Use of High Dose Radiation Followed by Chemotherapy and Radiation to Treat Locally Advanced NSCLC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of High Dose Radiation Followed by Chemotherapy and Radiation to Treat Locally Advanced NSCLC (NCT03141359), a na phase 2 study. The primary outcome is Number of Participants Progression Free and Surviving at 12 Months.

2. Clinical Question

The study is a Phase II prospective investigation in locally advanced non-small cell lung cancer. Its sequence of treatment combines radiation directed at the primary lung tumor with concurrent treatment directed at the mediastinum, and may include additional systemic therapy. Because everyone is assigned to one study group, the central statistical question is descriptive: what outcome was observed among those treated and evaluable under the registry definition? Without a comparison group, differences from another treatment approach cannot be estimated from this study alone. The registry record describes several secondary outcomes, including overall survival, response, and local, regional, locoregional, and distant control. Their presence indicates a broader outcome assessment, but the primary focus is progression-free survival at 12 months.

3. Trial Design

This is a prospective, single-group, single-stage Phase II study. The registry record describes 61 participants enrolled, while the brief study summary states that 60 subjects were to be enrolled over a 4 year accrual period. These are different record entries: one gives the listed enrollment and the other states the planned enrollment. The study is marked active, not recruiting. Its recorded start date is 2017-05-12, and its primary completion date is 2023-07-12.

The sole arm is described as stereotactic body radiation therapy followed by concurrent mediastinal chemoradiation, with the possibility of consolidation chemotherapy and adjuvant immunotherapy. Listed interventions include stereotactic body radiation therapy, carboplatin, paclitaxel, cis platinum, etoposide, intensity-modulated radiation therapy, and durvalumab. The description does not establish that every participant received each listed drug or optional treatment component. The registry record does not report the precise treatment-selection rules or how use of optional components varied among participants.

Allocation is listed as not applicable, and masking as none. There is no parallel control arm. The planned design therefore differs from a randomized trial that assigns participants to two or more strategies. Observed outcomes can describe the cohort treated in this study, but cannot isolate the effect of this regimen from other influences by comparison with a concurrent randomized control group.

The primary endpoint is a binary 12-month progression-free survival outcome. The registry record lists 19 outcome measures and 5 analyses. It does not report the statistical analysis plan, the planned handling of all secondary outcomes, or a detailed justification for the enrollment target. The description calls the study single-stage, but the registry record does not report a stopping boundary or interim analysis procedure. Those details should not be inferred from the design label alone.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The population evaluable for the 12-month PFS outcome is defined as all subjects who initiate treatment with SBRT and experienced a PFS event within 12 months of enrollment or have at least one year of radiologic follow-up from enrollment.

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 Progression Free and Surviving at 12 Months, measured over From date of treatment start to date of progression or death, or censored at 12 months, whichever occurred first..

The primary endpoint counts participants who are alive and progression-free at 12 months. It is recorded as a binary outcome for each subject: meeting the endpoint means progression-free survival at the specified time; progression or death from any cause within 12 months is a failure. Disease progression is determined according to RECIST version 1.1. The registry record describes the timeframe as extending from treatment start to progression or death, or censoring at 12 months, whichever occurs first. Its endpoint description also refers to status at 12 months after enrollment.

A fixed-time progression-free survival endpoint is useful because it expresses disease control and survival together at a clinically defined follow-up point. As a binary measure, it can be presented as the number of participants who meet the outcome within the defined evaluable population. That count is not interchangeable with the duration of progression-free survival across all follow-up times; it answers a time-specific question.

The registry record defines the evaluable population as subjects who initiate stereotactic body radiation therapy and either have a progression-free survival event within 12 months of enrollment or have at least one year of radiologic follow-up from enrollment. It does not report the observed count for the primary endpoint, the corresponding proportion, or an uncertainty interval. Therefore, the endpoint definition is available, but the registry record does not report the primary result needed to quantify how many evaluable participants were progression-free and alive at 12 months.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as a count of participants, with each subject’s 12-month progression-free survival status classified as a binary outcome. A binary outcome has two categories for the specified definition: the event of interest is either met or not met. In this study, progression or death from any cause within 12 months is a failure to meet the endpoint. Disease progression is assessed using RECIST version 1.1.

What does a fixed-time binary endpoint tell us?

In general, a fixed-time binary endpoint answers whether a participant met a defined outcome by a specified time. It can be reported as a count, and often as a proportion with an uncertainty interval. The count is easy to understand, but it does not retain all information about event timing. For example, a binary status at 12 months treats events within the period as failures without expressing how early or late they occurred. A time-to-event analysis instead uses the timing of events and can account for censoring during follow-up. The registry record describes a 12-month binary primary endpoint and lists progression-free survival as a secondary outcome, but the statistical methods and results for the secondary analysis are not reported in the registry record.

Who is included in the endpoint population?

The registry defines the evaluable population as participants who initiate stereotactic body radiation therapy and either experience a progression-free survival event within 12 months of enrollment or have at least one year of radiologic follow-up from enrollment. This definition matters because an endpoint count is interpretable only alongside the rules determining whose status is evaluated. Participants with a qualifying event can be classified without waiting for a full year of event-free follow-up; participants without an event need the specified follow-up period to establish their status. The registry record does not report a separate count for the evaluable population or detail how other incomplete follow-up situations were handled.

The timeframe description refers to the period from treatment start to progression or death, or censoring at 12 months. The endpoint description refers to progression-free and surviving at 12 months after enrollment, and the evaluable-population definition also uses enrollment as its reference point. These descriptions use different starting-point wording. The registry record does not explain whether these dates are equivalent in practice or how any difference was resolved in the analysis.

How should uncertainty be understood?

In general, a confidence interval describes the range of values compatible with the observed data under a statistical model and its assumptions. A narrower interval indicates greater precision, while a wider interval indicates more uncertainty. The registry record does not report the primary endpoint estimate or its confidence interval, so the precision of the 12-month outcome cannot be assessed from the record. A p-value, if reported, would address compatibility with a specified null hypothesis under an analysis plan; it would not by itself show the size or clinical importance of an outcome. No primary endpoint p-value is reported in the registry record.

For event counts, a general statistical concern is over-dispersion: variability can be greater than expected under a simple model. When that occurs, methods that assume less variability may produce intervals or tests that are too optimistic. Whether this issue arose in this study, and what model or variance method was used, is not reported in the registry record. The primary outcome is identified as a participant count, but details of the inferential model are absent.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They state that the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration gives a total number of events; for other outcomes, it gives participants per arm. These are planning assumptions for an illustration, not evidence that the trial randomized participants or included a second arm. This study is single-group, and the registry record explicitly indicates that it is not a randomized comparison. The assumptions therefore should not be mistaken for the trial’s own design, an observed power calculation, or a randomized analysis.

In general, sample-size planning illustrates how the amount of information needed can depend on the effect targeted, the chosen error rate, the allocation scheme, and the statistical approximation. A planning calculation does not establish that a study had adequate precision, and it cannot replace a reported estimate with its uncertainty. The registry record does not report a protocol-based sample-size justification or explain how the stated assumptions relate to the single-group design. No additional values should be inferred from the assumptions alone.

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("SBRT + Concurrent Mediastinal Chemoradiation +/- C")
n      <- c(59)
events <- c(37)
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  SBRT + Concurrent Mediastinal Chemoradiation +/- C  59  37  62.7  49.1  75.0  50.0  73.9  49.9  73.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 19 outcome measures and 5 analyses. It also names a range of secondary outcomes, including progression-free survival, overall survival, radiologic complete response, objective response, and local, regional, locoregional, and distant control at specified follow-up times. When a study assesses multiple outcomes, there are multiple opportunities to observe apparently notable findings. In general, multiplicity procedures can control the chance of false-positive conclusions across a defined family of tests. The registry record does not report whether any such procedure was planned or used, how outcomes were grouped for this purpose, or which analyses were considered primary within the secondary outcomes.

The primary endpoint population has a specific evaluability rule based on treatment initiation, a progression-free survival event within 12 months, or at least one year of radiologic follow-up from enrollment. The record does not report the number meeting that definition, the amount of missing follow-up, or how missing and unevaluable observations were handled beyond the stated population definition. It also does not report imputation methods, sensitivity analyses, or a comparison of participants with and without complete follow-up. These omissions limit assessment of whether the endpoint count could be affected by incomplete outcome ascertainment.

The record describes one primary endpoint, but does not report a detailed statistical analysis plan, adjustment for covariates, interim analyses, or the handling of multiple comparisons. These items should be treated as not reported in the registry record, rather than assumed to have been absent from the protocol. The record’s endpoint definition and outcome list make clear what was intended to be assessed, but do not establish the methods used to analyze every outcome or manage missing data.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lung infection (16.4%), respiratory failure (4.9%), respiratory, thoracic and mediastinal disorders - other (3.3%), febrile neutropenia (3.3%), neutrophil count decreased (3.3%).

The safety summary lists 61 participants at risk for serious adverse events, of whom 23 were affected. For other adverse events, 61 were at risk and 61 were affected. The registry record also lists 32 deaths. These are recorded safety figures; they should not be treated as evidence that a particular event or death was caused by treatment. The record does not report a control group for safety comparison, nor does it specify in these entries the attribution of deaths to treatment.

The most frequently listed serious adverse event terms are lung infection at 16.4%, respiratory failure at 4.9%, and respiratory, thoracic and mediastinal disorders - Other, febrile neutropenia, neutrophil count decreased, and pneumonitis, each at 3.3%. These percentages are reproduced as reported. They are event-term summaries and should not be added together: a participant may have more than one event, and the record does not explain whether events overlap across terms. The registry record also does not provide the full event narratives, timing, duration, severity grading details, or attribution needed to interpret individual cases. The safety summary describes what was recorded, not a comparative estimate of treatment-related risk.

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

The study addresses a defined statistical question: the number of participants progression-free and alive at 12 months after treatment, using a specified failure definition. Its prospective Phase II, single-group design provides a framework for describing outcomes among participants treated with stereotactic body radiation therapy followed by concurrent mediastinal chemoradiation, with possible additional chemotherapy and immunotherapy. The primary endpoint’s evaluable-population definition and RECIST-based progression assessment are important for understanding what the intended result would represent.

However, the primary endpoint result is not reported in the registry record. Consequently, the record does not establish how many participants were progression-free and alive at 12 months, the estimated rate, or the precision of that estimate. The listed enrollment of 61 does not reveal how many participants were evaluable for the primary outcome. Nor does the brief summary’s planned enrollment of 60 establish the endpoint result.

A single-group study can describe outcomes in its treated cohort, but it cannot make a randomized treatment comparison. Without a concurrent control arm, the study cannot separate the contribution of the treatment regimen from other factors that might influence outcomes. The registry record’s safety counts and adverse event terms likewise do not establish comparative safety or causation. They should be read as descriptive entries rather than proof that treatment caused any particular event.

The registry lists other outcomes, such as overall survival, response, and disease control at specified times, but their results are not reported in the registry record. Listing an outcome is not the same as reporting its estimate. The record also does not provide a full statistical analysis plan or missing-data sensitivity analyses. These limits mean that conclusions about the magnitude, precision, and robustness of outcomes cannot be drawn from the information recorded. The most defensible interpretation is therefore about the study’s design, definitions, and recorded safety summaries, not efficacy or comparative benefit.

14. Why This Trial Matters Statistically

This trial is statistically notable for using a fixed-time binary progression-free survival endpoint in a prospective single-group Phase II design. It illustrates why endpoint definitions and analysis populations matter. The primary outcome classifies participants based on progression-free survival at 12 months, while the evaluable-population definition requires treatment initiation and either an event within the period or at least one year of radiologic follow-up. Without those details, a count would be difficult to interpret; with them, the intended denominator is clearer, even though the registry record does not report that denominator or the primary result.

The design also highlights the difference between describing outcomes and estimating comparative effects. A single-group cohort can document what happened among participants in the study, but it lacks a randomized control group for a like-for-like treatment contrast. That distinction is especially important when interpreting a fixed-time outcome, safety events, and any planning illustrations framed around two-arm allocation. Statistical assumptions used for an illustration do not change the actual single-group structure.

Finally, the record shows why registration details alone may be insufficient for a full statistical appraisal. It defines the endpoint and lists numerous other outcomes, but does not report the primary estimate, its uncertainty, or detailed methods for multiplicity and missing data. Those omissions restrict assessment of precision and robustness. The safety summary adds descriptive context, but without treatment attribution or comparison it cannot answer comparative safety questions. Taken together, the design and reporting details clarify what the study set out to measure while marking the limits of what can be concluded from the registry record.

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 central limitation for interpretation is that the registry record does not report the primary 12-month progression-free survival result. It gives the endpoint definition and evaluable-population rule, but not the number of evaluable participants, the number meeting the endpoint, an estimate of the rate, or its precision. The secondary outcomes are listed, but their results are not reported in the registry record either.

The single-group design has no randomized control arm. Accordingly, outcomes from this cohort cannot establish a treatment effect relative to another strategy. The record states that allocation is not applicable and masking is none. It also does not report a detailed statistical analysis plan, the handling of multiplicity, interim analysis methods, or a protocol-based enrollment justification. These details cannot be inferred from the Phase II and single-stage labels.

The primary endpoint descriptions refer both to the period from treatment start and to status 12 months after enrollment. The evaluable-population definition likewise uses enrollment as a reference. The registry record does not explain whether these time origins coincide for participants or how any discrepancy was handled. It does not report the amount of missing follow-up, the number excluded from evaluability, imputation procedures, or sensitivity analyses.

The listed safety information is also limited for causal interpretation. Serious and other adverse event counts are reported, along with deaths and selected serious-event terms, but the record does not report treatment attribution or a comparison group. The listed percentages should not be treated as mutually exclusive categories. These limits leave the clinical outcomes and their statistical precision unresolved in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Use of High Dose Radiation Followed by Chemotherapy and Radiation to Treat Locally Advanced NSCLC — NCT03141359.
• Registry record last updated 2026-07-28; status last verified 2026-07.
• Results first posted 2024-08-29.
• 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 record describes a prospective, single-group, single-stage Phase II study of stereotactic body radiation therapy followed by concurrent mediastinal chemoradiation, with possible consolidation chemotherapy and adjuvant immunotherapy, for locally advanced non-small cell lung cancer. It lists enrollment of 61 and a planned enrollment of 60 in the brief study summary. The record is marked active, not recruiting, with a start date of 2017-05-12 and primary completion date of 2023-07-12.

The primary endpoint is the count of participants progression-free and alive at 12 months, with progression or death within that period counted as failure. The registry record does not report the primary outcome result. It lists safety counts, including 23 participants affected by serious adverse events and 32 deaths, but does not establish treatment causation. The absence of a control group limits comparative interpretation.