This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Effect of High Doses of Radiation on Bone Structure and Metabolism (NCT02323295), a non-randomized na study. The primary outcome is Change in Bone Mineral Density (Tb. BMD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02323295 |
| Phase | NA |
| Condition | Malignant Bone Tumors |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Patients with malignant bone tumors of the sacrum who received radiation, either as non-surgical treatment or in a pathway that also included tumor surgery. The registry record reports an enrollment of 12.
Intervention
Radiation is the central treatment exposure. The record describes a non-surgical radiation-only pathway and a surgical pathway involving radiation and malignant tumor surgery.
Comparator
The treatment pathways are non-randomized. They are not a like-for-like control comparison, and the record does not describe a separate untreated or randomized control group.
Primary question
How does trabecular bone mineral density change after treatment, measured from baseline to 3 months in the non-surgical arm and from baseline to 9 weeks in the surgical arm?
The study is intended to characterize changes in bone after high-energy radiation, including bone density and structure, and changes in blood markers related to bone metabolism. The registry’s stated motivation includes understanding radiation-associated bone changes and sacral fractures. That motivation is not itself an outcome finding: the record does not report a fracture comparison or the results for bone density or the listed blood markers.
The primary outcome is trabecular bone mineral density, measured with volumetric quantitative computed tomography. The timing differs by treatment pathway, and the two pathways also differ in whether surgery is part of treatment. Consequently, a difference between their observed changes could not be attributed to radiation alone from this design. The record describes a pilot study, not a randomized comparison intended to isolate the effect of a single treatment component.
3. Trial Design
The registry record identifies NCT02323295 as a completed pilot study sponsored by Massachusetts General Hospital. Its title concerns high doses of radiation and bone structure and metabolism in patients treated with radiation and surgery for sacral tumors. The listed phase is NA. The record gives a start date of 2015-07 and a primary completion date of 2019-07.
The design fields describe a non-randomized allocation, no masking, and a single-group model. The record also describes two treatment pathways: non-surgical radiation only, and malignant tumor surgery with radiation. Thus, although treatment groups are described, assignment was not randomized and the pathways should not be read as exchangeable treatment arms. Differences in patient characteristics, tumor histology, treatment selection, or other factors could contribute to differences between them; the registry record does not report enough information to assess those factors.
In the non-surgical pathway, radiation dose is described as depending on histology. In the surgical pathway, the record describes pre-operative radiation followed by a recovery period and surgery to remove the sacral tumor. It also describes a subsequent recovery period. The registry does not report comparative treatment assignment or a protocol for making patients eligible for one pathway rather than the other.
The primary outcome is a change in trabecular bone mineral density. Its assessment schedule is baseline and 3 months for the non-surgical arm, and baseline and 9 weeks for the surgical arm. Subjects 4 and 9 are identified as belonging to the non-surgical radiation group; the remaining subjects are assigned to the surgery-and-radiation column. The registry record reports 14 outcome measures, including bone and blood measures, but reports zero analyses. Statistical analysis methods, eligibility details, and an analysis population definition 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.
Overall Study
| Stage | Non Surgical-Radiation Only | Malignant Tumor Surgery And Radiation |
|---|---|---|
| STARTED | 2 | 10 |
| COMPLETED | 2 | 7 |
| NOT COMPLETED | 0 | 3 |
Reasons for not completing this period:
| Reason | Non Surgical-Radiation Only | Malignant Tumor Surgery And Radiation |
|---|---|---|
| Adverse Event | 0 | 1 |
| Withdrawal by Subject | 0 | 1 |
| Patient did not have surgery as planned. | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Subjects 4 and 9 are in the non-surgical radiation group and only have values for that column. The rest of the subjects are in the malignant tumor surgery and radiation and only have values in that column.
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.
| Characteristic | Unit | Non Surgical-Radiation Only | Malignant Tumor Surgery And Radiation | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 10 | 12 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 9 | 10 |
| Age, Categorical: >=65 years | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Female | Participants | 1 | 2 | 3 |
| Sex: Female, Male: Male | Participants | 1 | 8 | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 | 10 | 12 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 1 | 10 | 11 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Bone Mineral Density (Tb. BMD), measured over Non-surgical arm: baseline, 3 months Surgical arm: baseline, 9 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg/cm^3 |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is change in trabecular bone mineral density, expressed in mg/cm^3. It is measured using volumetric quantitative computed tomography of L1, L2, and the vertebrae adjacent to the tumor. The outcome focuses on trabecular bone, the inner, lattice-like part of bone, rather than describing bone density as a single undifferentiated measure.
Bone mineral density is used as a quantitative measure of bone status. A change over time can describe whether the measured density is different at a follow-up assessment than at baseline. The registry record’s stated interest in bone structure and radiation-related bone changes makes this measure relevant to the study’s aim. In general, a measurement can help characterize a biological response without establishing what caused it or whether it predicts a clinical event.
The assessment schedule is not the same in the two treatment pathways: baseline to 3 months for the non-surgical arm and baseline to 9 weeks for the surgical arm. These are not identical follow-up intervals. Interpretation therefore needs to keep the pathway and timing attached to each measurement rather than treating the observations as a common-time comparison.
The registry record gives the endpoint definition but does not report the observed baseline values, follow-up values, change estimates, variability, confidence intervals, or statistical tests. It also does not report the results for bone mineral density in the registry record. Accordingly, the endpoint’s measurement method and purpose can be described, but the magnitude and precision of any observed change cannot be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s subject, treatment pathways, assessment schedule, and intended bone-density measure. It does not provide numerical results for the primary outcome. There is therefore no reported estimate of change in trabecular bone mineral density to interpret, and no reported confidence interval or test result to describe its precision or statistical compatibility with different values.
The primary comparison is within each pathway over time: baseline to 3 months for non-surgical radiation, and baseline to 9 weeks for surgery and radiation. Because the follow-up intervals differ and the pathways involve different treatment components, these observations do not constitute a direct randomized comparison of radiation versus no radiation, or surgery versus no surgery. The record explicitly identifies the allocation as non-randomized and notes that the arms are not a like-for-like control comparison. Any between-pathway contrast would be vulnerable to differences in who received each treatment pathway.
The enrollment is 12, but the primary outcome description indicates that only subjects 4 and 9 are in the non-surgical group and that the remaining subjects are in the surgical group. This distribution makes the non-surgical measurements especially limited as a basis for broad conclusions. The registry record does not explain whether all enrolled participants contributed measurements at each assessment, how missing measurements were handled, or whether any analysis adjusted for differences between patients.
The record lists secondary measures of bone turnover and metabolism, including NTX, TRAP5b, osteocalcin, P1NP, phosphate, vitamin D, mineral apposition rate, and bone formation rate. It also reports 14 outcome measures overall, but no analyses. The existence of listed outcomes is not evidence that their results were measured, analyzed, or reported. Their numerical findings are not reported in the registry record.
General statistical interpretation: an estimate describes the observed size and direction of a change, while a confidence interval describes the range of values reasonably compatible with the data under the analysis assumptions. Neither is reported for the primary outcome. Without an estimate and its uncertainty, the registry record cannot establish whether the observed change was small or large, precise or imprecise. A p-value is also not reported, so statistical significance cannot be assessed.
General causal interpretation: in a non-randomized study, treatment pathways may differ for reasons that also relate to the outcome. A change from baseline can document a temporal pattern, but by itself it does not separate treatment effects from natural change, patient characteristics, tumor-related factors, surgery, or other influences. The registry record does not report a design or analysis that resolves those alternatives.
The record’s safety counts are descriptive. They report serious adverse events in the surgery-and-radiation group and none in the non-surgical radiation-only group, with no deaths reported in either group. The group sizes and treatment selection differ, and the study is a pilot; these counts do not support a reliable comparative safety estimate. The registry record does not report a formal safety comparison.
9. Statistical Methods Explained
What does the primary outcome measure?
The primary outcome is change in trabecular bone mineral density, in mg/cm^3, assessed by volumetric quantitative computed tomography. The scan sites are L1, L2, and vertebrae adjacent to the tumor. The registry describes baseline and follow-up assessments, with baseline to 3 months for the non-surgical group and baseline to 9 weeks for the surgery-and-radiation group.
General statistical explanation: a change score represents a follow-up measurement relative to a baseline measurement for the same participant. It can be useful when the scientific question concerns change over time. Its interpretation depends on how the change is defined, how measurements are paired, and whether all relevant observations are available. The registry record does not report the exact change-score calculation or the participant-level data.
What does non-randomized allocation imply?
The registry identifies the study as non-randomized and states that the arms are not a like-for-like control comparison. General statistical explanation: random assignment is one way to make treatment groups comparable on average with respect to measured and unmeasured baseline characteristics. Without random assignment, treatment choice can be related to clinical features that also affect outcomes. A difference between groups can therefore reflect treatment, selection, or both.
Here, the pathways differ in whether surgery is included, and the record says radiation dose in the non-surgical group depends on histology. The primary assessment times also differ. These design features mean that a simple group contrast would combine treatment-pathway differences with timing and patient-selection differences. No adjusted comparative analysis is reported in the registry record.
How should uncertainty be understood?
General statistical explanation: an estimate summarizes the observed data, while a confidence interval conveys the uncertainty associated with that estimate under a specified statistical model. A wide interval indicates that the data are compatible with a broad range of effects; a narrow interval indicates greater precision under the same assumptions. A confidence interval is not reported for the primary outcome in the registry record.
Small or uneven groups can make estimates unstable and uncertainty substantial, but the exact precision cannot be determined without reported estimates and variability. No standard deviations, standard errors, confidence intervals, or primary-outcome tests are reported. It would not be appropriate to infer an effect size or precision from the study’s enrollment alone.
What do the planning assumptions describe?
The sample-size assumptions describe a planning illustration based on the observed effect, rather than the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event calculations, the assumptions refer to the total number of events using Schoenfeld; other calculations refer to participants per arm.
General statistical explanation: a planning calculation estimates how much information a future study might need under chosen assumptions. Changing the target effect or assumptions changes the calculated requirement. Such a calculation is not evidence that the current study had a particular probability of detecting an effect. It is not observed power, and it does not replace an analysis of the trial data. The registry record does not report the trial’s own sample-size justification, and no numerical planning result is reported in the record details.
What can be inferred from the analysis record?
The registry reports 14 outcome measures and zero analyses. That distinction matters: listing an outcome identifies what was intended to be assessed, while an analysis would describe how data were evaluated and report resulting estimates or tests. The record does not report the statistical model, adjustment variables, handling of repeated measurements, or a method for comparing pathways.
General statistical explanation: with repeated measurements, an analysis may need to account for the fact that observations from the same participant are related. The appropriate method depends on the data structure and study question. The registry record does not identify whether a paired analysis, longitudinal model, or another approach was used, so none can be attributed to this study.
The record also does not report a multiplicity procedure. General statistical explanation: when many outcomes or tests are considered, the chance of at least one apparently unusual result can increase if each is interpreted independently. A prespecified hierarchy or adjustment can address some multiplicity concerns, but the registry record does not describe such a strategy. Because analyses and results are not reported, there is no basis for judging how multiplicity affected any finding.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 14 outcome measures, including the primary bone mineral density outcome and several secondary measures of bone turnover, bone formation, and mineral metabolism. It reports zero analyses. The multiplicity strategy, if any, is not reported in the registry record. There is no reported hierarchy of outcomes, adjustment method, or distinction between confirmatory and exploratory analyses.
General statistical explanation: interpreting many outcomes separately can increase the chance that at least one result appears notable by chance. A multiplicity approach can define how evidence is evaluated across outcomes, but its relevance depends on the planned analyses and scientific aims. With no analyses or results reported, it is not possible to determine whether multiplicity was addressed or how it might affect interpretation.
Missing-data handling is not reported in the registry record. The record does not state whether all participants contributed the primary outcome at baseline and follow-up, how unavailable scans or blood measures were treated, or whether any imputation or sensitivity analysis was used. The primary outcome description assigns subjects 4 and 9 to the non-surgical group and the remaining subjects to the surgery-and-radiation group, but does not describe completeness of measurements.
Analysis populations are also not reported in the registry record. It does not define an intention-to-treat, per-protocol, or other analysis set, nor explain exclusions from any outcome analysis. Without these details, readers cannot determine who was included in an analysis or assess the consequences of missing observations and exclusions.
The statistical analysis plan, model specifications, and rules for handling multiple assessments are not reported in the registry record. These omissions limit reproducibility and prevent assessment of whether analyses followed prespecified methods.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Non Surgical-Radiation Only | 0 | 2 | 0.0% |
| Malignant Tumor Surgery And Radiation | 1 | 10 | 10.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Non Surgical-Radiation Only | 0 of 2 |
| Malignant Tumor Surgery And Radiation | 0 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Non Surgical-Radiation Only | 0 of 2 |
| Malignant Tumor Surgery And Radiation | 0 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Non Surgical-Radiation Only | Malignant Tumor Surgery And Radiation |
|---|---|---|---|
| Allergic reaction | General disorders | 0 of 2 | 1 of 10 |
Serious events with the highest arm-level rate: allergic reaction (10.0%).
The registry reports serious adverse events for each treatment group. In the non-surgical radiation-only group, 2 participants were at risk, 0 were affected by serious adverse events, 0 were affected by other adverse events, and 0 deaths were reported. In the surgery-and-radiation group, 10 participants were at risk, 1 was affected by a serious adverse event, 0 were affected by other adverse events, and 0 deaths were reported.
The registry lists allergic reaction at 10.0% among the top serious terms. It does not provide a group attribution for that term in the information recorded here, so it should not be assigned to a particular treatment pathway on that basis alone.
These are descriptive counts from a small, non-randomized pilot study. The group sizes differ, the treatment pathways are not like-for-like controls, and the record does not report a formal comparison or uncertainty interval for safety outcomes. A count of zero in a group does not demonstrate that an event cannot occur, and the single serious-event-affected participant in the surgical pathway does not by itself establish a comparative risk. The registry record does not report additional details needed to characterize event timing, severity beyond the serious classification, or causal attribution.
12. What the Result Does, and Does Not, Mean
The registry record documents a pilot study designed to examine bone density, bone structure, and bone-metabolism measures in patients receiving radiation for sacral tumors, with a surgery-and-radiation pathway and a non-surgical radiation pathway. It specifies the primary bone-density measurement and its assessment schedule. It does not report the primary outcome values or analyses, so the direction, magnitude, and precision of any change cannot be established from the record.
The study does not provide a randomized treatment comparison. The groups are defined by different treatment pathways, allocation is non-randomized, and the primary assessment intervals differ. As a result, the record cannot isolate the effect of radiation from surgery, patient selection, tumor characteristics, or other factors. A within-group change over time, even if reported, would not alone establish that treatment caused that change.
The study’s stated motivation includes understanding radiation-related changes and the risk of sacral fractures. The primary outcome is bone mineral density, not a reported fracture endpoint. The registry record does not report fracture results, nor does it report results for the secondary bone and blood measures. It is therefore not possible to assess whether the study found a relationship between bone density, biochemical markers, and fractures.
The safety data describe serious and other adverse events in the registry’s treatment groups and report no deaths. They do not establish comparative safety because the pathways are non-randomized, the group sizes differ, and no comparative analysis is reported.
Overall, the record supports a description of the study’s aims, design, measurement approach, and recorded safety counts. It does not support a conclusion about the size or certainty of a bone-density change, a causal treatment effect, or the relative safety of the pathways. Those conclusions would require outcome estimates, uncertainty measures, and analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable because it asks a measurement-focused question in a setting where treatment pathways are clinically distinct. The primary outcome is a quantitative imaging measure of trabecular bone density, assessed at baseline and follow-up. The registry also lists biochemical and bone-formation measures, reflecting an interest in several aspects of bone metabolism rather than a single clinical endpoint.
The design features matter for interpreting such measurements. The registry describes non-randomized allocation, no masking, and a single-group model, while also specifying non-surgical and surgery-and-radiation pathways. Those pathways are not interchangeable controls. The treatment context and the different follow-up schedules limit the meaning of direct group contrasts, especially when the purpose is to attribute change specifically to radiation.
Precision is also central. The registry reports enrollment of 12 and identifies only subjects 4 and 9 as belonging to the non-surgical radiation group for the primary outcome. Yet it does not report outcome estimates, variability, confidence intervals, or analyses. Thus, a reader cannot judge the stability or precision of the primary result from the registry record.
The record’s planning assumptions illustrate another important distinction: planning calculations based on an observed effect are not the same as a trial’s original design justification, and they are not observed power. The record does not report a trial-specific sample-size justification. Statistical transparency would require reported estimates, uncertainty, analysis methods, missing-data handling, and the population included in each analysis.
The study’s statistical importance lies in the questions it raises about measuring radiation-associated bone changes and interpreting longitudinal data across treatment pathways. The available registry record describes those questions and methods, but does not report results that would answer them.
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 main trial-specific limitation is the non-randomized design. Treatment pathways may differ in patient or tumor characteristics, and the registry record does not report information sufficient to assess or adjust for those differences. The record also explicitly cautions that the arms are not a like-for-like control comparison. This limits causal interpretation of any contrast between pathways.
The primary outcome is assessed at different follow-up times: baseline to 3 months in the non-surgical group and baseline to 9 weeks in the surgical group. These schedules do not support an unqualified comparison at a shared follow-up time. The surgery-and-radiation pathway also includes a treatment component absent from the non-surgical pathway, so pathway differences cannot be attributed to radiation alone.
The registry reports enrollment of 12 and identifies subjects 4 and 9 as members of the non-surgical group for the primary outcome. The record does not report how many participants contributed complete primary measurements, whether all planned assessments occurred, or how missing observations were handled. The limited non-surgical observations restrict how broadly that pathway’s measurements can be interpreted.
The primary outcome results and statistical analyses are not reported in the registry record. Neither estimates nor uncertainty measures are available, and the record does not specify the statistical model, covariate adjustment, analysis population, or multiplicity handling. Although 14 outcome measures are listed, the registry reports zero analyses.
The adverse-event information is also limited to descriptive counts and a listed serious term. The record does not report a formal comparison or enough detail to assess differences in event timing or attribution. These limitations mean that the registry record is informative about study intent and structure, but not sufficient to evaluate the magnitude, precision, or cause of outcome changes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of High Doses of Radiation on Bone Structure and Metabolism — NCT02323295.
- Registry record last updated 2021-12-07; status last verified 2021-11.
- Results first posted 2021-12-07.
- 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.
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18. Record Summary
NCT02323295 is a completed pilot study sponsored by Massachusetts General Hospital, with an enrollment of 12 and a listed phase of NA. The registry describes a non-randomized, unmasked study with a single-group model and non-surgical radiation-only and surgery-and-radiation pathways.
The primary outcome is change in trabecular bone mineral density measured by volumetric quantitative computed tomography at L1, L2, and vertebrae adjacent to the tumor. Follow-up is baseline to 3 months for the non-surgical arm and baseline to 9 weeks for the surgical arm. The registry lists 14 outcome measures and reports zero analyses.
Outcome estimates, uncertainty measures, statistical methods, missing-data procedures, and analysis populations are not reported in the registry record. Safety counts include one participant affected by a serious adverse event in the surgery-and-radiation group, none in the non-surgical group, and no deaths in either group. The non-randomized pathways are not a like-for-like control comparison.