Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) in One Fraction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) in One Fraction (NCT04939246), a na na study. The primary outcome is Number of Participants With SABR Successfully Delivered in One Fraction.

2. Clinical Question

The registry record describes a feasibility study, not a comparison of treatments. Its primary question is whether stereotactic ablative body radiation therapy (SABR), delivered in one fraction with MRI guidance and adaptation, could be delivered according to specified timing and image-guidance criteria for people with inoperable primary or metastatic carcinoma.

The registry also lists one-year local control, one-year overall survival, acute and late toxicity, and change in participant-reported quality of life among the secondary outcomes. Numerical findings for these outcomes are not reported in the registry record. The record does not report a comparison of outcomes by tumor site, lesion, or another participant characteristic.

3. Trial Design

SMART ONE is a completed, multi-site, single-arm feasibility study. The registry lists an enrollment of 30 and identifies the intervention as stereotactic ablative body radiation therapy. The study title and treatment description specify one fraction; each lesion was to receive one radiation treatment, and a participant could be treated for up to ten lesions.

The registry lists the phase as NA, allocation as NA, and masking as none. Because there is one group and no control arm, the design is suited to describing treatment delivery and observed outcomes in the enrolled group, not to estimating a randomized treatment effect. The registry’s skip note also cautions against treating the arms as a like-for-like control comparison.

The study start date is 2021-06-18, and primary completion is listed as 2024-07-17. Its status is completed. The primary endpoint timeframe is described as through study completion, an average of 1 year. This timeframe does not establish that every participant had the same duration of follow-up; individual follow-up details are not reported in the registry record.

The feasibility endpoint concerns whether delivery met prespecified practical and technical criteria. The record describes completion to each lesion within 3 days of the intended treatment date, treatment-room duration within 90 minutes for at least 80% of treated lesions, and image-guidance verification within 5 mm of planned delivery. It does not report the number of participants who met those criteria.

The record lists six outcome measures and no analysis records. It does not report a protocol-level statistical analysis plan, a sample-size justification, or details of any interim analyses. These omissions limit assessment of how the study was planned and how its outcomes were analyzed.

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.

Screening

During Treatment

After Treatment

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 SABR Successfully Delivered in One Fraction, measured over through study completion, an average of 1 year.

The primary endpoint is the number of participants with SABR successfully delivered in one fraction. It is a count of participants, rather than a measurement of tumor response or a direct comparison of treatment strategies. The registry defines successful delivery using treatment timing, treatment-room duration, and image-guidance accuracy.

For timing, treatment to each lesion must be completed within 3 days of the intended treatment date. For duration, completion must occur within 90 minutes from the participant entering the treatment room until treatment completion for at least 80% of treated lesions. For image guidance, verification must place treatment delivery within 5 mm of planned delivery. The record presents these as the criteria for success; it does not report how the criteria were combined in analysis beyond describing the endpoint as a count of participants with successful delivery.

Such an endpoint is relevant to feasibility because it focuses on whether a complex treatment can be delivered within practical time and accuracy constraints. It does not, by itself, measure local control, survival, toxicity, quality of life, or comparative clinical benefit. Those outcomes require their own results and appropriate follow-up.

The primary endpoint result is not reported in the registry record. There is no reported count of participants meeting the success definition, nor a confidence interval for that count. Consequently, the feasibility outcome’s observed frequency and precision cannot be assessed from the available registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine what a study can estimate and how much uncertainty remains around an estimate. The registry record gives the study’s group structure and endpoint definition, but it does not report a statistical analysis plan or an analysis of the primary endpoint. The explanations below distinguish general statistical principles from the methods documented for this study.

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who receive the intervention. For a binary outcome, an analysis might report a count and the proportion of assessed participants meeting a defined condition, with a confidence interval to communicate uncertainty. That is a general description, not a claim about the analysis used in SMART ONE. The registry identifies the primary endpoint as a participant count but does not report a proportion, confidence interval, or analysis method.

Without a comparator group, the study cannot estimate a between-group treatment contrast. Observed outcomes can reflect the treatment and other influences, including participant characteristics, disease course, co-interventions, and follow-up. A single-group feasibility study can describe whether delivery criteria were met in its study setting, but it cannot establish what would have happened to the same participants under a different approach.

How should the primary endpoint be read?

The endpoint is defined at the participant level, while some of its criteria refer to lesions. The registry describes treatment completion to each lesion within 3 days of the intended date, a duration threshold applying to at least 80% of treated lesions, and image-guidance verification within 5 mm. This makes the success definition operational: it combines scheduling, treatment-room time, and technical verification. The record does not provide the endpoint result or participant-level detail showing how each condition was evaluated.

When an endpoint definition involves multiple conditions, it is important to know whether all conditions must be met for a participant to count as successful and how incomplete assessments are handled. The description gives criteria for success but does not report analysis rules for missing or unassessable criteria. Those rules are not reported in the registry record, so the precise handling of partial information cannot be evaluated.

What does a confidence interval add?

In general, a confidence interval presents a range of estimates compatible with the observed data under a specified statistical method. It helps readers assess precision: a point estimate alone does not show how much uncertainty accompanies it. For a count or proportion, interpretation also depends on the number assessed and the outcome definition. SMART ONE’s registry entry does not report a confidence interval for the primary endpoint, so its precision cannot be evaluated from the record.

Why does the planning illustration need careful interpretation?

The record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations concern total events; for other outcomes, they concern participants per arm. These are hypothetical planning assumptions and do not describe the study’s actual single-group design.

Such illustrations can help show how a future two-arm study’s required sample size would change under different assumed effect sizes. Smaller assumed effects generally require more information to distinguish them from no difference, while greater variability or less efficient measurement can also affect precision. This is a general statistical explanation. The registry record does not report the numerical planning values or an observed primary endpoint effect in the information available for this analysis. Any planning figures should be treated as design scenarios, not as observed power or evidence about the treatment’s effect.

Observed power is not a substitute for an estimate and its uncertainty. General statistical practice favors interpreting an observed effect together with its confidence interval and the design’s limitations, rather than using post-study power calculations to decide whether a result is meaningful. No primary endpoint estimate or interval is reported for SMART ONE in the registry record.

What role can over-dispersion play?

For count outcomes, a statistical model may assume a particular relationship between the average count and its variability. Over-dispersion means that the observed variability is greater than the model’s assumed variability. In general, ignoring over-dispersion can make standard errors too small and confidence intervals too narrow. This concept may matter for outcomes involving counts, but the primary endpoint is a count of participants meeting a definition, and the registry does not report a model or variance estimate. It would be inappropriate to claim that over-dispersion was assessed or adjusted for in this study.

There may also be dependence among lesions from the same participant because a participant could receive treatment to multiple lesions. General analyses of lesion-level data may need to account for clustering within participants. The primary outcome is described as a participant count, but the record does not provide lesion-level analyses or state whether any clustering adjustment was used.

Overall, the record supports a description of the endpoint rules and the trial design, but not a reconstruction of the statistical analysis. The methods used to calculate uncertainty, handle incomplete data, or analyze secondary outcomes are not reported in the registry record.

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("Single-fraction SABR")
n      <- c(30)
events <- c(30)
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  Single-fraction SABR  30  30  100.0  88.4  100.0  88.6  100.0  88.8  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary delivery-success endpoint and secondary outcomes for local control, overall survival, toxicity, and quality of life. When a study evaluates multiple outcomes, there is a general risk that some findings may appear notable by chance if each is tested separately. Statistical plans may address this through a prespecified hierarchy, adjustment, or a clear distinction between confirmatory and exploratory analyses. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how multiple testing was addressed.

The record lists no analysis records. It does not report which participants were included in each outcome analysis, how participants with incomplete follow-up were handled, or how missing questionnaire responses were treated. These details are important because analyses based only on participants with observed outcomes can differ from analyses that account for all enrolled participants, especially when missingness is related to health status or treatment experience. The registry record does not report reasons for missing data or methods for evaluating their possible impact.

For one-year outcomes, interpretation also depends on follow-up and censoring rules. The listed outcome names identify a one-year time horizon for local control and overall survival, but the record does not report the analysis method, event definitions, censoring details, or number at risk over time. Those elements are not reported in the registry record.

The record does not identify an intention-to-treat population, a per-protocol population, or another analysis population. It also does not report a prespecified plan for handling participants who did not receive treatment as intended. These omissions prevent a full assessment of selection, missingness, and multiplicity.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pericardial effusion (3.3%), acute respiratory failure (3.3%), lung infection (3.3%).

For the single-fraction SABR group, the registry records 3 participants with serious adverse events among 30 at risk, and 28 participants with other adverse events among 30 at risk. It also records 4 deaths. The listed serious adverse-event terms are Pericardial Effusion, Acute respiratory failure, and Lung infection, each reported as 3.3%.

These figures are descriptive safety counts. The registry information does not report the timing or cause of the deaths, whether they occurred during a particular follow-up interval, or whether they were considered related to treatment. It also does not provide detailed event-level data, so the counts should not be used to infer how events overlapped within participants. The percentages attached to the serious-event terms should be read as the registry’s reported values, not as evidence about causation.

In general, a serious adverse event is classified by its seriousness under defined criteria; seriousness is not the same as an assessment that treatment caused the event. Causal attribution and the event definitions used for this study are not reported in the registry record. The record also does not report comparative safety estimates, which is consistent with its single-group design. These counts describe what the registry records for the treated group; they do not establish comparative risk.

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

The study addresses a practical question: whether single-fraction SABR using MRI-guided adaptive radiation therapy could be delivered under specified time and image-guidance criteria in a multi-site feasibility setting. The registry gives a concrete definition of success, including delivery within 3 days of the intended treatment date, a treatment-room duration threshold for at least 80% of treated lesions, and image-guidance verification within 5 mm.

However, the registry record does not report the primary endpoint count. It therefore does not show how many participants met the success definition or how precise that result was. The completed status and enrollment of 30 do not establish that all enrolled participants were treated, assessed, or successful. The record does not report those details.

The study also lists clinical and patient-reported secondary outcomes, but their numerical findings are not reported in the registry record. Without those results, the record cannot support conclusions about local control, overall survival, toxicity beyond the listed safety counts, or quality-of-life change. The adverse-event counts are important descriptive information, but their timing and treatment attribution are not reported.

More generally, feasibility and clinical effectiveness are different questions. Meeting a delivery criterion would describe whether treatment was delivered according to the study’s operational definition; it would not, by itself, show that tumors were controlled or that participants lived longer. Likewise, an outcome observed in a single group cannot establish that the intervention caused the outcome or compare it with an alternative.

The registry information is therefore most informative about the study’s intended population, treatment approach, and feasibility criteria. It provides limited outcome evidence because the primary and secondary outcome results are not reported in the registry record. No treatment recommendation or conclusion about benefit can be drawn from these details alone.

14. Why This Trial Matters Statistically

Feasibility studies address whether an intervention can be delivered in practice, not only whether a clinical outcome changes. That distinction matters for a technically demanding approach such as stereotactic MRI-guided adaptive radiation therapy. SMART ONE defines delivery success through treatment timing, treatment-room duration, and verification against planned delivery, making the operational goal explicit.

Statistically, a clear endpoint definition is only one part of an interpretable result. Readers also need the observed number meeting the definition, the number assessed, and an indication of uncertainty. The registry record does not report the primary endpoint result or its precision. Consequently, the feasibility question is defined, but its observed answer cannot be evaluated from the registry information available.

The single-group design also makes the boundary of inference clear. It can describe experience within the enrolled group, but without a comparator it cannot estimate a contrast between treatment strategies. This is particularly important when interpreting safety counts or the listed one-year outcomes: descriptive observations are not comparative effects.

The record’s treatment description also highlights a distinction between participant-level and lesion-level information. The endpoint counts participants, while some success criteria apply to individual lesions. Multiple lesions may be treated for one participant, so lesion-level delivery information and participant-level outcomes are not interchangeable. The registry does not report those detailed data.

These features make the study statistically relevant as a feasibility design while underscoring the value of complete outcome reporting. A reported endpoint estimate with its denominator and uncertainty, alongside transparent missing-data and analysis details, would allow readers to judge what the study observed without implying more than a single-group feasibility study can establish.

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 main limitation for interpreting this registry record is that it does not report the primary endpoint result. Although the endpoint is defined and the study is marked completed, the number of participants meeting the delivery-success criteria and the precision of that estimate are not reported. Enrollment is not a substitute for an analyzed endpoint denominator.

The study has no control group, so it cannot support a direct comparison with another treatment or care strategy. Its single-group design also limits causal interpretation of any observed clinical or safety outcome. The registry record does not report numerical results for the listed secondary outcomes, including one-year local control, one-year overall survival, and change in participant-reported quality of life.

Important analysis details are not reported in the registry record, including the analysis populations, methods for missing data, follow-up and censoring rules, and statistical methods for the outcomes. The record lists six outcome measures but does not report a multiplicity strategy. These omissions make it difficult to assess selection, completeness, precision, and the interpretation of multiple outcomes.

The endpoint combines participant-level and lesion-level criteria, but the record does not give lesion-level results or explain in detail how incomplete criterion assessments were handled. Nor does the safety information specify timing or treatment attribution for adverse events and deaths. These limitations do not invalidate the study’s feasibility question, but they constrain what can be concluded from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) in One Fraction — NCT04939246.
• Registry record last updated 2025-07-17; status last verified 2025-04.
• Results first posted 2025-07-17.
• 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

SMART ONE is a completed, multi-site, single-group feasibility study of one-fraction stereotactic ablative body radiation therapy using MRI-guided adaptation. The registry lists enrollment of 30, phase NA, allocation NA, and masking none. The study began on 2021-06-18, with primary completion on 2024-07-17.

The primary endpoint is the number of participants with successful one-fraction SABR delivery, defined by treatment timing, treatment-room duration for treated lesions, and image-guidance verification. The registry record does not report the primary endpoint result. It also lists secondary outcomes for one-year local control, one-year overall survival, toxicity, and quality-of-life change, without numerical findings in the record.

The safety record lists 3 participants with serious adverse events, 28 with other adverse events, and 4 deaths in the single-fraction SABR group. The record does not report event attribution or death timing. Because the study has no comparator, its design supports description rather than a between-treatment estimate.