Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas (NCT00319735), a na phase 2 study. The primary outcome is Complete Pathologic Response (pCR).

2. Clinical Question

The trial’s stated purpose was to investigate the feasibility and activity of combining cetuximab with radiation therapy in people with surgically resectable disease. Its rationale in the registry describes proposed interactions between epidermal growth factor receptor (EGFR) inhibitory agents and radiation. Those statements explain the biological motivation for the study; they are not findings from the trial’s clinical outcomes.

The registry identifies complete pathologic response (pCR) as the primary endpoint and gives a timeframe of 36 months. It does not report the number or percentage of participants who achieved pCR. The recorded endpoint definition concerns the surgical specimen, so the question is about pathologic findings after resection, not simply a change in symptoms or an imaging-based response.

Because the design is single-group, the study can describe outcomes among participants treated on the regimen, but it does not offer a concurrent control group for estimating how outcomes would differ under another treatment. The registry record does not report a pCR result, so no treatment response estimate or comparison can be drawn from the posted primary outcome information.

3. Trial Design

This is a phase 2 pilot study recorded as completed, with a single-group model and no masking. Allocation is listed as not applicable. The registry reports enrollment of 41 participants. The study is titled as an investigation of cetuximab and radiation therapy for surgically resectable esophageal and GE junction carcinomas; the primary outcome description also names both locations.

The treatment description specifies cetuximab 400 mg/m2 intravenously over 120 minutes on Day -14 as a loading dose, then 250 mg/m2 intravenously over 60 minutes on Day -7. Further 250 mg/m2 doses are listed for Days 1, 8, 15, 22, 29 and 36, combined with radiation therapy for six weeks. Surgery for esophageal resection is described after a 6 to 8 week rest period. The record also lists radiation therapy, surgery and tissue sampling as interventions.

The record gives a start date of 2006-04 and primary completion date of 2009-01. It does not report the number of participants who underwent surgery or whether every enrolled participant received every planned treatment component. A protocol-level account of deviations, treatment adherence, or the timing of outcome assessments beyond the primary timeframe is not reported in the registry record.

A single-group pilot design can describe treatment delivery and outcomes in the enrolled group. It cannot, by itself, separate an outcome associated with the regimen from the natural course of disease, patient selection, or other influences. With no masking, participants and study staff were not blinded according to the registry. The record does not explain the reasons for that design choice. A randomized control comparison is not part of the design described in the registry, so results should not be interpreted as a head-to-head estimate against another regimen.

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 Complete Pathologic Response (pCR), measured over 36 months.

The primary endpoint is complete pathologic response (pCR), expressed as a percentage of participants. The registry defines pCR as the absence of tumor cells on the resected specimen in the esophagus and/or GE junction. Its stated timeframe is 36 months, and the primary objective is to evaluate the complete pathologic response rate in patients with esophageal and GE junction carcinomas.

Pathologic response is assessed from tissue removed during surgery, rather than inferred only from symptoms or scans. In general, a pathologic endpoint can provide a direct description of whether tumor cells are present in the examined specimen. Its interpretation depends on who underwent resection, how specimens were assessed, and how missing or unevaluable specimens were handled. Those details are not reported in the registry record.

The endpoint is a proportion: it describes the share of the relevant participant group meeting the pCR definition. The registry identifies the measure and its definition but does not post the observed pCR count, percentage, or uncertainty interval. Therefore, the primary endpoint’s outcome cannot be quantified from the registry information summarized in the record. The listed timeframe alone does not establish when each participant’s specimen was evaluated or which analysis population was used.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among people who receive the study regimen. If an outcome proportion is reported, its meaning depends on the defined population, the outcome definition, and how participants without an evaluable outcome are handled. Since there is no separate comparator group in this record, a within-study proportion would not be a treatment contrast. It would not estimate the difference between this regimen and another treatment or usual care.

The registry records a single-group model, allocation as not applicable, and no masking. These design labels describe how the study is structured; they do not establish that all participants completed the planned regimen. Treatment completion, protocol deviations, and the number who proceeded to surgery are not reported in the registry record.

What does a percentage measure?

In general, a percentage of participants with an event is a way to express a count relative to a defined group. For the primary endpoint, the event is pCR according to the registry’s specimen-based definition. A percentage is meaningful only alongside its denominator. The registry record does not report the pCR numerator or denominator, so it does not provide a result that can be interpreted as a response proportion.

Different choices about the analysis population can produce different interpretations. For example, a result among all enrolled participants answers a different descriptive question from a result among only participants with a resection specimen available for review. The record does not specify the population used for the primary endpoint. It also does not describe how an absent or unevaluable specimen would be classified.

What would an uncertainty interval tell readers?

In general, a confidence interval describes the range of values reasonably compatible with an estimate under the statistical model and assumptions used. It conveys precision, not the probability that a treatment is effective, and it does not correct for design limitations such as the absence of a comparator. A proportion based on a small group can be uncertain even when its point estimate appears clear. Here, the registry does not report a pCR estimate or a confidence interval, so the precision of the primary outcome cannot be assessed.

How should planning calculations be read?

In general, sample-size calculations are planning tools: they describe how many participants or events a hypothetical study might need under stated assumptions. They are not evidence about what happened in a completed trial, and they are not “observed power.” The registry record does not report a sample-size justification or a statistical plan for the original study. Any planning illustrations associated with posted analyses should be understood as conditional calculations, not as the study’s original design rationale or as results.

Calculations based on an observed effect can also be especially sensitive to uncertainty in that effect. A planning illustration that assumes a fraction of an observed effect is answering a hypothetical design question; it does not change the uncertainty in the original estimate. In this record, the primary response result is not reported, so readers should not treat planning figures as a substitute for a missing clinical outcome.

Why can event counts and rates differ?

In general, a binary outcome records whether an event occurred for each participant in a defined period. A count gives the number of participants with the event, whereas a percentage relates that count to a denominator. The registry lists serious and other adverse-event counts, but the primary response result is not reported. These safety counts do not provide a pCR estimate.

For outcomes that occur repeatedly or over time, simple participant percentages may not capture timing or duration. A time-to-event analysis can account for follow-up time and censoring, but its interpretation requires a defined event, a time origin, and information about follow-up. The secondary outcome “Time to Relief of Dysphagia” is listed, but the registry record does not report its result or analysis method.

What can be inferred from the analysis record?

The registry lists 10 outcome measures and 0 analyses. That indicates that outcome measures are named in the record but analysis results are not posted in the recorded analysis information. It does not reveal what analyses may have been performed outside the registry record. The protocol’s statistical methods, including any adjustment strategy, model specifications, handling of missing data, and interim analyses, are not reported in the registry record.

In general, a statistical method should be judged in relation to its outcome definition, study design, and assumptions. For a single-group response proportion, the central reporting needs include the analysis population, numerator, denominator, and an interval describing uncertainty. For a comparative question, an appropriate comparison group and a defined contrast are also needed. The registry record does not supply the primary outcome result needed to apply those interpretive steps.

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 Assignment")
n      <- c(39)
events <- c(14)
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 Assignment  39  14  35.9  21.2  52.8  22.7  51.6  22.7  51.7

11. Multiplicity, Missing Data and Analysis Populations

The record lists 10 outcome measures, including the primary pCR outcome and secondary measures concerning pathologic response, dysphagia, toxicity, molecular correlates, disease stage, and histology. It does not report the statistical plan for these outcomes or specify which analyses were intended to be confirmatory versus exploratory. The number of analyses recorded is 0. The registry record therefore does not indicate whether or how multiplicity was addressed.

In general, examining multiple outcomes or multiple subgroups creates more opportunities for apparently notable findings to arise by chance. A prespecified hierarchy or adjustment method can help clarify how results should be interpreted, but the registry record does not report such a plan. This limitation is especially relevant to the listed response outcomes by stage and histology: their definitions, denominators, and analysis procedures are not reported in the registry record.

Missing-data methods are also not described. The record does not state how participants without surgery, participants with unevaluable specimens, or incomplete follow-up were handled in the pCR analysis. It does not report the number of missing outcome observations. Without these details, the intended analysis population and the effect of missing outcomes on any response estimate cannot be assessed.

Analysis populations are not reported in the registry record. It is therefore not possible to determine whether the primary endpoint was intended to include all enrolled participants, only those who received treatment, or only those with an evaluable resection specimen. These are not interchangeable populations. The available record supports describing the endpoint and the named outcomes, but not reconstructing the prespecified analysis strategy.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (7.3%), dysphagia (difficulty swallowing) (4.9%), sodium, serum-high (hypernatremia) (4.9%), aspiration (2.4%), blood/bone marrow - other (specify, __) (2.4%).

The registry records 41 participants at risk for serious adverse events and 16 affected, and 41 at risk for other adverse events and 39 affected. These are participant counts, not measures of severity for every event or estimates of comparative risk. The record does not report deaths in the listed safety summary.

The most frequently listed serious adverse-event terms are dehydration (7.3%), dysphagia (difficulty swallowing) (4.9%), and sodium, serum-high (hypernatremia) (4.9%). Aspiration, blood/bone marrow - other (specify, __), and constitutional symptoms - other (specify, __) are each listed as 2.4%. These percentages are reproduced as recorded. The registry does not provide additional context about event timing, duration, recurrence, relatedness to treatment, or how terms were grouped.

In general, adverse-event summaries describe events observed during a study; without a comparison group, they do not establish how event frequency differs from another treatment or from background risk. The registry’s single-group design also means these figures should not be read as a comparative safety estimate. A participant count with an event does not imply that every participant experienced the same event, nor does it explain the clinical course. Further safety-analysis details are not reported in the registry record.

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

The registry record establishes that this was a completed phase 2 pilot study of a cetuximab and radiation regimen in patients described as having surgically resectable esophageal and GE junction carcinomas. It reports enrollment of 41 and names complete pathologic response as the primary endpoint, with a specimen-based definition. It also lists several secondary outcomes and adverse-event summaries.

The posted primary outcome information does not include an observed pCR count, percentage, or confidence interval. It therefore does not establish how often complete pathologic response occurred in the study group or how precisely that rate was estimated. The absence of a posted result should not be interpreted as a zero response rate, a failure to achieve response, or evidence of no effect.

Even if a response proportion were available, the single-group design would limit what it could show. A proportion could describe outcomes in the treated group, but could not by itself establish what would have happened under a different treatment. No randomized comparator is described, and the registry lists no masking. The study rationale is not a substitute for outcome evidence.

The registry’s safety counts and listed serious adverse-event terms describe reported events in the study group. They do not provide a comparative assessment or explain whether events were attributed to the regimen. The record does not report a full statistical plan, analysis populations, missing-data methods, or the methods used to assess secondary outcomes.

Accordingly, the record supports a careful description of the study question, planned regimen, endpoint definition, and selected safety data. It does not support a quantitative efficacy conclusion from the primary outcome as recorded. Interpretation should remain limited to what the registry reports, with the missing outcome and analysis details treated as unknown rather than inferred.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between registering an outcome and reporting an outcome result. The registry defines complete pathologic response in terms of tumor cells in a resected specimen and gives a timeframe, but does not post the count or percentage meeting that definition. Without the result and its denominator, the principal clinical question cannot be answered quantitatively from the record.

It also highlights why design labels matter. A single-group study can document treatment delivery and describe outcomes, but it does not provide a concurrent comparison. Even a precisely estimated response proportion would remain a description of the enrolled group rather than a direct estimate of a treatment difference. Readers need to separate the study’s biological rationale from evidence about clinical outcomes.

The record further demonstrates the importance of analysis transparency. A named endpoint does not reveal the analysis population, handling of missing specimens, uncertainty method, or approach to multiple outcomes. These details shape how a result should be interpreted and compared with results from other studies. Here, the registry lists 10 outcomes and 0 analyses, leaving those statistical details unreported.

Finally, the distinction between observed outcomes and planning calculations is important. Planning illustrations are hypothetical tools based on assumptions; they are not observed study findings and do not replace an outcome estimate. In this record, the absence of the primary response result means that a planning scenario cannot resolve the central evidentiary gap. The statistical lesson is that clear endpoint definitions are useful, but interpretable conclusions also require transparent denominators, results, uncertainty, and analysis methods.

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 the registry record is that it does not report the pCR result, despite identifying pCR as the primary endpoint. There is no reported numerator, denominator, percentage, or confidence interval for that outcome. The enrollment count of 41 cannot be assumed to be the denominator for the primary analysis because the record does not report how many participants underwent resection or had evaluable specimens.

The single-group design limits causal interpretation, and no randomized control comparison is described. The record also lists no masking. These features mean that any outcome proportion, if reported elsewhere, would need to be interpreted as a result in the treated group rather than as a randomized estimate of benefit over another approach.

The record does not report treatment completion, protocol deviations, analysis populations, or methods for missing data. It also does not report the statistical plan, multiplicity procedures, or detailed methods for the secondary outcomes. The listed response outcomes by disease stage and histology lack reported results and denominators in this record. These omissions prevent assessment of how outcomes were selected, analyzed, and qualified.

Safety information is limited to event counts and selected serious adverse-event terms. Deaths are not reported in the safety summary, and details such as timing, duration, attribution, and recurrence are not reported in the registry record. These gaps restrict interpretation of both efficacy and safety; they should be treated as unreported information, not as evidence that an event or analysis did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas — NCT00319735.
• Registry record last updated 2016-04-28; status last verified 2016-03.
• Results first posted 2016-04-28.
• 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 completed phase 2, single-group pilot study of cetuximab combined with radiation therapy for surgically resectable esophageal and GE junction carcinomas. Enrollment was 41. The treatment description includes cetuximab dosing, six weeks of radiation therapy, and planned esophageal resection after a rest period.

The primary endpoint is complete pathologic response, defined as absence of tumor cells in the resected esophagus and/or GE junction specimen, with a stated timeframe of 36 months. The primary result is not reported in the registry record. The record lists 10 outcome measures and 0 analyses, alongside selected serious and other adverse-event counts. It does not report the primary analysis population, missing-data approach, or statistical plan. The single-group design does not provide a randomized treatment comparison.