This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Serial [18F]Thymidine (FLT)PET/CT as a Biomarker of Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer (NCT02274038), a na na study. The primary outcome is Baseline 18F-thymidine PET/CT (FLT-PET/CT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02274038 |
| Phase | NA |
| Condition | Non-small Cell Lung Cancer, Starting Pemetrexed Based Therapy, Unresectable Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pennsylvania |
| Results posted | Yes |
2. Clinical Question
Population
People with unresectable non-small cell lung cancer who were starting pemetrexed-based therapy. The registry record lists an enrollment of 3 and says subjects were unable to be analyzed because of poor recruitment efforts.
Intervention
Serial 18F-thymidine (FLT) PET/CT imaging: a scan before therapy, a scan on the day pemetrexed began within 24 hours of starting it, and a scan at 2-4 weeks after starting therapy.
Comparator
There was no separate control group. The study is listed as single-group, and its planned comparison was between baseline and post-therapy imaging in the same study group.
Primary question
Could changes in tumor FLT accumulation on PET/CT serve as an early imaging measure of response to pemetrexed-based therapy?
The trial focused on imaging as a possible biomarker, not on a randomized comparison of treatments. Its stated hypothesis was that FLT PET imaging could rapidly assess treatment response in unresectable non-small cell lung cancer. The baseline scan was intended to provide a reference for evaluating post-therapy changes in tumor FLT accumulation. The post-therapy scans were also described as assessing a possible pemetrexed-induced FLT flare and changes in tumor proliferation.
This question depends on whether imaging changes can be measured and interpreted in relation to treatment timing. A scan taken before therapy establishes the planned reference point; scans around treatment initiation and in the following weeks were intended to capture early changes. The registry record does not report an analyzable result linking those imaging changes to response, overall survival, or progression-free survival. It therefore does not establish whether the proposed imaging approach distinguished response in this study.
3. Trial Design
The registry lists NCT02274038 as a single-group study with allocation recorded as NA and masking recorded as none. Its phase is listed as NA. The University of Pennsylvania is named as the sponsor. The study began in 2015-03, had primary completion in 2018-07, and is listed as terminated. The enrollment is recorded as 3.
All participants were to receive three 18F-thymidine PET/CT scans: before therapy, on the day pemetrexed therapy started within 24 hours of starting it, and at 2-4 weeks after starting therapy. The interventions describe baseline imaging and post-therapy imaging intended to assess a pemetrexed-induced FLT flare and changes in tumor proliferation. These are repeated observations in one study group, not treatment and control arms. The baseline scan was a reference for comparison with post-therapy scans, rather than an independent control condition.
Overall survival and progression-free survival are listed as secondary outcomes. The registry record does not report results for those outcomes. It also does not report an analyzed cohort for the primary outcome: the primary outcome description says that, based on poor recruitment efforts, subjects were unable to be analyzed. The record lists five outcome measures and zero analyses.
The registry does not report a statistical analysis plan, a sample-size justification, or details of interim analyses. The sample-size material associated with the posted results is described as a planning illustration based on an observed effect, rather than the study's own design. Those assumptions do not change the actual design: this was a single-group study, with no randomized comparator. Because the primary outcome could not be analyzed, the registry does not provide a trial-based estimate of the imaging change or its uncertainty.
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.
Before assignment: none of the enrolled patients were excluded from the study
Overall Study
| Stage | 18F-thymidine (FLT) PET/CT |
|---|---|
| STARTED | 3 |
| COMPLETED | 2 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | 18F-thymidine (FLT) PET/CT |
|---|---|
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: based on poor recruitment efforts subjects were unable to be analyzed
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.
Population: All patients had adenocarcinoma of the lung
| Characteristic | Unit | 18F-thymidine (FLT) PET/CT |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 1 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 3 |
| FLTmax | SUV | 4.2 (SD 2) |
6. Primary Endpoint
The registry lists the primary outcome as Baseline 18F-thymidine PET/CT (FLT-PET/CT), measured over Prior to starting pemetrexed based therapy.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is titled “Baseline 18F-thymidine PET/CT (FLT-PET/CT)” and is timed prior to starting pemetrexed-based therapy. The description says that the baseline scan was intended to be compared with post-therapy FLT PET/CT to assess change in tumor accumulation of FLT. The scan therefore served as a reference measurement for the planned longitudinal imaging question.
In general, a baseline measurement helps distinguish a later change from the participant's starting value. For an imaging biomarker, the planned comparison is meaningful only if the imaging measure is defined consistently and the relevant follow-up images are available. The registry does not specify a numerical imaging metric, its unit, or a summary measure for change. It also does not report an analyzed imaging result. Instead, the outcome description states that subjects were unable to be analyzed because of poor recruitment efforts.
The rationale was to use FLT accumulation as an indicator relevant to treatment response and tumor proliferation, including possible early changes after pemetrexed began. The registry does not report whether the intended flare or proliferation changes were observed. The endpoint's planned purpose should therefore be distinguished from an endpoint result: the record describes what the baseline scan was meant to support, but gives no analyzable estimate of change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record supports a description of the study's aims and conduct, but not an estimate of treatment-associated imaging change. It records enrollment of 3 and states that subjects were unable to be analyzed for the primary outcome because of poor recruitment efforts. No numerical primary outcome result, effect estimate, confidence interval, or analysis is reported. The record also lists zero analyses. Consequently, the posted results do not quantify how much tumor FLT accumulation changed or how precisely any change was estimated.
The absence of an analyzable primary result is not evidence that imaging did or did not change. It means the registry record does not provide a basis for assessing the direction, magnitude, or uncertainty of that change. The same distinction applies to the proposed early-response role: the trial's hypothesis and scan schedule are recorded, but no result establishes how well imaging assessed response. Overall survival and progression-free survival are listed as secondary outcomes, but their results are not reported in the registry record.
In general, a confidence interval describes a range of values compatible with the data under the analysis method; its width reflects uncertainty. No confidence interval is reported for this primary outcome, so its precision cannot be judged. Similarly, a significance test would address a specified statistical hypothesis, but no primary-outcome test or p-value is reported. It would be inappropriate to infer statistical significance or lack of significance from the enrollment count or the study's termination status.
The design also limits what a successful analysis could establish. A single-group comparison of scans over time can describe within-group changes, but without a separate control group it cannot isolate the contribution of pemetrexed from other explanations for a change. That general limitation is especially important when interpreting a proposed biomarker as a measure of treatment response. The record does not report a treatment-versus-control comparison, and none should be implied.
The study is listed as terminated, but the registry does not give a reason for termination beyond the primary outcome description's reference to poor recruitment efforts. The record does not establish why recruitment was poor or whether any particular operational or clinical factor contributed. The posted information is therefore best read as a record of an intended imaging study that did not yield an analyzable primary outcome, rather than as evidence for or against the imaging hypothesis.
Planning estimates should be distinguished from observed trial evidence. The stated sample-size assumptions describe an illustration based on an observed effect; such planning calculations do not supply the missing primary analysis and are not observed power. With no reported primary effect estimate or uncertainty, those calculations cannot be treated as a substitute for an outcome result.
9. Statistical Methods Explained
The design called for repeated FLT PET/CT scans in one study group. The scan before therapy was the planned baseline reference. The next scan was scheduled on the day pemetrexed began, within 24 hours of starting therapy, and the later scan at 2-4 weeks after starting. In general, repeated measurements allow within-participant comparisons over time. Such comparisons account for the fact that measurements from the same person are related; they are not equivalent to comparisons between unrelated groups.
What does a single-group comparison tell us?
In general, a single-group study can describe the course of a measured outcome among the participants observed. Comparing each participant's follow-up measurement with their baseline can reduce the influence of stable differences between participants. But a change over time alone does not show what would have happened without the treatment. Without a control group, the change cannot be attributed uniquely to pemetrexed. The registry lists no randomized comparison and no like-for-like control arm.
The registry record describes the baseline scan as a way to compare post-therapy FLT PET/CT and assess change in tumor FLT accumulation. It does not report the numerical imaging metric, its scale, or the exact statistical method for comparing scans. Those details matter because a method for paired measurements depends on how the imaging outcome is defined and on the structure and distribution of the measured changes. They are not reported in the registry record.
Why does over-dispersion matter in general?
In general, over-dispersion occurs when the observed variability in data is greater than a model assumes. If a statistical model understates variability, it may make estimates appear more precise than the data justify. Methods that account for extra variability can produce more realistic uncertainty. The registry record does not report whether over-dispersion was assessed or whether a model requiring such an adjustment was planned. Without a reported analysis, no conclusion can be drawn about how variability in imaging measurements was handled.
How should planning calculations be read?
The sample-size assumptions describe a planning illustration computed from an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are assumptions for an illustration, not a description of the trial's actual design: the study itself is single-group. A planning estimate does not show that the study achieved a particular power, and it is not an observed result. In general, sample-size planning estimates depend on the assumed effect, variability, allocation, and statistical method; changing those assumptions can change the estimated sample size.
The stated convention is that time-to-event planning entries give the total number of events using the Schoenfeld method, while other entries give participants per arm. These conventions describe how planning quantities are expressed, not what was observed in the trial. No numerical primary outcome estimate is reported in the registry record, and the primary outcome description says subjects were unable to be analyzed. The planning illustration cannot be interpreted as a substitute for observed follow-up or an outcome analysis.
What would a confidence interval add?
In general, a confidence interval communicates uncertainty around an estimate. An estimate alone gives a central value; the interval indicates which other values remain reasonably compatible with the data under the stated method. Its interpretation depends on the design, assumptions, and data quality. No interval is reported for the primary imaging outcome, so there is no reported measure of precision to interpret. The same applies to hypothesis tests: no primary-outcome p-value or analysis is reported.
These methodological concepts explain what an analysis could have addressed, not what this study found. The registry record does not report the planned statistical model, handling of repeated observations, or a numerical measure of imaging change. It states that poor recruitment efforts prevented subjects from being analyzed for the primary outcome. Conclusions about model performance, uncertainty, or the clinical interpretation of a measured imaging change are therefore not available from the posted results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures, including the primary baseline FLT PET/CT outcome and the secondary outcomes overall survival and progression-free survival. It records zero analyses. Because no primary analysis is reported, there is no reported family of statistical tests or set of outcome estimates whose multiplicity can be evaluated.
In general, multiplicity arises when several outcomes, time points, comparisons, or statistical tests are examined. Without a plan to control or otherwise interpret multiple testing, the chance of a false-positive result across a group of tests can be difficult to assess. The registry record does not report a multiplicity strategy, such as a hierarchy of outcomes or an adjustment method. It also does not report whether the secondary outcomes were analyzed.
The primary outcome description states that subjects were unable to be analyzed because of poor recruitment efforts. The record does not provide participant-level missingness, reasons for missing measurements, or a missing-data method. It does not report how incomplete scan sequences would have been handled, or whether an analysis population was defined. In general, missing-data methods rely on assumptions about why observations are unavailable; without information on missingness and the planned method, the impact of unavailable measurements cannot be assessed.
The registry record also does not describe an intention-to-treat or other analysis population. The enrollment entry alone should not be read as the number included in an outcome analysis, since the primary outcome description explicitly says subjects were unable to be analyzed. No alternative analyzed population is reported.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Baseline 18F-thymidine PET/CT (FLT-PET/CT) | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Baseline 18F-thymidine PET/CT (FLT-PET/CT) | 1 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Baseline 18F-thymidine PET/CT (FLT-PET/CT) | 0 of 3 |
The registry's adverse-event entry lists the baseline FLT PET/CT group with 3 at risk for serious adverse events and 0 affected. It separately lists 3 at risk for other adverse events and 0 affected. The record also lists 1 death for this group. These entries should be read as separate recorded counts, not combined into an overall event total.
The registry does not report a serious adverse-event term, and the top serious terms list is empty. It does not explain the death's cause, timing, or relationship to study procedures or treatment. The death count alone does not establish that the death was an adverse event, was caused by the intervention, or was unrelated to it. No such interpretation is reported in the registry record.
In general, an at-risk count identifies the group used for an event count, while an affected count records participants with an event under the registry's reporting framework. These entries do not provide detail about event definitions, duration of observation, or event-level circumstances. With the primary outcome not analyzable and limited safety detail, the counts should be described as recorded rather than used to make broader claims about safety.
12. What the Result Does, and Does Not, Mean
The study records a plan to use serial FLT PET/CT imaging to assess early changes after pemetrexed-based therapy in unresectable non-small cell lung cancer. It documents a baseline scan and two post-start time points, and it identifies tumor FLT accumulation as the imaging feature of interest. The primary outcome description says that the scans were intended to be compared to assess change in accumulation.
What the registry does not provide is an analyzable estimate of that change. It states that subjects were unable to be analyzed because of poor recruitment efforts, and it lists zero analyses. There is no reported result that shows the amount or direction of imaging change, its precision, or an association between imaging and a clinical outcome. The listed secondary outcomes, overall survival and progression-free survival, also have no reported results.
In general, a biomarker's proposed role and its demonstrated performance are different questions. A study may specify a plausible use for a measure, but establishing how well it reflects response requires analyzable observations and a suitable analysis. This record describes the hypothesis and measurement schedule; it does not demonstrate that FLT PET/CT assessed response in this study. Nor does the absence of a reported analysis demonstrate that the imaging approach failed.
The design was single-group, with no randomized control condition. Even if within-group scan changes had been reported, they would not by themselves separate treatment-related changes from other causes of change over time. The registry's status of terminated and its reference to poor recruitment describe the study's limited record, not a conclusion about the imaging method or pemetrexed. The appropriate interpretation is narrow: the registry documents the intended study question and reports that the primary outcome could not be analyzed.
13. Why This Trial Matters Statistically
This record illustrates an important distinction between a study's scientific question and the evidence it ultimately contributes. The study proposed a timely imaging question: whether FLT PET/CT could assess response soon after pemetrexed-based therapy began. It also specified a sequence of scans intended to compare tumor FLT accumulation over time. Those design details clarify the intended measurement, but they do not constitute an outcome result.
Statistically, the central issue is analyzability. The registry records enrollment of 3 and says subjects were unable to be analyzed for the primary outcome because of poor recruitment efforts. Without an analyzable endpoint, there is no estimate to interpret, no uncertainty interval to assess, and no basis for a test of the primary hypothesis. This is a different situation from a precise estimate near no change or an imprecise estimate that includes a range of possible changes.
The study also highlights why design and analysis must be considered together. Repeated scans in a single group can describe within-person patterns, but cannot provide the same causal contrast as a controlled comparison. Planning illustrations based on hypothetical assumptions should not be confused with observed evidence, and they cannot repair the absence of an analyzed outcome. Likewise, listed secondary outcomes are not results unless their analyses and estimates are reported.
For clinical researchers, the record underscores the value of distinguishing protocol intent, recruitment, analysis, and interpretation. The record preserves the intended biomarker question and identifies a limitation that prevented primary analysis. Its statistical contribution is therefore chiefly methodological: it shows why recruitment and availability of outcome data are essential to estimating a biomarker's behavior, while leaving the proposed performance question unresolved.
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 direct limitation is that the primary outcome was not analyzable. The registry attributes this to poor recruitment efforts and records enrollment of 3. It reports no primary imaging estimate, no uncertainty measure, and no analysis. The termination status further describes the study's recorded state, although the registry does not report a reason for termination beyond the reference to poor recruitment in the primary outcome description.
The single-group design is another limitation for interpretation. The repeated scans could have been compared within the study group, but the absence of a control group limits attribution of any time-related imaging change to pemetrexed. The registry lists masking as none, and no randomized comparison is described.
The registry does not specify the numerical imaging metric, its unit, or a statistical method for comparing scans. It also does not report an analysis population, missing-data approach, or multiplicity strategy. These omissions mean that measurement definition, handling of incomplete data, and the planned interpretation of multiple outcomes cannot be evaluated from the registry record.
Overall survival and progression-free survival appear as secondary outcomes without reported results. The adverse-event entry gives counts but no event descriptions or detail about the death. These limitations do not establish that an event was related or unrelated to study procedures; they limit what can be inferred from the record. In combination, the missing primary analysis and lack of supporting detail leave the intended biomarker question unresolved.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Serial [18F]Thymidine (FLT)PET/CT as a Biomarker of Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer — NCT02274038.
- Registry record last updated 2021-05-12; status last verified 2021-05.
- Results first posted 2021-05-12.
- 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.
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18. Record Summary
NCT02274038 is a University of Pennsylvania single-group study of serial 18F-thymidine PET/CT imaging in people with unresectable non-small cell lung cancer starting pemetrexed-based therapy. The planned scans were before therapy, on the day pemetrexed began within 24 hours of starting, and at 2-4 weeks after starting. The study is listed as terminated, with enrollment of 3; its start is recorded as 2015-03 and primary completion as 2018-07.
The primary outcome concerned baseline FLT PET/CT as a reference for assessing changes in tumor FLT accumulation. The registry says subjects were unable to be analyzed because of poor recruitment efforts and lists zero analyses. Overall survival and progression-free survival are listed as secondary outcomes, without reported results. The posted record therefore documents the intended imaging question and study schedule, but does not provide an analyzable primary result.