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

1. Trial at a Glance

This page covers the registry results for Reduced Radiation in Patients With Diffuse Large B-cell Lymphoma (NCT01186978), a na na study. The primary outcome is Number of Participants With Local Control.

2. Clinical Question

The study’s stated aim is to evaluate whether reducing radiation dose and field size can maintain a high rate of local control while minimizing acute and late toxicity. That is a question about balancing disease control and treatment burden, but the registry’s stated endpoint directly measures local control. The record lists progression-free survival, overall survival, and local, distant, or combined failure among the secondary outcomes. Their results are not reported in the registry record.

Because there is no concurrent control group, the study cannot directly compare outcomes between reduced-radiation treatment and another assigned treatment within the trial. The historical value of 0.90 supplies a reference for the primary objective, not a randomized comparator. How historical-control data were selected or assessed is not reported in the registry record.

3. Trial Design

The registry identifies NCT01186978 as a completed, single-group study sponsored by Duke University. Its title is “Reduced Radiation in Patients With Diffuse Large B-cell Lymphoma,” and the official title describes dose-reduced consolidation radiation therapy in this population. The record reports an enrollment of 63. The study start date is 2010-09-20, and the primary completion date is 2019-06-04.

The intervention is radiation therapy. The study summary describes a plan to reduce radiation dose from 30 Gy to 20 Gy and reduce treatment field size. It places the treatment after rituximab-containing chemotherapy for patients with complete response and a negative post-chemotherapy PET scan; the arm description specifies 4 to 6 cycles of chemotherapy. Specific eligibility criteria, radiation schedules, and details of the delivered treatment are not reported in the registry record.

The model is single-group, allocation is recorded as NA, and masking is none. A phase is not reported in the registry record. This is not a randomized comparison, and the single arm does not provide a concurrent control group. The primary objective instead refers to a historical-control value for local control. The record does not describe how the historical controls were assembled or whether their clinical characteristics and follow-up were comparable.

The primary endpoint is the number of participants with local control at 5 years, estimated from a Kaplan-Meier curve of time to local failure. The registry record also lists progression-free survival at 5 years, overall survival, and counts of local, distant, or local-plus-distant failure as secondary outcomes. Although four outcome measures are listed, outcome results and analyses are not reported in the registry record. The completed status therefore describes the study’s registry status; it does not, by itself, supply evidence about the endpoint findings.

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:

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 With Local Control, measured over 5 years.

The primary outcome is titled “Number of Participants With Local Control” and has a 5-year timeframe. Its description defines the primary objective in terms of local control at 5 years, estimated from the Kaplan-Meier curve for time to local failure. The registry record does not report the resulting estimate or the number of participants with local control.

In general, local control concerns whether disease remains controlled at the treated site. A time-to-event approach can account for different lengths of follow-up: participants without a recorded local failure may contribute information up to their last known follow-up, rather than being treated as though they had been observed for the entire period. The Kaplan-Meier method estimates the probability of remaining free of the event over time, provided its assumptions are appropriate. The registry record does not report censoring rules, the number at risk over time, or checks of those assumptions.

The endpoint is used because the stated objective is to assess whether a lower radiation dose and smaller treatment field can retain local control. The protocol description names 0.90 as the historical-control value for comparison. This reference is not a result from the current single-group study. Without the current study’s estimate, its uncertainty, and the analysis details, the registry record cannot establish how the observed local-control experience relates to that reference.

The endpoint title’s count wording and its description’s Kaplan-Meier estimation are not identical ways of expressing an outcome. A raw count depends on follow-up completeness, while a time-to-event estimate accounts for follow-up and censoring. The registry record does not provide enough result detail to reconcile those forms for this study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help interpret the stated design and endpoint, even though detailed analysis methods and outcome results are not reported in the registry record.

Why use a time-to-event endpoint?

In general, time-to-event analysis uses both whether an event occurred and when it occurred. For this study, the event of interest is local failure. A participant who has not had a recorded local failure by the end of observed follow-up may have incomplete event information rather than a confirmed event-free outcome for all future time. Such follow-up is commonly censored at the last time the participant is known to be event-free. The registry record does not report its censoring rules or how follow-up ended for participants.

The Kaplan-Meier method estimates event-free probability over time while incorporating censored observations. It relies on assumptions, including that censoring is not systematically related to the future event risk in a way the analysis fails to account for. It also assumes that the event and censoring times are recorded adequately. The registry record does not report whether these assumptions were assessed, how local failure was defined, or whether independent review was used.

What does the 5-year endpoint represent?

The primary outcome description refers to local control at 5 years, estimated from the Kaplan-Meier curve of time to local failure. In general, a time-specific estimate is a probability derived from the event-time curve, whereas a simple count records how many people meet a particular status definition. These are related but not interchangeable summaries, especially when follow-up differs. The outcome title uses count language, while the description specifies a Kaplan-Meier estimate. No detailed results are reported to show how the registry operationalized or presented this endpoint.

A confidence interval would normally accompany a time-specific estimate to convey statistical uncertainty. It would help distinguish a fairly precise estimate from one compatible with a broad range of possible local-control values. Neither the estimate nor its uncertainty is reported in the registry record. A test against the historical value is also not described, so no testing procedure or inferential conclusion should be presumed.

How should a historical benchmark be understood?

The primary objective names 0.90 as the local-control value observed in historical controls. In general, a single-group study can assess whether its outcome is consistent with a prespecified benchmark, but this is not equivalent to a randomized comparison. Historical evidence may differ in patient selection, outcome definitions, follow-up, supportive care, or other aspects of study conduct. The record does not describe the source or comparability of the historical controls, or the statistical method used to compare the study with that benchmark.

A benchmark is also not a guarantee about what the current study should observe. Sampling variability means that a study estimate may differ from a reference even when the underlying outcome is similar. Interpretation therefore depends on the estimate, its uncertainty, the benchmark’s basis, and the clinical context. The registry record does not report the elements needed for that assessment.

What can the single-group design establish?

In general, a single-group study describes outcomes among participants receiving the study intervention. Without a concurrent control arm, it cannot isolate the effect of the intervention from changes in patient characteristics, background care, or other factors. The record’s allocation entry is NA and its model is single-group; there is no like-for-like randomized comparison. Thus, any observed outcome would need cautious interpretation as an experience in the enrolled group rather than a direct estimate of the difference between treatment strategies.

The study hypothesis concerns reducing dose from 30 Gy to 20 Gy and reducing field size. A conclusion about the intervention would require adequate detail on treatment actually received, outcome ascertainment, follow-up, and analysis, as well as the results themselves. Those details are not reported in the registry record. The hypothesized reduction is a planned question, not a finding.

What do the safety counts convey?

In general, counts describe how many participants had recorded events, while rates and time-to-event summaries may answer different questions when follow-up varies. Safety interpretation also depends on definitions, severity grading, attribution, and the observation period. The record gives counts for serious and other adverse events and lists serious-event terms with percentages. It does not report event timing, attribution to radiation, or detailed definitions. Those counts should be read as descriptive registry entries, not as proof of causation or a comparative safety effect.

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")
n      <- c(62)
events <- c(61)
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  62  61  98.4  91.3  100.0  91.4  99.7  91.5  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures: the primary local-control outcome and secondary outcomes covering progression-free survival at 5 years, overall survival, and local, distant, or combined failure. The number of analyses recorded is 0. Results for the listed outcomes are not reported in the registry record.

When a study evaluates multiple outcomes, there is a general statistical concern that repeated testing can increase the chance of finding at least one apparently notable result by chance. Analysis plans may address this through prespecified outcome hierarchies, adjustment procedures, or a clear distinction between primary and exploratory analyses. Whether this study used any such approach is not reported in the registry record. The order and timing of analyses, and any interim analyses, are also not reported in the registry record.

The registry identifies a primary endpoint and names secondary outcomes, but does not report the detailed statistical analysis plan. It does not state how missing outcome data were handled, how censoring was defined, which analysis population was used, or how participants with incomplete follow-up were treated. In general, missingness can affect both the estimated outcome and its uncertainty, particularly when missing follow-up is related to prognosis or event status.

Enrollment of 63 is reported, but the registry record does not give participant flow, eligibility counts, exclusions from analysis, or the amount of missing outcome information. These omissions prevent assessment of whether all enrolled participants contributed to the primary analysis and whether missing data could have influenced the findings. No conclusion about the effects of missingness or multiplicity can be drawn without the analysis details and outcome results.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: squamous cell carcinoma (3.2%), papillary thyroid cancer (1.6%), papillary carcinoma of the kidney (1.6%).

The registry record lists 4 participants with serious adverse events and 16 participants with other adverse events; each group has 63 recorded at risk. It also records 3 deaths. These are descriptive figures for the single arm. The record does not report whether events were considered related to radiation, how serious events were defined, or the timing and follow-up period for these counts. The deaths should not be assumed to have been caused by treatment or to represent a particular cause.

The serious adverse event terms with the largest listed percentages are squamous cell carcinoma at 3.2%, papillary thyroid cancer at 1.6%, and papillary carcinoma of the kidney at 1.6%. The registry record does not explain the basis for each percentage or provide additional detail about the events. The listed terms do not establish that the events were treatment-related.

In general, adverse-event counts do not by themselves show comparative risk. Interpretation would require consistent event definitions, observation periods, attribution rules, and a suitable comparison group. This study has no concurrent control group, and comparative safety results are not reported in the registry record. The listed counts therefore describe what the registry records for this arm, without establishing whether the intervention increased or decreased adverse events.

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

The study asks whether radiation dose and treatment field size can be reduced while retaining local control among patients described as having diffuse large B-cell lymphoma, complete response, and a negative post-chemotherapy PET scan after rituximab-containing chemotherapy. The stated dose hypothesis is a reduction from 30 Gy to 20 Gy, accompanied by a decrease in field size. This is the intended question, not a reported outcome.

The registry record reports a completed single-group study and enrollment of 63. It describes a primary endpoint based on local control at 5 years, estimated from time to local failure, and cites 0.90 as the historical-control value. However, the primary endpoint result, its precision, and the comparison with that historical value are not reported in the registry record. Consequently, the posted information does not establish whether the study met its objective.

The record also does not report results for progression-free survival, overall survival, or failure categories. Safety counts are available, but event attribution, definitions, and timing are not. Those counts cannot establish a treatment effect or a causal relationship. Nor can the absence of an outcome result be interpreted as evidence that an outcome was favorable or unfavorable.

More generally, a single-group study can describe observed outcomes but does not provide a concurrent randomized comparison. Historical benchmarks can offer context, but their relevance depends on comparability and on the analysis approach, neither of which is detailed in the registry record. Without outcome estimates and their uncertainty, it is not possible to judge how compatible the study’s experience is with the stated benchmark.

The registry information therefore supports a description of the study’s design, planned clinical question, endpoint, and recorded safety counts. It does not support a conclusion about efficacy, comparative safety, or whether reduced-dose radiation maintained local control.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a clinical hypothesis and an observed result. The hypothesis proposes a lower radiation dose, from 30 Gy to 20 Gy, alongside a smaller treatment field, with the aim of maintaining local control and minimizing toxicity. The registry record describes that question, but does not report the primary endpoint estimate. A clear hypothesis is not itself evidence that the intended outcome was achieved.

It also illustrates how endpoint definition affects interpretation. A count of participants with local control and a Kaplan-Meier estimate of local control at 5 years are not necessarily the same summary. The time-to-event approach can account for differing follow-up, but its meaning depends on event definitions, censoring, and analysis details. Those details and the result are not reported in the registry record.

The single-group design makes the historical benchmark especially important. A value of 0.90 is cited in the objective, but it is not a concurrent comparator. Assessing a single-group result against historical experience requires both a sufficiently precise estimate and confidence that the reference is relevant. The registry record does not report the comparison method or the current study’s estimate and uncertainty.

Finally, the record shows why completion status, enrollment, endpoint descriptions, and safety counts should be kept distinct from outcome evidence. These details describe what the study was intended to examine and what registry information is recorded. They do not answer the primary statistical question without the outcome results and analysis information.

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 interpreting this trial from the registry record is that the primary local-control result is not reported. There is no estimate, confidence interval, test result, or event-time summary with which to assess the stated historical benchmark of 0.90. Secondary outcome results are also not reported.

The study is single-group, with no concurrent control arm. Its primary objective refers to historical controls, but the source, selection, and comparability of those controls are not reported in the registry record. This limits the strength of any treatment-effect interpretation that could be made from a result, even if one were available.

Important methods are not reported in the registry record, including detailed eligibility criteria, the treatment actually delivered, local-failure definitions, censoring rules, follow-up completeness, analysis populations, handling of missing data, and the statistical comparison with the historical value. The registry identifies a primary and secondary outcome structure, but does not report a multiplicity plan or analysis details.

The safety information is limited to counts and selected serious-event terms with percentages. Event attribution, timing, definitions, and observation windows are not reported in the registry record. The counts therefore cannot be used to determine whether events were related to treatment or to make a comparative safety assessment.

The registry reports enrollment of 63 and completed status, but does not provide participant flow or detailed outcome data. Those omissions restrict assessment of follow-up, precision, and possible selection or missing-data effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Reduced Radiation in Patients With Diffuse Large B-cell Lymphoma — NCT01186978.
• Registry record last updated 2020-06-02; status last verified 2020-05.
• Results first posted 2020-06-02.
• 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

NCT01186978 is a completed, single-group study sponsored by Duke University, with enrollment of 63. The registry reports a start date of 2010-09-20 and a primary completion date of 2019-06-04. The study concerns reduced-dose and reduced-field radiation therapy for diffuse large B-cell lymphoma after rituximab-containing chemotherapy in patients described as having complete response and a negative PET scan.

The primary outcome is local control at 5 years, estimated from time to local failure, with a historical-control value of 0.90 stated in the objective. The primary endpoint result and the listed secondary outcome results are not reported in the registry record. Safety entries include 4 participants with serious adverse events, 16 with other adverse events, and 3 deaths; the record does not report event attribution. The registry therefore describes the design and planned question but does not provide the outcome evidence needed to evaluate the primary objective.