Study of Palliative Radiation Therapy vs. no Palliative Radiation Therapy for Patients With High Risk Bone Metastases That Are Not Causing Significant Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Palliative Radiation Therapy vs. no Palliative Radiation Therapy for Patients With High Risk Bone Metastases That Are Not Causing Significant Pain (NCT03523351), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Skeletal Related Events (SREs).

2. Clinical Question

The trial addresses whether offering selective radiation upfront changes the occurrence of clinically consequential skeletal events compared with standard care in this population. The endpoint combines events that can arise from bone metastases with treatment-related actions, including palliative radiation and orthopedic surgery to bone. This makes the endpoint a measure of the overall occurrence of the defined events, rather than a measure of pain alone or tumor response.

The registry record identifies this as a randomized comparison, but does not report a result for the primary endpoint or an estimated difference between groups. It therefore does not establish whether the groups differed in skeletal-related events, nor how precisely such a difference was estimated.

3. Trial Design

This was a randomized, parallel-group trial with no masking. The registry lists Phase 1 and Phase 2 and reports enrollment of 78. Memorial Sloan Kettering Cancer Center is identified as the sponsor. The record gives a study start date of 2018-05-01, primary completion date of 2024-04-18, and status of completed.

The two arms were standard of care and selective radiation to up to five highest-risk bone metastases. In the standard-of-care arm, treatment was determined by the treating oncologist; patients could continue their existing therapy or transition to another standard-of-care therapy. In the other arm, selective radiation was directed to the highest-risk bone metastases. The registry description includes risk criteria such as bulky osseous disease and disease involving specified bones or joints, but the arm description is incomplete in the registry record. Further selection details are therefore not reported in the registry record.

Systemic therapy and radiation therapy are listed among the interventions. The record does not give a uniform systemic regimen or describe how therapies were selected beyond the information in the arm descriptions. Because masking was none, participants and clinicians were not blinded to the assigned strategy, according to the registry design information.

Random assignment is intended to make treatment groups comparable at the start of a trial, on average, though it cannot ensure that every measured or unmeasured characteristic is balanced in a particular trial. A parallel design means participants are assigned to a group and followed under that group’s strategy. The registry record does not report additional design details such as stratification factors, allocation concealment, or the planned analysis population.

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 Number of Participants With Skeletal Related Events (SREs), measured over 1 year.

The primary endpoint is the number of participants with skeletal-related events over one year. The registry defines these events as pathological fractures, spinal cord compression, or palliative radiotherapy and orthopedic surgery to bone. The endpoint is recorded as a number of participants, so its intended interpretation is a count of people meeting the event definition rather than a count of every event occurrence.

Such an endpoint is used to capture important consequences of bone metastases and interventions directed at bone. Fracture and spinal cord compression are clinical events, while palliative radiotherapy and orthopedic surgery are treatments that may be undertaken in response to disease. Including these treatment events broadens the outcome beyond spontaneous complications alone. The endpoint should therefore be interpreted using its full registry definition, not as a measure of any single component or of pain alone.

The registry record does not report the primary-outcome counts by group, an effect estimate, a confidence interval, or a statistical test. It also does not specify further details about endpoint assessment, such as adjudication procedures. Without the reported group results, the magnitude and precision of the primary comparison cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to treatment strategies by chance. In general, this reduces the risk that treatment choice is systematically linked to factors that also affect outcomes. It does not guarantee identical groups, and it does not eliminate the need to report the analysis, outcome data, and uncertainty. This registry describes a randomized, parallel-group design, but further details about the randomization procedure and allocation concealment are not reported in the registry record.

What kind of endpoint is reported?

The primary endpoint is a binary participant-level outcome: whether a participant had at least one event meeting the skeletal-related-event definition during the one-year timeframe. The registry describes the measure as the number of participants with an event. In general, a binary outcome can be compared by reporting the number of participants with the event in each group and an effect measure with its uncertainty. The registry record does not report the primary-outcome group counts or an effect estimate, so no such comparison can be interpreted from the posted primary results.

How should uncertainty be assessed?

In general, a confidence interval expresses statistical uncertainty around an estimated effect. A narrower interval indicates greater precision under the assumptions of the analysis; a wider interval indicates less precision. The interval also helps readers judge which effect sizes remain compatible with the data, rather than forcing interpretation to depend on a threshold for statistical significance. The registry record does not report a confidence interval for the primary endpoint. It also does not report a primary-outcome p-value or a test result.

What is the role of a statistical analysis plan?

A statistical analysis plan ordinarily specifies how outcomes will be analyzed, including the analysis population, model or test, treatment of missing data, and handling of multiple outcomes or analyses. These choices matter because different methods can answer different questions or produce different estimates. The statistical analysis plan is not reported in the registry record. The record does not say whether analyses were adjusted for baseline characteristics, whether the primary analysis followed randomized assignment, or whether interim analyses were planned or performed. None of those details should be inferred from the trial’s randomized design alone.

Why can over-dispersion matter?

In general, over-dispersion describes variability in count data that exceeds what a simple model expects. When present, a model that assumes less variability than the data contain can understate uncertainty and make results appear more precise than warranted. The primary endpoint is a count of participants meeting a binary event definition, not a reported recurrent-event count. The registry record does not describe a model for the primary outcome or provide data that would support an assessment of over-dispersion. This general concept therefore does not supply a missing analysis for this trial.

How should planning calculations be read?

In general, sample-size calculations are planning tools: they describe the size of a study that might be needed under stated assumptions. They do not measure the probability that a completed study found a true effect, and they are not a substitute for observed results. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such planning illustrations should not be mistaken for observed power. In this record, the primary-outcome comparison and observed effect are not reported, so readers cannot assess a primary-outcome planning illustration against a reported effect estimate.

In general, sample-size requirements depend on the outcome, the effect considered important, variability, allocation, and the chosen error rates. Planning calculations rely on assumptions and are sensitive to them. They do not repair missing outcome data and do not establish what the trial found. The registry record does not report a protocol-based sample-size justification or enough primary-outcome results to evaluate one.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity procedure, such as an adjustment for testing multiple outcomes or comparisons. It also does not report a statistical analysis plan specifying which analyses were considered confirmatory. The record lists one primary outcome measure, but the available outcome information indicates that it has multiple categories or time points and is not reduced to a single comparison. This means that a single primary treatment contrast cannot be reconstructed from the posted results.

Missing-data methods and the number of participants with unavailable primary-outcome measurements are not reported in the registry record. The analysis population is also not reported: readers cannot determine from this record whether the analysis used all randomized participants, participants who received the assigned strategy, or another defined group. The record does not say how participants with incomplete follow-up or uncertain endpoint status were handled.

These omissions matter because the results can depend on how outcomes are defined, which participants are included, and how missing observations are treated. In general, clear reporting of these choices allows readers to judge whether the analysis preserves the intended randomized comparison and whether alternative reasonable approaches might change conclusions. Without those details and the primary-outcome results, the registry record does not support an assessment of multiplicity, missing-data impact, or the analysis population used for the main comparison.

11. 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: back pain (2.6%), anemia (2.6%), dysphagia (2.6%), esophageal varices (2.6%), gastritis (2.6%).

The registry lists serious adverse events for 4 participants among 39 at risk in the standard-of-care group and 2 participants among 39 at risk in the selective-radiation group. Other adverse events are listed for 34 and 35 participants, respectively, with 39 at risk in each group. Deaths are listed as 28 in the standard-of-care group and 19 in the selective-radiation group. These are descriptive counts; they do not show whether events were caused by study treatment.

The registry lists back pain, anemia, dysphagia, esophageal varices, gastritis, and esophagitis among serious adverse-event terms, each with a reported percentage of 2.6%. The record does not assign these terms to a particular group in the information presented, and does not indicate whether the terms overlap within participants. The percentages should therefore not be combined or treated as group-specific rates.

These figures do not provide event timing, duration, severity grading details, exposure-adjusted rates, or a statistical comparison. In general, safety counts are interpreted in context, including follow-up and treatment exposure. Such context is not reported in the registry record, so the counts should not be treated as a complete comparative safety analysis.

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

The record establishes that the study compared standard care with selective radiation to high-risk bone metastases in a randomized, parallel-group design. It also specifies a primary endpoint focused on participants with skeletal-related events over one year. Those design details clarify the question the trial was intended to address.

However, the primary outcome results are not reported as a single comparison. There are no posted group counts, effect estimate, confidence interval, or statistical test for the primary endpoint in the registry record. Consequently, the available information does not establish whether the strategies differed in skeletal-related events, the direction or size of any difference, or the precision of an estimate. This is not evidence that the groups were equivalent; it is an absence of a reported primary comparison in this record.

The safety entries provide descriptive counts for serious adverse events, other adverse events, and deaths. These figures should not be interpreted as proof of benefit or harm, or as evidence that an event was attributable to radiation or systemic therapy. The listed serious-event terms also do not provide an arm-specific comparison in the record.

In general, a trial’s conclusion depends on more than whether a numerical difference is present. The definition and analysis of the endpoint, uncertainty around the estimate, completeness of follow-up, and relevance of the study population all matter. The registry record does not report enough primary-outcome analysis detail to evaluate these elements. It therefore supports understanding the intended comparison and the posted descriptive safety information, but not a conclusion about the primary treatment effect.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it poses a randomized comparison in a population whose bone metastases were described as asymptomatic or minimally symptomatic. The treatment strategies differ in whether selective radiation is added upfront to standard care, while the primary endpoint captures a set of consequential skeletal events over a defined follow-up timeframe. The endpoint includes both clinical complications and interventions on bone, so its interpretation depends on the full event definition.

The registry record also illustrates why study design and study results must be read separately. Randomization can strengthen a treatment comparison, but readers still need the group outcome data, an effect estimate, and a measure of uncertainty to judge what the trial found. Those primary-outcome results are not reported as a single comparison in this record. Thus the design may be clear while the central statistical conclusion remains unavailable.

The safety information adds context but cannot fill that gap. Counts for serious adverse events, other adverse events, and deaths are descriptive and lack a reported statistical comparison or detail about timing and exposure. They do not establish a causal relationship or answer the primary skeletal-event question.

For clinical researchers and biostatisticians, the record highlights the importance of transparent reporting of endpoint results, analysis populations, missing-data handling, multiplicity decisions, and uncertainty. Without these elements, readers cannot assess the magnitude and precision of the primary contrast or test the robustness of its interpretation. The trial’s statistical importance therefore lies both in the question it set out to examine and in the limits of what its posted results permit readers to conclude.

14. 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 this trial from the registry record is that the primary endpoint is not reported as a single group comparison. The record gives the endpoint definition and timeframe, but not the number of participants with skeletal-related events by arm, an effect estimate, or uncertainty. The registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison; the relevant breakdown is not reported in the registry record.

Further limitations include the absence of a reported statistical analysis plan, analysis population, missing-data approach, multiplicity method, and primary-outcome test. These omissions make it impossible to determine how the primary analysis was specified or carried out, and whether it retained the intended randomized comparison. The record does not report whether endpoint events were independently adjudicated or how event ascertainment was standardized.

The arm description for selective radiation is incomplete in the registry record. Although the strategy is described as radiation to up to five highest-risk bone metastases and some selection criteria are named, the full criteria are not available in the record. The systemic therapy strategy is also not described as a common regimen. No additional treatment or follow-up details should be inferred.

The trial had no masking, according to the registry. This is a design feature that can matter for care decisions and outcome ascertainment, particularly because the endpoint includes treatment actions as well as clinical events. The record does not report procedures that would clarify how such potential influences were addressed.

Finally, the safety counts are not accompanied by event timing, duration, exposure-adjusted rates, or a comparative analysis. The listed serious adverse-event terms are not assigned to arms in the available information. These limitations restrict interpretation of both the primary endpoint and safety findings to the descriptive details recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Palliative Radiation Therapy vs. no Palliative Radiation Therapy for Patients With High Risk Bone Metastases That Are Not Causing Significant Pain — NCT03523351.
• Registry record last updated 2025-04-20; status last verified 2025-04.
• Results first posted 2025-04-20.
• 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.

18. Record Summary

The registry describes NCT03523351 as a completed randomized, unmasked, parallel-group Phase 1/2 trial sponsored by Memorial Sloan Kettering Cancer Center. Enrollment is listed as 78. The study compared standard of care with selective radiation to up to five highest-risk bone metastases in patients with metastatic solid tumors and asymptomatic or minimally symptomatic bone metastases.

The primary endpoint was the number of participants with skeletal-related events over one year, defined to include pathological fractures, spinal cord compression, and palliative radiotherapy or orthopedic surgery to bone. The registry record does not report a single primary-outcome comparison, its effect estimate, or its uncertainty. It lists safety counts and serious adverse-event terms, but these do not replace the missing primary analysis or establish causal effects.

The record does not report the statistical analysis plan, analysis population, missing-data methods, or multiplicity approach. Its posted information supports a description of the trial design and selected safety entries, but does not support a conclusion about the primary treatment effect.