Evaluation of Circulating T Cells and Tumor Infiltrating Lymphocytes (TILs) During / After Pre-Surgery Chemotherapy in Non-Small Cell Lung Cancer (NSCLC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Circulating T Cells and Tumor Infiltrating Lymphocytes (TILs) During / After Pre-Surgery Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) (NCT01820754), a na phase 2 study. The primary outcome is Percentage of Subjects With Detectable Circulating T Cells After Treatment.

2. Clinical Question

The question concerns an immune measurement after a treatment sequence given before surgery, rather than a comparison of clinical outcomes between randomized treatment groups. The registry describes the target population as early-stage lung cancer patients and identifies tumor-associated antigen (TAA)-specific circulating T cells as the primary focus. Its definition of detectable responses uses CD8, CD4, and double-positive lymphocyte measurements against a threshold and an unstimulated background control.

The clinical context also includes surgical resection and postoperative ipilimumab. Secondary outcomes listed in the registry cover feasibility and tolerability, disease-free survival, metastasis by site, and pathologic and RECIST response. However, those listed outcomes do not establish that results for each were posted. A primary endpoint value, detailed outcome estimates, and comparative effects are not reported in the registry record. The study therefore poses a biomarker-focused question, but the available record does not permit a complete assessment of the observed response or its precision.

3. Trial Design

This is a completed Phase 2 clinical trial with an open-label, single-group design. The registry lists an enrollment of 24 and identifies Duke University as sponsor. It records the start as 2013-03 and primary completion as 2018-04-30. No masking was used, and allocation is listed as not applicable. With no independent control group, the design does not directly compare the treatment sequence with another assigned regimen or with no treatment.

Eligible participants were described as having clinical stage 1B (>4 cm), 2 (N0-2), or 3 NSCLC and no prior therapy for the current diagnosis. The planned sequence began with three cycles of neoadjuvant paclitaxel plus cisplatin or carboplatin. Ipilimumab was added during cycles 2 and 3. Participants were to undergo clinically indicated surgical resection following neoadjuvant treatment, with postoperative ipilimumab described in the intervention information. The registry summary mentions up to four cycles alone after surgery; the regimen description specifies two postoperative doses followed by two maintenance doses.

The primary outcome is the percentage of participants with detectable circulating T cells after treatment, assessed at 3 months. The listed analysis population is intent to treat, with a note that participants who had detectable responses after treatment also had responses at baseline. Secondary outcomes include feasibility and tolerability of the combined treatment and surgery, median disease-free survival, metastasis by site, and pathologic and RECIST response patterns.

The registry lists five outcome measures, but no analyses are listed. The statistical plan, any sample-size justification, interim monitoring, and the handling of protocol deviations are not reported in the registry record. Completion status describes the trial's administrative status; by itself, it does not show that every planned endpoint has a posted result.

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

Analysis population for the primary outcome, as defined in the registry: Intent to treat. Note that the 16.7% of patients that had detectable T-cell responses also had responses at baseline

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 Percentage of Subjects With Detectable Circulating T Cells After Treatment, measured over 3 months.

The primary endpoint is the percentage of participants with detectable circulating T cells after treatment, with a stated timeframe of 3 months. The target cells are described as specific to tumor-associated antigens. Detectability is defined using CD8, CD4, and double-positive (CD4+CD8+) lymphocyte percentages: each value must be at least 0.05% and at least twice the background unstimulated control value.

This endpoint measures an immune response in circulating blood, not tumor shrinkage, recurrence, or survival. A percentage is a way to report how common a defined response is among the participants included in the analysis. It depends on both the biological measurements and the threshold used to classify a response. The registry's definition therefore specifies not only which cell populations count, but also how their measured percentages are judged against background.

As a general statistical point, a binary endpoint such as detectable versus not detectable can make an outcome easier to summarize, but it compresses a continuous laboratory measurement into categories. Participants near a threshold may be classified differently from those with measurements farther from it, and the result can depend on assay performance and background controls. The registry does not report the primary endpoint's observed percentage, the number of participants meeting its criteria, or an uncertainty interval. It does note that the 16.7% of patients with detectable T-cell responses also had responses at baseline, which is important context when interpreting a post-treatment endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes an open-label Phase 2 study with a single group and no masking. These design features determine what kinds of statistical conclusions are possible. The treatment sequence was administered without a separate randomized control arm, so the principal endpoint is a proportion among participants receiving that sequence. It is not a direct estimate of a treatment contrast between groups.

What does a percentage endpoint represent?

For a binary outcome, each participant is classified according to whether the prespecified condition is met. The percentage is the share of the analyzed group classified as having a detectable response. As a general statistical concept, this estimate has uncertainty because another group of similar participants could yield a different observed share. The amount of uncertainty depends, among other things, on the number evaluated and the number meeting the definition.

In this trial, the endpoint is not simply any measurable T cell. The registry defines detectability using CD8, CD4, and double-positive lymphocyte percentages, requiring each value to reach at least 0.05% and to be at least twice the unstimulated background value. This operational definition matters: the reported percentage would refer to participants meeting that rule, not to every possible measure of immune activity. The registry does not report the primary endpoint count or percentage, so neither the observed estimate nor its precision can be assessed.

Why does baseline status matter?

The registry states that the 16.7% of patients with detectable responses also had detectable responses at baseline. A post-treatment proportion alone cannot distinguish responses already present before treatment from newly detected responses. For that distinction, an analysis would need to account for each participant's measurements at both time points. The record does not report such a paired analysis or the individual transition counts. The baseline note is therefore relevant context, but it is not enough to calculate a change or attribute detection to treatment.

What can a single-group design establish?

A single-group study can describe outcomes in the enrolled group and can assess whether a regimen is feasible within the study's setting. It does not directly estimate a comparative effect against an assigned alternative. General statistical reasoning distinguishes a within-group observation from a between-group contrast: a change over time may be consistent with a treatment effect, but other explanations, including natural fluctuation and measurement variation, remain possible in the absence of a concurrent comparison. The registry does not report a statistical model or adjusted analysis.

How should uncertainty be read?

As a general explanation, a confidence interval gives a range of values reasonably compatible with the data under the method used to calculate it. A narrow interval indicates greater precision than a wide interval, while neither interval alone resolves bias or establishes causation. The registry record does not report an interval for the primary outcome or a method for calculating one. No p-value or inferential analysis is listed, and the record lists zero analyses.

For an endpoint expressed as a percentage, the denominator is essential. It identifies how many participants contributed evaluable endpoint data. The primary population is described as intent to treat, but the number assessed at the endpoint and any missing-data procedure are not reported in the registry record. It is therefore not possible to establish whether all enrolled participants contributed to the primary endpoint estimate.

What do the planning illustrations mean?

The registry's planning assumptions describe an illustration based on the observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The description says that non-time-to-event illustrations are participants per arm for the stated power, while time-to-event illustrations give the total number of events. These are planning quantities, not observed outcomes or observed power. Because no analyses are listed and the primary effect estimate is not reported, the record does not support interpreting such planning assumptions as evidence about the precision or success of this completed single-group study. The equal-allocation, two-arm assumptions also do not describe the registered single-group design.

Over-dispersion is a general issue when observed variation exceeds what a simple statistical model assumes. It can make standard errors too small if the model fails to account for extra variation. The registry does not report a model for the primary outcome, so there is no basis to say whether over-dispersion was assessed or relevant to the sponsor's analysis.

Finally, endpoint definitions, analysis populations, missing-data rules, multiplicity procedures, and sensitivity analyses are part of interpreting statistical results. Some details, such as the detectability threshold and intent-to-treat label, are present. Other elements, including a full statistical analysis plan, are not reported in the registry record. Their absence from the record should not be filled in by assumption.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Ipilimumab")
n      <- c(24)
events <- c(4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Ipilimumab  24  4  16.7  4.7  37.4  6.7  35.9  6.8  36.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes: feasibility and tolerability of neoadjuvant chemotherapy plus ipilimumab and surgery, median disease-free survival, metastasis by site, and pathologic and RECIST response patterns. It does not list analyses for these outcomes. The existence of multiple outcome questions can raise a multiplicity issue: when several hypotheses are examined, the chance of at least one apparently notable finding can increase. As a general statistical matter, studies may address this through a prespecified hierarchy or adjustment, but neither a multiplicity strategy nor a statistical analysis plan is reported in the registry record.

The primary analysis population is described as intent to treat. The registry does not report the number with evaluable primary endpoint measurements, the number excluded from an endpoint analysis, or the handling of missing measurements. It is also not reported in the registry record whether missingness was addressed through imputation, complete-case analysis, or another method. Without those details and the endpoint denominator, the effect of missing observations on the reported proportion cannot be assessed.

The record's note that the 16.7% with detectable responses also had responses at baseline signals that baseline status is relevant to interpretation. However, the record does not provide a baseline-by-follow-up breakdown or describe a method for analyzing repeated measurements. Whether participants with baseline responses were handled differently in any analysis is not reported in the registry record.

These limitations concern what the registry documents; they do not establish that the trial team did or did not perform additional analyses. The posted record simply does not provide enough detail to evaluate multiplicity control, missing-data assumptions, or the relationship between the stated analysis population and endpoint evaluability.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (8.3%), thromboembolic event (8.3%), abdominal pain (4.2%), diarrhea (4.2%), dysphagia (4.2%).

The registry lists one group, Ipilimumab, with 24 participants at risk for serious adverse events and 6 participants affected. It reports 24 participants at risk for other adverse events and 24 affected. No deaths are listed. These figures describe participants reported as affected; they should not be read as counts of distinct event episodes unless the record explicitly defines them that way.

The serious-event terms with the highest listed percentages are dehydration (8.3%), thromboembolic event (8.3%), abdominal pain (4.2%), diarrhea (4.2%), dysphagia (4.2%), and rectal hemorrhage (4.2%). The registry gives these percentages but does not provide further event-level detail in the record, such as timing, duration, recurrence, or attribution to a particular component of the regimen. The listed terms should therefore be read as reported safety categories, not as a complete clinical narrative for each participant.

As a general statistical point, adverse-event summaries depend on how events are defined, collected, coded, and attributed, and on the number of participants under observation. The group is small, so the reported figures describe this study group and do not by themselves establish how often such events would occur in a broader population. The registry record does not report additional detail about exposure-adjusted rates or comparative safety. These figures are descriptive, not a comparison with another treatment group.

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

The registry record establishes that a completed Phase 2, open-label, single-group trial evaluated a treatment sequence involving neoadjuvant chemotherapy, ipilimumab, and surgery in NSCLC. It defines a biomarker endpoint based on detectable circulating T cells specific to tumor-associated antigens and gives the assessment timeframe as 3 months. The registry also lists an enrollment of 24 and reports limited adverse-event information.

It does not report the observed primary endpoint percentage, the number of participants meeting the endpoint, or an uncertainty interval. The stated goal of reaching 20% after treatment is an objective, not a result. The note that the 16.7% of patients with detectable T-cell responses also had responses at baseline makes it especially important not to equate post-treatment detection with a newly induced response. The record does not provide enough detail to estimate a change from baseline.

The single-group design also limits causal interpretation. There is no separate randomized comparator with which to estimate how the biomarker outcome might differ under another treatment strategy. Even a complete within-group endpoint estimate would describe the study participants and would not, on its own, establish that the treatment caused the observed biomarker pattern.

Secondary outcomes are listed, but their results are not reported in the registry record. The available safety figures describe reported adverse events in the study group; they are not comparative evidence and do not resolve the efficacy question. A reader should distinguish the trial's planned questions, its posted safety counts, and the outcome estimates that are absent. The registry entry supports understanding what investigators intended to study, but it does not supply the result detail needed to judge the primary biomarker endpoint's magnitude or precision.

14. Why This Trial Matters Statistically

This trial raises several statistical issues that are common in early clinical biomarker research. Its primary outcome is a proportion defined by laboratory thresholds, so interpretation depends on both the underlying assay measurements and the rule used to classify a response. The requirement that values meet a minimum percentage and exceed background helps make the endpoint operational, but a binary classification can conceal differences in the magnitude of measurements among participants.

Baseline information is particularly important. The registry notes that the 16.7% with detectable responses after treatment also had responses at baseline. That makes the distinction between detecting a response at follow-up and observing a response that newly appeared after treatment central to interpretation. Without a reported paired analysis, the record does not show how those patterns were evaluated.

The study also illustrates the limits of drawing comparative conclusions from a single-group design. A treatment sequence can be described, and outcomes among enrolled participants can be counted, but there is no randomized control group to separate treatment-associated changes from other explanations. The registry's planning illustration assumes equal allocation between two arms, whereas the registered study is single group; those planning assumptions should not be mistaken for the design actually used.

Finally, a completed trial record can still leave important statistical questions unanswered. Here, the primary result, its precision, endpoint evaluability, and the analysis methods are not reported in the registry record. The distinction between an endpoint being specified and its result being posted is essential. This distinction helps readers assess what can be learned from a registry entry without treating a study objective or outcome list as evidence of an observed treatment effect.

15. 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 in interpreting the record is the absence of a reported numerical result for the primary endpoint. Without the endpoint count, percentage, denominator, or uncertainty interval, the frequency and precision of detectable post-treatment responses cannot be assessed. The stated objective of 20% does not substitute for an observed estimate.

The single-group design offers no randomized treatment comparison. Although the endpoint concerns measurements after treatment, the design cannot by itself distinguish a treatment-associated change from other possible influences. The registry's baseline note is also consequential: the 16.7% with detectable T-cell responses had detectable responses at baseline. No participant-level transitions or paired change analysis are reported.

The endpoint is a threshold-based biomarker classification. Its meaning depends on the stated CD8, CD4, and double-positive criteria and their relationship to the unstimulated control. The registry does not report additional assay-performance information or the number of participants with evaluable measurements at the stated 3-month timeframe. Such details would affect interpretation of a proportion based on laboratory classification.

Although secondary outcomes are listed, their results and analyses are not reported in the registry record. The record also does not report the statistical analysis plan, sample-size justification for this trial, multiplicity approach, missing-data handling, or interim analyses. These omissions prevent evaluation of several aspects of analysis and reporting, but do not establish what was or was not done outside the registry entry. The safety data are descriptive, with no comparator group, and should be interpreted within the context of the study's listed enrollment and reported at-risk group.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Circulating T Cells and Tumor Infiltrating Lymphocytes (TILs) During / After Pre-Surgery Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) — NCT01820754.
• Registry record last updated 2021-02-26; status last verified 2021-02.
• Results first posted 2018-05-22.
• 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.

19. Record Summary

The registry describes a completed, open-label Phase 2 trial sponsored by Duke University, with enrollment of 24 and a single-group design. Participants with specified clinical stages of NSCLC were to receive neoadjuvant paclitaxel with cisplatin or carboplatin, ipilimumab during chemotherapy cycles 2 and 3, and surgery, followed by postoperative ipilimumab as described in the regimen information.

The primary endpoint is the percentage with detectable circulating T cells specific to tumor-associated antigens at 3 months. Detectability is defined using CD8, CD4, and double-positive cell percentages relative to a threshold and background control. The registry notes that the 16.7% with detectable responses also had responses at baseline, but does not report the primary endpoint estimate or its precision.

Serious adverse events were reported for 6 of 24 participants at risk; other adverse events were reported for 24 of 24 at risk, with no deaths listed. Secondary outcomes are named, but analyses are not listed. The record documents the study question, design, and some safety information, while the primary result and key statistical analysis details are not reported in the registry record.