Radiation Therapy to Treat Musculoskeletal Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Radiation Therapy to Treat Musculoskeletal Tumors (NCT00186992), a na phase 2 study. The primary outcome is Cumulative Incidence of Local Failures at 5 Years in Patients With Image Guided Radiation Therapy.

2. Clinical Question

3. Trial Design

This was a Phase II prospective evaluation of image-guided radiotherapy for musculoskeletal tumors, sponsored by St. Jude Children’s Research Hospital. The registry identifies the study model as single-group, with allocation listed as not applicable and masking listed as none. It therefore does not provide a randomized, masked treatment comparison. The design is suited to describing outcomes among treated patients, but the record does not establish how those outcomes would compare with outcomes under another treatment or without the intervention.

The registry reports enrollment of 202 patients. Its primary endpoint population description says 199 patients were treated with radiation therapy and three were off study before radiation therapy. Eligible patients were to be entered at the time of irradiation, undergo a pre-radiotherapy evaluation and treatment planning, receive image-guided radiotherapy, and have evaluations during and after irradiation. These procedures describe the planned sequence of study activities; they do not establish how complete each assessment was.

The intervention is identified as image-guided radiotherapy. The study summary describes the use of computed tomography, magnetic resonance imaging, and positron emission tomography images to locate the tumor and plan radiation delivery. The stated goal was to improve local control while minimizing radiation-related side effects. That goal is the study rationale and should not be read as a finding that either aim was achieved.

The listed primary endpoint is cumulative incidence of local failures at five years after completion of therapy. The registry also names secondary outcomes involving bone growth and length, bone density, muscle development and function, organ-specific toxicities, muscle function over time, and imaging parameters. The record lists five outcome measures, but no analyses are reported. Details of the statistical analysis plan, including the methods used for the primary endpoint, are not reported in the registry record.

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.

Before assignment: A total of 202 patients were enrolled in the study. Of 202 patients, 167 patients completed the study requirements, progression, death, and secondary malignancy, 9 patients still are in follow-up, and 26 patients were off study early due to parent or patient request, PI discretion, physician's discretion, Ineligible, and not returning to St. Jude. Completed ACT trial.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of 202 patients enrolled in the study, 199 patients were treated with radiation therapy. Three patients were off study before radiation therapy. Cumulative incidence of local failure is calculated from completion of RT to dates of local failure, distant failure (metastatic), the secondary malignancy, death, or off study (last contact) while distant failure (metastatic), the secondary malignancy, and death are considered as competing risks.

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 Cumulative Incidence of Local Failures at 5 Years in Patients With Image Guided Radiation Therapy, measured over 5-years follow-up after completion of therapy..

The primary endpoint is the cumulative incidence of local failures at five years after completion of therapy. It is reported as a percentage of patients, with a 95% confidence interval specified as the measure of uncertainty. The registry says that local-failure incidence is used to report control of local failures in patients with primary musculoskeletal tumors treated with image-guided radiation therapy.

General statistical explanation: cumulative incidence describes the probability of experiencing a particular event over time while accounting for the possibility that another event can occur first and prevent the event of interest from being observed in the same way. The endpoint description says that the calculation runs from completion of radiation therapy to dates of local failure, distant failure, or secondary malignancy. The precise estimator and rules for handling these events are not reported in the registry record, so the specific implementation cannot be verified from the record.

The percentage provides an interpretable summary of local failures over the stated follow-up horizon. The confidence interval is intended to express uncertainty around that estimate: a narrower interval would indicate greater precision, while a wider interval would indicate less precision. Neither the five-year estimate nor its interval is reported in the registry record. The endpoint definition alone therefore gives no numerical evidence about the frequency of local failure or the precision of its estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record names a percentage endpoint and a 95% confidence interval, but it does not report the numerical estimate or identify the statistical procedure used to obtain it. General explanations below clarify what these statistical terms mean without attributing unreported procedures to this study.

What does a cumulative-incidence endpoint represent?

General statistical explanation: cumulative incidence describes the probability of an event of interest occurring by a specified time, with competing events taken into account. In this study, the event of interest is local failure and the stated time horizon is five years after completion of therapy. The endpoint description identifies distant failure and secondary malignancy among the event dates relevant to the calculation. A competing event is not simply a missing observation: it can change whether a later event of interest can occur or be observed.

Different statistical procedures can estimate cumulative incidence, and their assumptions and handling of competing events differ. The registry record does not identify the estimator, the precise event coding, or how censoring was handled. It is therefore not possible to confirm from the record whether a particular competing-risk procedure was used, or whether the stated endpoint was calculated in a way that fully accounts for the listed events.

What does the confidence interval communicate?

General statistical explanation: a confidence interval gives a range of values compatible with the observed data under the method’s assumptions. It communicates precision as well as the central estimate. A comparatively narrow interval indicates greater precision; a comparatively wide interval indicates greater uncertainty. The interval does not guarantee that the true value lies within its particular endpoints, and it does not address every source of bias, such as incomplete follow-up or limitations of a single-group design.

The registry specifies a 95% confidence interval for the primary endpoint but does not report its endpoints or the estimate. As a result, neither the size of the estimated cumulative incidence nor its statistical precision can be evaluated. The confidence level alone is not evidence that the outcome estimate is precise, unbiased, or clinically important.

Why does the single-group design matter?

General statistical explanation: a single-group study can describe outcomes in the people who receive the intervention. Without a comparison group, it cannot directly estimate how those same patients would have fared under a different treatment. Differences between groups are especially difficult to interpret causally when there is no randomized allocation, because characteristics associated with treatment and prognosis may also influence outcomes.

The registry identifies this study as single-group, with allocation not applicable and no masking. These design features do not invalidate descriptive outcome measurement, but they constrain comparative interpretation. Even if an outcome estimate were available, attributing it to the intervention would require caution and information beyond the single-group estimate. A comparative effect estimate is not reported in the registry record.

What can the sample-size illustrations say?

The sample-size calculations accompanying the statistical material are described as planning illustrations based on the observed effect, rather than as the trial’s original design. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The calculations describe participants per arm for 80% power or another stated power level, according to the relevant illustration. They are not observed power and do not show that this single-group study was designed or conducted with those two arms.

General statistical explanation: a planning calculation asks how much information might be needed to detect a specified effect under stated assumptions. The resulting sample size depends on the target effect and the statistical model. An effect smaller than the assumed effect generally requires more information to distinguish it from random variation. These calculations do not demonstrate that an effect exists, nor do they repair the lack of a randomized comparator. The numerical planning results are not because they are not part of the registry entries described for this analysis.

How should event percentages and counts be read?

The adverse-event record distinguishes participants at risk from participants affected. General statistical explanation: a count of affected participants describes how many people had an event under the registry’s reporting rules; it is not necessarily the total number of individual event episodes. Participants may have more than one event, and categories can overlap unless the reporting rules say otherwise. The registry record does not specify whether the serious and other adverse-event groups are mutually exclusive, nor does it give the detailed rules used to attribute events to treatment.

The serious-event terms include percentages, but the record does not provide a complete account of the event-level data, timing, duration, or attribution. These percentages should therefore be read as the reported proportions for the named terms, not as comparative risk estimates. Without a control group and further event definitions, they cannot establish whether treatment changed the risk of those events.

What analysis details remain unknown?

The registry record does not report the primary endpoint estimator, the analysis population actually used, a missing-data procedure, a prespecified statistical analysis plan, or details of interim analyses. The record lists five outcome measures and zero analyses. That listing does not reveal whether analyses were planned but not posted, whether results were unavailable, or whether outcomes were not analyzed. Those possibilities cannot be resolved from the registry record. The endpoint definition and enrollment information alone are not enough to reconstruct the analysis.

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("Treatment")
n      <- c(199)
events <- c(27)
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  Treatment  199  27  13.6  9.1  19.1  9.5  19.0  9.5  19.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including the primary local-failure endpoint and secondary outcomes involving bone growth and length, bone density, muscle development and function, organ-specific toxicities, muscle function over time, and imaging parameters. The record does not report how many statistical comparisons were planned, whether outcomes were tested at multiple time points, or whether any adjustment for multiple testing was used. The number and type of analyses are therefore not reported in the registry record.

General statistical explanation: when many outcomes or comparisons are examined, the chance of finding at least one apparently unusual result by chance can increase. A multiplicity strategy can define which outcome is primary, control the overall error rate, or distinguish confirmatory from exploratory analyses. Without an analysis plan or results, it is not possible to tell whether the registry’s primary endpoint was treated as confirmatory, how secondary findings were interpreted, or whether any adjustment was intended.

The record reports 202 enrolled patients, 199 treated with radiation therapy, and three who left the study before radiation therapy. It does not give the number with complete endpoint follow-up, the number included in the primary analysis, or the number missing at each follow-up time. It also does not describe imputation, censoring rules, sensitivity analyses, or reasons for missing observations. These missing-data and analysis-population details are not reported in the registry record.

The endpoint description refers to follow-up after completion of therapy, and the calculation is described in relation to local failure, distant failure, and secondary malignancy. However, the record does not explain how participants with incomplete follow-up or competing events were handled in the analysis. Enrollment and treatment counts should not be treated as the primary endpoint denominator without confirmation of the actual analysis population.

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: musculoskeletal-other (1.5%), wound-infectious (1.0%), middle ear/hearing (0.5%), hepatic-other (0.5%), chest pain (non-cardiac and non-pleuritic) (0.5%).

The registry reports 199 participants at risk for the adverse-event summaries. It lists 9 participants affected by serious adverse events, 50 affected by other adverse events, and 2 deaths. These are descriptive figures for the treated group; the record does not provide a comparison group or an analysis attributing these events to radiotherapy.

The serious-event terms with the largest listed percentages are musculoskeletal-other at 1.5% and wound-infectious at 1.0%. Middle ear/hearing, hepatic-other, chest pain (non-cardiac and non-pleuritic), and tumor pain (onset or exacerbation of tumor pain due to treatment) are each listed at 0.5%. These are percentages as reported in the registry. The record does not explain whether the categories overlap, how terms were coded, or whether the percentages refer to participants or event episodes beyond the stated adverse-event reporting context.

General statistical explanation: an adverse-event count records events under a study’s reporting definitions; it does not by itself establish that the intervention caused them. Interpretation also depends on timing, severity rules, follow-up completeness, and whether the same events could be counted in more than one category. The relationship of the 2 deaths to treatment is not reported in the registry record. These figures should be read as reported safety observations, not as a comparative estimate of treatment risk.

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

The registry record establishes that a prospective Phase II, single-group study evaluated image-guided radiotherapy for musculoskeletal tumors and defined cumulative incidence of local failure at five years as its primary endpoint. It also reports enrollment and treatment counts and lists safety observations. These details clarify the study question, design, and scope.

The primary endpoint result and 95% confidence interval are not reported in the registry record. Therefore, the posted results do not establish the observed five-year local-failure percentage or the precision of that estimate. The endpoint’s name and intended use cannot substitute for the missing numerical result. No conclusion about the amount of local failure in the treated group can be drawn from the endpoint description alone.

Even if an outcome estimate were available, the design would support a description of outcomes in the treated group, not a direct randomized comparison. The record identifies no comparator arm and no random allocation. It consequently does not provide a basis for concluding that image-guided radiotherapy caused a change in local failure, growth, function, toxicity, or another outcome relative to an alternative.

The study summary states that image guidance was intended to define tumor location and plan treatment while protecting nearby healthy tissues. This describes the rationale for the intervention. It is not evidence that local control improved or that radiation-related side effects were reduced. Similarly, the listed secondary outcome domains show what the study intended to assess, but outcome values and analysis details are not reported in the registry record.

The adverse-event counts and listed terms provide descriptive safety information for the reported group. They do not establish attribution, comparative risk, or the relation between deaths and treatment. The registry record also does not report the completeness of follow-up, the analysis population used for the primary endpoint, or the handling of missing data. These uncertainties limit how far the available record can be interpreted.

14. Why This Trial Matters Statistically

This trial raises a statistical question that is important in studies of tumors treated with radiation: how to describe local failure over a defined follow-up period when other events may occur first. Cumulative incidence is relevant because it focuses on the probability of a particular event over time while recognizing that other events can affect its observation. The registry explicitly identifies local failure as the primary endpoint and mentions distant failure and secondary malignancy in describing the calculation.

The study also illustrates why endpoint definition and endpoint results must be distinguished. The registry gives a five-year time horizon, a percentage unit, and a 95% confidence interval specification. Those details explain what was intended to be estimated and how uncertainty was to be expressed. Without the estimate and interval, however, readers cannot judge the observed outcome or its precision. A well-defined question does not itself supply an answer.

The single-group design is also central to statistical interpretation. It can provide a structured account of outcomes among treated patients, but it does not create a randomized treatment contrast. This distinction prevents descriptive findings from being mistaken for evidence of a causal difference. The registry’s study goals are clinically relevant, but the design information and missing endpoint result constrain what can be concluded from the posted record.

Finally, the record includes both patient-level treatment counts and adverse-event summaries, while leaving important analysis details unstated. Clarifying the analyzed population, follow-up completeness, competing-event methods, and outcome results would be necessary to assess precision and potential bias more fully. These are not technical details separate from interpretation: they determine what population and event experience an estimate can represent.

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 trial is that the registry record does not report the five-year cumulative-incidence estimate or its 95% confidence interval. The stated primary endpoint is therefore identifiable, but its observed magnitude and precision cannot be assessed. The record also reports zero analyses, leaving no posted statistical analysis to evaluate.

The single-group design has no reported comparator and no random allocation. This restricts the study’s ability to support comparative conclusions. Any outcomes in the treated group could reflect the patients’ underlying disease, treatment selection, follow-up, or other factors, as well as the intervention. The registry does not report a method that would permit a causal comparison with another treatment.

The registry gives enrollment and treatment counts but does not identify the actual primary analysis population. It does not state how many participants contributed to the five-year endpoint, how many had complete follow-up, or how missing information was handled. It also does not specify the method for estimating cumulative incidence or the exact handling of distant failure and secondary malignancy. These omissions prevent independent assessment of the endpoint calculation.

The record names several secondary outcome areas but does not report their results, time-specific analyses, or any multiplicity approach. It also does not describe a statistical analysis plan or interim analyses. The safety summaries lack detail about event timing, overlap between categories, attribution, and the relationship of deaths to treatment. These limitations are specific to the information recorded for this study and should be kept in view when interpreting its stated aims and reported counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Radiation Therapy to Treat Musculoskeletal Tumors — NCT00186992.
• Registry record last updated 2026-03-04; status last verified 2026-02.
• Results first posted 2025-03-06.
• 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

NCT00186992 is a Phase II prospective evaluation of image-guided radiotherapy for musculoskeletal tumors, sponsored by St. Jude Children’s Research Hospital. The registry describes a single-group study with no masking and no randomized allocation. Enrollment was 202; 199 participants received radiation therapy, and three were off study before treatment.

The primary endpoint is cumulative incidence of local failures at five years after completion of therapy, expressed as a percentage with a 95% confidence interval. The endpoint result and interval are not reported in the registry record. The record lists secondary outcomes concerning bone, muscle function, organ-specific toxicities, and imaging measures, but reports zero analyses.

For safety, the record lists 9 participants affected by serious adverse events, 50 affected by other adverse events, and 2 deaths among 199 at risk. The relationship of deaths to treatment is not reported in the registry record. The single-group design and absence of a posted primary endpoint result limit comparative and outcome-specific interpretation.