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 Proton Radiation for Chordomas and Chondrosarcomas (NCT01449149), a na na study. The primary outcome is Feasibility of Proton RT for Chordomas and Chondrosarcomas.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01449149 |
| Phase | NA |
| Condition | Chordomas, Chondrosarcomas |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 54 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Abramson Cancer Center at Penn Medicine |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with chordomas or chondrosarcomas. The primary endpoint description specifies tumours of the skull base and spine. The registry record does not report further participant characteristics in the information available for this analysis.
Intervention
Participants received proton therapy. The arm description gives a total dose of 72.00 to 79.2 Gy(RBE) in 40-44 fractions. The study objectives include evaluating feasibility, acute side effects, clinical outcomes, and long-term side effects.
Comparator
There is no comparison group: the design is single-group, with allocation recorded as NA. The results therefore describe people treated in the proton group; they do not estimate a contrast with another treatment or with no treatment.
Primary question
The primary question is whether dose-escalated proton beam therapy can be delivered according to the registry's feasibility and safety criteria. Those criteria refer to dosimetry, treatment completion timing and breaks, and the frequency of grade 3 or higher radiation toxicity. The registry record does not report the numerical primary-endpoint result, so the proportion meeting or not meeting the stated definition cannot be assessed from the posted information.
3. Trial Design
NCT01449149, titled “Proton Radiation for Chordomas and Chondrosarcomas,” is recorded as a completed, single-group study sponsored by Abramson Cancer Center at Penn Medicine. The listed enrollment is 54. The study began in 2010-03, and the primary completion date is 2025-07. Its phase is recorded as NA. Allocation is NA, and masking is listed as none.
The intervention is proton therapy. The arm description states that the proton group received a total dose of 72.00 to 79.2 Gy(RBE) in 40-44 fractions. There is no control arm or randomized treatment assignment described. As a result, the study design can describe treatment delivery and outcomes in the enrolled group, but cannot by itself separate treatment effects from other explanations for observed outcomes or establish how outcomes compare with an alternative.
The stated objectives are to evaluate the feasibility and acute side effects of proton therapy for chordomas and chondrosarcomas, and to evaluate clinical outcomes and long-term side effects. The primary outcome is feasibility, with a timeframe from enrollment to treatment completion or withdrawal, whichever occurred first, assessed up to 133 months. Acute toxicities and late toxicities are listed as secondary outcomes. The registry record lists three outcome measures, but does not provide analysis entries.
Study status and outcome reporting are different kinds of information. A completed status indicates the registry's recorded status; it does not supply a numerical result for the primary endpoint. The available record also does not describe a comparison group, masking procedures beyond none, or a statistical analysis plan. These omissions limit the questions that can be answered from the posted information.
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 | Proton Group |
|---|---|
| STARTED | 54 |
| COMPLETED | 54 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Follow-up
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 | Proton Group |
|---|---|---|
| Participants analysed | 54 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 41 |
| Age, Categorical: >=65 years | Participants | 13 |
| Age, Continuous | years | 54 (23 to 87) |
| Sex: Female, Male: Female | Participants | 32 |
| Sex: Female, Male: Male | Participants | 22 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 54 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 |
| Race (NIH/OMB): White | Participants | 49 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 54 |
| Histology: Chordoma | Participants | 42 |
| Histology: Chondrosarcoma | Participants | 12 |
| Lesion site: Clivus/skull base | Participants | 39 |
| Lesion site: C spine | Participants | 3 |
| Lesion site: T spine | Participants | 0 |
| Lesion site: L spine | Participants | 1 |
| Lesion site: Sacrum/coccyx | Participants | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Feasibility of Proton RT for Chordomas and Chondrosarcomas, measured over From enrollment to treatment completion or withdrawal, whichever occurred first, assessed up to 133 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of patients did not meet this |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled “Feasibility of Proton RT for Chordomas and Chondrosarcomas.” Its purpose is to assess the feasibility and safety of dose-escalated proton beam therapy for chordomas and chondrosarcomas of the skull base and spine. The registry defines feasibility using treatment-delivery and toxicity conditions: at least 10% of patients experiencing either unsatisfactory dosimetry or inability to complete all treatments within 10 days of the estimated completion date while requiring no break greater than 5 days, and no greater than 20% of patients experiencing grade 3 or higher radiation toxicity.
The outcome unit is described as the percentage of patients who did not meet the feasibility definition. This type of endpoint is intended to capture whether treatment can be delivered under specified conditions while keeping severe toxicity within the stated boundary. It combines aspects of technical planning, treatment completion, and safety rather than measuring a single clinical event or time-to-event outcome.
The timeframe begins at enrollment and ends at treatment completion or withdrawal, whichever occurred first, with assessment up to 133 months. The registry record does not report the observed percentage or the underlying count for this primary measure. Consequently, it is not possible to determine from the posted results how many participants met the criteria, how many did not, or how precisely the endpoint was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a single-group study of proton therapy for chordomas and chondrosarcomas, with a listed enrollment of 54. Its central statistical question is whether treatment delivery and toxicity satisfy the prespecified feasibility definition. The definition refers to dosimetry, completion timing and treatment breaks, and grade 3 or higher radiation toxicity. However, a numerical result for this primary endpoint is not reported in the registry record. The main question therefore remains unanswered by the posted numerical results: the proportion meeting or not meeting the feasibility definition cannot be read from the record.
The design also sets limits on interpretation. Because the study is single-group and has no comparator, its outcome data cannot provide a like-for-like estimate of how proton therapy outcomes differ from outcomes with another treatment. Observed events can be described in the treated group, but a causal treatment contrast is not available. The registry identifies no allocation and no masking. This is not a randomized comparison, and the registry itself flags that arms are not a like-for-like control comparison.
Safety reporting gives counts for the proton group. The record lists 15 participants with serious adverse events among 54 at risk, 45 with other adverse events among 54 at risk, and 3 deaths. It also lists serious-event terms with percentages, including fatigue at 7.4%, headache at 5.6%, epistaxis at 5.6%, leukocytosis at 3.7%, skin infection at 3.7%, and sensory neuropathy at 1.9%. These are descriptive safety figures. The record does not give enough detail to interpret them as treatment-caused events, to determine how categories overlap, or to establish the duration of risk for each participant.
Counts and percentages are not interchangeable with evidence of comparative risk. Without a concurrent comparison group and without an endpoint estimate for feasibility, the posted information does not quantify a treatment effect. Nor does the listed enrollment alone establish how precisely clinical outcomes were estimated. Precision would depend on the particular endpoint, its observed data, and its analysis; the primary result and an associated uncertainty interval are not reported in the registry record.
The study status is completed, but that status should not be treated as a substitute for an outcome result. The posted record identifies the planned purpose, intervention, primary-endpoint criteria, and some adverse-event information. It does not report an analysis entry for the primary endpoint or analyses for other clinical outcomes. Conclusions should therefore be confined to the design and descriptive safety figures actually recorded, rather than extending to claims about effectiveness, comparative benefit, or the overall feasibility result.
9. Statistical Methods Explained
What does a single-group design estimate?
In a single-group study, outcomes are observed among people receiving the study intervention. The resulting summaries can describe treatment delivery and events in that group. They do not directly estimate what would have happened to the same population under a different treatment. A comparison requires an appropriate comparator and a defined contrast. Here, the registry records a single-group model and no allocation, so there is no concurrent randomized group from which to estimate such a contrast.
This matters because an outcome can have multiple possible explanations. The condition being treated, participant characteristics, clinical care, follow-up, and the intervention may all contribute. A single-group description cannot distinguish these influences. It may still be useful for describing whether a complex treatment was delivered and what events were recorded, but it answers a narrower question than a controlled comparison.
How should the feasibility definition be read?
The primary endpoint is based on criteria rather than a single clinical event. The description names unsatisfactory dosimetry, completion outside the specified timing condition or a treatment break beyond the stated limit, and grade 3 or higher radiation toxicity. It also describes a threshold involving at least 10% of patients for delivery-related difficulties and a limit of no greater than 20% for grade 3 or higher toxicity. These criteria concern different aspects of feasibility and safety.
A threshold-based endpoint needs a clearly reported numerator, denominator, and rule for combining its component conditions. The registry provides the definition and a unit description referring to the percentage who did not meet the definition, but no observed endpoint value or component counts. The actual result and how the component criteria were combined in the analysis are not reported in the registry record. Without those details, readers cannot reproduce the endpoint or determine which condition, if any, drove the result.
What does a confidence interval contribute?
In general, a confidence interval expresses the uncertainty around an estimate under the statistical model used. A narrow interval indicates greater precision than a wide interval, while an interval spanning a broad range of plausible values signals substantial uncertainty. An interval does not correct weaknesses in design, replace a comparison group, or establish that a result is clinically important.
No confidence interval for the primary endpoint is reported in the registry record, and its point estimate is also absent. It is therefore not possible to characterize the precision of that result. A confidence interval should not be inferred from the enrollment count alone: the relevant outcome count, analysis population, and method would also matter.
Why do event counts need their context?
Adverse-event counts summarize how many people in the recorded group were affected, according to the registry's categories. They are descriptive and depend on how events were defined, collected, and attributed. A participant can experience more than one event, and different event categories may overlap. For that reason, category counts should not be added to infer a total number of affected participants.
The record reports 15 participants with serious adverse events and 45 with other adverse events, each among 54 at risk, as well as 3 deaths. It does not specify in the posted information whether the serious and other categories are mutually exclusive, whether events were considered treatment-related, or the follow-up exposure used for each category. The listed term percentages are presented as recorded; they should not be treated as comparative risks or interpreted as proof of causation.
What is an unadjusted recalculation?
In general, a recalculation from posted summary statistics can check a simple, unadjusted contrast if the necessary group summaries are available. Such a calculation is not the sponsor's analysis and may not account for adjustment, clustering, censoring, or other features of the original analysis. If a recalculation conflicts with the sponsor's own analysis, the sponsor's analysis takes precedence.
The registry record has no analysis entries and does not report the primary endpoint estimate needed to characterize a recalculated effect. A planning illustration based on an observed effect is a different use of statistics: it describes a hypothetical design under stated assumptions, not the trial's actual power or an observed outcome. Any such illustration is not observed power and should not be read as evidence that the study detected or failed to detect an effect.
Why can over-dispersion matter?
In general, count data are over-dispersed when their variability exceeds what a simpler count model expects. Ignoring over-dispersion can make standard errors too small and uncertainty intervals too narrow. More flexible models or robust uncertainty estimates may be needed, depending on the outcome and design. This is a general statistical consideration, not a claim that over-dispersion occurred in this study. The registry record does not report a count-model analysis or describe a statistical model for the outcomes.
What can be said about multiplicity?
When a study assesses multiple endpoints, time points, or subgroups, the chance of obtaining at least one apparently unusual result can increase if each is tested separately. Statistical approaches can address multiplicity, but the appropriate approach depends on the planned hypotheses and analysis. The registry lists a primary endpoint and secondary outcomes of acute toxicities and late toxicities. The number of analyses is recorded as zero, and no multiplicity strategy is reported in the registry record. It is not possible to determine whether any adjustment was planned or used.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies feasibility as the primary outcome and lists acute toxicities and late toxicities as secondary outcomes. It does not report a multiplicity strategy, such as which secondary comparisons would be confirmatory or whether any adjustment for multiple testing was planned. The number of analyses is recorded as zero. That record does not establish what analyses may have been performed outside the registry entry; it means analysis details are not reported in the registry record.
The primary-endpoint result is not numerically reported, and the record does not provide an analysis population for that outcome. It also does not describe how missing endpoint observations, withdrawal, or incomplete treatment information were handled. Since the endpoint timeframe ends at treatment completion or withdrawal, whichever occurred first, the treatment of withdrawals could affect which participants contribute to an endpoint estimate. The registry record does not state how this was handled.
Details such as an intention-to-treat approach, a per-protocol population, imputation, or sensitivity analyses are not reported in the registry record. These are analysis choices, not assumptions that can be recovered from the study status or enrollment figure. Without the endpoint numerator and denominator, missing-data method, and analysis population, readers cannot assess whether exclusions or incomplete observations could have influenced the reported result. No such result or assessment is available in the posted information.
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 |
|---|---|---|---|
| Proton Group | 15 | 54 | 27.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Proton Group | 3 of 54 |
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 |
|---|---|
| Proton Group | 45 of 54 |
Most frequent serious adverse event terms
| Event term | Organ system | Proton Group |
|---|---|---|
| Fatigue | General disorders | 4 of 54 |
| Headache | Nervous system disorders | 3 of 54 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 3 of 54 |
| Leukocytosis | Blood and lymphatic system disorders | 2 of 54 |
| Skin infection | Infections and infestations | 2 of 54 |
| Sensory neuropathy | Nervous system disorders | 1 of 54 |
| Optic nerve disorder | Eye disorders | 1 of 54 |
| Abdominal pain | Gastrointestinal disorders | 1 of 54 |
| Anorectal infection | Infections and infestations | 1 of 54 |
| Lymph gland infection | Infections and infestations | 1 of 54 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Proton Group |
|---|---|---|
| Fatigue | General disorders | 33 of 54 |
| Dermatitis radiation | Injury, poisoning and procedural complications | 24 of 54 |
| Nausea | Gastrointestinal disorders | 15 of 54 |
| Anorexia | Metabolism and nutrition disorders | 15 of 54 |
| Insomnia | Psychiatric disorders | 12 of 54 |
| Alopecia | Skin and subcutaneous tissue disorders | 10 of 54 |
| Dysgeusia | Nervous system disorders | 9 of 54 |
| Headache | Nervous system disorders | 9 of 54 |
| Constipation | Gastrointestinal disorders | 8 of 54 |
| Dry mouth | Gastrointestinal disorders | 8 of 54 |
Serious events with the highest arm-level rate: fatigue (7.4%), headache (5.6%), epistaxis (5.6%), leukocytosis (3.7%), skin infection (3.7%).
The proton group safety figures list 15 participants with serious adverse events among 54 at risk and 45 participants with other adverse events among 54 at risk. The record also lists 3 deaths. These are counts in the registry's adverse-event summary; the record does not establish from these figures alone whether an event or death was caused by proton therapy. The relationship to treatment and the timing of events are not reported in the information.
The most frequently listed serious adverse-event terms are fatigue at 7.4%, headache at 5.6%, and epistaxis at 5.6%. Leukocytosis and skin infection are each listed at 3.7%, and sensory neuropathy at 1.9%. These term percentages describe the registry's reporting, not a comparison with another treatment. The denominator and event-attribution details for each term are not stated in the posted information, so the percentages should be read as reported rather than converted into additional counts.
Serious and other adverse-event categories may not be mutually exclusive, and one participant may have more than one event. The figures should not be added to create a total. The registry does not report event grades for these listed terms, exposure-adjusted rates, or a comparative safety analysis. The safety data therefore provide a descriptive account, not a treatment-attributable risk estimate.
12. What the Result Does, and Does Not, Mean
The posted record documents a study designed to evaluate feasibility and safety of dose-escalated proton beam therapy for chordomas and chondrosarcomas of the skull base and spine. It specifies treatment delivery criteria and a toxicity threshold, and it gives some adverse-event counts for the proton group. Those details are relevant to understanding what the investigators intended to assess and what safety information was recorded.
The record does not report the numerical primary-endpoint result. It therefore does not show whether the stated feasibility criteria were met, how often any individual criterion occurred, or the uncertainty around the primary outcome. A completed study status does not fill in these missing results. The posted record also contains no analysis entries, so it does not supply a statistical analysis of the listed outcomes.
The adverse-event figures are descriptive. They do not show that proton therapy caused the reported events, and they do not compare event rates with another treatment. The 3 deaths are listed in the safety summary, but a cause or relationship to treatment is not stated. The serious-event terms and percentages likewise do not establish treatment attribution or comparative risk.
Because the design is single-group, the data cannot answer how outcomes would differ under another intervention. The study description does not provide a randomized comparison, and no like-for-like control arm is recorded. Accordingly, these registry results cannot establish comparative effectiveness or quantify a treatment effect. They also do not support a conclusion that treatment does or does not work.
The most defensible reading is narrower: the registry records the intervention, study purpose, feasibility criteria, study status, and selected safety summaries. It does not report the primary endpoint's observed value, a precision estimate, or outcome analyses that would support broader conclusions. Further claims about efficacy, causal safety, or comparative outcomes are not established by the posted information.
13. Why This Trial Matters Statistically
This study raises a statistical question that is distinct from a conventional treatment comparison: can proton therapy be delivered under stated dosimetry and scheduling conditions while remaining within a defined toxicity boundary? A feasibility endpoint can be valuable when treatment planning and delivery are central concerns. Its interpretation depends on transparent definitions, reported component data, and an estimate with enough context to judge uncertainty.
The registry gives a detailed operational description, including the timing of completion, permitted treatment breaks, and the grade threshold for toxicity. That specificity can help readers understand what feasibility was intended to mean. At the same time, the registry does not report the numerical primary result. A clear definition without the observed result cannot establish whether the criteria were satisfied, and it prevents readers from examining the estimate's precision or the contribution of each component.
The single-group design makes the distinction between feasibility evidence and comparative effectiveness especially important. Describing outcomes in the treated group can inform what was observed in that setting, but it does not show how those outcomes compare with another treatment. The design also makes careful reporting of participant follow-up and adverse-event attribution important, since there is no control group to help interpret background events.
Statistically, the record illustrates why outcome definitions, denominators, analysis populations, missing-data procedures, and uncertainty measures belong alongside event counts. The posted safety figures are useful descriptions, but they do not replace an analysis of the primary question. The central statistical value of the study depends on its feasibility result and how fully that result is reported; those outcome details are not reported in the registry record.
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 key limitation for interpreting this study is the absence of a numerical primary-endpoint result. Although the registry defines feasibility using dosimetry, treatment completion, breaks, and toxicity criteria, it does not report the observed percentage or the component counts. This prevents evaluation of whether the stated criteria were met and prevents assessment of the primary estimate's precision.
The single-group design has no comparator, so the results cannot provide a like-for-like treatment contrast. The registry records allocation as NA and masking as none. The design is not a randomized comparison, and the record itself notes that arms are not a like-for-like control comparison. Causal effects and comparative effectiveness are therefore not established by these data.
The available record does not report participant characteristics beyond the conditions and study description, or explain the analysis population. Missing-data handling, withdrawals in the endpoint analysis, and sensitivity analyses are not reported in the registry record. Although the primary timeframe allows assessment up to 133 months, the posted information does not explain follow-up completeness or how observations at different follow-up durations were handled.
Safety interpretation is also limited. The record lists serious and other adverse-event counts, deaths, and selected serious-event terms, but does not state the treatment relationship for the listed events or provide a comparative safety analysis. It does not specify whether event categories overlap, how long participants were at risk, or how the term percentages were calculated. These omissions restrict the figures to descriptive interpretation.
Finally, no analysis entries are reported, and no statistical plan or multiplicity method is described. Study completion does not resolve these reporting gaps. The posted record supports description of the study design and listed safety summaries, but not a full statistical evaluation of the primary or secondary outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Proton Radiation for Chordomas and Chondrosarcomas — NCT01449149.
- Registry record last updated 2025-12-05; status last verified 2025-11.
- Results first posted 2025-12-05.
- 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
NCT01449149 is a completed, single-group study of proton therapy for chordomas and chondrosarcomas, sponsored by Abramson Cancer Center at Penn Medicine. The registry lists enrollment of 54, with a treatment dose of 72.00 to 79.2 Gy(RBE) in 40-44 fractions. The primary objective concerns feasibility and safety; acute and late toxicities are listed as secondary outcomes.
The primary endpoint definition covers dosimetry, treatment completion conditions, and grade 3 or higher radiation toxicity, with a timeframe from enrollment to treatment completion or withdrawal, whichever occurred first, assessed up to 133 months. Its numerical result and analysis are not reported in the registry record. Safety information lists 15 participants with serious adverse events, 45 with other adverse events, and 3 deaths, among the recorded group figures. These summaries are descriptive and do not establish treatment causation or comparative risk.
There is no comparator, and analysis entries are not reported. The posted information therefore does not establish a comparative treatment effect or answer whether the primary feasibility criteria were met.