18F- Fluorothymidine to Evaluate Treatment Response in Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 18F- Fluorothymidine to Evaluate Treatment Response in Lymphoma (NCT00775268), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With the Presence/Absence of Abnormal 18F- Fluorothymidine (FLT) Uptake, and Positive/Negative Biopsy.

2. Clinical Question

The study asks whether uptake of the experimental radiotracer FLT on PET/CT can help assess lymphoma treatment response, including the evaluation of masses that remain FDG-positive after therapy. The primary outcome concerns participants with residual masses: whether FLT uptake was classified as abnormal and whether biopsy was positive or negative for malignant cells. The record describes these findings as being correlated; it does not report the resulting counts or association measure.

The protocol description includes two participant groups with different imaging pathways. One group was scanned at baseline, after 2 courses of chemotherapy, and after chemotherapy was completed, using both FLT and FDG PET/CT. Participants with an FDG-positive residual mass after treatment could enter the other group, which received an FLT scan and biopsy or fine-needle aspiration if clinically indicated. This is not a randomized comparison, and the groups are not a like-for-like control comparison.

The clinical question is therefore about the descriptive and diagnostic role of FLT imaging in this study setting. The registry record does not establish a treatment comparison or report whether FLT classification agreed with biopsy in the observed participants.

3. Trial Design

This was a phase 1 and phase 2, non-randomized, single-group study. The registry lists enrollment of 31 and describes a pilot evaluation of FLT PET/CT in lymphoma. The study began on 2008-09-29, had a primary completion date of 2014-10-23, and is listed as terminated. The reason for termination is not reported in the registry record.

The arm descriptions set out two imaging pathways rather than randomized treatment arms. Participants in the baseline and post-chemotherapy group were scheduled for FLT and FDG PET/CT at baseline, after 2 courses of chemotherapy, and after treatment completion. Participants with an FDG-positive residual mass after therapy could be enrolled in the residual-mass group. In that group, participants who had completed treatment and had a remaining mass on FDG-PET underwent FLT PET/CT; biopsy or fine-needle aspiration was also performed if clinically indicated.

These pathways differ in eligibility and timing, so comparisons between their results would not have the structure of a randomized controlled comparison. The record lists no masking and describes the study as single-group. It does not report a separate concurrent control arm or an allocation process beyond stating that allocation was non-randomized.

The primary outcome timeframe is up to 3.5 years. The stated primary outcome is a participant count relating abnormal or non-abnormal FLT uptake to positive or negative biopsy. The registry record reports that 21/22 participants were analyzed for this outcome because one participant was not treated and was ineligible per CT criteria. It also says that data for this outcome came only from the group with residual masses. The record does not describe the sample-size justification or explain the termination decision.

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.

Baseline

Reasons for not completing this period:

After 2 Cycles

Reasons for not completing this period:

After Completion

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 21/22 participants were analyzed because one participant was not treated ineligible per CT criteria. Data was collected for only the Arm/Group of participants with residual masses.

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 Number of Participants With the Presence/Absence of Abnormal 18F- Fluorothymidine (FLT) Uptake, and Positive/Negative Biopsy, measured over Up to 3.5 years.

The primary endpoint counts participants according to the presence or absence of abnormal FLT uptake and positive or negative biopsy. The endpoint description defines a positive malignant residual mass as focal FLT uptake within the mass greater than the normal mediastinal background uptake. Uptake lower than the mediastinal background was considered non-malignant. The imaging classification was correlated with biopsy results for the presence or absence of malignant tumor cells.

This type of endpoint is used to describe how an imaging finding corresponds with a tissue-based assessment in the residual mass. A biopsy result can provide a reference for evaluating the imaging classification, but the registry record does not report the endpoint’s observed category counts, an agreement statistic, or a measure of diagnostic accuracy. It also does not specify how uptake exactly equal to the mediastinal background was classified.

The analysis population is described as 21/22 participants, with one participant excluded because the person was not treated and was ineligible per CT criteria. The endpoint applies only to the residual-mass group, not to every participant enrolled in the study. Thus, it should be read as a count-based assessment in a selected post-treatment group, not as a comparison of randomized treatments or a result applicable to all lymphoma patients.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a participant-level count with binary classifications: FLT uptake is described as abnormal or non-malignant, and biopsy is described as positive or negative for malignant tumor cells. The registry record says the imaging classification was correlated with biopsy findings. It does not give the observed counts in the resulting categories or name a statistical test or summary measure.

What does a binary count show?

General explanation: A binary count records how many participants fall into each defined category. When two binary classifications are considered together, a cross-classification can show how often they agree and how often they differ. For an imaging assessment compared with biopsy, readers would usually want to see the counts for both positive and negative imaging findings against both positive and negative biopsy findings. Those cells are not reported in the registry record here, so the association cannot be reconstructed from the endpoint description alone.

The endpoint definition uses a threshold relative to normal mediastinal background uptake. Focal FLT uptake within a residual mass greater than that background is defined as positive for a malignant residual mass; uptake lower than the background is considered non-malignant. The record does not specify how a value exactly equal to the background was handled. It also does not report whether all participants had biopsy, how clinically indicated biopsy decisions were made, or whether biopsy assessment was blinded to imaging. These details matter when interpreting a diagnostic comparison.

How should precision be considered?

General explanation: A confidence interval describes a range of values compatible with the observed data under a specified statistical method. It helps readers assess precision rather than relying only on a point estimate. For a small participant group, estimates may be imprecise, especially when one or more outcome categories contain few participants. The registry record does not report a confidence interval or the primary outcome’s category counts, so precision for the main endpoint cannot be evaluated from the information presented.

A p-value, if reported, would address how compatible the data are with a specified null model; it would not quantify the size or practical importance of an imaging association. No primary-endpoint p-value or null hypothesis is reported in the registry record. There is also no inferential plan described for the primary outcome. Consequently, readers should not infer statistical significance or lack of significance from the endpoint wording or from the study’s status.

Why does the study structure matter?

General explanation: Random assignment can help balance measured and unmeasured characteristics between treatment groups, while a non-randomized study does not have that design protection. Here, the registry describes a single-group, non-randomized study and two different imaging pathways. The residual-mass pathway is used after treatment when FDG-PET shows a remaining mass. This selection means that the residual-mass outcome applies to a particular post-treatment group, rather than an unselected group or a randomized comparison.

The repeated scans in the first pathway are scheduled at different treatment stages. Repeated measurements on the same participant are related rather than independent. General explanation: An analysis of repeated measurements may need to account for that within-participant dependence; treating all scans as independent observations can misstate uncertainty. The registry record lists secondary outcomes at baseline, mid-treatment, and completion, but does not report the statistical methods used to account for repeated measurements.

What about dispersion and modeling?

General explanation: Over-dispersion arises when observed variability exceeds what a statistical model assumes. It is relevant to some count models, particularly when counts vary more than a simple model allows. The primary endpoint is described as participant counts with binary classifications, not as a rate or a repeated count process. No model for the primary endpoint is reported, so there is no basis for saying whether over-dispersion was assessed or whether a particular modeling approach was used.

The sample-size section uses 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 frames the effect to detect as a stated fraction of the observed effect. These are illustrative assumptions, not evidence of the study’s own design calculations. The record does not report a sample-size justification, and a planning illustration is not observed power. In addition, the trial itself is not a randomized two-arm comparison, so the illustration should not be read as describing the actual allocation or design.

The registry lists 10 secondary outcomes and 2 analyses. The outcome descriptions cover uptake, standardized uptake values, dynamic imaging measures, and time to progression. The statistical plan for these outcomes, the handling of multiple testing, and the analysis methods are not reported in the registry record. No additional methods should be attributed to the investigators without that information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 secondary outcomes and 2 analyses in addition to the primary endpoint. The secondary outcomes cover several types of information, including FLT uptake between baseline and treatment completion, maximum standardized uptake values at specified imaging times, FDG measurements, an FLT dynamic influx parameter, time to progression, and uptake in malignant residual tumors versus benign lesions. Considering multiple outcomes and time points can raise the chance of finding an apparently notable result by chance when many tests are conducted.

General explanation: A multiplicity plan may define which outcomes are confirmatory, how tests are ordered, or whether the threshold for interpreting statistical evidence is adjusted. The registry record does not report whether any such plan was used. It also does not state which secondary analyses were exploratory or how the 2 listed analyses relate to the outcomes. The results cannot be assessed for multiplicity adjustment based on the information available.

The primary outcome population is reported as 21/22 participants, with one participant excluded because the person was not treated and was ineligible per CT criteria. The outcome applies only to participants with residual masses. Other missing-data details are not reported in the registry record: there is no description of missing scans, missing biopsy results, incomplete follow-up, or methods for handling missing observations. It is therefore not possible to determine whether the analyzed participants differed from those not included in the primary endpoint population.

The registry record does not report a prespecified analysis population beyond the stated primary endpoint group, nor does it describe sensitivity analyses or imputation. The analysis approach should not be inferred from the outcome count or from the fact that the study was terminated.

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.

Most frequent non-serious adverse event terms

The safety summaries list serious adverse events separately for each imaging group. In the group scanned at baseline and after chemotherapy, 0 serious adverse events were recorded among 8 participants at risk; in the residual-mass evaluation group, 0 were recorded among 21 participants at risk. The record lists 1 other adverse event among 8 participants in the first group and 1 among 21 in the second.

Deaths are listed as 3 in the first group and 5 in the second. These are counts in the registry’s safety summaries, not evidence by themselves that an event was caused by FLT, PET/CT, biopsy, or treatment. The registry record does not report the relationship of the deaths or other adverse events to study procedures or treatment. It also does not provide event descriptions for the other adverse events or list serious adverse-event terms.

Because the groups reflect different imaging pathways and are not randomized, their safety counts should not be treated as a comparative estimate of risk. The denominator is the number at risk shown for each safety category and group, not necessarily the primary endpoint analysis population. The counts are descriptive; they do not establish that an intervention caused or prevented an event.

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

This record is useful for understanding how a pilot imaging study was organized and how its primary outcome was defined. It describes an FLT PET/CT assessment in lymphoma, including imaging at several treatment stages and a separate pathway for participants with residual FDG-positive masses after therapy. For the primary endpoint, the key comparison is between FLT uptake classification and biopsy findings in the residual-mass group.

The available information does not report the actual primary endpoint category counts or a summary of agreement between FLT and biopsy. It therefore cannot establish how often the imaging classification corresponded with the tissue findings, nor how precisely that correspondence was estimated. A definition of an outcome is not the same as a reported result.

The study design also limits what comparisons can mean. It is non-randomized and described as single-group, with pathways that differ according to imaging time and residual-mass status. Those pathways do not support a direct causal comparison between groups. The record does not show that FLT changed treatment decisions or outcomes, and it does not report comparative evidence about treatment effectiveness.

The registry lists 31 participants enrolled and states that 21/22 were analyzed for the primary outcome, with one not treated and ineligible per CT criteria. These figures describe different aspects of the record and should not be assumed to represent identical populations. The record does not provide enough participant-flow detail to explain all denominators or missing observations.

The results and methods support a careful description of the registered question, study structure, and listed safety counts. They do not support a claim that FLT imaging does or does not identify malignant disease accurately, or that it improves clinical outcomes. The reason the study was terminated is also not reported in the registry record.

13. Why This Trial Matters Statistically

This study raises a statistical question that is distinct from a treatment comparison: whether a novel imaging signal corresponds with biopsy findings in residual masses after lymphoma therapy. That requires clear outcome definitions, transparent reporting of the paired imaging and biopsy classifications, and information about the participants who were assessed. The registry defines an uptake threshold relative to mediastinal background and identifies biopsy as the tissue-based finding, but does not report the underlying endpoint counts.

The design illustrates why denominators and selection pathways matter. The primary outcome is restricted to participants with residual masses, while another group is described as undergoing scans across treatment stages. These pathways address different questions and should not be treated as exchangeable groups. Reporting the analyzed population as 21/22 and explaining the stated exclusion helps readers interpret scope, though further participant-flow and missing-data information is absent.

The record also lists a broad set of secondary imaging and time-to-progression outcomes. Multiple outcomes can provide a fuller picture of how a test behaves, but they increase the importance of a transparent statistical plan and clear distinction between primary and exploratory analyses. The registry record does not report the multiplicity approach or the detailed analysis plan, so statistical conclusions across those outcomes cannot be evaluated from this information alone.

Finally, the safety counts and terminated status require restraint. Descriptive adverse-event and death counts do not establish causation, and termination does not disclose the reason the study stopped. Statistically, the central contribution of the record is therefore its definition of a question and a study pathway; the missing endpoint results and analysis details limit what readers can infer about the imaging assessment.

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 important limitation for interpretation is that the registry record does not report the observed primary endpoint counts or a measure of correspondence between FLT uptake and biopsy. Without those results, readers cannot assess the apparent frequency of agreement, disagreement, or uncertainty. The endpoint definition also leaves the classification of uptake exactly equal to the mediastinal background unspecified.

The primary endpoint is limited to the residual-mass group. Participants entered that pathway after treatment when FDG-PET showed a remaining mass, so the endpoint does not represent an unrestricted lymphoma population. The registry reports 21/22 analyzed and explains one exclusion, but does not give a complete flow of participants through enrollment, imaging, biopsy, and analysis. It does not say how many participants had biopsy, whether all residual masses could be sampled, or how missing biopsy or imaging data were handled.

The non-randomized, single-group design and different eligibility pathways prevent a like-for-like comparison between the described groups. The record does not report masking, and it does not specify whether biopsy assessors knew the imaging results or whether image interpretation was blinded. The stated absence of masking does not clarify those assessment procedures.

Other limitations include the lack of a reported statistical analysis plan, confidence intervals, primary-endpoint test, sample-size justification, and multiplicity approach. The reason for termination is not reported. These omissions constrain interpretation of both the study conduct and the precision of its findings; they should not be filled in by assumptions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: 18F- Fluorothymidine to Evaluate Treatment Response in Lymphoma — NCT00775268.
• Registry record last updated 2021-03-11; status last verified 2021-02.
• Results first posted 2021-03-11.
• 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.

18. Record Summary

This is a phase 1 and phase 2, non-randomized, single-group pilot study of FLT PET/CT in lymphoma. The registry lists 31 participants enrolled, a start date of 2008-09-29, a primary completion date of 2014-10-23, and terminated status. The reason for termination is not reported in the registry record.

The primary endpoint counts participants by abnormal or non-malignant FLT uptake and positive or negative biopsy in the residual-mass group. The record states that 21/22 participants were analyzed and identifies one participant who was not treated and was ineligible per CT criteria. It does not report the primary endpoint’s observed category counts or statistical result.

Safety summaries list 0 serious adverse events in each group, 1 other adverse event in each group, and deaths of 3 and 5 in the respective groups. The record does not establish a relationship between these events and the study procedures or treatment. Overall, the posted information describes the study question and pathways but does not provide enough endpoint results or analysis detail to assess imaging performance.