Determination of Peripheral Immune Cell Activity During Treatment With Either Surgery or Radiotherapy in Patients With Early Stage NSCLC

Study Overview
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Brief Summary
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Rationale: An anatomical surgical resection is considered to be the standard of care in fit patients who present with early stage non-small cell lung cancer (NSCLC). However, surgery is less frequently performed in both elderly patients (aged ≥75 years), who represent the fastest-growing group of patients with stage I/II NSCLC, and in patients who have significant co-morbidity. Following the introduction of stereotactic ablative radiotherapy (SABR), an outpatient treatment that is typically delivered in between 3-8 fractions, the median survival of all elderly patients undergoing radiotherapy in The Netherlands increased by 9.3 months. Randomized trials comparing SABR and surgery have yet to be completed and results of the ongoing ACOSOG Z4032 studies will not be available in the within 5 years. A recent data retrospective study comparing both modalities has raised interesting questions about the impact of local therapy on recurrence patterns. It was found that a better loco-regional disease control rate was achieved with SABR. Objective: To study the effect of surgery and SABR on both immunostimulatory (with primary endpoint CD8 positive cells) and immunosuppressive cells in peripheral blood in patients with early stage non-small cell lung cancer who are treated with either modality. Study population: 40 patients with cT1-2aN0M0 either cytologically or histologically proven NSCLC. Main study parameters/endpoints: To determine whether an increase in CD8 activity can be established after SABR in patients with early stage lung cancer and to compare this increase with that in patients undergoing a surgical intervention. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Only risks in participation are the risks with drawing blood. Subjects will not have any benefits. This pilot study will be used to generate information concerning both treatments useful for the decision to plan a future study in a larger series of patients.

Official Title
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Determination of Peripheral Immune Cell Activity During Treatment With Either Surgery or Radiotherapy in Patients With Early Stage Non-small Cell Lung Cancer HAMLET Study

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Procedure: Surgery
* Radiation: SABR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically or histologically proven cT1-2aN0M0 NSCLC Patients ≥ 18 years old Patients should be fit to undergo both treatments in accordance with institutional protocols Exclusion Criteria: Patients with any signs of any co-existing infectious disease or immunosuppressive treatment (inhalation steroids are permitted) Mentally incapacitated subjects

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Surgery<br>An anatomical surgical resection of primary tumor | Procedure: Surgery<br> <br> |
| Active Comparator: Radiotherapy<br>Stereotactic Ablative Radiotherapy (SABR), outpatient treatment that is typically delivered in between 3-8 fractions | Radiation: SABR<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of IFN-gamma/ Granzyme B producing CD8 T cells | Number and activation status of peripheral CD8+ T cells | Baseline (week 0) | 
| Number of IFN-gamma/ Granzyme B producing CD8 T cells | Number and activation status of peripheral CD8+ T cells | Week 1 | 
| Number of IFN-gamma/ Granzyme B producing CD8 T cells | Number and activation status of peripheral CD8+ T cells | Week 2 | 
| Number of IFN-gamma/ Granzyme B producing CD8 T cells | Number and activation status of peripheral CD8+ T cells | Week 3 | 
| Number of IFN-gamma/ Granzyme B producing CD8 T cells | Number and activation status of peripheral CD8+ T cells | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4/CD8 ratio in peripheral blood |  | Baseline | 
| CD4/CD8 ratio in peripheral blood |  | Week 1 | 
| CD4/CD8 ratio in peripheral blood |  | Week 2 | 
| CD4/CD8 ratio in peripheral blood |  | Week 3 | 
| CD4/CD8 ratio in peripheral blood |  | Week 6 | 
| number of regulatory T cells |  | Baseline | 
| number of regulatory T cells |  | Week 1 | 
| number of regulatory T cells |  | Week 2 | 
| number of regulatory T cells |  | Week 3 | 
| number of regulatory T cells |  | Week 6 | 
| Activation marker expression on T cells |  | Baseline | 
| Activation marker expression on T cells |  | Week 1 | 
| Activation marker expression on T cells |  | Week 2 | 
| Activation marker expression on T cells |  | Week 3 | 
| Activation marker expression on T cells |  | Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune monitoring, T cell activation, early stage