Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer (NCT00889187), a non-randomized phase 1, phase 2 study. The primary outcome is Dose Limiting Toxicity (DLT) [Phase I].

2. Clinical Question

3. Trial Design

This was a Phase I/II, non-randomized, single-group study with no masking. Dana-Farber Cancer Institute was the sponsor. The recorded start was 2009-12, primary completion was 2011-12-30, and the study status is terminated. Enrollment was 10. The registry record does not report why the study was terminated.

The Phase I component evaluated short-course photon radiation dose schedules with capecitabine. The cohort descriptions include 30 Gy in 10 fractions, given at 3 Gy per day over 12 days; 25 Gy in 5 fractions at 5 Gy per fraction over 11 days; and 25 Gy in 5 fractions at 5 Gy per fraction over 5 days. Capecitabine was described as oral treatment at 825 mg/m2 BID, for a total of 1650 mg/m2 per day, on ten consecutive weekdays. The full timing details are not reported in the registry record.

The Phase II description says participants received the radiation regimen established in Phase I, together with capecitabine. A concurrent comparison arm is not described. Although the study purpose mentions local control relative to historical controls, the registry record does not report the historical-control data, the comparison method, or a comparative result. Consequently, differences among the Phase I cohorts should not be read as randomized treatment contrasts: the record identifies dose schedules but does not establish that the cohorts were exchangeable.

The primary outcome was Phase I dose-limiting toxicity. Listed Phase II secondary outcomes were local recurrence rate, pathologic response rate, progression-free survival, surgical morbidity rate, and surgical mortality rate. There are eight outcome measures recorded, but the registry record does not report analyses for them. It also does not report a detailed statistical analysis plan, the sample-size justification, interim analyses, or a reason for ending the study.

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

Analysis population for the primary outcome, as defined in the registry: The analysis dataset is comprised of all treated patients.

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 Dose Limiting Toxicity (DLT) [Phase I], measured over within 3 weeks of the start of chemoradiation therapy.

The primary endpoint counts treated patients who had a dose-limiting toxicity within 3 weeks of the start of chemoradiation therapy. The registry record defines qualifying events to include specified severe hematologic or non-hematologic toxicity, treatment interruption or delay, treatment-related death, and delays in surgery attributed to treatment-related toxicity. It also treats a 30% increase in certain surgical complication rates beyond previously established rates as a dose-limiting toxicity. Those reference rates are listed as readmission rate: 16%; pancreatic fistula/intra-abdominal abscess/infection rate: 27%; major intra-abdominal bleeding requiring return to OR: 1.6%; delayed gastric emptying: 4.4%; and superficial wound infection rate: 8%.

This endpoint is used in dose-finding research to identify treatment toxicity that may constrain a regimen. In general, a count makes the number of affected participants explicit, while its interpretation depends on the number treated, the event definition, and the period of observation. The registry record specifies the endpoint population as all treated patients and gives the time window, but it does not report the number with a dose-limiting toxicity. It therefore does not support a numerical estimate of the primary endpoint from the record.

The endpoint combines several kinds of events and clinical consequences under one definition. That can support a practical assessment of tolerability during regimen development, but it also means that a total count alone would not describe which event types occurred or their severity. The registry record does not report an endpoint breakdown or an analysis of the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record names dose-limiting toxicity as the primary endpoint and defines it as a count of patients. It does not report a statistical analysis for that endpoint. The method discussion below explains general statistical ideas relevant to this design; it does not describe undocumented procedures used by the investigators.

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who received the study regimen. Without a concurrent comparison group, it does not directly estimate the contrast between the regimen and another treatment assigned under the same study conditions. This study is described as non-randomized and single-group, with no masking. Its Phase I cohorts used different radiation schedules, but the registry record does not describe random assignment to those schedules. Thus, differences in posted cohort counts would be descriptive rather than evidence of a causal dose-schedule effect.

The study purpose refers to comparing local control with historical controls. In general, historical comparisons can be informative but are vulnerable to differences in eligibility, clinical care, follow-up, and outcome definitions across settings or periods. A valid interpretation requires details about how the historical group was selected and analyzed. Those details and the comparative data are not reported in the registry record.

How should event counts be understood?

For a binary outcome, each participant is classified according to whether an event occurred during the specified period. A count is the number classified as having the event; its denominator is the number assessed or at risk. The primary outcome uses a count of patients with dose-limiting toxicity, and the adverse-event entries report affected and at-risk counts for each cohort. General interpretation depends on a consistent event definition, complete follow-up, and an appropriate denominator. The primary endpoint window is stated as within 3 weeks of starting chemoradiation therapy, but the primary result is not reported.

Small denominators make estimates unstable: the outcome of a single participant can materially change a cohort's observed proportion. In general, uncertainty intervals can communicate that imprecision more clearly than a point estimate alone. The registry record does not report confidence intervals or other inferential statistics for the primary endpoint or the adverse-event counts. No precision estimate should be inferred from the counts alone.

Why does the endpoint definition matter?

The primary definition groups several qualifying events, including toxicity grades, treatment interruption, death, and surgery delay, and incorporates specified increases in surgical complication rates. A composite definition can capture multiple ways a regimen might create a clinically important problem. In general, however, a composite count does not show which components drove the result. Component-specific counts and the adjudication process would help explain what contributed to any total. Such a breakdown is not reported in the registry record.

The listed benchmark rates for surgical complications are part of the recorded definition: readmission rate: 16%; pancreatic fistula/intra-abdominal abscess/infection rate: 27%; major intra-abdominal bleeding requiring return to OR: 1.6%; delayed gastric emptying: 4.4%; and superficial wound infection rate: 8%. These are stated reference rates within the endpoint description. The registry record does not report a statistical procedure for determining whether the defined 30% increase criterion was met in this study.

What can be said about planning assumptions?

General sample-size planning asks how much information a proposed study needs to detect an effect under specified assumptions. The planning illustration associated with this trial uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. For time-to-event outcomes, the planning quantity is total events; for other outcomes, it is participants per arm. These are planning conventions, not observed trial results or observed power. They do not describe the actual single-group Phase I/II design, and the registry record does not report the trial's own sample-size justification.

In general, over-dispersion matters when observed variability exceeds what a simple model assumes. Ignoring it can make uncertainty estimates too narrow. The registry record does not report a dispersion parameter or an analysis model for the primary endpoint; the outcome is recorded as a count, and no analysis is listed.

What analysis information is absent?

The registry record reports zero analyses. It does not report a detailed statistical analysis plan, any interim analyses, methods for handling missing outcomes, or confidence intervals and hypothesis tests for the endpoint. It states that the primary endpoint population comprises all treated patients, but does not provide an analysis population count or a primary endpoint result. General statistical interpretation should distinguish these omissions from evidence that a particular method was or was not used: the relevant procedures are simply 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("Phase 1 Cohort 1: Photon Rad (30 Gy/12 Days)+Capec", "Phase I Cohort 2: Photon Rad (25 Gy/11 Days)+Capec", "Phase I Cohort 3: Photon Rad (25 Gy/5 Days)+Capeci")
n      <- c(3, 3, 4)
events <- c(0, 0, 0)
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  Phase 1 Cohort 1: Photon Rad (30 Gy/12 Days)+Capec  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Phase I Cohort 2: Photon Rad (25 Gy/11 Days)+Capec  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Phase I Cohort 3: Photon Rad (25 Gy/5 Days)+Capeci  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome, Phase I dose-limiting toxicity, and five named Phase II secondary outcomes: local recurrence rate, pathologic response rate, progression-free survival, surgical morbidity rate, and surgical mortality rate. It records eight outcome measures and zero analyses. The additional outcome names and their results are not reported in the registry record.

In general, multiplicity arises when several outcomes or statistical tests are examined. Testing many hypotheses can increase the chance of at least one apparently notable result, so a prespecified analysis plan may define which outcomes are primary and whether any adjustment or hierarchy will be used. The registry record does not report a multiplicity adjustment, a hierarchy among the secondary outcomes, or a detailed statistical analysis plan. With no analyses reported, there are no posted test results to interpret for multiplicity.

Missing-data methods are also not reported in the registry record. The primary endpoint description says its analysis dataset comprises all treated patients, but that statement does not specify how a treated patient with incomplete toxicity follow-up would be handled. The record does not report the number with missing endpoint information, the completeness of follow-up, or any imputation or sensitivity analysis. It would be inappropriate to assume that missing values were absent or handled in a particular way.

The listed Phase II outcomes can require distinct definitions and observation periods. The record names them but does not report their operational definitions, analysis populations, censoring rules for progression-free survival, or results. Those details matter for interpreting any analysis; they cannot be reconstructed from the outcome names alone.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (33.3%), diarrhea (33.3%), lymphopenia (33.3%), infection-other (33.3%), hemorrhage/bleeding-other (33.3%).

The safety entries list serious and other adverse events by Phase I cohort. For serious events, Cohort 1 reports 2 affected among 3 at risk, Cohort 2 reports 2 among 3, and Cohort 3 reports 0 among 4. For other events, the corresponding posted counts are 3 among 3, 3 among 3, and 4 among 4. No deaths are listed in any of the three cohorts.

These figures are descriptive counts. They do not establish that one radiation schedule is safer than another: the study was non-randomized, did not use a like-for-like control comparison, and the cohorts are small. The registry record does not report statistical comparisons, confidence intervals, or a complete account of event timing and duration. A count of affected participants also does not necessarily represent the total number of event episodes.

The listed serious terms are nausea, diarrhea, lymphopenia, infection-other, hemorrhage/bleeding-other, and vomiting, each at 33.3%. The registry record does not clarify the denominator or whether terms could overlap within a participant. These percentages should be read as the recorded term frequencies, not added together or treated as separate groups of people. The record does not report further detail about severity, attribution, or outcomes for these terms.

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

The record establishes that this was a Phase I/II study of neoadjuvant short-course photon radiation with capecitabine for resectable pancreatic cancer, with enrollment of 10 and a terminated status. It describes three Phase I radiation schedules and defines dose-limiting toxicity as the primary endpoint within 3 weeks of starting chemoradiation therapy. It also posts cohort-level adverse-event counts, including no deaths listed in those cohorts.

Those details do not establish the primary endpoint result. The registry record does not report how many treated participants experienced a dose-limiting toxicity, nor does it report a primary endpoint analysis. It also does not report analyses for the named Phase II outcomes. Therefore the record does not support conclusions about local recurrence, pathologic response, progression-free survival, surgical morbidity, or surgical mortality.

In general, an observed count describes the participants recorded in a study; it is not automatically a precise estimate for other patients or settings. This is especially important when cohort sizes are small. The registry record does not provide confidence intervals or comparative analyses that would quantify uncertainty or support a treatment contrast.

The study purpose mentions evaluating local control relative to historical controls, but no historical-control results or comparative methods are reported. A stated aim is not itself evidence that the comparison was conducted or that a difference was observed. Likewise, a terminated status does not explain why the study ended; the reason is not reported in the registry record.

The appropriate reading is therefore limited to the design, endpoint definition, and posted safety counts. The registry entry does not establish a causal treatment effect, a comparative safety advantage, or a definitive estimate of toxicity. Missing outcome results should not be interpreted as evidence of either favorable or unfavorable findings.

14. Why This Trial Matters Statistically

This study is statistically notable for combining a dose-finding phase with a Phase II evaluation in a single-group, non-randomized design. Phase I explores dose schedules, while a Phase II component is described as using the regimen established in Phase I. That structure makes clear why dose selection and outcome evaluation are different questions: identifying a regimen for further study does not, by itself, provide a controlled estimate of its effect on clinical outcomes.

The primary endpoint also illustrates the importance of a transparent event definition. Dose-limiting toxicity includes several toxicity grades and treatment consequences, as well as a specified criterion involving increases in surgical complication rates. Such a definition can capture more than one type of potential harm, but interpretation depends on knowing which components occurred and how the composite was applied. The registry record gives the definition but does not report the primary result or component breakdown.

The small cohort counts emphasize the distinction between descriptive observations and precise estimates. In general, with limited numbers, a few outcomes can substantially affect the apparent frequency. Statistical uncertainty and design limitations are important even when the count itself is simple to understand. The record does not report confidence intervals or hypothesis tests for the posted safety counts.

Finally, the stated interest in historical local-control comparisons shows why the choice of comparator matters. Without concurrent randomization, any historical comparison requires careful assessment of comparability and methods. Those data and methods are not reported. The record thus offers a useful example of how a registry can describe a study rationale and design while leaving the central outcome analysis unavailable for interpretation.

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 registry record does not report the primary dose-limiting toxicity result, despite defining the endpoint and its observation window. It also reports zero analyses, so the named primary and secondary outcomes cannot be assessed from reported statistical results. This prevents estimation of the study's primary endpoint and limits interpretation to the design description and posted safety counts.

The non-randomized, single-group design has no concurrent control arm. The Phase I cohorts should not be treated as comparable treatment groups, and any historical comparison would require data and methods that are not reported in the registry record. The record does not report a reason for termination, a sample-size justification, interim analyses, or a detailed analysis plan.

The recorded enrollment is 10, and the adverse-event entries show small cohort counts. These data provide limited precision for describing uncommon events or comparing schedules. Confidence intervals and statistical comparisons are not reported. The registry record also does not report participant characteristics, completeness of follow-up, handling of missing data, or whether all enrolled participants were treated.

The primary endpoint combines multiple toxicity and surgical criteria, but the registry record does not report the number of events by component or how the surgical complication threshold was evaluated. For the listed serious terms, the denominator and possible overlap among terms are not specified. These omissions constrain interpretation of both the composite endpoint and the safety listings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer — NCT00889187.
• Registry record last updated 2018-05-11; status last verified 2018-04.
• Results first posted 2017-07-14.
• 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

This terminated Phase I/II study enrolled 10 participants and evaluated short-course photon radiation with capecitabine before surgery for resectable pancreatic cancer. It was non-randomized, used a single-group model, and had no masking. Phase I descriptions include three radiation schedules; Phase II used the regimen established in Phase I.

The primary outcome was the number of treated patients with dose-limiting toxicity within 3 weeks of starting chemoradiation therapy. The registry record lists local recurrence, pathologic response, progression-free survival, surgical morbidity, and surgical mortality as Phase II secondary outcomes. It posts cohort-level adverse-event counts and lists no deaths in those cohorts, but reports zero analyses. The primary endpoint result, Phase II results, historical-control comparison, reason for termination, and detailed statistical analysis plan are not reported in the registry record.