Sentinel and/or Axillary Lymph Node Biopsy With or Without Axillary Reverse Mapping in Reducing Incidence and Severity of Arm Lymphedema in Stage 0-2 Patients.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sentinel and/or Axillary Lymph Node Biopsy With or Without Axillary Reverse Mapping in Reducing Incidence and Severity of Arm Lymphedema in Stage 0-2 Patients. (NCT01276054), a randomized phase 2 study. The primary outcome is Whether or Not a Patient Has Developed Grade 1+ LE.

2. Clinical Question

The clinical question is whether adding ARM to lymph-node biopsy changes the occurrence of postoperative arm lymphedema. The proposed comparison is between biopsy with ARM and biopsy without ARM. This is a randomized phase II study, but random allocation alone does not establish whether the groups were comparable in practice or whether the intervention affected the outcome. Those questions depend on analyzable outcome data, which the registry says were unavailable because of early termination.

The trial also lists bioimpedance spectroscopy, quality-of-life assessment, and lymphedema management among its interventions. Their intended role in the primary comparison, and the details of how they were implemented, are not reported in the registry record. The primary question therefore needs to be kept distinct from broader questions about screening, quality of life, and management. The posted record does not provide an estimate of the comparative lymphedema outcome.

3. Trial Design

The registry describes a randomized, open-label, parallel phase II trial sponsored by the University of Southern California. It enrolled 4 participants and is marked terminated. The recorded start is 2010-12, and primary completion is recorded as 2011-10. The study concerns lymph-node biopsy, with or without ARM, in patients with resectable stage 0-II breast cancer.

In the ARM group, participants underwent SNB and/or ALND using technetium Tc 99m sulfur colloid, followed by methylene blue or indocyanine green solution tracer to locate the arm lymph node, and then underwent ARM. The comparator group underwent SNB and/or ALND using the described tracers, without ARM. The registry uses flexible descriptions of the biopsy procedures, including SNB, ALND, or combinations of them; it does not report how many participants received each procedure.

Open-label means masking was not used, as also recorded in the registry. The record does not report allocation concealment, the randomization sequence method, or whether the procedure teams and outcome assessors were distinct. It also does not report the reasons for early termination. Although the registered intervention list includes bioimpedance spectroscopy, quality-of-life assessment, and lymphedema management, further details about their timing and use are not reported in the registry record.

The small enrollment and early termination are central to interpreting the trial: the study did not produce an analyzable primary-outcome comparison. The record does not provide a sample-size justification or enough information to determine the intended enrollment target. No conclusion about comparative efficacy can be drawn from the design description alone.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: The study has no pre-assignment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Unable to analyze due to early termination of the study

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 Whether or Not a Patient Has Developed Grade 1+ LE, measured over During the first year post-operatively.

The primary endpoint asks whether a patient developed grade 1+ LE during the first year after surgery. The registry defines LE using the CTCAE v3 definition: a >5-10% increase in inter-limb volume in the operated-side arm compared with the unaffected arm. It is a binary clinical outcome: the question is whether the defined threshold was met, rather than the amount of swelling considered as a continuous measurement.

In general, a defined threshold can make an outcome easier to interpret consistently across participants and can identify a change considered clinically relevant by the chosen grading system. Comparing the arms on the proportion meeting that definition would address whether the occurrence of threshold-defined lymphedema differed between the biopsy strategies. The registry does not report details of the measurement schedule, assessor procedures, or handling of measurements near the threshold.

Most importantly, the registry states that the primary outcome was unable to be analyzed because the study terminated early. It therefore provides no primary-outcome counts, group comparison, effect estimate, or measure of uncertainty. The endpoint is specified, but its comparative result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization is a way to assign participants to treatment groups using chance. In general, it is intended to reduce systematic differences between groups at the start of a study, including differences that investigators may not have measured. It does not guarantee identical groups, especially when enrollment is very small, and it does not address missing outcome data after allocation.

The registry calls this study randomized and parallel. A parallel design means participants are assigned to a group and the groups are compared during the study, rather than each participant receiving both procedures in sequence. The registry does not describe the randomization sequence or allocation-concealment process. Those details matter because concealment can help prevent knowledge of an upcoming assignment from influencing enrollment or assignment.

What does open-label mean for interpretation?

Masking is listed as none, so the study was open-label. In general, masking can limit the influence of treatment knowledge on participant reports, clinical decisions, and outcome assessment. Its importance depends on the outcome and how it is measured. Here, the primary outcome is based on arm-volume comparison and a threshold definition, but the registry does not explain who made the measurements, whether measurements were assessed independently, or whether the people measuring them knew the assigned group.

Open-label status does not automatically invalidate an outcome. It does mean that readers should consider whether knowledge of the assigned procedure could have affected measurement or follow-up. The registry record does not contain enough detail to assess that possibility for this trial.

How should the endpoint be understood?

The primary outcome is whether grade 1+ LE developed during the first year after surgery. The specified definition is a >5-10% increase in inter-limb volume in the ipsilateral arm compared with the unaffected arm, using CTCAE v3. This turns a volume comparison into a categorical outcome: each participant either meets the definition or does not, based on the recorded assessment.

For a binary outcome, a randomized comparison would ordinarily summarize the number or proportion meeting the definition in each group and then estimate a between-group contrast with uncertainty. These are general features of analysis, not results from this trial. The registry does not report the necessary outcome counts or an estimated contrast, and explicitly says the outcome could not be analyzed because of early termination.

What does a confidence interval communicate?

In general, a confidence interval gives a range of values compatible with the data under the statistical model used. Its width communicates precision: a wider interval reflects less precise information, while a narrower interval reflects greater precision. A confidence interval does not repair limitations in data collection or prove that all values within it are equally plausible in every practical sense.

No primary-outcome confidence interval is reported in this registry record. It is therefore not possible to describe the precision of a treatment-effect estimate for lymphedema, because no such estimate is reported. The lack of an interval should not be described as a broad interval or as evidence that the groups were equivalent.

What can be inferred from the sample-size illustration?

The record describes a planning illustration computed from an observed effect, using a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. In general, such illustrations explore how much information might be needed to detect a specified effect under stated assumptions. They are not evidence that a study actually had a given chance of detecting an effect, and they are not a substitute for a trial's own prospective design justification.

The record does not report a sample-size justification for this trial. It also does not report enough primary-outcome information to interpret an observed treatment effect. Sample-size outputs should therefore be read as planning scenarios, not as observed power or as proof that the trial was adequately sized. The sample-size assumptions describe the effect as a fraction of an observed effect; they do not establish that this effect is a reliable target for future research.

Why does early termination matter?

Early termination curtailed the study and, according to the registry, left the primary outcome unable to be analyzed. In general, terminating a trial early can limit the amount of follow-up and the number of outcome events available for comparison. The implications depend on why the trial stopped, when it stopped, and how much data had been collected. The reason for termination and any interim analyses are not reported in the registry record.

Without those details, it is not possible to determine whether termination was related to recruitment, feasibility, safety, or another reason. Nor can the record establish whether outcome data existed but were incomplete, or whether the primary analysis was never conducted. The appropriate conclusion is limited to the registry's statement that the primary outcome was not analyzable due to early termination.

What analysis details are missing?

The registry does not report a statistical analysis plan, a model for the primary outcome, an analysis population, handling of missing measurements, or adjustments for baseline factors. It also does not report interim analyses. These omissions prevent a detailed assessment of how the investigators intended to estimate the primary comparison and how uncertainty or missing data would have been handled.

General statistical principles can explain why these details matter, but they cannot fill in the trial's unreported methods. In particular, no adjusted or unadjusted result should be inferred, and no treatment effect should be reconstructed from the enrollment or adverse-event entries. The primary finding from the record is that a planned endpoint and comparison are described but no analyzable primary result is reported.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity refers to the challenge of interpreting results when a study tests several outcomes, groups, or time points. In general, conducting many statistical tests can increase the chance that at least one result appears unusual by chance. A prespecified primary endpoint can help focus interpretation, while any additional analyses may need to be treated as secondary or exploratory. The registry identifies a primary outcome of grade 1+ LE during the first year after surgery, but does not report a statistical plan describing multiplicity handling.

The record lists quality-of-life assessment, bioimpedance spectroscopy, and lymphedema management among the interventions, but does not describe how these relate to a planned outcome-analysis hierarchy. The registry reports 1 outcome measure, while the primary endpoint itself was unable to be analyzed. It is not possible to determine whether other outcomes were collected or analyzed, or whether there were additional time points or subgroup comparisons.

Missing-data methods and analysis populations are also not reported in the registry record. It is not stated how participants with incomplete follow-up, unavailable measurements, or deviations from assigned procedures would have been handled. No intention-to-treat or per-protocol analysis population is identified. These details matter because the analysis population and missing-data assumptions can affect a treatment comparison.

The record also does not report an interim-analysis plan or the reason for early termination. Without those details, readers cannot determine whether any decisions were based on accumulating outcomes or whether a prespecified stopping rule applied. The registry's statement that the primary outcome could not be analyzed remains the key limitation; no method can be assumed to resolve the missing outcome comparison.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: fatigue (100.0%), depression (50.0%), edema - limbs (50.0%), breast pain (50.0%).

The registry lists two groups: SNB plus ARM or ALND with or without SNB plus ARM, and SNB or ALND with or without SNB. For each group, the serious adverse event listing reports 2 participants at risk and 2 affected. The other adverse event listing also reports 2 at risk and 2 affected in each group. These entries should be read as the posted counts, not as a basis for a comparative safety conclusion.

The registry lists Fatigue at 100.0%, and Depression, Edema - limbs, and Breast Pain at 50.0% each among the top serious terms. It does not report sufficient context to determine the event-specific denominators, timing, severity details, relationship to the procedures, or whether the same participants experienced multiple terms. The percentages therefore should not be treated as direct comparisons between randomized groups.

The death entries are not reported in the registry record. With enrollment of 4 and early termination, these safety listings are limited observations. They cannot establish the frequency of harms in a wider population or determine whether either procedure caused a reported event. The registry does not provide an analyzable comparative safety assessment.

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

The trial addresses an important methodological and clinical question: whether mapping arm lymphatics during breast-cancer lymph-node surgery is associated with a different occurrence of threshold-defined arm lymphedema. The registry documents a randomized phase II comparison and specifies a primary outcome during the first year after surgery. These features make the intended question clear.

What the record does not provide is the answer to that question. It states that the primary outcome could not be analyzed because the study terminated early. There is no reported comparison of outcome occurrence between groups, no estimate of the size or direction of a difference, and no measure of the estimate's precision. The record therefore cannot establish benefit, lack of benefit, or equivalence for the lymphedema outcome.

This distinction matters statistically. A study with a result near no difference and a sufficiently precise interval could provide a different kind of evidence from a study with no analyzable result. Here, the absence of an estimate is not evidence that the procedures have the same outcome. Nor does it demonstrate that either procedure changes the risk of lymphedema.

The small enrollment, early termination, open-label design, and unreported analysis details further constrain interpretation. The serious adverse-event listings describe recorded entries, but they do not support a reliable comparison of safety. No sample-size illustration can substitute for the missing clinical outcome data or turn this trial into a completed comparative analysis.

The responsible reading is narrow: the registry records the study's rationale, procedures, and intended endpoint, but does not report an analyzable primary result. Any broader conclusions about the effectiveness or safety of ARM would go beyond what this trial record establishes.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a well-defined research question and an answerable result. The record specifies a randomized comparison, describes the two procedural approaches, and defines a primary endpoint. Yet early termination left that endpoint unable to be analyzed. A clear protocol question is necessary for a useful trial, but it is not sufficient without outcome information and an interpretable analysis.

The enrollment of 4 also shows why numerical results from very small studies need careful context. In general, a small study may provide little precision, and individual observations can have substantial influence. In this case, the outcome comparison is not merely uncertain; the registry does not report it. Statistical interpretation must distinguish lack of evidence from evidence that there is no difference.

The record also demonstrates why methodological details matter. Randomization is reported, but sequence generation and allocation concealment are not. Masking was not used, while outcome-assessment procedures are not described. Analysis populations, missing-data handling, and interim analyses are likewise not reported. These gaps limit the ability to judge how the planned comparison would have been carried out, even apart from the unavailable endpoint result.

Finally, planning calculations and safety entries serve different purposes from an efficacy analysis. Planning illustrations are not observed power, and adverse-event counts from a very small, terminated study do not establish comparative safety. Keeping these distinctions clear prevents the design, ancillary records, or planning assumptions from being mistaken for the missing primary finding.

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 most consequential trial-specific limitation is early termination: the registry states that the primary outcome was unable to be analyzed. Enrollment was 4, and the record does not report why the study ended early or whether termination was due to recruitment, feasibility, safety, or another consideration. Without that explanation, the impact of stopping on the intended comparison cannot be characterized further.

The registry does not report the actual lymphedema outcomes, group-specific follow-up, or the number of participants with complete primary-endpoint measurements. It also does not describe measurement timing beyond the first-year timeframe, the assessor, or the handling of values around the stated threshold. Thus the outcome definition is available, but its implementation and results are not.

The study was open-label. The registry does not state whether outcome assessors were masked or whether an independent assessment process was used. Details of sequence generation and allocation concealment are also not reported. These limitations restrict assessment of potential bias in assignment and outcome measurement.

Further information absent from the registry record includes the sample-size justification, analysis plan, analysis populations, missing-data methods, interim analyses, and the reason for termination. The adverse-event record lacks context on event timing, attribution, and denominators, and death information is not reported. Together, these limitations mean that neither the primary comparison nor a robust comparative safety assessment can be recovered from the posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sentinel and/or Axillary Lymph Node Biopsy With or Without Axillary Reverse Mapping in Reducing Incidence and Severity of Arm Lymphedema in Stage 0-2 Patients. — NCT01276054.
• Registry record last updated 2014-08-01; status last verified 2014-02.
• Results first posted 2014-08-01.
• 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

NCT01276054 is a randomized, open-label, parallel phase II trial sponsored by the University of Southern California. It studied SNB and/or ALND with ARM compared with biopsy without ARM in patients with resectable stage 0-II breast cancer. The registry records enrollment of 4, a start of 2010-12, primary completion of 2011-10, and terminated status.

The primary outcome was whether grade 1+ LE developed during the first year after surgery, defined as a >5-10% increase in inter-limb volume in the ipsilateral arm compared with the unaffected arm. The registry says this outcome was unable to be analyzed because of early termination. It reports no comparative primary-outcome estimate.

Serious adverse event counts and several serious event terms are listed, but the record does not provide the context needed for a comparative safety conclusion. The reason for termination, sample-size justification, statistical analysis plan, missing-data procedures, and analysis populations are not reported in the registry record.