The Detection Of Circulating Tumor Cells (CTC) In Patients With NSCLC Undergoing Definitive Radiotherapy Or Chemoradiotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Detection Of Circulating Tumor Cells (CTC) In Patients With NSCLC Undergoing Definitive Radiotherapy Or Chemoradiotherapy (NCT02135679), a registered phase not stated study. The primary outcome is To Describe the Pattern of CTCs Before and After Definitive Radiotherapy for Each Treatment Stratum.

2. Clinical Question

The central aim is descriptive: characterize CTC counts around treatment within the distinct strata. The record does not frame the primary question as a randomized estimate of one treatment’s effect relative to another. Differences between strata, if described, would need to be interpreted in light of their different disease settings and treatment approaches, rather than as direct evidence from a controlled comparison.

The brief summary also mentions correlating CTC levels collected before surgery with pathological samples. The registry record does not report the results of that correlation or specify how it relates analytically to the primary outcome. It therefore remains important to distinguish the stated primary question about patterns before and after radiotherapy from the additional brief-summary objective.

3. Trial Design

The registry record describes a completed study sponsored by Abramson Cancer Center at Penn Medicine. It lists an enrollment of 204 and gives a study start of 2012-09 and primary completion of 2019-12. The study is not described as a randomized comparison; allocation is not stated.

The record organizes participants into seven treatment strata. These cover early-stage NSCLC treated with stereotactic radiotherapy; locally advanced disease treated with standard chemoradiotherapy; stage I-III disease treated with standard, fractionated radiotherapy alone; locally advanced disease treated with chemoradiotherapy that includes nelfianvir; resectable stage IIIa disease treated with pre-operative chemoradiotherapy; suspected early-stage disease without tissue diagnosis treated with stereotactic radiotherapy; and locally advanced disease treated with stereotactic radiotherapy followed by concurrent mediastinal chemoradiotherapy. The registry states that Cohorts 4 and 7 had no enrolled patients.

The primary outcome is a description of CTC counts per mL before and after definitive radiotherapy, summarized by median and full range for each treatment stratum, with a 24-month timeframe. The record notes that the number analyzed does not match participant flow because not all patients underwent the sequential assays needed for analysis. It says only 114 out of 204 patients were included in the relevant sequential-assay analysis, although the population description is truncated.

The registry record does not report the protocol’s detailed schedule of measurements, the planned follow-up visits, or a statistical analysis plan. It lists one outcome measure and no analyses. The posted information therefore supports describing the study structure and intended biomarker summary, but not reconstructing a detailed protocol or analysis strategy.

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.

Only the first 6 of 7 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: There were no enrolled patients in Cohorts 4 and 7. The Overall Number of Participants Analyzed in the Arms/Groups is not consistent with numbers provided in the Participant Flow module because not all patients underwent sequential (multiple) assays necessary for analysis. Only 114 out of 204 patients fulfilled the analysis criteria such as sequential PET/CT scans performed in the home institution.

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: There was no eligible participant for cohort 4 and cohort 7

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as To Describe the Pattern of CTCs Before and After Definitive Radiotherapy for Each Treatment Stratum, measured over 24 months.

The primary endpoint concerns CTC counts per mL measured before and after definitive radiotherapy in each treatment stratum. The specified summary is the median, accompanied by the full range, over a 24-month timeframe. The endpoint is therefore focused on describing the distribution and pattern of a blood-based biomarker around treatment, rather than on a clinical event such as survival or tumor response.

In general, a median describes the middle of an observed distribution and is less affected by unusually high or low values than an arithmetic mean. A full range conveys the observed spread from the smallest to the largest value, but it can be strongly influenced by extreme observations and does not show how values are distributed between the endpoints. These summaries can be useful when biomarker counts vary substantially across people, but they do not by themselves quantify uncertainty or establish whether a change is statistically reliable.

In general, measuring a biomarker before and after treatment can describe how its observed values vary over time. A CTC count is a measure of cells detected in blood; the endpoint as recorded does not establish that a particular pattern predicts a clinical outcome or explains a treatment effect. The registry record does not report the observed medians, ranges, or paired changes. It also does not provide enough detail to determine the exact measurement schedule within the stated timeframe.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a median and full range as the primary summaries, but it does not report numerical CTC results or analyses. The explanations below describe general statistical concepts; they should not be taken as a claim that a particular unreported method was used in this study.

What does a median describe?

In general, the median is the central value after measurements are ordered. It describes the middle of a distribution and can be a useful summary when observations are skewed or include unusually large values. A median alone does not describe the distribution’s precision, and two groups with the same median may still have very different patterns of observations. The registry’s choice of a median is a descriptive specification; the record does not explain why it was selected or report the observed values.

What does the full range add?

In general, a full range states the lowest and highest observed values. It makes the extremes visible, but it is sensitive to unusual measurements and does not indicate whether most observations cluster near the median or are spread across the interval. A range is not a confidence interval. A confidence interval, in general, expresses uncertainty about an estimated quantity under a statistical model; the registry record does not report confidence intervals for this endpoint.

Why does the before-and-after structure matter?

In general, measurements made on the same person before and after treatment are paired. Their analysis should account for the fact that the two observations are related, rather than treating them as independent observations. A summary of separate before-treatment and after-treatment distributions can describe each time point, but it does not by itself give the distribution of within-person changes. The registry record does not state the precise measurement schedule, how paired observations were summarized, or whether a formal paired analysis was planned.

Why keep treatment strata distinct?

In general, stratified descriptions preserve differences among clinically distinct groups. That can be useful when the study includes different disease settings and treatment approaches. However, comparisons across non-randomized strata can be confounded: group differences may arise from the populations or treatment contexts as well as from the treatments themselves. Randomization can balance measured and unmeasured factors on average, while a non-randomized design does not guarantee that balance. The registry does not state an allocation method and explicitly does not identify the cohorts as a like-for-like control comparison.

What does over-dispersion mean for count data?

In general, count measurements can vary more than a simple statistical model expects. This is called over-dispersion. If it is present, a model that assumes too little variability can understate uncertainty and produce overly narrow confidence intervals or overly small p-values. The registry record does not report a count-data model or provide enough results to assess whether over-dispersion was present. Because the primary outcome is described using medians and ranges, no particular count model should be presumed.

What can a planning calculation show?

In general, a sample-size calculation estimates the amount of information that a future study might need to detect a specified effect under stated assumptions. The recorded planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a stated fraction of the observed effect. Such values are planning illustrations, not observed power and not evidence that the completed study had a particular probability of detecting an effect. The record does not provide the numerical calculations or a trial-specific design justification in the information.

Statistical interpretation also depends on the amount and quality of available data. For repeated biomarker measurements, incomplete assay sequences can reduce the number of people contributing to a before-and-after description. If availability is related to CTC levels, treatment, or clinical status, analysis limited to those with sequential assays may not represent everyone enrolled. General approaches can include describing missingness, defining analysis populations, and testing sensitivity to assumptions, but the registry record does not report whether these approaches were used.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analyses. It does not report a plan for handling multiplicity, such as adjustments for multiple comparisons or a hierarchy for interpreting several endpoints. The stated primary outcome is also separated by treatment stratum, so there may be multiple descriptive summaries, but the record does not specify a formal set of hypothesis tests or how any such tests would be interpreted. No multiplicity adjustment should be assumed.

Missing data are directly relevant to this outcome because the registry states that not all patients underwent the sequential assays necessary for analysis. It attributes the mismatch between analyzed numbers and participant flow to this issue and reports only 114 out of 204 patients for the relevant analysis. The population description is truncated. The record does not report reasons for missing assays, the timing of unavailable measurements, whether missingness differed by cohort, or how missing values were handled. It therefore does not establish whether the analyzed participants represent all enrolled participants.

The registry record does not define the analysis population in enough detail to determine precisely who contributed to each summary. It also does not report whether all enrolled participants were considered for every treatment stratum or whether eligibility for the primary analysis required complete paired assays. These omissions matter because a before-and-after endpoint depends on the availability of measurements at both time points.

General methods for addressing missingness include reporting the extent and pattern of missing observations, explaining the analysis set, and assessing how conclusions change under alternative assumptions. These are methodological possibilities, not methods documented for this study. The registry record does not report whether any such analyses were conducted.

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

The registry record establishes that the study was intended to describe CTC counts before and after definitive radiotherapy in different treatment strata. It also documents important features of the available analysis population, including the lack of sequential assays for some participants and the absence of enrollment in Cohorts 4 and 7. These details help define the scope of the intended descriptive question.

The record does not report the CTC medians or ranges, so it cannot show the direction or magnitude of any observed pattern. It lists no analyses and does not report confidence intervals, p-values, or other measures of uncertainty. Consequently, the record does not support a claim that CTC counts changed, that groups differed, or that any difference was statistically reliable.

Even if numerical group summaries were available, comparisons across these strata would not establish the effect of one treatment relative to another. The groups represent different treatment settings, allocation is not stated, and the record says the arms are not a like-for-like control comparison. Differences could reflect population or treatment-context differences. The registry does not report an approach that would address those sources of confounding.

The endpoint also should not be interpreted as a validated surrogate for a clinical outcome. In general, a biomarker can be measured and described without demonstrating that it predicts outcomes or captures treatment effects on those outcomes. The registry record does not report a relationship between CTC patterns and clinical outcomes. Although the brief summary mentions correlation with pathological samples collected before surgery, results for that objective are not reported in the registry record.

Thus, the record supports an account of the study’s intended biomarker assessment and its reporting limitations. It does not establish a treatment benefit or lack of benefit, and it does not provide enough results to assess the magnitude or precision of a CTC pattern.

12. Why This Trial Matters Statistically

This study illustrates a statistical distinction between describing a biomarker and estimating a comparative treatment effect. CTC counts before and after radiotherapy can be framed as a descriptive question within treatment strata. That is different from comparing treatments under a design that supports causal interpretation. The registry’s cohort structure and lack of a stated allocation method make that distinction central to interpretation.

It also highlights why the analysis population matters for repeated measurements. A before-and-after description requires sequential assays, and the registry states that not all patients underwent them. The reported analyzed population therefore differs from participant flow. Without details about assay availability and missingness, readers cannot determine how representative the analyzed observations are of the enrolled population.

The endpoint’s choice of median and full range reinforces another useful lesson: a concise descriptive summary is not a substitute for an estimate of uncertainty. A median and range convey central location and observed extremes, but they do not alone quantify precision, account for paired observations, or establish the significance of a change. Those interpretations require further analysis and adequate reporting.

Finally, the record shows the limits of drawing conclusions from registry outcome labels without numerical results. The outcome definition is informative about what was intended to be measured, but the record lists no analyses and does not report the observed CTC summaries. Statistical transparency requires the results, analysis population, handling of missing observations, and inferential methods to be available before readers can judge the evidence’s strength.

13. 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 registry record does not provide the observed endpoint values. The primary outcome is defined in terms of medians and full ranges, but those results are not reported in the registry record. No numerical comparison, assessment of uncertainty, or direction of change can therefore be described from this record.

The description of the primary analysis population is incomplete. It states that only 114 out of 204 patients contributed to the relevant sequential-assay analysis and that the analyzed number does not align with participant flow because not all patients underwent the assays needed for analysis. The population text is truncated, and the record does not explain missing assay reasons or their distribution across cohorts.

The study includes distinct treatment strata rather than a stated randomized comparison. The record notes that allocation is not stated and that the arms are not a like-for-like control comparison. Cohorts 4 and 7 had no enrolled patients, limiting description across all planned strata. Cohort 6 includes suspected early-stage NSCLC without tissue diagnosis, which also differs from cohorts defined by established disease stage.

Further protocol details are not reported in the registry record, including a detailed measurement schedule, prespecified statistical methods, missing-data procedures, and a multiplicity plan. The registry lists no analyses. The brief summary’s mention of correlation with pathological samples does not include reported results or analysis details. These limitations restrict interpretation to the study’s stated aim and design rather than conclusions about biomarker patterns or treatment effects.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: The Detection Of Circulating Tumor Cells (CTC) In Patients With NSCLC Undergoing Definitive Radiotherapy Or Chemoradiotherapy — NCT02135679.
• Registry record last updated 2024-11-20; status last verified 2024-11.
• Results first posted 2024-10-08.
• 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.

17. Record Summary

The record describes a completed study of circulating tumor cells in people with NSCLC undergoing definitive radiotherapy or chemoradiotherapy. It lists an enrollment of 204, a start of 2012-09, and primary completion in 2019-12. The primary outcome is CTC counts per mL before and after definitive radiotherapy, summarized by median and full range over a 24-month timeframe.

The study includes seven treatment strata, with no enrolled patients in Cohorts 4 and 7. The registry states that sequential assays were not available for all patients and reports only 114 out of 204 patients in the relevant analysis description. The record lists one outcome measure and no analyses. It does not report observed CTC results, inferential statistics, a detailed statistical plan, or missing-data methods.

The registry supports a description of the intended biomarker question and key limitations in the available reporting. It does not support conclusions about the direction, size, or precision of CTC changes or comparative treatment effects.