Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma (NCT03681535), a na na study. The primary outcome is Local Control Rate.

2. Clinical Question

3. Trial Design

The registry describes a phase II, single-group interventional study of radiation therapy for diffuse large B-cell lymphoma. The listed allocation is NA, and masking is NONE. There is no concurrent control arm in the record, so the design does not provide a like-for-like comparison between dose-reduced radiation and a higher-dose regimen. The study hypothesis proposes reducing dose and treatment volume while maintaining high local control among patients with a negative PET-CT scan after rituximab-containing chemotherapy.

The intervention description specifies radiation therapy at 19.5-20 Gy after 3 cycles of rituximab-containing chemotherapy. Treatments are described as daily, 5 days per week, in 1.5-2 Gy fractions. The hypothesis refers to reduction from 30 Gy to 20 Gy; however, the record does not list a separate group receiving 30 Gy. It also does not quantify the treatment-volume reduction in the intervention description.

The registry lists enrollment of 243. This is the enrollment figure in the record, not evidence that every listed participant received the intervention or contributed data to the primary endpoint. The study status is active, not recruiting. Its recorded start date is 2019-02-13, and its primary completion date is 2025-07-10. These dates and status describe the registry entry; they do not establish that follow-up or outcome reporting is complete.

The primary outcome is local control at 2 years. Secondary outcomes listed are disease-free survival, overall survival, and patterns of failure. The registry record does not report the primary result, an analysis population, or a detailed statistical analysis plan. Without a control group, the design can describe outcomes in the treated group, but cannot isolate a treatment effect by comparison with a concurrent group.

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

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 Local Control Rate, measured over 2 years.

The primary endpoint is the local control rate at 2 years. It is defined as the proportion of participants with absence of disease recurrence within the radiation therapy field, assessed through standard-of-care imaging obtained per National Comprehensive Cancer Network guidelines. This definition focuses on recurrence in the treated field rather than recurrence anywhere in the body.

A proportion endpoint represents the share of the defined analysis population meeting the endpoint definition. For this outcome, that means participants whose imaging assessment meets the registry’s definition of no recurrence within the radiation field. The definition identifies what counts as local control, but the registry record does not report the observed number meeting that definition, the denominator used in the analysis, or the resulting estimate.

Local control is relevant to the study’s stated question because the hypothesis is that radiation dose and treatment volume can be reduced while maintaining high rates of control in the radiation field. The endpoint does not, by itself, describe disease-free survival, overall survival, patterns of failure outside the field, or treatment toxicity. Those are separate outcomes, and the registry lists disease-free survival, overall survival, and patterns of failure as secondary outcomes.

The registry identifies a 95% confidence interval as the measure of precision for the primary outcome, but the actual estimate and interval are not reported in the registry record. A confidence interval is a statistical range intended to express uncertainty around an estimate under the analysis assumptions. Its width and position cannot be assessed without the reported endpoint estimate and interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is local control?

The primary outcome is a binary outcome at the participant level: the definition distinguishes absence of recurrence within the radiation field from failure to meet that definition. A rate for a binary outcome is expressed as a proportion of participants in a specified analysis population. The registry labels the outcome as a proportion and identifies the measure of precision as a 95% confidence interval. It does not report the observed proportion or the analysis population used to calculate it.

The endpoint’s definition also sets its scope. It concerns recurrence within the radiation therapy field, assessed with standard-of-care imaging obtained per National Comprehensive Cancer Network guidelines. It is not a measure of every possible recurrence, all disease-related outcomes, or toxicity. The stated assessment timeframe is 2 years. The record does not further specify how the timeframe is anchored for each participant or how imaging assessments outside that window would be treated.

What does a confidence interval add?

In general, a confidence interval communicates statistical uncertainty around an estimate. The point estimate describes the observed proportion in the analyzed group; the interval indicates the range of values compatible with the data under the statistical method and its assumptions. The interval is not a guarantee that the true value lies within its endpoints. Interpreting it requires both the estimate and the interval, as well as an understanding of the analysis population and method.

The registry identifies a 95% confidence interval for local control, but the numerical result and interval are not reported in the registry record. Therefore, the estimate’s precision cannot be described. The enrollment figure alone does not recover the endpoint denominator: not every person listed as enrolled must necessarily have an evaluable assessment at the specified timeframe, and the record does not state who was analyzed.

What follows from a single-group design?

In a single-group study, the endpoint can be described in the group receiving the intervention. A proportion and its confidence interval, if reported, would characterize that group’s observed outcome. The design lacks a concurrent control group in the registry record, so it does not directly estimate a difference between dose strategies. The hypothesis compares reduced radiation with a higher dose in its rationale, but the described trial does not list a separate 30 Gy group.

That distinction is not a criticism of the endpoint. It is a limit on the question the design can answer by itself. A group-level local-control estimate cannot show what would have occurred in comparable participants under another dose. Differences from outcomes reported in other settings would not automatically be attributable to dose, because the registry record does not establish that populations, follow-up, imaging, or other care were comparable.

What analysis details are available?

The record lists 4 outcome measures and names disease-free survival, overall survival, and patterns of failure as secondary outcomes. It identifies 0 analyses. No model, estimator, hypothesis test, adjustment procedure, or decision threshold for the primary endpoint is reported in the registry record. The registry lists the confidence-interval level, but does not describe how the interval would be calculated.

The sample-size planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes planning for a stated fraction of an observed effect. These are assumptions for a planning illustration, not a description of the single-group trial’s own design: the trial record lists no two-arm allocation or comparison group. The planning illustration is not observed power, and it does not provide evidence about the local-control result. Its effect input and the resulting planning figures are not reported in the registry record.

General statistical context: normal approximations can be less dependable when an outcome proportion is near a boundary or when the analyzed sample is small. A method suited to the data can matter for interval accuracy. The registry record does not identify the interval method, so it is not possible to assess that choice or determine whether an alternative method was used.

Why might over-dispersion matter in other settings?

Over-dispersion means observed variability is greater than a statistical model expects. It can lead a model to understate uncertainty if the extra variability is ignored. This is a general concept for outcomes and models where variability is modeled; the record does not report an over-dispersion analysis for this binary local-control endpoint. No claim about over-dispersion in this study can be made from the listed information.

What should readers take from the method information?

The endpoint definition and confidence-interval level are stated, while the observed estimate, analysis denominator, and calculation method are not. The single-group design supports description of outcomes in the treated group once results are reported, but does not by itself supply a controlled dose comparison. Any interpretation of precision or statistical evidence would require the missing result and analysis details.

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("Single Arm Interventional Study")
n      <- c(243)
events <- c(2)
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  Single Arm Interventional Study  243  2  0.8  0.1  2.9  0.2  3.0  0.3  2.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies 4 outcome measures and lists disease-free survival, overall survival, and patterns of failure as secondary outcomes. It does not report a multiplicity strategy for interpreting several outcomes, such as a prespecified hierarchy or adjustment for multiple statistical tests. The record identifies 0 analyses, so no testing results or analysis plan are available to clarify how the outcomes would be handled together. Without those details, the statistical interpretation of any future set of outcome findings would depend on information not reported in the registry record.

Missing-data handling is also not reported in the registry record. There is no stated approach for participants without imaging at the 2-year timeframe, incomplete follow-up, or unavailable endpoint assessments. The primary endpoint’s analysis population is blank in the record, and no distinction among treated, enrolled, or evaluable participants is specified for the endpoint analysis. The listed enrollment of 243 should therefore not be assumed to be the endpoint denominator.

The registry does not report whether interim analyses were planned or conducted, whether any analysis populations were prespecified, or how participants who did not receive the described intervention would be handled. These details are relevant to understanding how outcome estimates were formed, but cannot be inferred from the study’s phase, status, or endpoint definition. Until analysis and missing-data methods are reported, the local-control estimate’s scope and susceptibility to incomplete outcome ascertainment cannot be assessed.

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

Serious events with the highest arm-level rate: secondary cancer (10.3%), cardiac complications (7.4%), hypothyroidism (6.2%).

For the listed single arm, the registry records 25 participants with serious adverse events among 243 at risk. It records 0 participants with other adverse events among 243 at risk, and lists 18 deaths. These are distinct registry fields; the record does not explain whether deaths overlap with the adverse-event counts or provide further detail about their timing or causes.

The serious adverse-event terms listed include secondary cancer at 10.3%, cardiac complications at 7.4%, and hypothyroidism at 6.2%. The record does not specify the denominator or assessment period for these term percentages in the information. They should not be treated as a complete description of all safety events or as evidence of treatment causation.

Adverse-event counts describe events recorded in the study; they do not, by themselves, show that the intervention caused those events. The registry record does not provide attribution, severity detail beyond the serious-event category, timing, or a comparison group for safety. It also does not state how the listed terms relate to each participant or to the death count. The figures therefore describe what is recorded, but do not establish comparative safety or the cause of an event.

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

The study is designed around a specific question: whether dose-reduced consolidation radiation therapy can maintain high local control in patients with diffuse large B-cell lymphoma who had a negative PET-CT scan after rituximab-containing chemotherapy. The intervention is described as 19.5-20 Gy after 3 cycles of chemotherapy. Local control is defined as absence of recurrence within the radiation field at the 2-year timeframe.

The registry record does not report the observed local-control result or its 95% confidence interval. As a result, it cannot establish whether the observed local-control rate was high, whether it met a prespecified target, or how precisely it was estimated. The hypothesis in the study description is not a result. No conclusion about maintaining local control can be drawn from that statement alone.

The study also does not list a concurrent 30 Gy group. Although the hypothesis frames the intervention as reducing dose from 30 Gy to 20 Gy, the design recorded is single group, with allocation listed as NA. It therefore cannot directly quantify a difference between those dose strategies. A comparison with an external outcome would require evidence that the comparison populations and assessment methods were sufficiently alike; the registry record does not establish that.

The enrollment figure of 243 is not necessarily the number included in the primary analysis. The number with an evaluable imaging assessment, the analysis denominator, and the handling of missing follow-up are not reported in the registry record. Those details are needed to understand the population to which an eventual proportion applies.

The safety entries likewise do not show that radiation caused the recorded adverse events or deaths. The listed counts and terms have no concurrent control comparison in the record, and details about timing, attribution, and overlap are not reported. The findings can be interpreted only as registry safety observations, not as a causal or comparative estimate.

In short, the record documents the study question, regimen, endpoint definition, and selected safety fields. It does not report the principal outcome result needed to answer the study question, nor does its design provide a direct comparison of radiation doses. The findings should not be extended beyond those limits.

14. Why This Trial Matters Statistically

This trial is statistically relevant because it asks whether a treatment strategy can be evaluated through a clearly field-specific endpoint. Local control focuses on recurrence within the radiation therapy field, while the listed secondary outcomes address disease-free survival, overall survival, and patterns of failure. Keeping these outcomes distinct matters: success on a local endpoint would not automatically establish a result for survival or for disease outside the treated field.

The single-group design also illustrates the difference between estimating an outcome and estimating a treatment contrast. A well-defined proportion can describe local control among analyzed participants. A comparison between radiation doses requires a comparison group or other design and analysis information that supports such a contrast. The registry describes a dose-reduction hypothesis but does not list a higher-dose arm, so the design’s direct comparative reach is limited.

Precision is central to interpreting a proportion. The registry identifies a 95% confidence interval, but does not report the endpoint estimate or interval. Without these, readers cannot judge how much uncertainty surrounds the outcome or whether the estimate is compatible with a range of clinically relevant values. The enrollment figure cannot substitute for the endpoint denominator or interval.

The record also underscores why analysis populations, missing-data methods, and multiplicity plans matter. The primary outcome depends on imaging at the stated timeframe, yet the record does not explain how unavailable assessments would be handled. Multiple outcomes are listed without a reported strategy for interpreting them together. These are not reasons to assume bias or a particular result; they are limits on what can be assessed from the registered information.

Thus the study is informative as a defined research question and intervention description, but its statistical contribution cannot be judged from the local-control outcome until the estimate, precision, and analysis details are reported.

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 consequential limitation for interpreting the study is that the registry record does not report the primary local-control estimate or its 95% confidence interval. Although the endpoint and timeframe are defined, there is no posted result with which to evaluate the hypothesis. The record also does not provide the analysis denominator, making it impossible to determine how many participants contributed to the endpoint assessment.

The single-group design limits dose comparisons. The study hypothesis refers to reducing radiation from 30 Gy to 20 Gy, but the registry lists no concurrent 30 Gy group. The record therefore does not support a direct estimate of the difference between the dose strategies. It also does not quantify the planned reduction in treatment volume within the intervention description.

Other key analysis details are not reported in the registry record: the statistical method for the proportion and confidence interval, the analysis population, the handling of missing imaging or follow-up, and any multiplicity strategy for the primary and secondary outcomes. Interim analyses and a detailed analysis plan are also not reported. These omissions prevent assessment of how the results would be derived or how uncertainty and multiple outcomes would be addressed.

The safety information is limited to selected counts and serious-event terms. The record does not give timing, attribution, overlap among events, or a comparative safety group. The term percentages are listed without a denominator or assessment period in the information available. These limitations constrain interpretation of safety observations and do not establish causation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma — NCT03681535.
• Registry record last updated 2026-07-07; status last verified 2026-06.
• Results first posted 2026-07-07.
• 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 phase II, single-group interventional study of dose-reduced consolidation radiation therapy for diffuse large B-cell lymphoma. The listed regimen is 19.5-20 Gy after 3 cycles of rituximab-containing chemotherapy, delivered daily, 5 days per week, in 1.5-2 Gy fractions. The study hypothesis concerns reducing radiation dose and treatment volume while maintaining local control.

The primary endpoint is local control at 2 years, defined as absence of recurrence within the radiation therapy field on standard-of-care imaging obtained per National Comprehensive Cancer Network guidelines. The actual local-control estimate and 95% confidence interval are not reported in the registry record. Secondary outcomes are disease-free survival, overall survival, and patterns of failure.

The registry lists enrollment of 243 and status active, not recruiting. The record includes selected adverse-event counts and terms but does not establish their cause. It lists no concurrent higher-dose control group, and key analysis and missing-data details are not reported in the registry record.