TraceIT Tissue Marker to Mark the Primary Resection Bed Margins of Oropharyngeal Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for TraceIT Tissue Marker to Mark the Primary Resection Bed Margins of Oropharyngeal Cancers (NCT03713021), a na na study. The primary outcome is Percent Change in Total Mean Clinical Target Volumes (CTV) Between the Standard of Care Treatment Plan and the Treatment Plan Based on the TraceIT Hydrogel Markers.

2. Clinical Question

The study asks whether marking the resection bed with TraceIT changes the treatment-planning measurements being considered. Its rationale is that identifying the edges of negative tumor margins could help tailor the area receiving radiation and potentially avoid including areas that are cancer-free. That rationale is a study motivation, not evidence that the approach achieved a particular planning or clinical benefit.

The primary outcome description names sites that include the left and right submandibular glands, parotid glands and pharynx constrictors, as well as the oral cavity, lips, larynx and spinal cord. The registry says mean total dose for each targeted site was totaled for each plan, while the endpoint title refers to total mean CTV. Because the listed sites and the stated measurement use both volume and dose terminology, the exact intended estimand is not fully clear from the record.

The study is a pilot evaluation of a planning approach, not a trial designed in the registry record as a randomized test of patient outcomes. Its primary question concerns plan measurements. The registry does not report whether any difference in those measurements led to differences in treatment delivery, cancer control, quality of life or other patient outcomes.

3. Trial Design

NCT03713021 is a pilot study titled “Evaluation of TraceIT Tissue Marker to Mark the Primary Resection Bed Margins of Oropharyngeal Cancers.” The sponsor is Washington University School of Medicine. The condition listed is oropharyngeal cancer. The study record describes a single-group model, with allocation listed as NA and masking listed as none. The phase is listed as NA.

The intervention is the TraceIT Tissue Marker device. Following successful tumor resection, the arm description says the marker is applied in 0.2 to 0.5 mL injections at 5 tumor-bed locations: superiorly, inferiorly, laterally, medially and at the center of resection. The marginal injections are described as being within 3 mm of the resection edge and within 5 mm deep. The brief summary describes TraceIT as a gel that dissolves in the body over time and can be seen on many types of images used in treatment planning.

The primary outcome compares a standard-of-care treatment plan with a plan based on TraceIT tissue markers. For this outcome, the registry states that 12 participants had both plans available. This is not a parallel-group control comparison: the record does not describe a separate untreated or placebo group, and allocation is listed as NA. The within-participant availability of both plans permits a paired comparison in principle, but the registry does not say which statistical method was used.

The study started on 2019-05-15, reached primary completion on 2021-02-17, and is listed as terminated. The registry record does not report why it was terminated. It lists 27 participants as enrolled, but the primary outcome population is described separately as 12 participants with both plans available. The record does not explain the gap between those counts or specify how participants without both plans were handled.

Three outcome measures are listed, including the primary endpoint and secondary outcomes concerning adverse events related to TraceIT injection and visibility of markers relative to standard treatment fields. The record reports 0 analyses. A detailed statistical analysis plan, protocol-based sample-size justification, or explanation of interim analyses 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: 12 participants had both standard of care treatment plans and TraceIT tissue marker treatment plans available for this outcome measure.

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 Percent Change in Total Mean Clinical Target Volumes (CTV) Between the Standard of Care Treatment Plan and the Treatment Plan Based on the TraceIT Hydrogel Markers, measured over At the treatment planning (2-5 weeks after TraceIT hydrogel placement).

The primary endpoint is titled “Percent Change in Total Mean Clinical Target Volumes (CTV) Between the Standard of Care Treatment Plan and the Treatment Plan Based on the TraceIT Hydrogel Markers.” Its timeframe is treatment planning, 2-5 weeks after TraceIT hydrogel placement. The record says 12 participants had both plans available for this outcome.

The stated purpose of comparing the plans is to assess whether using the marker changes the planning measurements for targeted sites. In general, a planning endpoint can help describe how a proposed marking method affects the contours or treatment volumes considered during planning. Such a measure is not itself a patient outcome and does not establish that a change in a plan improves treatment or health.

The registry’s endpoint description is difficult to reconcile internally. The title refers to percent change in total mean CTV, but the description says mean total dose for each targeted site was totaled for each plan and describes subtracting the marker-based value in cGy from the standard-field value in cGy as a “percent change in CTV (in cGy).” A difference expressed in cGy is a dose difference, while the title names CTV and percent change. The record does not clarify whether the intended measure is volume, dose, a percentage, or another quantity, and no numerical endpoint result is reported.

That lack of definition matters for interpretation: the direction and magnitude of a result would depend on precisely what was measured and how it was calculated. The record also does not report a confidence interval or other uncertainty measure for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the design allow?

General: A single-group study can describe what happens after participants receive or undergo the study intervention, and it can compare measurements collected under different conditions for the same participant when both measurements are available. Such a comparison differs from a randomized trial with separate intervention and control groups. Random allocation can help balance known and unknown differences between groups; allocation is listed as NA in this record, and no separate control group is described.

Here, the named comparison is between the standard-of-care plan and the TraceIT-based plan. The registry says 12 participants had both plans available for the primary endpoint. This makes a paired analysis a possible approach in general, because each participant could contribute measurements under both planning approaches. However, the record reports 0 analyses and does not identify a paired test, model, or other method. It is not appropriate to claim that a particular analysis was performed.

What does the endpoint measure?

General: An endpoint definition should identify the quantity measured, its units, the time of assessment and the population included. A clearly defined quantity lets readers understand what an estimate represents and compare it with other measurements. The title refers to percent change in total mean CTV, while the description refers to total dose and uses cGy in its subtraction statement. Since these terms do not describe the same quantity in an obvious way, the registry record leaves the exact estimand unclear. No alternative definition or clarification is reported.

The outcome is assessed at treatment planning, 2-5 weeks after TraceIT hydrogel placement. The listed targeted sites include paired structures and other anatomical sites. The registry does not state whether the primary endpoint combines all sites into a single participant-level value, how site-level measurements are weighted, or how values are aggregated across participants. Those details matter because different aggregation rules can produce different summaries.

Why do uncertainty measures matter?

General: An estimate describes the observed effect in the analysed data. A confidence interval conveys uncertainty around that estimate under a statistical model and its assumptions. A narrow interval indicates greater precision than a wide interval, but neither the estimate nor its interval automatically establishes clinical importance. The registry record does not report a primary estimate or confidence interval, so neither the magnitude nor precision of the comparison can be evaluated.

General: A p-value is conditional on a statistical model and a null hypothesis. It is not the probability that a treatment works, and it does not express the size of an effect. The registry record reports no analyses and no primary p-value. Consequently, the record does not support a statement that the comparison was statistically significant or not statistically significant.

What is the role of sample-size planning?

The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. These are hypothetical planning assumptions and do not describe the single-group design listed for this study. Any sample sizes generated under them are planning illustrations, not observed power and not proof that the study had adequate power.

General: Sample-size calculations depend on the target effect, variability, statistical test, allocation and assumptions about the data. A planning calculation can help explore the resources that might be needed for a future study, but it does not change the precision of results already collected. Observed power is not a substitute for an effect estimate and its confidence interval. The registry record does not report a protocol-based sample-size justification or explain a planned target for this pilot study.

Why can over-dispersion matter?

General: Over-dispersion occurs when observed variability exceeds what a statistical model assumes. If a model understates variability, its standard errors may be too small and its confidence intervals too narrow. Methods that account for over-dispersion can be important for count outcomes when the data show greater variation than a basic count model allows. The primary endpoint is described using CTV and dose terminology rather than as a count outcome, and the registry provides no analysis or distributional information with which to assess over-dispersion. No claim about whether it was relevant or handled can be made from the record.

What can the safety counts establish?

General: A count of zero observed events does not establish that the underlying event risk is zero. The interpretation depends on the number and characteristics of people observed, how events were defined and collected, and the duration of observation. Estimates of uncertainty are useful for showing how much a zero count can still be compatible with nonzero risk. No such interval is reported in the registry record for the safety counts. The reported 0 serious events and 0 other events among 14 at risk should therefore be understood as recorded counts, not as proof that the intervention carries no risk.

Finally, statistical interpretation depends on the analysis population and handling of incomplete observations. The record identifies a subset with both plans but does not state whether all available data were analysed, how missing plan data were handled, or whether exclusions were specified in advance. Without those details and a reported analysis, the statistical properties of the primary comparison cannot be independently assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and reports 0 analyses. It does not describe a multiplicity strategy, such as designating a hierarchy among outcomes or adjusting inference for testing more than one outcome. Since no statistical analyses are reported, the record does not show whether or how multiplicity was handled. General: When several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for the number and relationship of tests. This concern cannot be quantified for this study from the registry record.

Missing data are also insufficiently described. The primary outcome population is stated as 12 participants who had both standard-of-care and TraceIT-based plans available, while the enrollment count is 27. The record does not give reasons for missing plans, counts by reason, or a comparison of participants with and without complete plans. It does not report imputation, sensitivity analyses or another missing-data method. The impact of incomplete outcome data on the primary result is therefore not assessable.

The analysis population is not defined beyond the statement about participants with both plans available. The registry does not report whether participants were analysed according to an intention-to-treat principle, whether any participants were excluded after enrollment, or how protocol deviations were treated. Because the record reports 0 analyses, it also does not identify the number included in any fitted statistical model or test.

These omissions limit the ability to judge whether the analysed participants and outcomes match the intended study question. They do not demonstrate that a particular bias occurred, but they prevent readers from evaluating its possibility or likely direction from the registry record.

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 0% reporting threshold.

The TraceIT Tissue Marker safety summary lists 14 participants at risk. It records 0 serious adverse events, 0 other adverse events and 0 deaths. The listed secondary outcome includes the percentage of participants experiencing an adverse event related to TraceIT injection, but the registry record does not provide a percentage result or further event details.

These counts are observations in the safety summary, not proof that the true risk of an event is zero. General: When no events are observed, uncertainty remains, particularly when the amount of observation is limited. A confidence interval or other uncertainty estimate can help express that uncertainty, but none is reported for these counts. The record also does not describe the duration or completeness of adverse-event monitoring.

The registry does not list serious adverse-event terms. That means no serious-event terms appear in the posted summary; it does not independently establish how events were defined, assessed or collected. The counts should be read narrowly as the recorded safety figures for this group, without extending them to unreported outcomes or populations.

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

The registry record establishes that TraceIT was studied as a marker applied after tumor resection, with the intended role of identifying the resection bed during radiation treatment planning. It also describes a comparison between standard-of-care plans and plans based on the marker. For the primary outcome, 12 participants had both plans available.

It does not report the numerical primary endpoint result. The record therefore does not show whether the two planning approaches differed, in which direction they differed, or how large any difference was. It also does not provide an interval or other measure of precision. The endpoint definition itself is ambiguous because the title refers to percent change in CTV while the description refers to dose in cGy.

The result does not establish that TraceIT changed the delivered radiation treatment, improved targeting, reduced radiation to cancer-free areas, or affected cancer or other patient outcomes. Those are not reported primary results in this registry record. The rationale in the brief summary describes a possible planning benefit; it should not be read as an observed finding.

Likewise, the recorded safety counts do not establish that there is no risk. The registry summary reports 0 serious events, 0 other events and 0 deaths among 14 at risk, but provides no uncertainty estimate or detailed account of event monitoring.

The study is listed as terminated, and the reason is not reported in the registry record. Without the primary result, analysis details, missing-data explanation and clarification of the endpoint, readers cannot assess the strength or precision of evidence about the planning comparison. The appropriate conclusion is limited: the registry describes the study question and procedures, but does not report enough outcome information to determine what the primary comparison showed.

13. Why This Trial Matters Statistically

This study raises a statistical question that is distinct from whether a marker is clinically beneficial: can a treatment-planning measurement be defined clearly and compared fairly across planning approaches? For the answer to be interpretable, readers need to know what quantity was measured, how values from the anatomical sites were combined, and how the comparison was analysed. The registry’s use of both CTV and dose terminology leaves the primary measure uncertain.

The study also illustrates why outcome availability matters. The registry lists 27 enrolled, while the primary endpoint is described for 12 participants with both plans. Without an account of missing plans and the analysis population, it is difficult to judge how well the reported endpoint would represent the enrolled study population, even if a result were available.

A paired planning comparison can be useful because it evaluates two plans for the same participant, reducing some differences between people that can affect comparisons. In general, however, a paired design still requires a specified analysis and a clear account of which paired observations are included. The registry reports 0 analyses, so it does not show how the paired information was used.

Finally, a pilot study can inform the design and measurement choices for later research, but a planning endpoint should not be mistaken for a patient outcome. The record’s rationale is that marker-based delineation might allow more personalized planning. Whether that possibility translated into a measurable planning change, and whether any such change mattered clinically, cannot be answered from the reported registry information.

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 main trial-specific limitation is that the primary outcome result is not reported in the registry record. No effect estimate, confidence interval or p-value is available, and the record lists 0 analyses. The primary comparison’s direction, size and statistical precision therefore cannot be evaluated.

The outcome description also has a measurement ambiguity. Its title identifies percent change in total mean CTV, while its description refers to total mean dose, subtraction of values in cGy, and a percent change in CTV. The record does not explain the relationship among these measures or give a calculation definition that resolves the inconsistency. It also does not state how site-specific values were combined into a participant-level or study-level endpoint.

Outcome completeness is another limitation. The primary endpoint is described for 12 participants with both treatment plans, whereas 27 participants are listed as enrolled. The registry does not explain why both plans were unavailable for other enrolled participants, how missing data were handled, or whether missingness could relate to the outcome.

The design is listed as single-group, with allocation NA and no masking. The standard-of-care plan is a planning comparator, not a randomized parallel control group. The registry does not describe an analysis method or provide details that would allow assessment of potential sources of bias in creating or comparing the plans.

The study status is terminated, but the reason is not reported. The registry also does not report a protocol-based sample-size justification, an analysis plan, or a detailed account of adverse-event collection. These gaps constrain interpretation without establishing why the study ended or what its unreported results might have been.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: TraceIT Tissue Marker to Mark the Primary Resection Bed Margins of Oropharyngeal Cancers — NCT03713021.
• Registry record last updated 2022-07-12; status last verified 2022-07.
• Results first posted 2022-07-12.
• 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

NCT03713021 is a pilot study of TraceIT Tissue Marker for marking primary resection-bed margins of oropharyngeal cancers. The sponsor is Washington University School of Medicine. It is listed as a single-group study, with allocation NA, masking none, and phase NA. The record lists 27 enrolled and a terminated status; the reason for termination is not reported.

TraceIT was applied after successful resection. The primary endpoint compares standard-of-care planning with planning based on TraceIT markers, and 12 participants had both plans available. The registry does not report the numerical primary result or an analysis. Its endpoint title and description use inconsistent CTV and dose terminology.

The record lists 3 outcome measures and 0 analyses. The safety summary reports 0 serious events, 0 other events and 0 deaths among 14 at risk. The record does not provide an uncertainty estimate for these counts or explain the missing primary plans.