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 Intraoperative Radiotherapy After Local Recurrence in Breast Cancer (NCT02386371), a na na study. The primary outcome is The Tolerance of RIOP (Intra Operative Radiotherapy) in Patients With Delayed Local Recurrences, After a Second Conservative Treatment of Breast Cancer.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02386371 |
| Phase | NA |
| Condition | Breast Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 66 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Institut du Cancer de Montpellier - Val d'Aurelle |
| Results posted | Yes |
2. Clinical Question
Population
Patients with breast carcinoma and a delayed local recurrence after earlier breast-conserving treatment. The registry describes the intended population as patients receiving a second conservative treatment; further eligibility details are not reported in the registry record.
Intervention
Repeat breast-conserving surgery, described as tumorectomy to obtain clear margins, followed by intraoperative radiotherapy (IORT). The registry’s brief summary presents the study as evaluating the feasibility of this combined approach after local recurrence.
Comparator
There is no concurrent control group in the registry design. Allocation is listed as NA, and the study model is single group. The registry record therefore does not describe a like-for-like comparison with another treatment strategy.
Primary question
The primary endpoint concerns tolerance, assessed through fibrosis of grade 2 or higher at 12 months after IORT according to NCI CTCAE v4.0. The record labels the endpoint a fibrosis rate, but its unit and parameter are participants and number. The observed endpoint count and its analysis are not reported in the registry record.
The stated clinical question is about the feasibility and tolerance of combining a second breast-conserving operation with IORT after local recurrence. The registry also names outcomes concerning early and late toxicities, local relapse-free survival, metastasis relapse-free survival, disease-free survival, overall survival, and the interval without mastectomy. These outcomes broaden the study’s descriptive scope beyond the primary fibrosis measure, but they do not create a control comparison. Without a reported primary outcome value or comparative group, the record cannot establish how the observed endpoint compares with another treatment or what would have occurred under an alternative approach.
3. Trial Design
The registry describes a prospective, multicenter, single-arm Phase II feasibility study. Its registered phase field is NA, so the registry record does not assign a phase there; Phase II appears in the brief study summary. Enrollment is listed as 66, and the study status is completed. The recorded start is 2014-03, with primary completion on 2020-06-12.
The intervention combines tumorectomy and intraoperative radiotherapy. The surgical description says tumorectomy is performed according to current standards with the aim of obtaining clear margins. The description also says axillary lymph node control depends on initial management and clinical and ultrasound assessment of N0 patients, with the approach chosen by the teams. The IORT intervention is named, but further procedural detail is not reported in the registry record.
The study has a single group described as surgery and intraoperative radiotherapy. Masking is listed as none, and allocation is listed as NA. These entries are consistent with a design without a randomized comparator, but the registry does not report a detailed allocation procedure or an account of blinding beyond those labels. The group description does not make the study a controlled comparison.
The registry lists toxicity and several time-to-event outcomes, including relapse-free survival, disease-free survival, overall survival, and the interval without mastectomy. It reports seven outcome measures and zero analyses. The analysis methods, analysis populations, follow-up completeness, and results for these outcomes are not reported in the registry record. In particular, enrollment cannot be treated as the endpoint denominator: the number of participants with an evaluable primary endpoint is 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 | Surgery and Intra Operative Radiotherapy |
|---|---|
| STARTED | 66 |
| COMPLETED | 53 |
| NOT COMPLETED | 13 |
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 | Surgery and Intra Operative Radiotherapy |
|---|---|---|
| Participants analysed | 53 | |
| Age, Continuous | years | 68 (50 to 93) |
| Sex: Female, Male: Female | Participants | 53 |
| Sex: Female, Male: Male | Participants | 0 |
| Race and Ethnicity Not Collected | Participants | — |
6. Primary Endpoint
The registry lists the primary outcome as The Tolerance of RIOP (Intra Operative Radiotherapy) in Patients With Delayed Local Recurrences, After a Second Conservative Treatment of Breast Cancer, measured over Up to 12 months post radiation.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the tolerance of IORT in patients with delayed local recurrence after a second conservative breast cancer treatment. Its description focuses on fibrosis at 12 months after IORT, classified using NCI CTCAE v4.0. The record identifies grade 0 as the better outcome and grade 2 or higher as the worse outcome. This makes the endpoint a threshold-based toxicity measure: it concerns whether fibrosis reaches the stated grade threshold during the specified follow-up period.
The endpoint is relevant to the study’s stated feasibility and tolerance question because it records a local tissue toxicity after surgery and IORT. A standardized grading system can make toxicity definitions more consistent across assessments, although the record does not report how assessors were trained, whether grading was blinded, or how assessments were handled across centers.
There is a reporting distinction to keep in view. The endpoint title refers to tolerance, and its description calls the outcome a fibrosis rate, while the registered unit is participants and the parameter is number. The outcome count, the number assessed at 12 months, and any rate estimate are not reported in the registry record. Enrollment of 66 does not establish the denominator used for this endpoint. No confidence interval, test result, or analysis of the primary endpoint is reported in the registry record, so the magnitude and precision of the endpoint cannot be assessed from the registered information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s intended question and design, but it does not report the primary outcome result. It specifies fibrosis of grade 2 or higher at 12 months after IORT as the primary measure, yet gives no observed count or rate for that endpoint. Without an outcome value and an endpoint denominator, the frequency of the specified fibrosis outcome cannot be assessed. The record also reports zero analyses, so there is no registered analysis result to interpret for the primary endpoint.
The study is single group, with no concurrent control arm described. Its findings, even if a primary result were available, would characterize outcomes observed among participants who received surgery and IORT. A single-group observation cannot by itself separate effects associated with the intervention from other explanations, such as the clinical course of recurrence, patient selection, or differences in care. Those alternatives are not measured by a concurrent control in this design. No causal comparison with another treatment strategy is available from the registry structure.
Precision is also not assessable for the primary endpoint. A point estimate alone would not show how much uncertainty surrounds the observed outcome; an interval estimate would help communicate that uncertainty. Neither an estimate nor an interval is reported in the registry record. The enrollment figure of 66 is not a substitute for the number assessed at the endpoint, and it does not reveal how many participants contributed to any analysis.
The safety record does contain group-level adverse-event counts. It lists 59 at risk and 3 affected for serious adverse events, and 59 at risk and 59 affected for other adverse events; deaths are listed as 6. The serious adverse event terms include lumbosacral radiculopathy, postoperative wound infection, and mastitis, each reported at 1.7%. These entries describe what the registry lists, but they do not supply timing, attribution, severity grades for each event, or a comparative safety context. The deaths count alone does not establish cause or relationship to treatment.
Other registered outcomes concern toxicities and disease-control or survival measures. Their names indicate the topics the study intended to capture, not the results observed. Outcome estimates, follow-up details, and statistical analyses for them are not reported in the registry record. Consequently, the registry supports a description of the trial design and selected safety counts, but not a conclusion about the size, precision, or comparative meaning of the primary endpoint or the other outcomes.
9. Statistical Methods Explained
For a binary endpoint, the basic descriptive result is the number of participants who meet the defined event criterion, considered in relation to the participants assessed for that endpoint. Here, the event criterion is fibrosis of grade 2 or higher at 12 months after IORT. The registry describes the measure as a rate while specifying participants as the unit and number as the parameter. Because neither the event count nor the number assessed is reported, no endpoint proportion can be read from the registered information. Enrollment does not establish how many participants had an evaluable assessment.
What does an interval estimate add?
In general, a confidence interval communicates the uncertainty around an estimated outcome under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that spans a broad range of plausible values leaves more uncertainty about the underlying frequency. An interval does not repair missing outcome data or remove bias from study design. No confidence interval for the primary endpoint is reported in the registry record, so its statistical precision cannot be described.
Why does the single-group design matter?
In general, an uncontrolled study can describe outcomes among participants who received the study intervention, but it cannot directly estimate a contrast against an alternative strategy. A treatment contrast requires outcomes under both strategies, with a design and analysis that support comparison. The registry identifies a single group receiving surgery and IORT and does not describe a control arm. Therefore, no comparative treatment effect is available from this record. The allocation field is NA, and the record also notes that the arms are not a like-for-like control comparison; the registered design itself is single group.
What does the planning illustration represent?
The registry’s planning assumptions describe an illustration based on the observed effect, rather than the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. The sample-size assumptions specify that time-to-event calculations give a total event count using Schoenfeld, while other calculations give participants per arm. These calculations are planning illustrations, not observed power and not evidence that the completed single-group trial was designed with those assumptions. In particular, equal allocation between two arms does not describe the registered single-group design. The observed effect details and the trial’s own sample-size justification are not reported in the registry record.
In general, an assumed effect size determines the scale of a planning calculation: planning for a smaller effect generally requires more information than planning for a larger effect, all else equal. Such calculations depend on assumptions about the outcome, allocation, significance level, and analysis. They are not retrospective proof that a study could detect a particular effect. No numerical sample-size illustration values are reported in the registry record details, and the planning assumptions should not be mistaken for evidence of a planned or achieved power level.
How should time-to-event outcomes be understood?
Time-to-event outcomes measure the time until an event, such as relapse or death, while accounting for the fact that some participants may not experience the event during observed follow-up. General methods for these outcomes use both event information and follow-up information; an event count alone does not describe the timing or completeness of observation. The registry lists local relapse-free survival, metastasis relapse-free survival, disease-free survival, overall survival, and the interval without mastectomy. It does not report event counts, time estimates, censoring information, or analysis methods for these outcomes. Accordingly, their statistical results cannot be interpreted from the registry record.
Over-dispersion is a general issue for count outcomes when variability exceeds what a chosen count model expects. If a model does not allow enough variability, its uncertainty estimates can be too small and its inferences too confident. This is a general statistical consideration, not a feature established for this trial: the registry record does not report a count model, an over-dispersion assessment, or any primary endpoint analysis.
Statistical significance and clinical importance are distinct general concepts. A test result addresses compatibility with a null hypothesis under specified assumptions; it does not itself convey the size or relevance of an outcome. An effect estimate and its uncertainty are needed to assess magnitude and precision, and clinical interpretation requires appropriate context. No primary endpoint estimate, confidence interval, or test result is reported in the registry record. The registered description alone therefore supports neither a significance judgment nor a claim about clinical importance.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists toxicity, local relapse-free survival, metastasis relapse-free survival, disease-free survival, overall survival, and the interval without mastectomy as secondary outcomes, alongside the primary fibrosis endpoint. Assessing multiple outcomes creates a general multiplicity issue: the chance of at least one apparently notable result can increase when many statistical tests are considered. Methods such as prespecifying a primary analysis or adjusting for multiple comparisons can address different aspects of this issue, but the appropriate approach depends on the study’s aims and analysis plan. A multiplicity strategy is not reported in the registry record.
The registry lists seven outcome measures but zero analyses. It does not report analysis populations, such as which participants were included in each endpoint analysis, nor how missing assessments or incomplete follow-up were handled. Missing-data methods are not reported in the registry record. This matters because the number enrolled may differ from the number assessed for an endpoint, and the pattern of missing assessments can affect how an observed frequency should be interpreted. No assumption about the reason for missing assessments or its effect can be made from the registry.
The registry also does not report an analysis plan, prespecified statistical tests, covariate adjustment, or interim analyses. Those details should not be inferred from the study’s completed status or from the endpoint names. With no registered analysis results, missing-data approach, or multiplicity strategy, readers cannot evaluate the robustness of outcome estimates or determine how analyses were selected and interpreted.
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 |
|---|---|---|---|
| Surgery and Intra Operative Radiotherapy | 3 | 59 | 5.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Surgery and Intra Operative Radiotherapy | 6 of 59 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Surgery and Intra Operative Radiotherapy | 59 of 59 |
Most frequent serious adverse event terms
| Event term | Organ system | Surgery and Intra Operative Radiotherapy |
|---|---|---|
| lumbosacral radiculopathy | Musculoskeletal and connective tissue disorders | 1 of 59 |
| postoperative wound infection | Infections and infestations | 1 of 59 |
| mastitis | Infections and infestations | 1 of 59 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Surgery and Intra Operative Radiotherapy |
|---|---|---|
| musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | 49 of 59 |
| skin and subcutaneous tissue disorders | Skin and subcutaneous tissue disorders | 37 of 59 |
| reproductive system and breast disorders | Reproductive system and breast disorders | 29 of 59 |
| vascular disorders | Vascular disorders | 25 of 59 |
| general disorders and reaction at the site of administration | General disorders | 16 of 59 |
| gastrointestinal disorders | Gastrointestinal disorders | 4 of 59 |
| psychiatric disorders | Psychiatric disorders | 4 of 59 |
| Infections and infestations | Infections and infestations | 3 of 59 |
| medical exams | Investigations | 3 of 59 |
| visual system disorder | Eye disorders | 2 of 59 |
Serious events with the highest arm-level rate: lumbosacral radiculopathy (1.7%), postoperative wound infection (1.7%), mastitis (1.7%).
The safety record lists a single group titled surgery and intraoperative radiotherapy. For serious adverse events, it reports 59 at risk and 3 affected. For other adverse events, it reports 59 at risk and 59 affected. The listed death count is 6. The three serious adverse event terms shown are lumbosacral radiculopathy, postoperative wound infection, and mastitis, each reported at 1.7%.
These figures should be read as the registry’s event summaries, not as a comparison between treatments. The record does not report a control group, so the counts do not estimate a difference in safety between strategies. It also does not provide event timing, participant-level overlap among categories, attribution to the intervention, or details about how the adverse-event categories were defined. The death count should not be interpreted as treatment-related mortality: cause and relationship to treatment are not reported in the registry record. The listed percentages are reproduced as reported and should not be treated as a complete account of adverse-event risk without further information on definitions and follow-up.
12. What the Result Does, and Does Not, Mean
The registered study addresses a practical question: whether repeat breast-conserving surgery combined with IORT can be evaluated for feasibility and tolerance after local recurrence of breast carcinoma. It identifies fibrosis at 12 months as the primary toxicity endpoint and names additional toxicity, relapse, survival, and mastectomy-free interval outcomes. The record also provides selected adverse-event counts. These details help readers understand the study’s purpose and the outcomes it intended to monitor.
However, the primary endpoint result is not reported in the registry record. There is no observed count or rate for fibrosis of grade 2 or higher, no stated endpoint denominator, and no estimate of uncertainty. As a result, the registry does not show how frequently the specified endpoint occurred or how precisely that frequency was estimated. The study’s completed status and enrollment figure do not fill that gap.
The single-group design also limits what can be concluded. The registry does not provide a concurrent control comparison, so the record cannot show whether outcomes differ from those under another treatment strategy. A result observed in a single group would describe that group; it would not, on its own, establish that the intervention caused an outcome or that outcomes would differ under an alternative approach.
The safety counts are descriptive, and the deaths count has no reported cause or treatment attribution. Likewise, the listed secondary outcomes identify intended topics rather than demonstrated results. Their estimates and analyses are not reported in the registry record. The appropriate reading is therefore bounded: the record documents the study design, primary endpoint definition, selected safety summaries, and stated outcomes, but it does not provide enough outcome analysis to judge endpoint frequency, precision, comparative effect, or causal impact.
13. Why This Trial Matters Statistically
Statistically, the trial matters because it illustrates the difference between a defined endpoint and an interpretable result. The registry identifies a specific fibrosis threshold and follow-up time, which gives the primary outcome a recognizable operational definition. But a definition alone is not an estimate. Without the event count, the assessed denominator, and an uncertainty measure, readers cannot quantify the endpoint or judge its precision.
The design also makes the distinction between feasibility description and comparative efficacy especially important. A prospective, multicenter, single-group study can organize observations across participating settings, but the registry does not describe a control group. It therefore cannot provide a direct comparison of outcomes under surgery plus IORT versus another strategy. This limitation is not resolved by naming several secondary disease-control and survival outcomes; those outcomes also require reported estimates and appropriate analysis.
The registry’s planning assumptions provide another statistical lesson. They describe an illustration using equal allocation between two arms, while the registered study model is single group. Planning illustrations can help readers understand how assumptions relate to a hypothetical design, but they should not be confused with the trial’s own sample-size rationale or a retrospective measure of power. The record does not report that rationale or the outcome analyses needed to judge what the completed study established.
Finally, the discrepancy between the endpoint’s description as a rate and its registered unit and parameter as participants and number highlights the value of clear reporting. A reader needs the event definition, numerator, denominator, analysis population, and uncertainty to understand a binary endpoint. The registry supplies the definition, but the remaining 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.
Several limitations specific to this trial follow from the registered information. The trial is single group, with no concurrent comparator described, so it cannot directly estimate a contrast with another treatment. Allocation is listed as NA and masking as none. The registry does not report details that would allow readers to assess the consistency of endpoint grading across the multicenter study, including assessor procedures or any quality-control approach.
The primary endpoint description contains an important reporting ambiguity: it calls fibrosis at 12 months a rate but specifies participants as the unit and number as the parameter. The observed endpoint count, number assessed, and rate estimate are not reported in the registry record. Enrollment of 66 should not be assumed to be the primary endpoint denominator. The record also does not report how incomplete follow-up or missing toxicity assessments were handled.
The registry states that axillary lymph node control depends on initial management and clinical and ultrasound assessment of N0 patients, with the approach chosen by the teams. This description indicates that care could vary by team and clinical context; the record does not report an adjustment strategy for such variation. Further details of the IORT procedure and the actual administration received are not reported in the registry record.
Finally, the registry lists zero analyses. It does not report outcome estimates, uncertainty intervals, analysis populations, multiplicity handling, or statistical methods for the primary and secondary outcomes. Safety counts are available, but event timing, attribution, and causes of death are not reported. These omissions limit interpretation of both efficacy-related outcomes and safety summaries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Intraoperative Radiotherapy After Local Recurrence in Breast Cancer — NCT02386371.
- Registry record last updated 2025-02-06; status last verified 2025-02.
- Results first posted 2025-02-06.
- 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
The registry record describes a completed prospective, multicenter, single-group Phase II feasibility study of repeat breast-conserving surgery with intraoperative radiotherapy after local recurrence of breast carcinoma. Enrollment is listed as 66; the recorded start is 2014-03 and primary completion is 2020-06-12. The registered phase field is NA, allocation is NA, and masking is none.
The primary endpoint concerns fibrosis of grade 2 or higher at 12 months after IORT, classified using NCI CTCAE v4.0. Its outcome count, denominator, and analysis are not reported in the registry record. The record lists seven outcome measures and zero analyses. Safety summaries include 3 affected for serious adverse events among 59 at risk, 59 affected for other adverse events among 59 at risk, and 6 deaths. No concurrent control group is described, and comparative outcome estimates are not reported in the registry record.