Cryotherapy and GM-CSF in Treating Patients With Lung Metastases or Primary Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cryotherapy and GM-CSF in Treating Patients With Lung Metastases or Primary Lung Cancer (NCT00514215), a na phase 2 study. The primary outcome is Immunologic Response as Measured by ELISPOT Assay and Flow Cytometry.

2. Clinical Question

The clinical question is consequently about whether immune measurements changed or indicated a response during the treatment course, not about a randomized comparison of cryosurgery plus sargramostim against another treatment. The registry rationale describes freezing tumor cells and using GM-CSF around cryotherapy. The arm description, however, specifies inhaled sargramostim on treatment days and does not describe an injection schedule. A further description associated with the primary outcome refers to CT-guided biopsy and peritumoral GM-CSF, and includes criteria for radiographic tumor response. These details do not fully align with the immunologic endpoint title. The record does not explain the relationship between the immune measurements, the radiographic criteria, and the listed treatment schedule. The study enrolled 8 participants, and results for the primary question are not reported in the registry record.

3. Trial Design

This was a phase II, completed, single-group study with enrollment of 8 participants. The record lists allocation as not applicable, no masking, and a single-group model. It therefore does not describe random assignment, blinding, or a concurrent control arm. The registry record does not report a statistical comparison between treatment groups, and the study should not be read as a like-for-like controlled comparison.

The study title describes cryotherapy and GM-CSF for patients with lung metastases or primary lung cancer. The listed population for the primary outcome is patients who had metastatic renal cell carcinoma. The record does not clarify whether every participant had this diagnosis or how the population wording relates to the broader title. The sponsor was Barbara Ann Karmanos Cancer Institute. The study started in 2006-01, reached primary completion in 2010-03, and is marked completed.

The arm description lists sargramostim, flow cytometry, biopsy, immunoenzyme technique, and cryosurgery. Sargramostim was inhaled at 250 μg two times a day on days 4-10 and days 36-42. Flow cytometry, immunoenzyme technique, and CT-guided biopsy were scheduled on days 1 and 32; cryosurgery was scheduled on days 1 and 32. The brief rationale also mentions an injection of GM-CSF before cryotherapy, but the arm schedule does not specify such an injection. The record does not explain this difference in wording.

The trial lists clinical response by CT criteria, toxicity of grade 1 or higher, and immune function and cancer-specific response as secondary outcomes. The registry record does not report its sample-size justification, detailed analysis plan, or the rationale for the selected enrollment. The reported design describes an exploratory, one-group treatment course rather than a controlled estimate of comparative benefit.

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: Patients who had metastatic Renal Cell carcinoma

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 Immunologic Response as Measured by ELISPOT Assay and Flow Cytometry, measured over Days 1 & 32.

The registry names the primary endpoint as immunologic response measured by ELISPOT assay and flow cytometry. Its unit is participants, and the stated timeframe is days 1 and 32. A participant-count endpoint would ordinarily report how many people met a prespecified response definition; however, the registry record does not report a response count or the definition used to classify immunologic response. It also does not report assay values, changes between measurement days, or a statistical analysis of those measurements.

General: immune assays can be used to characterize biological activity, while clinical outcomes such as tumor response address changes in disease status. An assay-based endpoint may therefore answer a different question from an imaging endpoint. The registry description for this endpoint also includes CT-guided biopsy, peritumoral GM-CSF, and definitions of complete response, partial response, stable disease, and progressive disease based on CT appearance. Those criteria describe radiographic tumor status, but they do not establish how the primary immunologic endpoint was scored. The record does not explain whether the CT criteria were intended as part of the primary endpoint or as separate clinical response measures.

The immune endpoint is relevant to the study’s stated interest in immune function following cryosurgery and sargramostim. Without a reported response definition and result, it is not possible to determine what counted as an immunologic response or how many participants met that criterion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a single-group study and no statistical analysis results for its outcomes. The following concepts are general explanations of how the listed endpoint types are commonly interpreted; they are not a description of an analysis plan that the record does not report.

What does a participant count represent?

The primary endpoint is expressed in participants, which indicates a count-based outcome rather than a continuous measurement in the way it is presented in the record. To interpret such an endpoint, readers need a clear rule for classifying each participant as having or not having the event or response. They also need the number assessed, the number meeting the criterion, and the time point or period used. The record gives the primary timeframe as days 1 and 32, but does not report the response count or the immunologic response rule. The CT response definitions in the description do not resolve that gap because they define radiographic categories rather than an ELISPOT or flow-cytometry response.

How should a confidence interval be read?

General: a confidence interval communicates uncertainty around an estimated quantity. It is not a guarantee that the true value lies within a particular interval, nor does it describe the results for individual participants. A narrow interval generally indicates greater precision than a wide one, under the chosen method and its assumptions. No confidence interval for the primary endpoint is reported in the registry record. With no reported endpoint estimate or interval, the precision of the primary result cannot be judged.

What does a p-value address?

General: a p-value is calculated relative to a statistical model and a null hypothesis. It describes how unusual the observed data, or more extreme data, would be if that null hypothesis and model were true. It does not measure the size or clinical importance of an effect, and it does not by itself show that a result is reliable. Its interpretation depends on the endpoint, analysis population, model, and any multiplicity considerations. The registry record does not report a primary endpoint p-value, a hypothesis test, or a detailed statistical plan. No inferential conclusion should be reconstructed from the enrollment count or safety figures alone.

Why does the single-group design matter?

General: a one-group study can describe outcomes among people who received the study regimen. When measurements are repeated, it may also describe changes within those participants if both measurements and an analysis are reported. A comparator group serves a different purpose: it enables a direct contrast under the study design. This trial is described as single group, with allocation not applicable and no masking. The record therefore does not describe a randomized or blinded comparison. A before-and-after measurement, even if reported, would not by itself establish what would have happened under another treatment or without the study regimen.

How should the planning illustration be understood?

The documented assumptions for the planning illustration specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is based on fractions of an observed effect and is described as planning rather than as the trial’s own design. For outcomes other than time-to-event outcomes, the stated convention is participants per arm; time-to-event planning uses a total number of events. These are hypothetical planning assumptions, not features of the actual single-group study. The record does not provide a trial-specific sample-size justification. The planning assumptions do not turn the 8 enrolled participants into evidence of observed power, and no power estimate should be inferred from them.

Why can outcome definitions and analysis choices matter?

General: response rules determine which observations count as events, while analysis choices determine how those observations are summarized and compared. For laboratory measures, interpretation may depend on whether the endpoint uses a threshold, a change from baseline, or another prespecified rule. For imaging outcomes, criteria and assessment timing can affect classification. Missing measurements also matter because participants without follow-up data may not be classifiable under the endpoint rule. The registry record lists CT categories and assay names, but does not report the immunologic response definition, the method for combining assay results, or the handling of missing values.

General: over-dispersion occurs when counts vary more than a simple statistical model expects. When relevant, it can affect uncertainty estimates and model fit. The registry record does not report a count model or dispersion assessment, and the primary endpoint results are not available for judging whether such issues arose. It would be inappropriate to assign a model or a specific statistical property to the analysis without a reported plan or result. The same caution applies to adjustments, covariates, and repeated-measures methods: none is described in the registry record.

Overall, the available methodological information supports a clear description of the design and endpoint label, but not a reconstruction of the trial’s analysis. The registry record does not report the primary analysis method, confidence intervals, hypothesis tests, analysis populations, or missing-data approach. Those omissions mean that no effect estimate or precision assessment can be independently described from the posted results.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 4 outcome measures and includes a primary immunologic endpoint alongside secondary outcomes for CT-based clinical response, toxicity of grade 1 or higher, and immune function and cancer-specific response. When a study evaluates several outcomes, multiplicity is a general statistical concern: testing many outcomes can increase the chance that at least one result appears notable by chance. Prespecifying a primary endpoint and analysis can help clarify which result is central, while adjustment methods may be used in some settings. The record does not report whether any multiplicity strategy was planned or used.

The record lists 0 analyses. It does not report a statistical analysis plan, the number of tests actually conducted, or any adjustment for multiple comparisons. No p-values or endpoint estimates are reported for the primary or secondary outcomes. Therefore, multiplicity cannot be assessed by examining results, and no adjustment should be assumed.

Missing-data handling and analysis populations are also not reported in the registry record. It does not specify whether every enrolled participant was assessed for each endpoint, how participants without day 32 measurements were treated, or whether analyses included all enrolled participants or a defined subset. These are important details for interpreting participant counts and repeated measurements. Their absence does not establish that data were missing or that a particular analysis population was used; it means the registry record does not describe those procedures.

The safety group counts use 8 participants at risk for both serious and other adverse events. The record does not give comparable detail about the denominator used for each efficacy outcome. As a result, the reported safety counts should not be taken to establish the completeness of endpoint follow-up. The primary immunologic results and their analysis remain unreported in the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for the single study group as 0 of 8 participants and other adverse events as 7 of 8 participants. These are participant counts, not a comparison between treatment groups. The record does not list the serious adverse event terms, and the number of deaths is not reported in the registry record. It also does not provide the event-level detail needed to understand the timing, duration, or severity distribution of the other adverse events.

The registry outcome list includes toxicity of grade 1 or higher, but the adverse-event counts alone do not give a grade-by-grade account or clarify how that outcome relates to the serious and other categories. The definitions and collection procedures for those categories are not reported in the registry record. The group count with serious adverse events should therefore be read as the recorded count, not as evidence that serious events are impossible or that risks are absent.

General: safety counts are most informative when their definitions, observation period, and participant denominator are clear. In a single-group study, counts describe what was recorded among participants receiving the regimen; they do not establish how those counts compare with an alternative. The small enrollment and lack of a control group limit comparative interpretation. No medical conclusion about an individual participant should be drawn from these aggregate figures.

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

The registry record establishes that a completed phase II study enrolled 8 participants in a single group receiving cryosurgery and sargramostim. It identifies immunologic response measured by ELISPOT assay and flow cytometry as the primary endpoint, with measurements scheduled on days 1 and 32. The record also lists CT-based clinical response, toxicity, and immune function and cancer-specific response among the outcomes. These details identify what the study set out to examine, but the registry does not report numerical results for the primary endpoint or the listed secondary outcomes.

The posted safety counts show 0 of 8 participants with a serious adverse event and 7 of 8 with other adverse events. These counts describe the registry record’s categories for the study group; they do not establish relative safety compared with another regimen. Deaths are not reported in the registry record, and serious event terms are not listed. The figures cannot answer questions about event timing, severity distributions, or risk in another population.

The primary outcome description includes CT-based definitions of complete response, partial response, stable disease, and progressive disease. Those definitions do not supply outcome counts and do not substitute for the missing immunologic results. The record also does not explain how its radiographic criteria relate to the endpoint title or how assay data were interpreted.

General: the meaning of a treatment study depends on both the outcomes observed and the design used to interpret them. A single-group study can describe experience in its participants, but without a comparator it cannot produce a randomized treatment contrast. Here, the absence of reported primary results means the registry record does not establish the direction, magnitude, or precision of an immunologic response. It also does not support a conclusion that the regimen does or does not affect tumors or immune function. The appropriate reading is limited to the study design, scheduled assessments, and reported safety counts; the clinical outcome findings are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why an endpoint label, an outcome definition, and a reported result are distinct pieces of evidence. The primary endpoint is named as immunologic response measured by ELISPOT assay and flow cytometry, while the description includes CT-based criteria for tumor response. Without an explanation connecting those measures, readers cannot tell how the primary outcome was operationalized. Clear endpoint definitions are essential for deciding what a participant count means and whether different outcome measures answer the same question.

The single-group design also sets an important boundary on interpretation. The study can be described as an experience among participants who received cryosurgery and sargramostim, but it does not provide a concurrent treatment contrast. This distinction matters when readers encounter language about how well a regimen works: a treatment question may be clinically motivated, while the design and reported analysis determine what can be estimated.

The registry reports enrollment of 8 and gives safety counts, but no primary endpoint result or analysis is listed. Statistical significance, effect size, and precision cannot be assessed without an outcome estimate and its uncertainty. The absence of results in the registry record is not the same as a result showing no effect; it leaves the primary statistical question unanswered in the posted information.

The record also illustrates the value of reporting analysis populations, missing-data procedures, and multiplicity plans. These details help readers understand which participants contributed to each result and how multiple outcomes were handled. They are not reported. The study therefore matters statistically as a reminder that a completed trial and a defined endpoint do not, by themselves, yield an interpretable effect estimate. Transparent reporting is needed to connect the design to the results and to communicate what the data can support.

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 limitation for interpreting this study is that primary and secondary outcome results are not reported in the registry record. Enrollment is listed as 8, but no immunologic response count, assay values, CT response counts, or statistical estimates are available. Without those results, the direction and magnitude of any endpoint finding cannot be described, and precision cannot be evaluated.

The design is single group, with allocation not applicable and no masking. No comparator arm is listed, so the study does not supply a concurrent controlled contrast. Any outcome count would describe the study group rather than estimate a difference against another treatment. The small enrollment further limits how much information the reported group counts can convey, although no new precision estimate can be calculated from the registry entries.

There is ambiguity in the outcome description. The primary endpoint title refers to immunologic response assessed with ELISPOT assay and flow cytometry, while its description includes CT-guided biopsy, peritumoral GM-CSF, and radiographic response definitions. The arm schedule lists inhaled sargramostim but does not explain the injection language in the rationale. The record does not clarify how these descriptions fit together.

The registry record does not report the immunologic response rule, analysis method, analysis population, missing-data handling, multiplicity strategy, or trial-specific sample-size justification. The number of deaths is not reported, and serious adverse event terms are absent. These gaps limit assessment of outcome classification, follow-up completeness, safety detail, and statistical precision. They are limitations of what can be interpreted from the registry record and do not establish what investigators may have done outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cryotherapy and GM-CSF in Treating Patients With Lung Metastases or Primary Lung Cancer — NCT00514215.
• Registry record last updated 2020-03-05; status last verified 2020-02.
• Results first posted 2015-02-23.
• 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

This completed phase II trial evaluated cryosurgery with sargramostim in a single group. Enrollment was 8; allocation was not applicable and masking was none. The listed primary endpoint was immunologic response measured by ELISPOT assay and flow cytometry, with a timeframe of days 1 and 32. The arm description lists inhaled sargramostim at 250 μg two times a day on days 4-10 and days 36-42, and cryosurgery on days 1 and 32.

The registry lists clinical response by CT criteria, toxicity of grade 1 or higher, and immune function and cancer-specific response among secondary outcomes. It reports 0 of 8 participants with serious adverse events and 7 of 8 with other adverse events. Deaths are not reported in the registry record. Primary and secondary outcome results, statistical analyses, and analysis populations are not reported in the registry record. The design does not include a concurrent comparator, so the posted information does not provide a controlled treatment contrast.