or to interpret a multiplicity-adjusted finding.

Missing-data methods are also not reported. The record does not state how many participants had an evaluable week-4 assessment, why data might be missing, or whether missing measurements were excluded, imputed, or handled in another way. These choices can affect both the estimated response percentage and its uncertainty. The enrollment entry of 55 should not be treated as proof that all participants contributed to the primary endpoint.

The analysis population is not described. The record does not say whether the endpoint was analyzed among all enrolled participants, those who received radiotherapy, those with a week-4 assessment, or another defined group. It also does not report exclusions, protocol deviations, or sensitivity analyses. These omissions limit assessment of bias and make the intended denominator for the endpoint unclear.

12. 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: diarrhea (1.8%), nausea (1.8%).

The registry lists 1 serious adverse event among 55 at risk and 7 other adverse events among 55 at risk for the Radiotherapy Fractionation group. It also lists 2 deaths. The serious adverse-event terms shown are Diarrhea and Nausea, each reported as 1.8%.

These entries should be read as safety counts recorded for the group, not as a comparison between randomized treatment arms. The study is listed as single-group, and no like-for-like control comparison is described. The record does not provide event definitions, severity details beyond the serious-event classification, timing, duration, or whether events were judged related to radiotherapy. It also does not state whether the other adverse-event count includes events classified as serious, so the categories should not be added together.

The relationship between the 2 deaths and the study treatment or adverse events is not reported in the registry record. The entries do not establish causation. They also do not give enough detail to assess exposure duration, completeness of safety follow-up, or the range of events experienced. The counts are descriptive registry information and should be interpreted in that limited context.

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

The registry record describes a study designed to use PSI to select radiotherapy fractionation and assess whether participants achieve a defined early tumor-volume response. It states an objective of a 63% response rate, compared with an expected 49%. Those figures identify the target and reference in the outcome description; they do not indicate what participants actually experienced.

The record does not report the observed week-4 response percentage or count, the denominator assessed, a confidence interval, or a statistical test. Therefore, it is not possible to determine from the registry record whether the objective was met, how precisely a response rate was estimated, or how any estimate compared statistically with the stated expectation. The complete-response secondary outcome is listed, but its result is not reported either.

Even if a response estimate were available, the single-group design would limit causal interpretation. Without a concurrent control group described in the record, an observed response rate could not by itself establish that PSI-guided selection caused a change relative to another fractionation strategy. The record also does not provide the treatment-selection algorithm or outcomes by fractionation option, so it cannot show which option was associated with which response pattern.

The safety entries describe adverse events and deaths recorded for the study group, but they do not establish that treatment caused those events. The registry does not report the timing or attribution of the deaths or sufficient detail to compare safety across strategies.

Accordingly, the registry supports a description of the study question, design, stated response target, and recorded safety counts. It does not supply the outcome evidence needed to judge the observed response, its uncertainty, or a treatment effect. Missing analysis and follow-up details further constrain interpretation.

14. Why This Trial Matters Statistically

This trial raises a statistical question about personalization: whether a patient-level index can guide selection between radiotherapy fractionation approaches in a way that is associated with an early response endpoint. Such a question requires more than a target rate. It requires a transparent definition of the index-based selection rule, clear outcome measurement, and reported results with their denominators and uncertainty.

The registry’s single-group design is important to interpreting the question. A single-group response rate can describe outcomes under the study strategy, but it does not directly separate the contribution of PSI-guided selection from other influences. The stated expected rate of 49% provides a reference point in the outcome description, while the target of 63% expresses the objective. Their relevance depends on how the expectation was established and whether it is comparable to the study population; that information is not reported in the registry record.

The record also illustrates why reporting the analysis population and missing data matters. Enrollment is listed as 55, but the number with an evaluable week-4 assessment is not given. Without the endpoint denominator, readers cannot independently assess the response estimate or its precision. Reporting the actual response count and percentage, along with uncertainty and analysis methods, would be necessary to evaluate the statistical evidence.

Finally, the listed planning assumptions should be distinguished from the trial design and from observed evidence. Planning illustrations can explore assumptions about effects and allocation, but they do not establish that an effect occurred. Here the record describes a single-group study and does not report the primary analysis. Keeping those distinctions clear prevents an objective or planning assumption from being mistaken for a result.

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 registry record does not report the observed primary endpoint result, its numerator or denominator, or an uncertainty interval. This is the central limitation for evaluating the study’s response question. Enrollment is listed as 55, but the number contributing an evaluable week-4 measurement is not reported. Missingness, exclusions, and the analysis population are also unspecified.

The single-group design, allocation listed as NA, and absence of a described concurrent control limit comparison. The stated expected rate of 49% is not accompanied by its source or enough information to assess comparability with the study population. The record does not explain whether a formal comparison with that expectation was planned.

Key implementation details are not reported, including the PSI-based treatment-selection rule, the number receiving each fractionation approach, and the assessment procedures for tumor volume. The registry also does not describe the statistical analysis plan, handling of missing data, or multiplicity approach. It lists a secondary complete-response outcome at 2-3 Months but gives no result.

Safety interpretation is limited by the absence of event timing, attribution, follow-up completeness, and detail about the listed deaths. The adverse-event counts do not establish causal relationships. These limitations are specific to the information recorded and do not establish that such information was absent from other study materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Use of a Proliferation Saturation Index to Determine Personalized Radiotherapy for HPV + Oropharyngeal Cancers — NCT03656133.
• Registry record last updated 2026-02-20; status last verified 2026-02.
• Results first posted 2023-12-11.
• 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

NCT03656133 is listed as a completed, single-group study sponsored by H. Lee Moffitt Cancer Center and Research Institute. It concerns PSI-guided selection of radiotherapy fractionation for HPV+ oropharyngeal cancers. The registry lists an enrollment of 55, start date 2018-09-26, and primary completion date 2022-03-14.

The primary outcome is the percentage of participants with at least 32% tumor-volume reduction at 4 weeks of treatment. The outcome description states a target of 63% and an expected rate of 49%, but the observed primary result is not reported in the registry record. Complete response at 2-3 Months is listed as a secondary outcome, without a reported result. The record lists 0 analyses.

Safety entries include 1 serious adverse event, 7 other adverse events, and 2 deaths. Diarrhea and Nausea are each listed among serious adverse-event terms at 1.8%. The record does not report event attribution or the relationship of the deaths to treatment.