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 Combination Chemotherapy Before or After Surgery in Treating Patients With Colorectal Cancer With Liver Metastases That Could Be Removed By Surgery (NCT01189227), a randomized phase 3 study. The primary outcome is Recurrence-free Survival (RFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01189227 |
| Phase | Phase 3 |
| Condition | Colorectal Cancer, Metastatic Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | NSABP Foundation Inc |
| Results posted | Yes |
2. Clinical Question
Population
Patients with colorectal cancer and liver metastases that could potentially be removed by surgery. The registry record does not provide further eligibility details or a description of the population included in the primary-outcome analysis.
Intervention
Perioperative chemotherapy: mFOLFOX6 or FOLFIRI before hepatic resection, followed by chemotherapy after surgery. The arm description specifies 6 preoperative cycles and says postoperative treatment began 31-56 days after surgery, but the available description ends before its postoperative schedule is complete.
Comparator
Postoperative chemotherapy: hepatic resection followed by mFOLFOX6 or FOLFIRI beginning 31-56 days after surgery. The registry describes treatment every 2 weeks for 12 cycles.
Primary question
How does recurrence-free survival compare between the perioperative and postoperative chemotherapy strategies? The primary endpoint is described as time to recurrence or death, from study entry through a maximum of 5 years.
This is a question about treatment timing around surgery, not simply a comparison of chemotherapy with no chemotherapy. Both strategies include postoperative chemotherapy; the perioperative strategy also begins chemotherapy before resection. The record describes the rationale as potentially shrinking the tumor before surgery or treating remaining tumor cells after surgery, but it does not report a comparative result that answers whether one strategy produced longer recurrence-free survival.
Random allocation is recorded, while masking is listed as none. The registry record does not report additional eligibility criteria, the intended analysis population, or a treatment-effect estimate for the primary outcome. The trial is marked terminated, and enrollment is listed as 9. These details frame the question but do not establish the reason for termination or the outcome of the comparison.
3. Trial Design
The registry record describes a randomized, open-label, parallel-group Phase III study of perioperative chemotherapy for potentially resectable colorectal cancer liver metastases. Participants were assigned to postoperative chemotherapy or perioperative chemotherapy. Masking is listed as none, so the record does not describe the study as blinded. The sponsor is NSABP Foundation Inc. The recorded start is 2010-08, primary completion is 2011-12, enrollment is 9, and status is terminated.
In the postoperative-chemotherapy group, participants underwent hepatic resection first. Chemotherapy with mFOLFOX6 or FOLFIRI began 31-56 days after surgery, with treatment repeated every 2 weeks for 12 cycles. The registry describes intravenous treatment on day 1 over 3 hours and an additional fluorouracil dose over 46 hours using a portable pump.
In the perioperative group, the record describes mFOLFOX6 or FOLFIRI before surgery, repeated every 2 weeks for 6 cycles, followed by hepatic resection. It then says postoperative treatment began 31-56 days after surgery. The arm description is incomplete at that point, so the postoperative regimen and schedule for this group are not reported in the registry record.
The primary endpoint is recurrence-free survival, described as time to recurrence or death from study entry through a maximum of 5 years. Secondary outcomes listed include overall survival, resection rates, postoperative complications, and adverse events. Although the registry identifies these outcome areas, the primary-outcome data are not reduced to a single comparison. The record lists no analyses. The reason for termination, recruitment history, and details about treatment adherence are not reported in the registry record. Termination alone does not explain why the study stopped or what its findings would have been.
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 | Arm 1: Postoperative Chemotherapy | Arm 2: Perioperative Chemotherapy |
|---|---|---|
| STARTED | 6 | 3 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 6 | 3 |
Reasons for not completing this period:
| Reason | Arm 1: Postoperative Chemotherapy | Arm 2: Perioperative Chemotherapy |
|---|---|---|
| Study terminated due to low accrual | 6 | 3 |
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 | Postoperative Chemotherapy | Perioperative Chemotherapy | Total |
|---|---|---|---|---|
| Participants analysed | 6 | 3 | 9 | |
| Age Continuous | years | 64 (SD 14.9) | 55 (SD 13.9) | 61 (SD 14.4) |
| Sex: Female, Male: Female | Participants | 5 | 0 | 5 |
| Sex: Female, Male: Male | Participants | 1 | 3 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Recurrence-free Survival (RFS), measured over From study entry until the date of recurrence or death or for a maximum of 5 years..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
Recurrence-free survival (RFS) is the primary endpoint. The registry defines it as time from study entry until recurrence or death, with follow-up for a maximum of 5 years. This time-to-event measure combines two clinically relevant events into a defined endpoint: recurrence and death. A participant is counted as having an event when either occurs, according to the endpoint definition.
General: Time-to-event endpoints retain information about when an event occurs, rather than treating all events as if they happened at the same moment. They can also accommodate participants whose event has not been observed by the end of follow-up, provided the analysis handles that follow-up appropriately. Such observations are commonly described as censored: they contribute information up to the last time their event status is known, but are not treated as if an event occurred then.
The registry record does not report the censoring rules, the method used to estimate RFS, the analysis population, or a numerical comparison between treatment groups. It also lists the primary outcome as having several categories or time points and not reduced to one comparison. Consequently, the endpoint definition alone does not show whether recurrence-free survival differed between strategies, how large any difference was, or how precisely it was estimated. The reason RFS was selected over other outcomes is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and design, but it does not provide a single primary-outcome comparison that can be interpreted as an estimate of the difference in recurrence-free survival. The primary outcome is time to recurrence or death, yet the record flags that the outcome has several categories or time points and was not reduced to one comparison. No numerical RFS estimate, treatment-effect estimate, confidence interval, or p-value is reported in the available primary-outcome record. The record lists no analyses.
Enrollment is listed as 9, and the study status is terminated. These registry entries matter when assessing how much information the study might contribute, but they do not identify why the study stopped or establish what the results would have been under continued enrollment. A reason for termination and a recruitment history are not reported in the registry record. The enrollment figure should not be used to infer the number included in any particular outcome analysis or the allocation to each arm.
General: A treatment-effect estimate describes the direction and size of a contrast between groups. A confidence interval communicates the range of values reasonably compatible with the observed data and the analysis assumptions. The interval’s width is important: a broad interval indicates limited precision, while a narrower interval indicates greater precision. A p-value addresses compatibility with a specified null hypothesis under a statistical model; it does not quantify the clinical importance of an effect. None of these quantities can be interpreted for the primary comparison without a reported estimate and analysis.
Secondary outcomes are named, including overall survival, resection rates, postoperative surgical complications, and adverse events. Their inclusion in the registry does not supply findings for them. The serious and other adverse-event counts are reported separately, but they do not substitute for the missing primary RFS comparison. Nor can the safety entries establish an overall balance of benefit and harm: the record does not provide the full treatment exposure, analysis methods, or complete clinical context needed for such an assessment.
Accordingly, the registry record supports describing what was intended to be compared and what outcome was designated as primary. It does not support a conclusion that either strategy improved or worsened recurrence-free survival, nor a claim that the strategies were equivalent. Absence of a reported comparison is not evidence that the groups had the same outcome. The posted information leaves the magnitude, direction, and precision of the primary treatment contrast unresolved.
9. Statistical Methods Explained
The registry identifies random allocation, no masking, a parallel-group model, and recurrence-free survival as the primary outcome. It does not report the statistical analysis plan or a completed primary-outcome comparison. The concepts below explain how these methods are generally used; they should not be read as a description of analyses performed in this study unless the registry record explicitly says so.
What does random allocation contribute?
General: Random allocation uses a chance-based process to assign participants to study groups. When implemented and maintained appropriately, it helps make the groups comparable at the start with respect to both measured and unmeasured characteristics. This reduces the risk that the treatment comparison is systematically shaped by clinical decisions about who receives which strategy. Randomization does not guarantee that groups will be perfectly balanced, especially when enrollment is limited, and it does not remove the need for a suitable analysis. The registry records that allocation was randomized, but the sequence-generation method, concealment procedures, and any stratification factors are not reported in the registry record.
What does no masking mean?
General: Masking means keeping knowledge of assigned treatment from participants, clinicians, outcome assessors, or analysts. The registry lists masking as none. In an open-label comparison, awareness of treatment can influence care or the measurement and recording of outcomes, depending on the outcome and how it is assessed. Recurrence and death are comparatively concrete events, but the registry does not describe independent outcome review, adjudication, or safeguards against differences in ascertainment. Those procedures are not reported in the registry record.
How is recurrence-free survival usually analyzed?
General: Time-to-event analysis accounts for both whether an event occurred and when it occurred. A survival curve can display the proportion remaining free of the defined event over follow-up, while a hazard ratio or another contrast may summarize the relative event experience between groups. These approaches require assumptions and clear definitions, including how censoring is handled and how the event date is determined. A registry endpoint definition is not, by itself, a statistical analysis plan. The RFS analysis method, censoring rules, model specification, and any checks of model assumptions are not reported in the registry record.
The registry describes RFS as time to recurrence or death from study entry through a maximum of 5 years. Combining recurrence and death means that either event satisfies the endpoint definition. This can be useful when both outcomes are important, but a combined endpoint does not show which event contributed to a group-level result. The record does not provide separate component results or a reduced comparison for the primary outcome.
Why do precision and uncertainty matter?
General: An estimate is more informative when read together with its uncertainty. A confidence interval can show the range of effect sizes compatible with the data under the chosen method. A narrow interval may allow more precise conclusions than a wide interval. A non-significant test result, if one were reported, would not on its own demonstrate equivalence or rule out effects that matter; the estimate and its interval are needed to understand what remains plausible. No primary-outcome estimate, confidence interval, or test result is reported in the registry record, so the precision of the comparison cannot be evaluated.
What do planning calculations mean?
General: Sample-size calculations are planning tools based on assumptions about the effect to detect, the error rate, allocation, and analysis method. The record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says that time-to-event calculations give a total number of events, while other calculations give participants per arm. These are planning illustrations, not observed power and not evidence that the study achieved a particular probability of detecting an effect. The record does not report the study’s own sample-size justification or establish that these planning assumptions were the study’s design assumptions.
General: Over-dispersion occurs when variability in observed outcomes is greater than a statistical model assumes. If unaccounted for, it can make standard errors and confidence intervals too optimistic. The registry record does not describe an over-dispersion assessment or a model for count outcomes. This general issue does not imply that over-dispersion was present or that any particular method was used in this study.
The record does not report interim analyses, stopping rules, adjustments for the primary-outcome analysis, or a prespecified statistical plan. These omissions prevent a detailed assessment of how the investigators intended to handle uncertainty, outcome timing, and analysis decisions. They should not be filled in by assuming standard practice.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcome areas alongside recurrence-free survival: overall survival, resection rates, postoperative complications, and adverse events. Testing or estimating several outcomes can raise multiplicity concerns. General: When many statistical hypotheses are examined, the chance of at least one apparently notable result can increase if no adjustment or interpretive strategy is specified. Researchers may address this through prespecified outcome hierarchies, adjusted testing, or careful emphasis on estimates and uncertainty rather than isolated p-values. The registry record does not report a multiplicity strategy or a statistical analysis plan.
The primary outcome is described as having several categories or time points and not reduced to one comparison. The record lists no analyses. Therefore, there is no single primary treatment contrast available for interpretation, and no reported inferential results that can be checked for multiplicity handling. The precise structure of the categories or time points is not reported in the registry record.
Missing-data procedures and the primary analysis population are also not reported in the registry record. General: In a time-to-event analysis, incomplete follow-up is often handled through censoring, but valid interpretation depends on when follow-up ends and on assumptions about why it ends. For other outcomes, investigators may specify how missing measurements or withdrawals are handled. The registry’s RFS timeframe does not establish the censoring method, the completeness of follow-up, or how missing outcome information was treated.
The record does not state whether the primary analysis was intended to follow randomized assignment, whether participants were analyzed according to treatment received, or how deviations from assigned treatment were handled. It also does not report an interim-analysis plan or stopping rules. These are not grounds for assuming that the analysis was inappropriate; they are unreported details that limit assessment of the analysis and its potential biases.
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 |
|---|---|---|---|
| Postoperative Chemotherapy | 1 | 5 | 20.0% |
| Perioperative Chemotherapy | 0 | 2 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Postoperative Chemotherapy | 3 of 5 |
| Perioperative Chemotherapy | 1 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Postoperative Chemotherapy | Perioperative Chemotherapy |
|---|---|---|---|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 5 | 0 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Postoperative Chemotherapy | Perioperative Chemotherapy |
|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 0 of 5 | 1 of 2 |
| Alkaline phosphatase increased | Investigations | 1 of 5 | 0 of 2 |
| Anemia | Blood and lymphatic system disorders | 1 of 5 | 0 of 2 |
| Anorexia | Metabolism and nutrition disorders | 1 of 5 | 0 of 2 |
| Dehydration | Metabolism and nutrition disorders | 1 of 5 | 0 of 2 |
| Diarrhea | Gastrointestinal disorders | 1 of 5 | 0 of 2 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 5 | 0 of 2 |
| Fatigue | General disorders | 1 of 5 | 0 of 2 |
| Hypokalemia | Metabolism and nutrition disorders | 1 of 5 | 0 of 2 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 1 of 5 | 0 of 2 |
Serious events with the highest arm-level rate: respiratory failure (20.0%).
The registry reports adverse-event counts by treatment group. For postoperative chemotherapy, serious events are listed as 1 affected among 5 at risk, and other events as 3 affected among 5 at risk. For perioperative chemotherapy, serious events are listed as 0 affected among 2 at risk, and other events as 1 affected among 2 at risk. These are the registry’s reported counts; they should not be treated as a complete comparative safety analysis.
Respiratory failure is listed among the top serious terms at 20.0%. The registry entry does not identify its treatment-group attribution in this listing, so it should not be assigned to a group based on these figures. Death counts are not reported in the registry record. The registry separately lists frequencies of selected postoperative surgical complications and other adverse events within 30 days of surgery, and adverse events assessed by NCI CTCAE v4.0, but the listed outcome names do not provide their full results or analysis details.
General: “At risk” is the denominator recorded for the adverse-event entry; it does not necessarily describe the population used for the primary outcome. Differences in exposure duration, event definitions, follow-up, or reporting can affect safety comparisons. The record does not provide enough information to reconstruct those features or explain the group-specific denominators. The counts should therefore be read as descriptive registry entries, not as proof of a treatment-related difference.
12. What the Result Does, and Does Not, Mean
The record documents a randomized comparison of two chemotherapy-timing strategies for patients with potentially resectable colorectal cancer liver metastases. One strategy placed chemotherapy after hepatic resection; the other began chemotherapy before resection and continued after surgery. Recurrence-free survival, defined by time to recurrence or death, was the primary endpoint. These details make the intended clinical and statistical question clear.
The posted results do not answer that question with a single RFS comparison. The registry states that the primary outcome had several categories or time points and was not reduced to one comparison, and it lists no analyses. No effect estimate, confidence interval, or p-value for RFS is reported. Consequently, the result does not establish the direction or size of a difference, the precision of any difference, or whether the strategies had similar outcomes.
Enrollment is listed as 9 and the status is terminated. These registry entries indicate the recorded enrollment and status, not the reason the study terminated or the quality of the outcome data. The reason for termination, the primary analysis population, and the statistical analysis plan are not reported in the registry record. The listed safety counts provide descriptive information but do not resolve the efficacy question or establish a full safety comparison.
General: A missing or unreported statistical result should not be interpreted as a finding of no effect. Equivalence requires a defined margin and an analysis precise enough to exclude differences outside that margin; neither is reported in the registry record. Similarly, the trial’s planned purpose and a statistical planning illustration do not stand in for observed evidence. The defensible interpretation is limited to the design and the information actually recorded: a treatment-timing comparison was registered, but the primary comparative outcome is not available as an interpretable estimate.
13. Why This Trial Matters Statistically
This study raises a statistically important design question: whether starting chemotherapy before surgery and continuing it afterward changes recurrence-free survival compared with giving chemotherapy after surgery. Because both strategies include postoperative treatment, the intended contrast concerns timing and the addition of a preoperative treatment period, rather than chemotherapy versus no chemotherapy. Clear definition of that contrast is essential when interpreting an estimate.
Recurrence-free survival is a time-to-event endpoint, so its analysis requires more than comparing event counts. The time until recurrence or death and the handling of participants without an observed event both matter. The registry defines the endpoint and its maximum follow-up period, but does not report the analysis method, censoring rules, or a primary treatment-effect estimate. This illustrates why endpoint wording alone cannot convey the statistical result.
The record also shows why study status and enrollment must be read separately from evidence about treatment effects. Enrollment is listed as 9, and the study is marked terminated, but the reason for termination is not reported. Neither detail can establish whether the trial was able to answer its question. The absence of a reduced primary comparison leaves the direction and precision of any difference unresolved.
Finally, the record includes multiple secondary outcome areas and descriptive adverse-event counts. These can be relevant to a complete assessment, but they do not replace an interpretable primary comparison or a prespecified approach to multiple outcomes. Without the statistical plan and reported analyses, readers cannot assess how outcomes were prioritized or how uncertainty was handled. The trial therefore matters statistically as an example of the distinction between a registered question, a defined endpoint, and a reported treatment-effect result.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation in the registry record is that recurrence-free survival is not reduced to a single comparison. The outcome is defined as time to recurrence or death from study entry through a maximum of 5 years, but no group-level estimate or uncertainty interval is reported. The record lists no analyses. This prevents assessment of the primary treatment contrast and its precision.
Enrollment is recorded as 9 and the study status is terminated. The reason for termination is not reported in the registry record, and the enrollment figure does not establish the size or composition of the primary-outcome analysis population. The record does not state how many participants were included in an RFS analysis, how follow-up ended for participants without events, or how missing outcomes were handled.
The treatment description for the perioperative group is incomplete after surgery. It reports preoperative cycles and says postoperative chemotherapy began 31-56 days after surgery, but the remaining postoperative schedule is not available in the registry record. This limits the ability to describe the full planned treatment contrast. The method of random sequence generation, allocation concealment, outcome adjudication, and adherence to assigned treatment are also not reported.
The statistical analysis plan, sample-size justification, primary analysis population, interim analyses, stopping rules, and multiplicity strategy are not reported in the registry record. The listed adverse-event denominators and counts are descriptive and do not include enough information to establish exposure, follow-up, or a comparative safety analysis. These limitations constrain interpretation of the posted information; they do not establish that unreported procedures were or were not performed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Combination Chemotherapy Before or After Surgery in Treating Patients With Colorectal Cancer With Liver Metastases That Could Be Removed By Surgery — NCT01189227.
- Registry record last updated 2013-05-10; status last verified 2013-05.
- Results first posted 2013-03-15.
- 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
NCT01189227 is a randomized, open-label, parallel-group Phase III study sponsored by NSABP Foundation Inc. It compared postoperative chemotherapy with chemotherapy given before and after hepatic resection for potentially resectable colorectal cancer liver metastases. Enrollment is listed as 9, the start as 2010-08, primary completion as 2011-12, and status as terminated.
The primary endpoint was recurrence-free survival, defined as time to recurrence or death through a maximum of 5 years. The registry record does not provide a single primary-outcome comparison and lists no analyses. The reason for termination, analysis methods, and primary analysis population are not reported in the registry record. Adverse-event counts are listed by group, but do not constitute a complete comparative safety analysis.