Photodynamic Therapy With HPPH Compared to Standard of Care Surgery in Treating Patients With Oral Cavity Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Photodynamic Therapy With HPPH Compared to Standard of Care Surgery in Treating Patients With Oral Cavity Cancer (NCT03090412), a randomized phase 2 study. The primary outcome is Rate of Tumor Response as Evaluated by Response Evaluation Criteria in Solid Tumors Version 1.1.

2. Clinical Question

This clinical question asks how tumor response was recorded under the two assigned approaches. It does not, by itself, establish that either approach is better. Random allocation describes how the study intended to assign participants; it cannot compensate for the limited information available from this prematurely terminated trial. The registry record does not report a formal statistical comparison of response between the arms, and the available description does not support a precise estimate of a difference between them.

3. Trial Design

This was a randomized, multicenter, parallel-group phase II study sponsored by Roswell Park Cancer Institute. The registry lists no masking, meaning the study was not described as blinded. Participants were assigned to standard-of-care surgery or HPPH with photodynamic therapy. The surgery arm description specifies surgery on day 1. The HPPH arm description specifies an intravenous HPPH infusion over 1 hour on day 0, followed by photodynamic therapy on day 1.

The registry lists a start date of 2018-03-07 and a primary completion date of 2021-08-01. Its current status is terminated. Enrollment is reported as 2. The outcome description attributes the early termination and small number of patients to the principal investigator’s departure. The registry record does not report a planned enrollment target, a reason for the original target, or a detailed account of the termination decision.

The primary outcome was tumor response at 24 months, assessed using Response Evaluation Criteria in Solid Tumors Version 1.1. The registry describes this as an overall tabulation of objective tumor response. Secondary outcomes listed are change in quality of life measured by the University of Washington Quality of Life Questionnaire Version 4 and adverse events graded using CTCAE Version 4.0.

These design details describe the intended comparison, but the small enrollment and early termination constrain what the trial can show. The record says that only event counts were calculated and that no testing was done. It does not report a statistical analysis plan, the method used to generate the random assignment, allocation concealment, the intended analysis population, or additional operational details. Such details should not be inferred from the randomized label alone.

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

Analysis population for the primary outcome, as defined in the registry: Due to PI departure and early termination with few patients, only the counts of events have been calculated and no testing was done

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 Rate of Tumor Response as Evaluated by Response Evaluation Criteria in Solid Tumors Version 1.1, measured over At 24 months.

The primary endpoint was the rate of tumor response at 24 months, assessed according to Response Evaluation Criteria in Solid Tumors Version 1.1. Response criteria provide a structured way to classify tumor change using defined clinical or imaging findings. In general, using prespecified criteria can make outcome assessment more consistent than relying on an informal description of whether a tumor changed.

The registry says objective tumor response was to be tabulated overall and identifies the outcome unit as participants. This endpoint therefore concerns the recorded number of participants with a response, rather than a continuous measurement such as a change in tumor size. The registry does not describe the response categories or explain how any category-level results were to be combined into a single rate. Its outcome description says that the primary outcome has several categories or time points and was not reduced to one comparison.

The registry record states that only event counts were calculated because of the investigator’s departure and early termination with few patients, and that no testing was done. It does not report the numeric response counts or an estimate comparing the assigned approaches in the record summarized. Consequently, the endpoint definition explains what the study intended to assess, but does not supply a comparative result or its precision.

In general, a response endpoint can describe tumor findings during follow-up, but it is not interchangeable with quality of life, adverse events, or other outcomes. Those outcomes address different aspects of a trial and should be interpreted separately. The registry does not report a response estimate with a confidence interval, so the precision of a treatment contrast cannot be assessed from the stated primary-outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, parallel-group, and unmasked. In general, randomization assigns participants to study groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the point of assignment. It does not guarantee that groups will be balanced in a very small study, and it cannot eliminate uncertainty caused by limited enrollment or incomplete outcome information. The registry does not report the randomization procedure or allocation concealment, so those details cannot be assessed.

A parallel-group design means that participants are assigned to one study approach rather than being described as crossing between approaches. Here, the registry names standard-of-care surgery and HPPH with photodynamic therapy as the comparison groups. No masking is reported. In general, masking can reduce the influence of knowledge about assignment on some aspects of care or assessment, but the record does not describe whether outcome assessors were masked separately.

The primary endpoint is a participant-count outcome: tumor response at 24 months under Response Evaluation Criteria in Solid Tumors Version 1.1. For a binary outcome, an analysis may compare the number or proportion of participants meeting an event definition across groups. The registry, however, says the primary outcome included several categories or time points and was not reduced to one comparison. It also says only event counts were calculated and no testing was done. The record does not provide the underlying response counts or a model, effect estimate, confidence interval, or test result for that endpoint.

In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the analysis. Its width conveys precision: a wider interval indicates more uncertainty. A p-value, when calculated under a specified model, measures how unusual the data would be under a stated null hypothesis; it does not measure the probability that a treatment works or that the null hypothesis is true. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record. No inferential result should be reconstructed from the enrollment alone.

The registry lists a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. Such an illustration addresses a hypothetical future study under stated assumptions. It is not observed power, does not show that the original trial was adequately sized, and cannot turn the trial’s event counts into a confirmatory analysis. The registry does not report the trial’s own sample-size justification or a planned enrollment target.

For count outcomes, the number of events and the number of participants at risk are both essential to interpretation. The adverse-event entries provide group-specific counts for participants at risk and participants affected, but their small scale limits what can be inferred about the frequency of events outside this study. A percentage for an adverse-event term also needs a clear denominator and definition. The registry lists two serious-event terms as 100.0%, but does not report the basis for those percentages. They should therefore be read as registry entries, not as a clear estimate of population risk.

The secondary outcomes are change in quality of life measured by the University of Washington Quality of Life Questionnaire Version 4 and adverse events graded according to CTCAE Version 4.0. These outcomes represent different types of information. Quality of life is an assessment of reported health-related experience, while adverse-event grading classifies harms by severity. The registry record does not report results for change in quality of life, details of the assessment schedule, or the statistical methods for either secondary outcome.

In general, multiplicity arises when a study evaluates multiple outcomes, time points, categories, or comparisons. If many statistical tests are conducted, the chance of at least one apparently notable result can increase unless the analysis accounts for that multiplicity. The registry lists several outcome measures and says the primary outcome had several categories or time points, but it does not report a multiplicity strategy. Since no testing was done for the primary outcome, there is no reported set of primary-outcome p-values to interpret or adjust.

Missing-data methods matter when outcomes are unavailable for some participants. In general, the consequences depend on how much information is missing and why it is missing; an analysis that excludes incomplete observations can be biased if missingness is related to outcome or group. The registry record does not report missing-data counts, reasons, imputation methods, or sensitivity analyses. It also does not specify whether the analysis followed an intention-to-treat, per-protocol, or other analysis population. These details cannot be inferred from the randomized design.

Finally, the record says the study was terminated early after the principal investigator’s departure and with few patients. It does not report interim analyses, stopping boundaries, or a statistical plan for early termination. In general, early stopping can reduce the amount of outcome information available and may leave estimates unstable. Here, the registry’s statement that no testing was done and only event counts were calculated is the appropriate limit on statistical interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists tumor response as the primary outcome, with quality-of-life change and adverse events as secondary outcomes. It also states that the primary outcome involved several categories or time points and was not reduced to one comparison. When a study examines multiple outcomes, categories, time points, or contrasts, multiplicity can affect how inferential results should be interpreted. In general, a prespecified testing strategy can clarify which comparisons are primary and whether adjustment is planned. No multiplicity strategy is reported in the registry record.

The record says no testing was done for the primary outcome and only event counts were calculated. It therefore provides no reported primary-outcome p-values to interpret, and the record does not describe whether any formal testing was planned for secondary outcomes. Details of a statistical analysis plan are not reported in the registry record.

Missing-data information is also not reported. The record does not state whether any primary or secondary outcome observations were missing, why data might have been missing, or how missingness was handled. In general, missing outcomes can affect an estimate when the availability of data is related to participants’ outcomes or group assignment; the direction and scale of that effect depend on the circumstances. Without missingness details, sensitivity to incomplete observations cannot be evaluated.

The registry does not identify an analysis population, such as an intention-to-treat or per-protocol population. It also does not describe exclusions from analysis or how participants were handled after randomization. These omissions limit assessment of whether reported counts correspond to all randomized participants or another group. The record’s statement that only event counts were calculated should be retained as the scope of the reported analysis, rather than replaced with assumptions about unreported methods.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchial obstruction (100.0%), haemorrhage (100.0%).

The registry reports serious and other adverse events separately by arm. For serious adverse events, the surgery arm lists 1 participant at risk and 0 affected; the HPPH with photodynamic therapy arm lists 1 at risk and 1 affected. For other adverse events, each arm lists 1 participant at risk and 1 affected. Deaths are reported as 0 in each arm.

These entries are counts from a trial with enrollment of 2 and should not be treated as precise estimates of event frequency in a broader population. A count of 0 does not establish that an event cannot occur, and a count of 1 does not provide a stable estimate of how often it might occur elsewhere. The registry does not report additional safety-analysis details or uncertainty intervals.

The listed serious-event terms are bronchial obstruction and haemorrhage, each recorded as 100.0%. The denominator and calculation basis for those percentages are not reported in the registry record. The percentage entries therefore cannot be interpreted confidently as participant-level risks or compared across arms. The record also does not establish whether an adverse event was caused by an assigned intervention; the counts describe reported events, not causal conclusions.

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

The trial record documents a randomized phase II comparison of HPPH with photodynamic therapy against standard-of-care surgery for oral cavity cancer. It identifies tumor response at 24 months as the primary outcome and describes use of Response Evaluation Criteria in Solid Tumors Version 1.1. It also reports selected adverse-event counts and lists quality-of-life change and adverse events as secondary outcomes.

At the same time, the trial was terminated, enrollment was 2, and the primary outcome description says that only event counts were calculated and no testing was done. Numeric primary response counts and a comparative estimate are not reported in the record summarized. The record therefore does not establish the size, direction, or precision of a difference in tumor response between the assigned approaches.

These results do not show that the approaches are equivalent, and they do not establish that one approach is superior. A lack of statistical testing is not evidence of no difference. Nor do the event counts support a precise conclusion about the comparative safety of the approaches. Counts from such limited enrollment can describe what was recorded in the study, but they cannot by themselves predict outcomes for other patients.

In general, a randomized trial can be designed to support a causal comparison, but the strength of that comparison depends on the data collected, the analysis, and the precision of the estimates. Here, the registry’s count-only description, early termination, and unreported analysis details leave substantial uncertainty. The reported design and outcomes remain informative as a record of what the study set out to assess, while the available outcome information does not support a definitive comparative conclusion.

The planning illustration described in the registry is a hypothetical sample-size exercise based on the observed effect and stated assumptions. It is not observed power and cannot resolve the lack of a tested primary comparison. No medical decision should be based on these registry entries alone; the statistical meaning is limited to the trial information recorded and its substantial uncertainty.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a randomized design and an informative comparative result. Randomization describes the intended assignment process, but the registry reports enrollment of 2 and early termination. With so little outcome information, the design label cannot by itself support a precise estimate of the difference between groups.

The primary endpoint was specified as tumor response at 24 months under Response Evaluation Criteria in Solid Tumors Version 1.1. Yet the registry states that only event counts were calculated and no testing was done, and it does not report numeric response counts or a comparative estimate in the record summarized. This makes the boundary between an endpoint definition and an interpretable treatment contrast especially clear: defining an outcome is not the same as providing evidence about a between-group effect.

The record also demonstrates why safety percentages need context. It lists bronchial obstruction and haemorrhage at 100.0%, but does not report the denominator or how those percentages were calculated. In a study with limited enrollment, an unclear denominator can make a percentage particularly easy to overinterpret. Counts, denominators, event definitions, and analysis methods need to be read together.

Finally, the registry describes a sample-size planning illustration based on the observed effect. Such planning calculations can explore how a future study might be designed under assumptions, but they are not observed power and do not compensate for an early-terminated study with no primary-outcome test. The record is a useful example of why statistical conclusions depend not only on randomization and endpoint choice, but also on adequate information, transparent analysis methods, and clear reporting of uncertainty.

14. 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 most immediate limitation is the small enrollment: the registry reports 2 participants. The study was terminated early, and its primary-outcome description attributes this to the principal investigator’s departure and the few patients enrolled. The registry does not provide further detail about the termination process or report whether the original recruitment target was met.

The primary outcome information is limited to a description of the intended measure and the statement that only event counts were calculated. The registry does not report numeric tumor-response counts or a comparative estimate in the record summarized, and it says no testing was done. It also says the primary outcome had several categories or time points and was not reduced to one comparison. These features prevent assessment of the response result’s magnitude and precision.

Several analysis details are not reported in the registry record, including the statistical analysis plan, the analysis population, handling of missing data, and any multiplicity strategy. The method of randomization, allocation concealment, and separate masking of outcome assessors are also not reported. The registry lists quality-of-life change as a secondary outcome but does not report its results or assessment details.

The safety entries contain very small counts, and the denominator for the two serious-event term percentages is not reported. This limits interpretation of those percentages and prevents reliable population-level safety estimates. The registry does not provide information that would establish whether the reported events were caused by an intervention.

The trial is described as multicenter, but the record summarized does not provide site-specific enrollment or outcome information. It also does not report participant characteristics that would allow assessment of how closely the enrolled participants match the broader target population. The listed sample-size exercise is a planning illustration based on the observed effect, not a substitute for missing outcome information or a basis for claiming observed power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Photodynamic Therapy With HPPH Compared to Standard of Care Surgery in Treating Patients With Oral Cavity Cancer — NCT03090412.
• Registry record last updated 2022-06-02; status last verified 2022-05.
• Results first posted 2022-06-02.
• 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.

18. Record Summary

NCT03090412 is a randomized, unmasked, parallel-group phase II study sponsored by Roswell Park Cancer Institute. It compared standard-of-care surgery with HPPH followed by photodynamic therapy in patients with oral cavity cancer. The registry lists enrollment of 2, a start date of 2018-03-07, a primary completion date of 2021-08-01, and a status of terminated.

The primary outcome was tumor response at 24 months assessed using Response Evaluation Criteria in Solid Tumors Version 1.1. The registry says that, because of the principal investigator’s departure and early termination with few patients, only event counts were calculated and no testing was done. Numeric primary response counts and a comparative estimate are not reported in the record summarized.

Secondary outcomes listed were change in quality of life measured by the University of Washington Quality of Life Questionnaire Version 4 and adverse events graded using CTCAE Version 4.0. The registry provides limited adverse-event counts, but the record does not report a statistical analysis plan, missing-data methods, or an analysis population. The available information supports a description of the study and its reported counts, not a precise comparative conclusion.