Patient-Reported Outcomes Following Chemoradiotherapy for Locally Advanced Non-small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Patient-Reported Outcomes Following Chemoradiotherapy for Locally Advanced Non-small Cell Lung Cancer (NCT03481114), a randomized phase 2 study. The primary outcome is Number of Patients With PRO-CTCAE Adverse Events With Score ≥ 3.

2. Clinical Question

3. Trial Design

This is a randomized, parallel-arm phase 2 trial sponsored by Albert Einstein College of Medicine. The registry record lists enrollment of 55 and a completed status. It identifies the study as unmasked, so masking is not reported. The stated objective is to evaluate patient-reported outcomes during and after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer.

The randomized comparison is between standard chemoradiotherapy and a PET-based, dose-painted, accelerated chemoradiotherapy schedule. The standard schedule delivers 60 Gy in 30 fractions over 6 weeks to involved lesions, including tumors and lymph nodes. In the dose-painting arm, the prescribed dose depends on Metabolic Tumor Volume: lesions exceeding 20 cc receive 55 Gy in 20 fractions over 4 weeks, and lesions below 20 cc receive 44 Gy in 20 fractions over 4 weeks. How lesions measuring exactly 20 cc are handled is not reported in the registry record.

The primary outcome is the number of participants with PRO-CTCAE adverse events scored 3 or higher, with a timeframe described as up to 6 weeks after initiation of chemoradiotherapy. Other listed outcomes include locoregional progression-free survival, progression-free survival, overall survival, grade 3-5 adverse events scored using CTCAE Version 4.0, and additional PRO-CTCAE summaries. Although the registry lists these outcomes, the analysis count is 0, and arm-specific results for the primary outcome are not reported.

The registry record does not report the randomization method, allocation concealment, detailed eligibility criteria, chemotherapy regimens, protocol deviations, or a statistical analysis plan. It also does not report a rationale for the enrollment target or planned sample size. Those omissions limit how fully the design and conduct can be assessed from the registry entry.

4. Participant Flow and Accounting

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

Before assignment: 55 patients were consented into the study. 5 patients failed to meet inclusion criteria and were excluded from the study. 50 patients were enrolled and randomized into one of the two study arms.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 9 patients did not report PRO-CTCAE data at 6 weeks post chemoradiotherapy, 4 in the PET-based, dose-painted arm and 5 in the Standard Chemoradiotherapy (Control Arm). There were no Grade 4 or Grade 5 PRO-CTCAE adverse events during the course of the study.

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 Patients With PRO-CTCAE Adverse Events With Score ≥ 3, measured over Up to 6 Weeks after initiation of Chemoradiotherapy.

The primary endpoint counts participants with patient-reported adverse events scored 3 or higher using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The registry describes PRO-CTCAE as an assessment tool developed by the National Cancer Institute to capture symptomatic adverse events reported by patients in cancer clinical trials. Participants completed a customized survey with 24 questions addressing 12 symptoms, at baseline and every two weeks during chemoradiotherapy. The outcome description says the number of participants with grade 3 or higher events was summarized by arm for each event type.

Patient reports add information about symptoms as experienced by participants. This can complement clinician-scored adverse events, which are separately listed among the trial’s secondary outcomes. A score threshold of 3 or higher focuses the endpoint on more severe reported symptoms, while the symptom-specific reporting retains information about which experiences were recorded. The registry states that there were no grade 4 or grade 5 PRO-CTCAE adverse events during the study.

The endpoint’s stated timeframe is up to 6 weeks after initiation of chemoradiotherapy, and the record notes missing reports at the 6-week assessment. It does not provide the primary outcome counts by arm or event type. Therefore, the endpoint’s definition and collection schedule can be described, but its observed between-arm contrast cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized parallel-arm trial, but it does not report the method used to generate the random allocation sequence, how allocation was concealed, or whether any stratification was used. It identifies masking as none. These details affect how readers assess the risk of systematic differences between arms, but their absence means they cannot be characterized further from the registry record.

What does the primary outcome count?

The primary measure is the number of participants with PRO-CTCAE adverse events scored 3 or higher. The survey is participant-reported and covers 12 symptoms through 24 questions. The record says participants completed it at baseline and every two weeks during chemoradiotherapy, and that event counts were summarized by arm for each event type. This is not a single continuous score or a time-to-event measure as described in the registry. The description does not state whether a participant reporting multiple qualifying symptoms is counted once for an overall measure, separately for each event type, or by another rule. It also does not provide the primary event counts.

What does a between-arm comparison require?

General statistical explanation: a comparison of two randomized arms needs an outcome definition applied consistently to both arms, an explicit analysis population, and reported outcome data. For a binary outcome, results are often presented as counts and proportions, with a contrast and an uncertainty interval. The choice of effect measure and analysis method should match the endpoint and the trial’s prespecified plan. The registry record does not report a primary-outcome contrast, its uncertainty, or a statistical model, so no such interpretation can be attributed to this trial.

The primary outcome has multiple event types and assessment times. The record explicitly indicates that it was not reduced to one comparison because it has several categories or time points. General statistical explanation: testing or emphasizing multiple outcomes can increase the chance of a seemingly notable finding arising by chance if multiplicity is not addressed. The registry does not report whether a multiplicity strategy was planned or used, so none should be assumed.

How should missing reports be considered?

The registry states that 9 participants did not report PRO-CTCAE data at 6 weeks after chemoradiotherapy, with 4 in the dose-painting arm and 5 in the standard arm. General statistical explanation: missing outcome data can affect an estimate if the participants without reports differ in relevant ways from those with reports. The impact depends on why the data are missing and on the analysis approach. The registry does not report reasons for the missing assessments, an imputation method, a sensitivity analysis, or the analysis population used. The missing assessment counts alone do not establish the direction or size of any resulting bias.

What does the planning information mean?

The record’s sample-size assumptions describe a planning illustration computed from the observed effect, not the trial’s own design. It specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is framed as participants per arm for 80% power or other stated power levels; time-to-event illustrations use a total number of events. These assumptions describe planning calculations, not the trial’s observed power. No numerical planning results or primary-outcome effect are included in the registry entries, so no planning value can be interpreted.

General statistical explanation: power is a design-stage probability of detecting a specified effect under stated assumptions. It is not a measure of whether a completed study has demonstrated an effect, and observed power should not be inferred from a p-value or from trial completion. A planning illustration based on an observed effect is especially dependent on that effect estimate and is not evidence that the original trial was planned around it. The registry does not report the trial’s own sample-size justification or statistical analysis plan.

How should safety counts be separated from efficacy analyses?

The serious adverse event summaries list participants at risk and affected by arm, alongside other adverse-event and death counts. These descriptive values are distinct from the primary PRO-CTCAE endpoint. General statistical explanation: an adverse-event count does not, by itself, establish a causal treatment effect. Interpretation depends on definitions, follow-up, exposure, event overlap, and the planned analysis. The registry does not report enough information to determine overlap among event categories or to reconstruct an adjusted safety comparison.

The listed secondary outcomes include survival endpoints and adverse-event measures. The record does not report their analysis methods, censoring rules, follow-up summaries, or estimates. General statistical explanation: survival analyses typically account for differing follow-up and censoring, while a simple event count does not communicate the timing of events. No survival estimate can be inferred from the outcome list or the death counts alone. Overall, the registry gives outcome definitions and selected descriptive safety information, but not the analysis details needed to evaluate inferential results.

10. Multiplicity, Missing Data and Analysis Populations

The primary PRO-CTCAE outcome is organized by event type and assessment time rather than as one reported comparison. The registry describes 24 questions addressing 12 symptoms and repeated assessments from baseline every two weeks during chemoradiotherapy. It explicitly indicates that the primary outcome has several categories or time points and is not reduced to one comparison. The registry record does not report whether the trial used a prespecified multiplicity adjustment, hierarchy, or other approach to interpreting multiple outcomes.

Missing primary outcome data are noted at the 6-week assessment: 9 participants did not report PRO-CTCAE data, with 4 in the dose-painting arm and 5 in the standard arm. The reasons for missing reports, the number assessed at other time points, and the methods used to handle missing data are not reported in the registry record. No imputation or sensitivity analysis is described.

The record does not identify whether the primary analysis used an intention-to-treat population, a per-protocol population, or another analysis set. It does not report whether participants were analyzed according to randomized assignment or how protocol deviations were handled. Since the primary outcome counts are also absent, the available information cannot establish the denominator for each event-specific comparison or assess how missingness affected results. These omissions limit both reproducibility and the interpretation of any potential between-arm difference.

11. 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: dyspnea (8.7%), stroke (8.7%), chest pain (4.3%), flu-like symptoms (4.3%), pneumonitis (3.7%).

The registry lists serious adverse event counts separately for each arm. For standard chemoradiotherapy, it reports 27 participants at risk and 4 affected. For the dose-painting arm, it reports 23 at risk and 6 affected. These are descriptive counts; the registry does not report an adjusted comparison, an uncertainty interval, or a test of the between-arm difference. They should not be read as the primary patient-reported endpoint.

The record also lists other adverse-event counts of 27 in the standard arm and 23 in the dose-painting arm, and death counts of 15 and 12, respectively. The observation period for the death counts is not reported in the registry record. Selected serious-event terms include Dyspnea and Stroke at 8.7% each, Chest Pain and Flu-like symptoms at 4.3% each, and Pneumonitis and Hypoxia at 3.7% each. The denominator and any overlap between terms are not specified, so these percentages should not be treated as mutually exclusive categories or converted into counts.

General statistical explanation: safety summaries depend on event definitions, exposure and follow-up time, and whether a participant can contribute to multiple event categories. The registry does not report those details sufficiently to establish a comparative safety effect. Counts alone do not determine whether an event was caused by treatment.

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

The record describes a randomized comparison of two radiotherapy schedules in the setting of concurrent chemoradiotherapy for locally advanced non-small cell lung cancer. Its primary focus is participant-reported toxicity measured with PRO-CTCAE, with particular attention to events scored 3 or higher. The record also states that no grade 4 or grade 5 PRO-CTCAE adverse events occurred during the study and identifies missing PRO-CTCAE data at the 6-week assessment.

However, the registry does not report the primary outcome counts by arm or event type, or a statistical analysis of those counts. As a result, it cannot establish the direction, magnitude, or precision of a primary-outcome difference between the radiotherapy schedules. The trial’s completed status and randomized design do not replace the missing outcome analysis. No conclusion about whether either schedule produced fewer or more patient-reported severe symptoms can be drawn from the information in the record.

The listed serious adverse event counts and selected event percentages provide additional descriptive safety information, but they are not a substitute for the primary PRO-CTCAE results. The registry does not give the follow-up period for death counts, the denominator underlying selected serious-event percentages, or a statistical comparison of safety outcomes. These data therefore do not support a causal interpretation or a broad conclusion about comparative safety.

General statistical explanation: a trial result is most informative when the outcome definition, analysis population, estimate, and uncertainty are all reported. A point estimate indicates the observed contrast, while an uncertainty interval helps readers judge how compatible the data are with a range of effects. Neither is reported for the primary endpoint. The absence of those results should be understood as an evidence-reporting limitation, not as evidence that the arms were equivalent or different.

The registry lists additional outcomes, including locoregional progression-free survival, progression-free survival, overall survival, and adverse-event summaries. Their inclusion identifies planned or tracked domains, but without results and methods it does not permit conclusions about tumor control, survival, or comparative toxicity.

13. Why This Trial Matters Statistically

This trial’s statistical question is notable because it places patient-reported toxicity at the center of the primary outcome while comparing two distinct radiotherapy schedules. The PRO-CTCAE tool is described as capturing symptoms directly from participants, complementing the separately listed clinician-scored adverse-event outcome. This distinction matters for interpretation: patient reports and clinician assessments describe related but not identical perspectives on treatment experience.

The endpoint also involves repeated assessment and multiple symptom categories. The registry describes a customized survey with 24 questions addressing 12 symptoms, completed at baseline and every two weeks during chemoradiotherapy. Those details make the collection plan visible, while also underscoring the importance of specifying how repeated assessments, different symptoms, and missing reports are handled in the analysis. The registry does not report those methods or the arm-specific primary outcome results.

The two schedules differ in duration and dose distribution. The comparator delivers 60 Gy in 30 fractions over 6 weeks; the experimental schedule uses 20 fractions over 4 weeks, with dose determined by PET-based Metabolic Tumor Volume. This creates a clinically specific randomized contrast, but the registry record alone does not show how that contrast affected patient-reported symptoms or other outcomes.

From a statistical reporting perspective, the record illustrates the difference between registering an outcome and reporting its analysis. Definitions, timeframes, and missing-assessment counts help readers understand what was intended to be measured. Without results, analysis populations, and uncertainty estimates, however, readers cannot assess the observed contrast. The trial therefore raises an important reporting issue: outcome measurement detail can be substantial even when the inferential results needed to interpret that measurement are not available in the registry record.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report arm-specific counts for the primary PRO-CTCAE outcome, an effect estimate, a confidence interval, or a p-value. Because the endpoint is described across multiple symptoms and assessment times, the absence of event-specific results prevents evaluation of both the pattern of reported symptoms and the precision of any comparison.

Missing reports are documented at the 6-week assessment, with 9 participants not reporting PRO-CTCAE data. The record does not give reasons for missingness, describe how missing data were handled, or report sensitivity analyses. It also does not identify the analysis population or explain the treatment of protocol deviations. These omissions make it difficult to assess the potential influence of missing outcome data.

The registry does not report a statistical analysis plan, multiplicity approach, randomization method, allocation concealment, or trial sample-size justification. It also does not describe the chemotherapy regimens or provide full follow-up information for the listed survival and death outcomes. These limits prevent detailed assessment of the planned analysis and of the comparability and timing of outcome ascertainment.

The dose-painting description specifies regimens for lesions with MTV exceeding 20 cc and below 20 cc, but does not state the approach for lesions equal to 20 cc. The serious-event percentages are listed without a denominator or information about overlap among event terms. The death counts lack a stated observation period. These are specific gaps in the registry’s description; they should not be filled by inference.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Patient-Reported Outcomes Following Chemoradiotherapy for Locally Advanced Non-small Cell Lung Cancer — NCT03481114.
• Registry record last updated 2026-04-22; status last verified 2026-04.
• Results first posted 2026-04-22.
• 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.

18. Record Summary

The registry record describes a completed randomized phase 2 parallel-arm trial sponsored by Albert Einstein College of Medicine, with enrollment of 55. It compares standard chemoradiotherapy, delivered as 60 Gy in 30 fractions over 6 weeks, with PET-based dose-painted accelerated chemoradiotherapy delivered over 4 weeks using 20 fractions. The primary outcome is the number of participants with PRO-CTCAE adverse events scored 3 or higher.

The record describes the survey and its assessment schedule, reports that 9 participants did not provide PRO-CTCAE data at 6 weeks, and states that no grade 4 or grade 5 PRO-CTCAE adverse events occurred during the study. It lists serious adverse event counts and selected event terms, but does not report the primary outcome counts by arm or a statistical analysis of the primary comparison. The registry record therefore defines the clinical question and provides selected descriptive information, while leaving the primary comparative result and its precision unavailable.