Testing the Addition of Targeted Radiation Therapy to Surgery and the Usual Chemotherapy Treatment (Pemetrexed and Cisplatin [or Carboplatin]) for Stage I-IIIA Malignant Pleural Mesothelioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing the Addition of Targeted Radiation Therapy to Surgery and the Usual Chemotherapy Treatment (Pemetrexed and Cisplatin [or Carboplatin]) for Stage I-IIIA Malignant Pleural Mesothelioma (NCT04158141), a randomized phase 3 study. The primary outcome is Overall Survival (OS).

2. Clinical Question

This is a question about treatment strategies, not radiation in isolation: both arms included surgery and chemotherapy, and the distinguishing treatment step was the addition of radiation in Arm II. The registry lists a randomized, parallel-group phase III trial with no masking. Its listed enrollment is 16, while the primary-outcome arm counts are 5 for Arm I and 6 for Arm II. Those counts describe different record entries and should not be combined into a participant total.

The clinical question is relevant to interpreting an add-on treatment comparison. Even if a difference between arms had been observed, the comparison would concern the whole treatment strategy as implemented, including its sequence and timing, rather than establishing the separate contribution of each treatment component. The registry record does not report a completed estimate of the difference in overall survival or its uncertainty.

3. Trial Design

This was a randomized phase III parallel-group study sponsored by NRG Oncology. The record lists no masking. Participants were assigned to one of two strategies: P/D and systemic chemotherapy, or the same initial strategy followed by IMRT or PBS proton therapy. The official title describes the radiation as adjuvant hemithoracic intensity-modulated pleural radiation therapy, or IMPRINT.

The registry describes the radiation step as occurring within 4–8 weeks after the end of Step 1 treatment. Arm II was to receive 25–28 fractions, delivered 5 days per week over 6 weeks. The record names pemetrexed and cisplatin or carboplatin as the chemotherapy drugs. It also describes P/D and systemic therapy timing, including a route for people who received allowed neoadjuvant systemic therapy before study entry. The full Arm I description is incomplete in the registry record, so further details of that sequence are not reported in the registry record.

The study started on 2020-01-29, and primary completion is listed as 2023-11-20. Its status is terminated. The primary outcome timeframe is randomization to death or last follow-up, with maximum follow-up from randomization of 25 months. The registry’s stated analysis plan called for a survival analysis after at least 105 deaths had been reported. Because the study closed early and had a small number of participants, the record says that only the number last reported alive at termination is reported.

Enrollment is listed as 16. The primary outcome results give arm counts of 5 for Arm I and 6 for Arm II. The record does not explain the relationship between the listed enrollment and the participants represented in those outcome counts. The dates and status establish that the trial ended, but the reason for termination is not reported in the registry record.

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.

Step 1: Registration

Reasons for not completing this period:

Step 2: Randomization

Step 2: As-treated Population

Analysis population for the primary outcome, as defined in the registry: Randomized patients

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: Not randomized: Eligible registered patients who did not continue to Step 2 (randomization). Arm 1 and Arm 2: Eligible randomized patients.

6. Primary Endpoint

The registry lists the primary outcome as Overall Survival (OS), measured over Randomization to the date of death or last follow-up. Maximum follow-up time from randomization was 25 months..

Overall survival (OS) is the time from randomization until death from any cause. For participants who have not died by their last recorded follow-up, that follow-up time contributes information while recognizing that their later survival is not known. OS is commonly used in trials because it captures a direct, clinically important event and does not depend on judging whether a particular symptom, scan finding or disease change counts as progression.

In this trial, the registry states that OS was to be estimated using the Kaplan–Meier method and compared between arms with a log-rank test. The outcome timeframe runs from randomization to death or last follow-up. The registry reports a maximum follow-up time from randomization of 25 months. It also states that the planned analysis was to take place when at least 105 deaths had been reported.

The posted OS result is not a Kaplan–Meier estimate or a comparison of survival distributions. Because of early study closure and the small number of participants, the registry reports only the count last reported alive at termination: 5 in Arm I and 4 in Arm II. These counts do not show when deaths occurred, how long participants were followed, or the pattern of censoring. They therefore cannot replace the planned time-to-event analysis or establish a treatment effect. The registry record does not report an OS estimate, confidence interval, hazard ratio or log-rank result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Overall survival is a time-to-event outcome: each participant contributes a duration from randomization until death or, if death has not been recorded, the last known follow-up. Unlike a simple count at one administrative cutoff, the analysis uses both whether an event occurred and when it occurred. Participants with no recorded event at their last observation contribute partial information rather than being assumed to have a later outcome.

What does Kaplan–Meier estimation do?

In general, the Kaplan–Meier method estimates the probability of remaining free of the event over time while accounting for censoring. At each time when an event occurs, the estimate updates using the participants still under observation just before that time. Participants who are censored contribute information up to their last follow-up. This makes the method useful when people enter follow-up at different times or are observed for different durations, provided the assumptions needed for the analysis are reasonable.

The registry identifies Kaplan–Meier estimation as the planned method for OS. It does not post the event times, censoring times, estimated survival curve, or summary at a specified time. The counts last reported alive cannot supply that missing time information. Therefore the planned estimates cannot be reproduced from the posted counts.

What does the log-rank test compare?

In general, a log-rank test compares the observed and expected event counts between groups across event times. It is designed to test whether the survival experience differs over the observed follow-up, while taking account of censoring. It is not a test of the difference between the number alive at one cutoff. The registry says this was the planned comparison, but no test result is reported in the registry record.

The plan specified analysis when at least 105 deaths had been reported. The record says early study closure and a small number of participants led to reporting only the number last reported alive at termination. It does not report that the planned threshold was reached. No result from the planned log-rank comparison is available in the registry record.

Why are the counts not a survival estimate?

A count at termination does not incorporate when a death occurred or how much follow-up was available for someone still alive. Two groups can have the same count alive at the cutoff while having different event timing or different follow-up patterns. Conversely, different counts do not by themselves quantify a difference in survival over time. The primary result is therefore a limited descriptive snapshot, not a time-to-event effect estimate.

In general, a confidence interval describes the range of effect sizes compatible with the data and the statistical model at the stated confidence level. It communicates precision as well as direction and magnitude. No confidence interval is reported for this OS result. A p-value, if available, would address compatibility with a specified null hypothesis under the analysis assumptions; it would not by itself communicate the size or clinical importance of an effect. No p-value is reported either.

How should planning illustrations be understood?

The registry’s planning assumptions describe illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation and a normal approximation. Such calculations are planning aids rather than evidence about the completed trial’s power. The record also states that the displayed effect is a stated fraction of the observed effect, and that time-to-event planning tables use total events while other planning tables use participants per arm. These assumptions do not describe the trial’s original design, and the record does not report the trial’s own sample-size justification.

In general, planning calculations depend on the effect size chosen, the outcome model, the allocation approach and the assumptions used to define the statistical error rates. A sample-size illustration is not “observed power” and cannot turn an incomplete result into a definitive comparison. The posted OS counts do not yield a reported effect estimate on which to base a trial-specific interpretation of such planning calculations.

The registry lists an outcome-analysis count of 0. That is consistent with the absence of a posted formal OS comparison, but it does not reveal why analyses were not entered or whether analyses were conducted outside the record. Further details of the statistical analysis plan, including model diagnostics, handling of deviations from assumptions and any alternative analysis, are not reported in the registry record.

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("Arm I (Step 1: Chemotherapy, P/D: Step 2: no Treat", "Arm II (Step 1: Chemotherapy, P/D, Step 2: IMRT/PB")
n      <- c(5, 6)
events <- c(5, 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  Arm I (Step 1: Chemotherapy, P/D: Step 2: no Treat  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  Arm II (Step 1: Chemotherapy, P/D, Step 2: IMRT/PB  6  4  66.7  22.3  95.7  30.0  90.3  29.0  90.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists OS as the primary outcome and lists secondary outcomes that include local-failure-free survival, distant-metastases-free survival, progression-free survival, treatment-related adverse events and change in a quality-of-life score. It reports 9 outcome measures and 5 posted secondary outcomes. The record does not report how the statistical plan addressed the risk of false-positive findings when examining multiple outcomes. No multiplicity adjustment or hierarchy among the secondary outcomes is reported in the registry record.

Missing-data methods are not reported in the registry record. For OS, the planned Kaplan–Meier method uses last follow-up for participants without a recorded death, but the available result is only the number last reported alive at termination. The record does not provide participant-level follow-up, reasons for loss to follow-up, or details on how incomplete observations were handled. It therefore is not possible to assess the completeness of follow-up or the implications of any missing information from the posted counts alone.

The primary outcome identifies the population as randomized patients. No further analysis-population details are reported in the registry record, such as exclusions from an intention-to-treat analysis or a per-protocol analysis. The record also does not explain the difference between listed enrollment of 16 and the arm-specific OS counts. No assumptions about those populations should be added beyond the labels and counts in the record.

Because the planned survival comparison is absent, multiplicity, missing-data handling and analysis-population choices cannot be evaluated against an actual inferential result. These omissions limit interpretation independently of the small number of participants and early study closure.

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 non-serious adverse event terms

The safety record separates a pre-randomization group from the two randomized arms. In the pre-randomization group, 13 were listed at risk for serious adverse events and 0 were recorded as affected. For Arm I, 4 were listed at risk and 0 were recorded as affected; for Arm II, 6 were listed at risk and 0 were recorded as affected. These are the serious adverse-event counts reported in the registry. No top serious adverse-event terms are listed.

The record also lists other adverse events: 13 of 13 in the pre-randomization group, 3 of 4 in Arm I and 3 of 6 in Arm II were recorded as affected. These are not the serious-event counts. The registry’s adverse-event information separately lists deaths of 0 in the pre-randomization group, 0 in Arm I and 2 in Arm II. The record does not establish that the listed deaths were caused by treatment, and these safety entries should not be substituted for the primary OS result.

Zero recorded serious events in these small at-risk groups does not demonstrate that serious harms could not occur. The safety counts cover the record’s stated groups and do not show event timing, duration, or a detailed description of every event. The primary outcome arm counts and the safety at-risk counts differ in places; the registry does not explain the relationship between them. Safety findings are therefore descriptive and should be read with the reported denominators and record limitations in mind.

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

The result means that the registry posts a limited set of status counts for the primary outcome rather than the planned survival comparison. At termination, 5 participants in Arm I and 4 in Arm II were last reported alive. The registry states that the study closed early and had a small number of participants, and that only those alive counts are reported. This is a description of the information available in the record, not a completed estimate of the treatment effect.

It does not establish that adding radiation improved or worsened overall survival. The counts do not contain enough information to compare survival over time, account for differences in follow-up, or calculate uncertainty. There is no posted Kaplan–Meier estimate, log-rank result, hazard ratio, confidence interval or p-value. The planned analysis was tied to at least 105 reported deaths; the record does not report that analysis.

The findings also do not establish a complete benefit–harm balance. The record lists several secondary outcomes but does not post analyses for them. The serious adverse-event counts are descriptive, and the registry’s death entries do not establish treatment causation. Nor does the available information resolve the differences between the enrollment entry, the primary outcome counts and the safety at-risk counts.

In general, a randomized design is intended to support comparisons between groups, but the strength and precision of the inference depend on the amount and completeness of outcome information and on the analysis performed. Here, early closure and sparse posted outcome information prevent the planned survival comparison from being interpreted. The record does not report why the study was terminated, so no reason should be inferred from the status alone.

The appropriate statistical reading is therefore narrow: the registry records the treatment strategies, the planned OS method and the alive counts at termination, but it does not provide an inferential answer to the trial’s primary question. These results should not be treated as proof for or against either strategy.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a randomized design and an informative completed comparison. Randomization defines the intended comparison, but a treatment effect still requires outcome data analyzed in a way that accounts for follow-up and uncertainty. For OS, the registry planned a Kaplan–Meier analysis and a log-rank comparison; the posted counts do not substitute for either.

The record also shows why the status and completeness of reporting affect interpretation. The trial is marked terminated, and the registry says early closure and a small number of participants led to reporting only the number last reported alive. With no posted time-to-event estimate or comparison, readers cannot judge the size, direction or precision of a survival difference. This is a reporting limitation as well as a limitation of the available outcome information.

There is a second statistical lesson in keeping outcome populations distinct. Enrollment, arm-specific OS counts and safety at-risk counts are listed separately. Their differences are not explained in the registry record, so combining or reconciling them would require assumptions that are not supported by the record. Clear population definitions are essential for interpreting both effectiveness and safety results.

Finally, the trial lists multiple secondary outcomes, while the registry record reports no analysis entries. Without their results and a stated approach to multiplicity, those outcomes cannot supply a substitute answer to the primary question. The record is useful for understanding the planned comparison and what was ultimately posted, but it leaves substantial uncertainty about the clinical and statistical results.

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 most important trial-specific limitation is that the primary outcome is not reported as the planned time-to-event analysis. The registry explains that early study closure and the small number of participants led to reporting only alive counts at termination. There are no posted survival curves, time-specific survival estimates, effect estimates, confidence intervals or log-rank results. The maximum follow-up time is listed as 25 months, but individual follow-up durations are not reported.

The record’s listed enrollment is 16, whereas the OS arms list 5 and 6 participants. Safety at-risk counts also differ from those outcome counts in Arm I. The registry does not explain these population differences. Consequently, the populations underlying the posted counts cannot be fully reconciled from the record, and no totals should be inferred from them.

The reason for termination is not reported in the registry record. Details of the original sample-size justification, recruitment experience and whether any interim analyses occurred are also not reported in the registry record. The stated threshold of at least 105 deaths is part of the planned primary analysis, but the record does not provide a completed analysis against that threshold.

Secondary outcomes are listed, but no analysis records are posted. The registry record does not report methods for multiplicity, missing data, protocol deviations or additional analysis populations. Safety information is limited to counts and does not provide event timing or detailed descriptions; no serious adverse-event terms are listed. These gaps prevent a broader assessment of the study’s outcomes and limit the conclusions that can be drawn from its registry results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Testing the Addition of Targeted Radiation Therapy to Surgery and the Usual Chemotherapy Treatment (Pemetrexed and Cisplatin [or Carboplatin]) for Stage I-IIIA Malignant Pleural Mesothelioma — NCT04158141.
• Registry record last updated 2026-07-13; status last verified 2026-06.
• Results first posted 2025-02-19.
• 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 randomized, parallel-group phase III trial sponsored by NRG Oncology, with no masking listed. It compares P/D and pemetrexed-based systemic chemotherapy, using cisplatin or carboplatin, with the same strategy followed by adjuvant hemithoracic radiation using IMRT or PBS proton therapy. The intended population had stage I–IIIA malignant pleural mesothelioma.

The primary outcome is OS, planned for estimation by Kaplan–Meier and comparison by log-rank testing after at least 105 deaths. The study is marked terminated. Because of early closure and a small number of participants, the record reports only the number last reported alive at termination: 5 in Arm I and 4 in Arm II. A survival estimate or formal comparison is not reported.

Enrollment is listed as 16, and the record also lists secondary outcomes and descriptive safety counts. The reason for termination, the relationship among the different population counts, and details of the statistical handling of missing data and multiplicity are not reported in the registry record.