Combined Immunochemotherapy Followed By Reduced Dose Radiation Therapy (RT) for Patients With Newly Diagnosed Primary Central Nervous System Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combined Immunochemotherapy Followed By Reduced Dose Radiation Therapy (RT) for Patients With Newly Diagnosed Primary Central Nervous System Lymphoma (NCT00594815), a na na study. The primary outcome is Total Number of Participants Who Experienced Acute Treatment Related Adverse Events.

2. Clinical Question

The study’s stated purpose was to assess the safety of adding rituximab to chemotherapy for primary central nervous system lymphoma. Its background description notes that chemotherapy and radiation are used for the condition and that relapse remains a concern; it presents improved tumor control as the investigators’ hope, not as an established finding of this study.

This is a safety-focused question in a pilot study, not a randomized estimate of how the combined regimen compares with another treatment. The record identifies the intervention and reports adverse-event counts, but it does not report a treatment-effect estimate for tumor control or a comparison of outcomes between groups. It also does not report a primary-endpoint count, so the named endpoint cannot be quantified from the registry record.

3. Trial Design

This completed pilot study examined combined immunochemotherapy followed by reduced-dose radiation therapy in participants with newly diagnosed primary central nervous system lymphoma. The study title and official title describe the sequence of treatment; the listed intervention names cytarabine, leucovorin, methotrexate, procarbazine, rituximab, and vincristine. The brief description characterizes rituximab as an addition to chemotherapy.

The design is recorded as single-group, with allocation listed as NA and masking as none. Enrollment was 52. These design features mean that the posted adverse-event counts describe participants in the study group; they do not furnish a randomized, concurrent control comparison. No arm description is recorded for the single group.

The registry lists the phase as NA. The study status is completed. The recorded start date is 2002-08-28, and the primary completion date is 2016-02-23. These registry dates describe the study record and do not, by themselves, explain the timing of individual participants’ treatment or follow-up.

The primary outcome is the total number of participants who experienced acute treatment-related adverse events, with a timeframe of 2 years. Its description says that toxicity would be measured using NCI CTC version 2.0. The record lists 2 outcome measures and 0 analyses. A result for the named primary endpoint is not reported in the registry record. The adverse-event section separately reports counts for participants with serious and other adverse events, but the record does not establish that those counts are the primary endpoint result.

Because this is a single-group pilot study, the design can describe observed events among enrolled participants, but it cannot isolate the effect of the regimen from other explanations through a randomized comparison. The registry record does not report the planned statistical analysis, a sample-size justification, or further details about the study protocol.

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 Total Number of Participants Who Experienced Acute Treatment Related Adverse Events, measured over 2 years.

The primary endpoint is the total number of participants who experienced acute treatment-related adverse events during a timeframe of 2 years. It is a participant count: the intended quantity is how many people met the endpoint definition, rather than how many separate events occurred. The endpoint description states that toxicity would be assessed using NCI CTC version 2.0.

Counting participants with an event can give a direct summary of how many people experienced the defined safety outcome. This is useful in a safety-focused pilot study because it expresses the burden in terms of participants, not just event episodes. In general, an event count and a participant count answer different questions: one person may experience more than one event, while a participant count records that person once for the defined outcome. The registry endpoint is explicitly framed as a count of participants.

The record does not report the numerical result for this primary endpoint, nor does it provide details of the operational definition used to decide which events counted as acute and treatment-related. It therefore cannot establish from the posted primary-outcome result how many participants met that endpoint. The separately posted adverse-event counts should be read as their own reported summaries, not substituted for the absent primary endpoint result.

In general, a clearly specified timeframe and event definition help readers understand what a safety count includes. Here, the record gives the timeframe and the toxicity grading reference but does not report additional endpoint definitions or the primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It describes a single-group study and provides participant counts for adverse events, but it does not report an analysis plan or a numerical result for the primary endpoint. General statistical concepts can help distinguish what those posted counts do and do not establish.

What does a participant count represent?

The primary endpoint is defined as a count of participants who experienced acute treatment-related adverse events. In general, a participant count counts each person who meets the endpoint definition, even if that person has multiple qualifying events. An event count instead tallies event episodes and can be larger when participants experience repeated events. The record identifies the primary endpoint as a participant count, but its numerical value is not reported in the registry record.

The adverse-event summary likewise gives participants at risk and participants affected. It reports 22 participants with serious adverse events and 43 with other adverse events, each among 52 at risk. These are descriptive counts. They do not indicate the number of total event episodes, and the record does not explain whether an individual could be included in both categories. In general, overlapping categories should not be combined unless the definitions establish that they are mutually exclusive.

What can a single-group study estimate?

In general, a single-group study can describe outcomes observed among the participants enrolled. A concurrent comparator helps address whether differences in outcomes are associated with treatment rather than other factors, because groups can be compared under a shared study context. This study has no randomized comparison arm: it is listed as single-group and allocation is NA. Its adverse-event counts therefore do not estimate a treatment difference against a control group.

That limitation does not make descriptive counts meaningless. They communicate what the registry reports for the enrolled group. However, interpretation should remain tied to the event definitions, follow-up information, and analysis details that are actually recorded. The registry record does not report further information about the primary endpoint’s operational definition or its result.

What would an interval add?

In general, a confidence interval expresses uncertainty around an estimate under a specified statistical approach. It helps readers distinguish a point estimate from the range of values that remain compatible with the data and model. The record does not report confidence intervals for the adverse-event counts or a numerical primary endpoint estimate. No interval can therefore be interpreted for these outcomes from the registry record.

A p-value, when reported, addresses compatibility between data and a stated null model; it is not a measure of the size or clinical importance of an effect. No p-value or inferential analysis is reported in the registry results. The record lists 0 analyses, which describes the registry’s analysis entries; it does not establish that no analysis was conducted outside the registry.

How should the serious-event percentages be read?

The serious-event list gives percentages for individual terms, including 7.7% for Infection without neutropenia, Leukocytes, Neutrophils/granulocytes, and Platelets, and 5.8% for Febrile neutropenia and Wound, infectious. These values should be quoted as listed. The record does not specify the denominator or counting method for these term percentages. In general, a percentage is interpretable only in relation to its denominator and the rule used to count events or participants. Without those details, the listed percentages cannot be translated into numbers of participants or treated as participant-level risks.

Seriousness and severity are also distinct concepts in general safety reporting. A serious adverse event is categorized using seriousness criteria, while severity describes the intensity of an event. The registry identifies a serious-event summary but does not provide enough detail to infer the severity of each event or to equate seriousness with a particular toxicity grade.

What does the sample-size information mean?

The registry record includes a general sample-size illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. Such illustrations are planning calculations, not evidence of what occurred in the study and not a measure of observed power. The record does not provide numerical planning outputs in the registry record, and it does not establish that this two-arm illustration was the study’s own design. This trial itself is recorded as single-group.

In general, power calculations depend on assumptions about the effect, variability, significance level, allocation, and analysis method. They can illustrate how a hypothetical design might perform under stated assumptions, but they do not show the probability that the trial’s findings are true. The registry record does not report a protocol-based sample-size justification for this study.

Over-dispersion is a general concern for count outcomes when variability exceeds what a simple model assumes; accounting for it can affect uncertainty estimates and inference. The primary outcome is described as a participant count, and the record does not report a model or dispersion estimate. It would be inappropriate to claim that an over-dispersion adjustment was used or needed for the posted results.

Overall, the reported counts support a limited descriptive reading. They do not supply the absent primary endpoint estimate, a comparative treatment effect, or a precision measure. Statistical interpretation should not extend beyond those documented quantities and design 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("Immunocompetent Pts With Newly Diagnosed Primary C")
n      <- c(52)
events <- c(52)
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  Immunocompetent Pts With Newly Diagnosed Primary C  52  52  100.0  93.2  100.0  93.1  100.0  93.3  100.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures and 0 analyses. It does not report a multiplicity procedure, such as an adjustment for testing several outcomes, or specify a hierarchy for interpreting outcomes. The number of listed outcome measures alone does not reveal how many hypotheses were tested or whether any adjustment was planned. Details of the statistical plan are not reported in the registry record.

The record also does not describe how missing outcome data were handled, whether all enrolled participants contributed to each outcome, or what analysis population was used. It does not report imputation, exclusions, or a sensitivity analysis for missing data. These details matter in general because incomplete follow-up or outcome measurement can affect both the estimate and its uncertainty. Their absence means readers cannot assess those potential effects from this record.

In general, an analysis population specifies which participants are included in an estimate—for example, whether the analysis includes everyone enrolled or only participants with available measurements. The registry record does not state the population used for the adverse-event summaries or give a separate population definition for the primary endpoint. It is therefore not possible to infer an intention-to-treat or other analysis population.

The record’s 0 analysis entries should be read as the number of analyses listed in the registry, not as proof that no statistical work occurred. Similarly, absent details should not be filled in by assuming standard practices. The primary outcome result, multiplicity approach, missing-data handling, and analysis populations are not reported in the registry record.

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: infection without neutropenia (7.7%), leukocytes (7.7%), neutrophils/granulocytes (7.7%), platelets (7.7%), febrile neutropenia (5.8%).

The safety summary reports 22 participants with serious adverse events among 52 at risk, and 43 participants with other adverse events among 52 at risk. It also reports 13 deaths. These are registry counts; the record does not specify a cause or treatment relationship for the deaths. The counts do not establish that all events were caused by the study regimen.

The serious-event terms listed with percentages are Infection without neutropenia, Leukocytes, Neutrophils/granulocytes, and Platelets at 7.7% each, followed by Febrile neutropenia and Wound, infectious at 5.8% each. The denominator and method used to calculate these term percentages are not reported in the registry record. They should not be read as percentages of all participants unless that denominator is confirmed.

The record does not say whether participants appear in both the serious and other adverse-event summaries. The counts therefore should not be added to produce a total number of affected participants. Nor do the serious-event counts give the number of separate event episodes. In general, safety summaries depend on event definitions, attribution, follow-up, and counting rules. Those details are not fully.

The primary endpoint’s result is not reported, so the safety summary cannot stand in for the specified count of acute treatment-related adverse events over 2 years.

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

The posted record establishes that this completed pilot study enrolled 52 participants in a single-group design and reports adverse-event counts for that group. It provides a structured description of the intended primary safety outcome and the method reference, NCI CTC version 2.0. It also lists serious-event terms and reports 13 deaths. These are useful descriptive elements of the registry record, but they do not form a complete statistical account of the primary outcome.

The primary endpoint asks for the number of participants who experienced acute treatment-related adverse events over 2 years. That numerical result is not reported in the registry record. The adverse-event counts—22 participants with serious adverse events and 43 with other adverse events, each among 52 at risk—have separate labels and should not be substituted for that missing result. The record does not provide enough detail to determine whether categories overlap, how deaths relate to treatment, or how the term-specific percentages were calculated.

The single-group design also limits causal interpretation. Without a concurrent randomized comparator, observed events cannot be contrasted with what would have occurred under another treatment in the same study context. The record therefore does not establish a treatment difference. The stated hope of improved tumor control describes the investigators’ motivation, not an efficacy finding reported in these results.

In general, a safety count describes events observed under the study’s reporting and follow-up procedures; it does not by itself determine whether a treatment caused those events. A fuller assessment would require clearly defined outcomes, follow-up and attribution details, an analysis population, and appropriate estimates of uncertainty. Several of these details, including the primary endpoint result and statistical analysis plan, are not reported in the registry record.

The appropriate reading is consequently narrow: the record documents a pilot study and provides descriptive adverse-event information, while leaving the primary endpoint’s numerical result and comparative evidence unavailable. It neither demonstrates nor rules out tumor-control benefit, and it does not support a causal safety comparison.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a clearly named endpoint and a reported endpoint result. The registry identifies a participant count for acute treatment-related adverse events over 2 years and specifies NCI CTC version 2.0 as the toxicity measurement reference. Yet the numerical result for that outcome is not reported in the registry record. Without the result, readers cannot estimate its frequency or assess its precision.

It also shows why study design shapes the conclusions that can be drawn. A single-group pilot can describe outcomes among its participants, but it does not provide the randomized comparison needed to estimate a treatment difference against a concurrent control. The adverse-event counts are therefore descriptive rather than comparative evidence.

The distinction between participant counts, event counts, and term-specific percentages is important for safety interpretation. The record reports participants affected for the broad adverse-event summaries, while the denominator and counting method for individual serious-event percentages are not reported. These quantities should not be combined or interpreted as if they shared a definition.

Finally, the registry lists a sample-size illustration based on an observed effect and hypothetical two-arm assumptions, even though this study is recorded as single-group. In general, such planning illustrations are not observed power and do not replace a protocol-based justification. The record does not report that justification or the analysis plan. Taken together, the study is a useful example of how design, endpoint reporting, denominator clarity, and analysis transparency set the boundaries of statistical interpretation.

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 principal limitation for interpreting the stated primary question is that its result is not reported in the registry record. Although the endpoint, timeframe, and toxicity measurement reference are named, no numerical count is available for participants experiencing acute treatment-related adverse events over 2 years. The adverse-event summaries do not resolve that gap because they are reported separately.

The single-group design and lack of masking limit what can be inferred from the posted results. There is no randomized, concurrent control comparison, so the adverse-event counts cannot estimate a difference between treatment strategies. The record also does not report details about outcome assessment beyond the NCI CTC version 2.0 reference, including how treatment relationship or acute events were operationalized.

Interpretation of the serious-event summary is constrained by missing denominator and counting information for the listed term percentages. The record does not explain whether the serious and other adverse-event categories overlap, how many event episodes occurred, or the timeframe and cause of the 13 deaths. No inference about treatment attribution should be made from those counts alone.

The record does not report the statistical analysis plan, the analysis population, handling of missing data, multiplicity procedures, or a protocol-based sample-size justification. It lists 2 outcome measures and 0 analyses, but those registry entries do not establish what analyses may have been conducted elsewhere. The registry also lists a sample-size illustration based on hypothetical two-arm assumptions; it does not make that illustration evidence about the single-group study’s observed precision or power.

Finally, the efficacy hope described in the study purpose is not accompanied by a reported tumor-control result in the registry record. The available record is therefore insufficient for a comparative efficacy assessment or a complete quantitative assessment of the primary safety endpoint.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Combined Immunochemotherapy Followed By Reduced Dose Radiation Therapy (RT) for Patients With Newly Diagnosed Primary Central Nervous System Lymphoma — NCT00594815.
• Registry record last updated 2017-04-06; status last verified 2017-04.
• Results first posted 2017-04-06.
• 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

NCT00594815 is a completed pilot study of combined immunochemotherapy followed by reduced-dose radiation therapy for newly diagnosed primary central nervous system lymphoma. The study is recorded as single-group, with allocation listed as NA, masking as none, phase as NA, and enrollment of 52. The recorded start date is 2002-08-28, and primary completion is dated 2016-02-23.

The primary outcome is the count of participants experiencing acute treatment-related adverse events over 2 years, measured using NCI CTC version 2.0. Its numerical result is not reported in the registry record. The adverse-event summary reports 22 participants with serious adverse events and 43 with other adverse events, each among 52 at risk, as well as 13 deaths. A concurrent control comparison, analysis plan, missing-data approach, and analysis population are not reported in the record.