Optimized Diffusion-Weighted Imaging for the Evaluation of Post-Treatment Squamous Cell Carcinoma in the Neck: Comparative Study With FDG PET/CT: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optimized Diffusion-Weighted Imaging for the Evaluation of Post-Treatment Squamous Cell Carcinoma in the Neck: Comparative Study With FDG PET/CT (NCT04685798), a na na study. The primary outcome is Apparent Diffusion Coefficient Mean (ADCmean).

2. Clinical Question

The broader study aim was to evaluate post-treatment changes and investigate whether an optimized DWI sequence could help identify recurrent tumors and early non-responders. Participants were to undergo research DWI MRI up to 3 weeks after treatment, followed by standard-of-care FDG PET/CT at 3 months after treatment. The primary endpoint was ADCmean during the 2-3 weeks post-standard of care treatment timeframe.

These aims do not establish that the imaging methods were compared head-to-head in a randomized design. The registry describes one study group receiving both imaging procedures, with DWI MRI occurring earlier than PET/CT. It also does not report the number of evaluable participants or define the two groups named in the primary endpoint description. No results are reported to establish whether ADC measurements differed between groups or how they related to treatment response.

3. Trial Design

The registry describes a single-group study with no masking and an enrollment of 8. Allocation is listed as not applicable, and the record explicitly cautions that this is not a randomized comparison. The study concerns squamous cell carcinoma of the neck and was sponsored by Washington University School of Medicine. Its status is terminated.

The described group was to receive optimized research neck DWI MRI up to 3 weeks after treatment and standard-of-care FDG PET/CT at the 3-month post-treatment assessment. The primary endpoint timeframe is 2-3 weeks post-standard of care treatment. These are different points in the follow-up sequence, so the design does not describe simultaneous imaging measurements at a shared timepoint.

The registry lists the start date as 2020-09-02 and primary completion date as 2023-09-26. It does not report why the study was terminated, whether enrollment reached its planned target, or how many participants completed both imaging assessments. The listed enrollment should not be treated as the evaluable population: the primary endpoint description defines evaluability using receipt of both procedures, measurable disease, and tumor persistence or recurrence, but the record does not give the number meeting those criteria.

The primary endpoint description proposes summarizing ADC measurements with a mean and standard deviation and comparing two groups with an independent-sample t-test. However, the registry describes the overall study as single-group, and the identities and formation of the endpoint’s two groups are not reported. No results analyses are listed. The record therefore does not establish whether the planned comparison was conducted or whether its assumptions and analysis details were finalized.

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: Evaluable patients include those that received the DWI MRI and the standard of care FDG PET/CT, had measurable disease on imaging, and had tumor persistence/recurrence.

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 Apparent Diffusion Coefficient Mean (ADCmean), measured over 2-3 weeks post-standard of care treatment.

The primary endpoint is the mean apparent diffusion coefficient, or ADCmean, measured in units of x 10-6 mm^2/s at 2-3 weeks post-standard of care treatment. ADC is described in the registry as a measure of the magnitude of water-molecule diffusion within tissue. The endpoint uses a continuous imaging measurement rather than a binary classification such as responder or non-responder.

For the stated measurement process, the primary tumor, suspicious lesion, and/or area of post-treatment change would be identified on anatomical images and outlined in the ADC sequence. Areas of cystic change and necrosis would be excluded. If multiple lesions were present, the dominant lesion with the lowest ADC would be selected. A histogram analysis would examine the distribution of ADC values within each region of interest, while ADCmean would characterize the average measurement in tumor or non-tumor tissue.

Mean ADC can provide a concise summary of a set of measurements; the standard deviation describes their spread. The registry says the mean was intended to be compared between two groups using an independent-sample t-test. It does not explain the clinical definitions of those groups or report any ADCmean estimates, standard deviations, or test results. Thus, the endpoint’s measurement rationale is described, but its observed values and clinical interpretation are not available in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: ADCmean, expressed in x 10-6 mm^2/s. For a continuous endpoint, a mean gives a summary of the central value of measurements, while the standard deviation describes variability among those measurements. The registry names both as the endpoint summary, but it does not report any observed mean or standard deviation. Consequently, the data distribution, the between-participant spread, and the extent of overlap between endpoint groups cannot be evaluated.

How the imaging measurement is defined

The registry describes ADC as the magnitude of water-molecule diffusion within tissue. Anatomical images would be used to identify the primary tumor, a suspicious lesion, and/or an area of post-treatment change. The identified area would then be outlined in the ADC sequence, with cystic change and necrosis excluded. When multiple lesions were present, the description specifies use of the dominant lesion with the lowest ADC. A histogram analysis would examine the distribution of measurements within each region of interest, and ADCmean would summarize that distribution.

These details matter because the endpoint depends on what tissue is selected and how it is delineated. Selecting a lesion with the lowest ADC when there are multiple lesions is a specified selection rule, while excluding cystic change and necrosis changes which pixels contribute to the summary. The record describes these procedures but does not report whether they were applied to every participant, how image readings were standardized, or whether readers were blinded to other clinical information. Those operational details are not reported in the registry record.

What the planned t-test would compare

The endpoint description states that an independent-sample t-test would compare ADC measurements between two groups. In general, this test evaluates whether the observed difference between group means is consistent with a null hypothesis of equal population means, under the test’s assumptions. Independence means the observations in one group are not paired with, or otherwise dependent on, observations in the other group. A standard t-test also relies on assumptions about the sampling distribution of the mean; the specific version of the test and its assumption checks are not reported.

The two endpoint groups are not defined in the registry record. That omission is especially important because the overall design is described as single-group and the listed arm includes both DWI MRI and standard-of-care FDG PET/CT. The record does not say whether the groups refer to different disease classifications, tissue types, response categories, or another distinction. It is therefore not possible to reconstruct the intended contrast or determine whether an independent-sample test matches the data structure.

Precision, uncertainty, and effect estimates

A confidence interval is a general way to express uncertainty around an estimated quantity. For a difference in means, it would indicate a range of values compatible with the data and analysis assumptions. A narrow interval generally indicates more precision than a wide interval, while an interval that includes no difference may indicate that the data do not clearly distinguish a difference from no difference under the chosen method. No confidence interval or estimated mean difference is reported for this study, so precision cannot be assessed.

A p-value is also a general inferential measure. It describes how unusual the data would be under a specified null hypothesis and model; it does not measure the size or clinical importance of a difference. No p-value or test statistic is reported. Even if a test result were available, interpretation would depend on the group definitions, analysis population, assumptions, and uncertainty around the effect estimate.

Planning calculations are not trial findings

Sample-size calculations are planning illustrations rather than observed outcomes. General planning calculations describe how many participants per arm might be needed under stated assumptions about the significance level, allocation, approximation, and effect to detect. Here, the stated illustration assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. The registry design, however, is listed as single-group, and no endpoint analysis or observed effect estimate is reported. Any such illustration should not be interpreted as evidence that the study had a particular probability of detecting an effect, nor as the study’s actual design justification. The registry record does not report a sample-size justification or planning rationale.

In general, over-dispersion means that observed variability is greater than a model assumes. When variability is understated, uncertainty estimates can be too small and inferential results can appear more precise than the data warrant. The registry reports a standard deviation as the planned dispersion summary but provides no observations or model diagnostics; there is no basis to assess over-dispersion or any other distributional issue for this endpoint.

Finally, the registry lists no analyses. The described method should therefore be read as the analysis approach stated for the endpoint, not as confirmation that the test was performed. No adjusted analysis, sensitivity analysis, or alternative model is reported. The posted results do not permit independent reconstruction of the planned comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and identifies ADCmean as the primary outcome. It also names a secondary outcome counting participants classified as non-responders by both DWI MRI and standard-of-care FDG PET/CT. The record does not describe a multiplicity adjustment, a hierarchy among outcomes, or how inferential error across multiple outcomes would be controlled. Those procedures are not reported in the registry record.

Missing-data handling is also not described. The endpoint population is defined as evaluable patients who received both imaging procedures, had measurable disease on imaging, and had tumor persistence or recurrence. However, the record does not report how many participants met that definition, whether data were missing for any endpoint, or how incomplete imaging or measurements would be treated. No imputation method, exclusion rule beyond the stated evaluability definition, or sensitivity analysis for missing data is reported.

The analysis population is not fully specified beyond that evaluability description. The record does not state whether the primary analysis would include all enrolled participants, only evaluable participants, or another prespecified set. It also does not report participant flow from enrollment through imaging and endpoint analysis. With enrollment listed as 8 and no analyses listed, the number contributing to any comparison cannot be established.

These omissions limit assessment of how selective reporting, incomplete follow-up, or multiple outcome testing might affect interpretation. They do not establish that such problems occurred; the relevant methods and counts are simply not reported.

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 registry lists a single group titled DWI MRI + Standard of Care FDG PET/CT. For that group, 8 participants were at risk for serious adverse events and 0 were recorded as affected. The same group lists 8 participants at risk for other adverse events and 0 affected. The record reports 3 deaths in the group. These are distinct entries: the death count should not be treated as a count of serious adverse events without further information.

The registry does not provide serious adverse event terms, and no top serious-event terms are listed. It also does not report the causes of death, their timing, or whether any event was considered related to either imaging procedure. The figures therefore describe the safety entries recorded for the group, but they do not establish causation or explain the deaths.

With enrollment listed as 8, these figures should be read alongside the record’s limited reporting of participant follow-up and analysis. The number at risk is recorded as 8 for both adverse-event categories, but the record does not describe event-collection procedures or provide further participant-level detail. The absence of recorded affected participants in these categories is not evidence that no unrecorded events occurred.

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

The registry record documents a study intended to examine optimized DWI MRI after treatment for squamous cell carcinoma in the neck, with standard-of-care FDG PET/CT also planned during follow-up. It describes how ADC measurements would be selected and summarized and names ADCmean as the primary endpoint. This information helps explain the intended measurement, but it does not establish what the study found.

No primary endpoint results or analyses are reported. There are no group means, standard deviations, estimated differences, confidence intervals, or p-values from which to judge the magnitude or precision of an ADC comparison. The number of evaluable participants is also not reported. Therefore, the registry does not establish whether ADCmean differed between the endpoint groups, whether DWI MRI identified non-response or recurrence, or how its classifications compared with PET/CT.

The design should not be interpreted as a randomized comparison of imaging strategies or treatments. It is listed as single-group, with DWI MRI and FDG PET/CT planned at different post-treatment timepoints. The identities of the two groups mentioned in the primary endpoint description are not reported. This prevents a clear interpretation of the proposed independent-sample comparison.

The reported enrollment, termination status, and safety figures are descriptive record information. They do not explain why the study was terminated, prove that every enrolled participant completed the planned imaging, or show that any death was caused by an imaging procedure. The registry does not report those details.

In general, imaging measurements can contribute evidence about tissue characteristics, but translating a measurement into a classification or clinical conclusion requires results, a defined comparison, and information on uncertainty and performance. Those elements are not available in the posted results. The study’s rationale and planned methods can be described; the available record does not support a conclusion about diagnostic performance or clinical benefit.

13. Why This Trial Matters Statistically

This study raises a statistical question about how a quantitative imaging measure is defined and compared after treatment. ADCmean is not simply a label for a scan result: it depends on the region of interest, lesion-selection rule, exclusions, and the distribution of values within the selected tissue. The registry’s description makes those measurement choices visible, including selection of the dominant lesion with the lowest ADC when multiple lesions are present.

It also illustrates why design and analysis descriptions need to align. The study is identified as single-group, while the primary endpoint description refers to an independent-sample comparison between two groups. Without definitions of those groups, readers cannot identify the estimand—the quantity the analysis is intended to estimate—or judge whether the planned test fits the data. Clear group definitions are central to interpreting any difference in means.

The follow-up schedule is another important feature: research DWI MRI was planned up to 3 weeks after treatment, whereas standard-of-care FDG PET/CT was planned at 3 months. Measurements made at different times do not automatically represent a direct, same-timepoint comparison. The registry does not report an analysis addressing that timing distinction.

Finally, the record demonstrates the difference between a stated study objective and an evidentiary result. A trial can describe an intended use for an imaging method and a statistical plan while offering no reported endpoint estimates. Here, the status is terminated and no analyses are listed, so the record supports discussion of design and measurement choices but not a quantified conclusion about the primary question. This distinction is important when reading registry records as evidence.

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 principal limitation for statistical interpretation is that no outcome analysis is reported. The registry gives no ADCmean values, group-specific summaries, comparison estimate, uncertainty interval, or test result. There is consequently no quantitative basis for assessing the primary endpoint.

The endpoint description refers to two groups, but their definitions are not reported, while the overall study is listed as single-group. This leaves the intended comparison unclear. The record also does not report the number of evaluable participants, the number contributing ADC measurements, or participant flow after enrollment. Enrollment is listed as 8, but it cannot be assumed that all enrolled participants met the endpoint eligibility criteria or completed both scans.

The study is terminated, but the reason for termination is not reported in the registry record. The listed assessment schedule places DWI MRI and FDG PET/CT at different post-treatment timepoints, and the record does not describe a method for accounting for that timing in a comparison. The registry also does not report imaging-reader procedures, reliability assessment, missing-data methods, multiplicity handling, or a sample-size justification.

Safety entries include 3 deaths, but causes, timing, and relationship to study procedures are not reported. The record lists 0 participants affected by serious adverse events and 0 affected by other adverse events in the stated group, without further event-collection detail. These limitations describe gaps in the registry record; they do not establish that any particular bias or adverse event occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Optimized Diffusion-Weighted Imaging for the Evaluation of Post-Treatment Squamous Cell Carcinoma in the Neck: Comparative Study With FDG PET/CT — NCT04685798.
• Registry record last updated 2024-09-19; status last verified 2024-09.
• Results first posted 2024-09-19.
• 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

NCT04685798 is a terminated, single-group study of optimized diffusion-weighted MRI for post-treatment assessment of squamous cell carcinoma in the neck, with standard-of-care FDG PET/CT also planned. Enrollment is listed as 8. The record gives a start date of 2020-09-02 and a primary completion date of 2023-09-26.

The primary endpoint is ADCmean in x 10-6 mm^2/s at 2-3 weeks post-standard of care treatment. The registry describes ROI selection and an intended independent-sample t-test but does not define the two comparison groups. No analyses or primary endpoint results are reported. The reason for termination, evaluable sample size, and missing-data and multiplicity methods are not reported in the registry record.

The safety record lists 0 participants affected by serious adverse events, 0 affected by other adverse events, and 3 deaths in the study group. Causes and relationships to study procedures are not reported.