5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer (NCT00308516), a non-randomized phase 2 study. The primary outcome is Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment.

2. Clinical Question

3. Trial Design

This is a phase II, nonrandomized, single-group study with two treatment cohorts described in the registry: a preoperative cohort and a postoperative or combined-modality cohort. The registry records enrollment of 66 participants and a completed study. Its recorded start is 2006-03, and primary completion is 2009-04. No random allocation or masking is recorded.

The study evaluated a regimen involving 5-fluorouracil, bevacizumab, and radiation, followed by modified FOLFOX6 and bevacizumab as described in the trial title. The intervention list also names oxaliplatin and leucovorin. The available descriptions of the cohort regimens are truncated, so details beyond the visible text are not reported in the registry record. The record does identify a 5-fluorouracil infusion and bevacizumab in both cohort descriptions, and radiation in the combined-modality cohort description.

The two cohorts do not constitute a randomized comparison. Their labels indicate differing treatment timing, and the record does not establish that participants in one cohort could serve as a valid control for participants in the other. Comparisons between their outcomes, if available, would therefore need to be interpreted cautiously and would not isolate the causal effect of one regimen versus another.

The registry lists overall survival as a secondary outcome, defined as time alive from the first date of protocol treatment until death. It records two outcome measures but no analysis entries. The statistical analysis plan, analysis populations, sample-size justification, and any interim analyses are not reported in the registry record. Thus, the design can be characterized from its phase, allocation, masking, cohort descriptions, and listed endpoints, but not from a detailed protocol or statistical plan.

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 Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment, measured over 24 months.

The primary endpoint is disease-free survival (DFS), expressed as the proportion of patients predicted to be alive without evidence of disease recurrence 24 months after completion of protocol treatment. This combines survival and recurrence status at a specified follow-up point: a participant contributes to the disease-free state only if alive and without documented recurrence at that time. The registry describes the measure as a predicted proportion and specifies a 95% confidence interval.

DFS is used in clinical trials as an outcome that captures whether disease has recurred as well as whether a participant remains alive. It can therefore describe disease control over follow-up without being identical to overall survival, which concerns time until death. The registry lists overall survival separately as a secondary outcome.

The specified time point matters because a proportion at a fixed follow-up horizon answers a different question from a median time-to-event estimate or a rate across all follow-up. Interpretation also depends on how recurrence, deaths, censoring, and incomplete follow-up were handled. Those analysis details are not reported in the registry record. Most importantly, the record does not report the DFS estimate or its confidence interval, so the endpoint is defined but its observed value and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record defines a binary primary outcome at a fixed follow-up point: alive and without evidence of recurrence 24 months after completion of protocol treatment. The measure is a percentage of participants. This is distinct from reporting how long each participant remained disease-free, although time-to-event methods may be relevant when follow-up varies or outcomes occur at different times. The registry does not report the estimation method, handling of censoring, or the details used to derive the predicted proportion.

What does a confidence interval describe?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical method. For a DFS proportion, the estimate describes the observed or modeled proportion, while the interval gives a range of values compatible with the data and method at the stated confidence level. A narrower interval indicates greater statistical precision than a wider interval, but precision alone does not establish that an estimate is unbiased or that a treatment caused the outcome.

The primary outcome specifies a 95% confidence interval, but the registry does not report the interval itself. There is consequently no basis in the recorded result to discuss its width, the endpoint estimate’s precision, or whether the interval is compatible with a range of clinically relevant outcomes. The confidence level is part of the outcome definition; it is not a substitute for the missing numerical estimate.

Why does the study design matter?

In general, randomization helps balance both measured and unmeasured prognostic factors between treatment groups, on average. This record is nonrandomized and single-group, with cohorts distinguished by treatment timing. Such a design can describe outcomes among participants treated in the study, but a contrast between the cohorts is vulnerable to confounding and selection. The registry does not report a randomized comparison, an adjustment strategy, or a formal between-cohort analysis.

Accordingly, the cohort counts should not be treated as if they came from interchangeable treatment arms in a controlled experiment. The descriptions indicate different clinical pathways. Without a reported design or analysis establishing comparability, differences in outcome cannot be attributed specifically to treatment timing or regimen. This issue remains even if a numerical difference is later available; statistical precision does not correct systematic differences between groups.

How should a percentage endpoint be read?

In general, a proportion is a summary of the share of participants meeting a defined condition. Its interpretation depends on the denominator, outcome ascertainment, follow-up, and rules for participants with missing status. A fixed-time disease-free proportion also depends on how participants who have not been observed through the specified time point are handled. Those methods are not reported in the registry record. The phrase predicted proportion suggests an estimate, but the record does not specify the model or calculation behind it.

The distinction between a proportion and a time-to-event analysis is important. A proportion at a fixed horizon summarizes status at that horizon. A time-to-event analysis uses information about when events occur and can account for differing observation times under specified assumptions. The registry lists overall survival as a secondary outcome with a time-based definition, but it does not provide outcome estimates or describe a method such as a survival curve, hazard model, or censoring procedure. No such method should be assumed.

What can planning calculations show?

In general, sample-size calculations estimate how many participants might be needed to detect a prespecified effect under stated assumptions. They are planning illustrations, not observed outcomes and not observed power. The registry record does not report the trial’s own sample-size justification or design assumptions. Any separately displayed planning scenario should therefore be distinguished from the study’s actual enrollment and from its clinical results.

The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those are assumptions for a planning exercise, not evidence that the trial used that design. They are also not a description of the actual study, which is recorded as nonrandomized and single-group. The study’s observed enrollment is 66; a planning calculation does not change that observed fact.

Over-dispersion is a general concern when data vary more than a statistical model assumes. If a model treats observations as more independent or less variable than they really are, uncertainty can be understated and intervals may be too narrow. This is a general statistical consideration, not a reported feature of this trial. The registry does not report the outcome model or enough analysis detail to determine whether over-dispersion was relevant.

Finally, the registry records no analysis entries. It does not report the prespecified statistical plan, handling of missing outcomes, analysis population, multiplicity procedures, or interim monitoring. These are not details that can be reconstructed from the outcome title or the study’s phase. They limit independent assessment of how the stated endpoint would have been analyzed and how the reported result, if available, should be interpreted.

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("Preoperative 5FU/Radiation/Bevacizumab", "Postoperative 5FU/Radiation/Bevacizumab")
n      <- c(35, 31)
events <- c(30, 30)
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  Preoperative 5FU/Radiation/Bevacizumab  35  30  85.7  69.7  95.2  70.6  93.7  70.5  93.6
ARM  Postoperative 5FU/Radiation/Bevacizumab  31  30  96.8  83.3  99.9  83.8  99.4  83.8  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists DFS as the primary outcome and overall survival as a secondary outcome. It records two outcome measures, but no analysis entries. A multiplicity strategy for evaluating more than one outcome, or multiple time points or subgroup analyses, is not reported in the registry record. Without that information, it is not possible to determine whether any reported statistical tests were adjusted or how the primary and secondary outcomes were prioritized analytically.

The primary endpoint is defined at 24 months after completion of protocol treatment. The registry does not report how incomplete follow-up, missing recurrence status, censoring, or participants who did not complete protocol treatment were handled. It also does not specify an analysis population such as all enrolled participants, all treated participants, or a subset with evaluable follow-up. These omissions matter because the population analyzed and the handling of unavailable outcome data can affect a proportion estimate.

Details of the statistical analysis plan, sample-size justification, and interim analyses are not reported in the registry record. The absence of these details should not be taken to mean that such procedures were or were not used; the registry record does not establish either. The nonrandomized cohort structure also means that any between-cohort comparison would require careful justification and methods for addressing differences between groups. No such comparative analysis is recorded.

12. Safety Results

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

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: perforation, gi (6.5%), infection - gi (6.5%), infection - nos (5.7%), obstruction - gi (5.7%), thrombosis/thrombus/embolism (5.7%).

The registry reports serious adverse events by cohort. In the preoperative cohort, 35 participants were at risk and 18 were affected by a serious adverse event. In the postoperative cohort, 31 participants were at risk and 15 were affected. These are counts within the respective cohorts, not results from a randomized safety comparison.

The listed serious adverse-event terms include Perforation, GI (6.5%), Infection - GI (6.5%), Infection - NOS (5.7%), Obstruction - GI (5.7%), Thrombosis/Thrombus/Embolism (5.7%), and Pain - Rectum (3.2%). The record does not clarify in the available information the denominators or calculation method for these term percentages. They should therefore be read as reported registry figures, not as a basis for recalculating risks or comparing cohorts.

Death counts are not reported in the registry record. The safety figures describe reported events in this study and do not establish whether a particular treatment caused an event. Differences between the cohorts cannot be interpreted as treatment effects because allocation was nonrandomized and the cohort pathways differ.

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

The registry record establishes that a phase II study was conducted to investigate a treatment strategy combining chemotherapy, bevacizumab, and radiation in stage II/III rectal cancer. It identifies a primary DFS outcome at 24 months after completion of protocol treatment, a secondary overall survival outcome, two treatment cohorts, and serious adverse-event counts. The record also shows that enrollment was 66 and that the study is completed.

It does not report the numerical DFS result or its 95% confidence interval. Therefore, the record cannot be used to state what proportion of participants were alive without recurrence at the specified follow-up point, or how precisely that proportion was estimated. The overall survival result is also not reported in the registry record. A defined endpoint is not itself an outcome, and an absence of a posted estimate does not indicate either a favorable or unfavorable result.

The study’s nonrandomized, single-group design does not support treating the preoperative and postoperative cohorts as randomized alternatives. Their differing treatment pathways and the absence of a reported comparative analysis prevent a causal interpretation of any apparent difference between them. The safety counts document events among participants in each cohort, but do not establish comparative safety or causation.

In general, clinical interpretation requires both the magnitude of an outcome and its uncertainty, alongside the study design and analysis methods. Here, the missing primary result, missing analysis details, and nonrandomized design leave substantial uncertainty about what can be concluded from the registry record. No conclusion about treatment benefit or lack of benefit follows from the information recorded.

14. Why This Trial Matters Statistically

Statistically, this study illustrates why an endpoint definition and a result must be kept distinct. The primary endpoint is specific about the health state of interest and when it is assessed: alive without evidence of recurrence 24 months after protocol treatment is completed. Yet the registry does not report the estimate or its confidence interval. Without those, readers cannot evaluate the result’s magnitude or precision, regardless of how clearly the endpoint is defined.

The design also matters to interpretation. A nonrandomized study with preoperative and postoperative cohorts can describe treatment experience, but the cohorts are not automatically valid controls for each other. Their treatment timing and pathway differ, and the registry does not report an analysis that supports a causal contrast. This is a useful distinction between describing outcomes and estimating a treatment effect.

The record also highlights the importance of reporting analysis methods alongside clinical outcomes. Details about analysis populations, missing data, censoring, multiplicity, and interim analyses are not reported in the registry record. These choices can influence how an endpoint is estimated and how confidently it can be interpreted. Their absence makes it harder to assess the strength and limitations of any result.

Finally, safety counts need context. The record reports serious adverse events in both cohorts, but the nonrandomized design and incomplete denominator details for listed term percentages limit comparisons. Clear reporting of outcome estimates, uncertainty, denominators, and analysis methods is essential for readers to distinguish observed data from conclusions that the design can support.

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 primary limitation for interpreting efficacy is that the registry record does not report the DFS estimate or its 95% confidence interval. The secondary overall survival outcome is listed, but a numerical result is not reported in the registry record. The record therefore describes the intended outcomes without supplying the results needed to assess their magnitude or precision.

The trial is recorded as nonrandomized and single-group, with preoperative and postoperative cohorts. These cohorts differ in treatment pathway and do not provide a like-for-like randomized control comparison. The registry does not report a statistical method for comparing them or an adjustment strategy to address potential differences between participants. Thus, cohort contrasts should not be interpreted causally.

Important implementation details are also absent or incomplete. The available cohort descriptions are truncated, and eligibility criteria, participant characteristics, follow-up completeness, endpoint ascertainment procedures, and the handling of missing data are not reported in the registry record. Statistical analysis details, including the analysis population, multiplicity procedures, interim analyses, and sample-size justification, are also not reported.

For safety, the registry gives cohort-level at-risk and serious-event counts and lists several serious-event terms with percentages. It does not report death counts, and the denominator or calculation method for the term percentages is not clear in the available record. These limits prevent a complete assessment of safety rates or reliable comparisons between cohorts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: 5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer — NCT00308516.
• Registry record last updated 2021-12-10; status last verified 2021-11.
• Results first posted 2013-05-14.
• 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

This completed phase II study is recorded as nonrandomized, unmasked, and single-group, with preoperative and postoperative treatment cohorts. It enrolled 66 participants and investigated a regimen involving 5-fluorouracil, bevacizumab, radiation, and subsequent chemotherapy. The primary endpoint was the predicted proportion alive without evidence of recurrence 24 months after completing protocol treatment.

The registry does not report the primary DFS estimate or its 95% confidence interval. Overall survival is listed as a secondary outcome, but its result is not reported in the registry record. Serious adverse-event counts are reported for both cohorts, while death counts and several statistical analysis details are not reported. Because the cohorts were not randomized and represent different treatment pathways, they should not be treated as a controlled comparison.