Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck (NCT01104922), a na phase 2 study. The primary outcome is 1-year Local Progression-free Survival (PFS).

2. Clinical Question

The study concerns a population already treated with radiation and then experiencing recurrent disease. Its stated purpose was to examine survival and toxicity with radiosurgery and cetuximab, including acute and late toxicities. The primary outcome is specifically 1-year local progression-free survival, while the listed secondary outcomes include 1-year progression-free survival, overall survival, overall response, changes in tumor glucose metabolism, changes in tumor hypoxia, and quality of life.

The clinical question is descriptive rather than a randomized comparative question. With one treatment group, the registry can describe outcomes among participants who received the regimen, but the design does not establish how those outcomes compare with a separate treatment or with no treatment. The primary outcome estimate, its confidence interval, and the number of participants evaluable for that outcome are not reported in the registry record. Therefore, the clinical question is identifiable from the protocol description, but its numerical answer cannot be read from the registry record.

3. Trial Design

This was a phase 2, single-group study with no masking. Allocation is listed as not applicable, consistent with the registry’s description of one treatment group rather than a randomized allocation between arms. The group received cetuximab and stereotactic radiosurgery. The registry lists enrollment of 48 participants and describes the population as patients with recurrent squamous cell carcinoma of the head and neck who had previously received irradiation.

The record gives a study start date of 2007-12-26 and a primary completion date of 2014-05-21, and lists the study status as completed. These dates describe the registry record’s study timeline; they do not by themselves specify when each participant was followed or how long each outcome was assessed. The primary endpoint has a timeframe of at 1-year. A more detailed follow-up schedule is not reported in the registry record.

The primary outcome is 1-year local progression-free survival, expressed as a percentage of participants and accompanied, in its stated measure, by a 95% confidence interval. The registry defines its analysis population as participants who received study therapy and were evaluable for response. The number in that evaluable population and the number included in the endpoint calculation are not reported in the registry record.

The record lists nine outcome measures and names several secondary outcomes, including survival, response, tumor metabolism, tumor hypoxia, and quality of life. It also lists one treatment group for adverse events. Although the study is completed, the primary outcome estimate and confidence interval are not reported in the registry record. A statistical analysis plan, details of outcome-specific analysis populations, and a sample-size justification for the trial are also not reported in the registry record. The design should therefore be read as a single-group phase 2 evaluation, not as a controlled estimate of comparative benefit or harm.

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

Analysis population for the primary outcome, as defined in the registry: Patients that received study therapy and were evaluable for response to treatment.

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 1-year Local Progression-free Survival (PFS), measured over At 1-year.

The primary endpoint is 1-year local progression-free survival (PFS), reported as a percentage of participants. It is intended to describe the proportion of the response-evaluable treated population without local progression at the specified 1-year time point. The registry names a 95% confidence interval as the measure of uncertainty, but the endpoint estimate and interval are not reported in the registry record.

The record defines progression using response assessment based on subjective interpretation of the first PET-CT and RECIST v1.0. Progression is defined as greater than 20% increase in the sum of the longest diameters of target lesions, using the smallest sum and longest diameter recorded since baseline as reference, or the appearance of one or more new lesions. If measurable disease was limited to a solitary lesion, the protocol specified confirmation of its neoplastic nature by cytology and histology.

Progression-free survival is used to describe time or status without documented progression under the outcome definition; the registry expresses this primary endpoint as a 1-year percentage. Local progression-free survival focuses the question on progression at the local disease site rather than presenting a direct comparison between treatment groups. The registry’s wording does not give further detail about the precise event and censoring rules used to calculate the percentage. Those rules, along with the number of participants contributing to the estimate, are not reported in the registry record.

The response-evaluable population matters for interpretation: the stated endpoint does not necessarily include every enrolled participant. The record does not report how evaluability was determined or how participants without an assessable response were handled. Thus, the endpoint’s clinical definition is described, but the reported information does not permit independent reconstruction of the estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint describe?

The primary outcome is a percentage of participants with an event status at 1-year: local progression-free survival. A percentage summarizes the share of the specified analysis population meeting the outcome definition. Its interpretation depends on both the numerator, the participants meeting the definition, and the denominator, the participants included in the calculation. The registry states that the primary population consists of treated participants evaluable for response, but does not report the number evaluable or the outcome numerator. The percentage therefore cannot be reconstructed from the enrollment total.

General statistical explanation: a percentage is a descriptive estimate for the analyzed group, not an automatic estimate for every person with the same diagnosis. Who enters the denominator and how people without a recorded assessment are handled can affect its interpretation. In this trial, evaluability criteria and missing-outcome handling are not reported in the registry record.

What does a confidence interval add?

The endpoint measure specifies a 95% confidence interval. General statistical explanation: a confidence interval is a range of values compatible with the data and the statistical method used, under the method’s assumptions. It communicates uncertainty around the estimate, rather than guaranteeing that the true value falls within a particular interval. The interval’s width depends in part on the amount and variability of information available. Since neither the endpoint estimate nor its interval is reported in the registry record, the primary result’s precision cannot be described.

The statistical method used to construct the stated interval is not reported in the registry record. Different interval methods can behave differently, especially when the observed percentage is near an endpoint of its possible range or when the analysis population is small. No method should be attributed to this trial without a registry description.

How is progression defined?

The registry’s definition references subjective interpretation of the first PET-CT and RECIST v1.0. It defines progression as greater than 20% increase in the sum of longest diameters of target lesions, relative to the smallest sum and longest diameter recorded since baseline, or the appearance of one or more new lesions. For measurable disease restricted to a solitary lesion, the protocol specified cytology and histology confirmation of neoplastic nature.

General statistical explanation: a clearly specified outcome rule helps make endpoint classification more consistent and interpretable. Here, the record gives a measurement threshold and a rule for new lesions, while also describing the PET-CT interpretation as subjective. It does not provide details about assessor roles, independent review, disagreement resolution, or blinding of response assessment. Those features can affect how reliably outcome status is classified, but their use in this trial is not reported in the registry record.

Why does the single-group design matter?

The study is listed as single-group, with allocation not applicable and no masking. Its treatment group received cetuximab and stereotactic radiosurgery. General statistical explanation: a single-group study can estimate outcomes among the participants observed, but without a concurrent comparator it cannot directly estimate a between-group treatment effect. Changes over time and characteristics of the participants may also contribute to observed outcomes. This is a design distinction, not a judgment about the treatment.

The listed enrollment is 48. That is the study’s enrollment figure, not necessarily the number analyzed for the primary endpoint. Because the endpoint population is described as response-evaluable participants who received therapy, and its actual size is not reported, the enrollment figure alone cannot establish the precision of the endpoint estimate.

How should planning illustrations be understood?

The record describes planning illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, such illustrations use a total event count, while other outcomes use participants per arm. These are planning assumptions, not a description of the actual single-group trial design. The registry does not report the trial’s own sample-size justification or the effect values used in any specific illustration.

General statistical explanation: a sample-size calculation asks how much information a hypothetical design might need to detect an effect under stated assumptions. A planning illustration based on an observed effect is not observed power and does not show that the completed trial had a particular probability of detecting an effect. Its relevance depends on the assumed effect, variability, allocation, endpoint, and analysis method. In this case, no numerical illustration values or underlying observed primary effect are reported in the registry record, so they cannot be interpreted as trial findings.

What analysis details are unavailable?

The registry record does not report the primary endpoint calculation method, the confidence-interval method, censoring rules, or the handling of participants lacking an evaluable assessment. It also does not report interim analyses, a formal statistical analysis plan, or outcome-specific analysis populations. These omissions matter because analysis choices determine how participant data are converted into an estimate and how uncertainty is quantified. They do not establish that the trial lacked such procedures; their details are not reported in the registry record.

General statistical explanation: for a time-to-event outcome, methods often need rules for when follow-up begins, what counts as an event, and how incomplete follow-up is treated. A fixed-time percentage and a time-to-event estimate are not necessarily calculated in the same way. The registry labels the primary endpoint as 1-year local PFS and gives a percentage measure, but does not supply enough analysis detail to determine the exact calculation approach. Interpretation should therefore remain at the level of the outcome definition and reported design rather than assume a specific estimator.

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("Cetuximab and Stereotactic Radiosurgery")
n      <- c(48)
events <- c(29)
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  Cetuximab and Stereotactic Radiosurgery  48  29  60.4  45.3  74.2  46.3  73.0  46.2  73.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes: the primary 1-year local PFS endpoint and secondary outcomes that include 1-year PFS, overall survival, overall response, changes in tumor glucose metabolism, changes in tumor hypoxia, and quality of life. When several outcomes are examined, general statistical explanation is that the chance of at least one apparently unusual finding can increase if each is tested separately without accounting for the number of tests. A multiplicity strategy may define which outcomes are confirmatory, how tests are ordered, or how error rates are controlled.

A multiplicity plan, hierarchy among outcomes, or adjustment method is not reported in the registry record. The record lists nine outcome measures and zero analysis records, but that does not show which outcomes were analyzed or whether any analyses were performed outside the recorded analysis fields. No claim about adjusted or unadjusted findings can be made from the record.

The primary endpoint population is described as participants who received study therapy and were evaluable for response. The actual evaluable denominator, reasons participants may not have been evaluable, and handling of missing outcome information are not reported in the registry record. The registry also does not report the extent of missing data for the listed secondary outcomes or any imputation, censoring, or sensitivity-analysis methods.

General statistical explanation: missing outcomes can affect both the number contributing to an estimate and the representativeness of the analyzed group. A complete-case estimate may describe those with recorded assessments, while a method that models or imputes missing values relies on additional assumptions. Because the registry record does not specify the approach, the primary endpoint should be understood as pertaining to the stated response-evaluable population, with uncertainty about its size and the treatment of non-evaluable participants.

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: dysphagia (2.1%), rash (erbiutx) (2.1%), hyperpigmentation (2.1%).

The adverse-event record gives one group, Cetuximab and Stereotactic Radiosurgery. It lists 48 participants at risk for serious adverse events and 3 affected. For other adverse events, it lists 48 at risk and 43 affected. It also records 42 deaths. These are counts in the registry record; they should not be treated as a comparison between treatments because the study has no comparator group.

The most frequent serious terms listed are dysphagia at 2.1%, rash (erbiutx) at 2.1%, and hyperpigmentation at 2.1%. The registry provides these percentages but does not give further event-level detail in the record described, such as timing, duration, severity beyond the serious classification, or treatment attribution. The listed terms and percentages should not be used to infer that the events were caused by the regimen.

The 42 deaths are not accompanied in the registry record by causes, timing, or attribution. The relationship between deaths and the adverse-event counts is not reported. The counts therefore describe recorded safety outcomes but do not establish why events occurred, when they occurred, or whether participants counted in different categories overlap.

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

The registry record establishes that a completed phase 2, single-group study evaluated cetuximab with stereotactic radiosurgery in previously irradiated patients with recurrent squamous cell carcinoma of the head and neck. It specifies 1-year local progression-free survival as the primary endpoint, defines progression using PET-CT interpretation and RECIST v1.0 criteria, and states that the primary population consists of treated participants evaluable for response.

The record does not report the primary endpoint percentage, its 95% confidence interval, or the endpoint denominator. Thus, it does not provide a numerical result from which to describe the observed level of 1-year local PFS or its precision. The listed enrollment of 48 cannot replace those missing outcome details. Results for the listed secondary outcomes are also not reported in the registry record described.

The design does not include a concurrent control group. General statistical explanation: an outcome observed in a single group can characterize that group, but cannot by itself show what would have happened to comparable participants under a different treatment. The record therefore does not support a randomized comparative conclusion. This design limitation remains distinct from the question of whether the regimen was feasible or what outcomes may have been observed; those questions require results and analysis details not reported in the registry record.

The adverse-event figures document counts for serious events, other events, and deaths, along with three serious-event terms and their listed percentages. Without timing, attribution, causes, or comparison data, these counts cannot establish causal safety effects or permit a comparative safety estimate.

In short, the record describes the question, population, treatment group, endpoint definition, and some safety counts. It does not report enough outcome information to quantify the primary result or determine its statistical precision. Any interpretation should distinguish the trial’s descriptive single-group design from a controlled estimate and avoid treating planning assumptions as observed trial results.

14. Why This Trial Matters Statistically

This trial illustrates why design and outcome reporting must be read together. A specific clinical endpoint is defined—1-year local progression-free survival—and its assessment criteria are described, including the PET-CT interpretation and RECIST v1.0 progression rule. Yet the numerical endpoint estimate and confidence interval are not reported in the registry record. Statistical interpretation depends not only on naming an endpoint but also on having its result, denominator, and uncertainty available.

The distinction between enrollment and analysis population is also important. The record lists enrollment of 48, but defines the primary population as treated participants evaluable for response. Without the evaluable count, readers cannot tell how many participants contributed to the primary estimate. This is especially relevant for a percentage endpoint, whose denominator gives essential context.

The single-group design provides another key statistical lesson. It can describe outcomes within the enrolled treatment group, but it does not supply a concurrent basis for estimating a treatment difference. A planning illustration that assumes two arms is a hypothetical design exercise, not a description of this trial or evidence of observed power. Keeping design assumptions separate from actual outcomes prevents a common interpretive error.

Finally, the record presents safety counts but lacks context on timing, attribution, and causes of death. Statistical reading requires attention to what counts establish and what they leave unresolved. This record is informative about the planned clinical question and the broad design, while its missing primary result and analysis detail constrain conclusions about outcome magnitude and precision.

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 efficacy is that the primary outcome estimate and its 95% confidence interval are not reported in the registry record. The number of participants evaluable for response is also not reported, although that is the stated primary analysis population. As a result, the endpoint cannot be assessed for magnitude, precision, or independent reproducibility from the registry record.

The single-group design has no concurrent comparator, so it cannot provide a randomized estimate of a difference between this regimen and another approach. The record lists no masking. It also describes response assessment based on subjective interpretation of the first PET-CT; assessor procedures, independent review, and disagreement handling are not reported in the registry record.

Important analysis details are unavailable, including the precise method for calculating the primary percentage and confidence interval, event and censoring rules, handling of non-evaluable participants, and missing-data methods. A trial-specific sample-size justification, interim-analysis details, and a statistical analysis plan are not reported in the registry record. The planning assumptions described for illustrations should not be mistaken for the trial’s own design justification.

The record names several secondary outcomes, but their numerical results and analysis details are not reported. It also does not report a multiplicity strategy. For safety, counts are listed, but the record does not give event timing, treatment attribution, death causes, or detail on overlap between categories. These limitations restrict both efficacy and safety interpretation without implying that unreported procedures or results did not exist outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck — NCT01104922.
• Registry record last updated 2022-02-14; status last verified 2022-02.
• Results first posted 2022-02-14.
• 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

The registry record describes a completed phase 2, single-group study of cetuximab with stereotactic radiosurgery in patients with recurrent squamous cell carcinoma of the head and neck after prior irradiation. Enrollment is listed as 48; the study started on 2007-12-26 and reached primary completion on 2014-05-21.

The primary endpoint is 1-year local progression-free survival among participants who received study therapy and were evaluable for response. Progression is defined using PET-CT interpretation and RECIST v1.0 criteria. The primary estimate and 95% confidence interval are not reported in the registry record. The record also lists secondary survival, response, tumor metabolism, tumor hypoxia, and quality-of-life outcomes without reporting their results in the record described.

Safety entries list 3 participants with serious adverse events, 43 with other adverse events, and 42 deaths, among 48 at risk in each adverse-event category. The design has no comparator group, and outcome analysis details are limited in the registry record.