Prevention of Radiation Pneumonitis After Three-dimensional Conformal Radiation Therapy (3D-CRT) in Patients With Non-small-cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the interest of breath holding for the prevention of radiation pneumonitis following conformal radiation therapy. Eligible patients will be randomly assigned in a 2-arm trial to free breathing or breath holding during conformal radiation. The primary objective of the study is to establish the efficacy of breath holding, compared to free breathing, in the prevention of early pulmonary toxicity following conformal radiation. Several departments of radiotherapy, many pneumology units and two basic and applied research laboratories take part in this multicentric study. The number of patients required to demonstrate a reduction in radiation pneumonitis from 45 % to 22.5 %, assuming an alpha risk of 5% in a two-sided test and 95% power, is 240 (120 per arm). With a planned accrual of 7 patients per month, it is estimated that the inclusion period should be approximately 3 years.

Detailed Description
-----------------
The secondary objectives are: Validation of the Lent-Soma toxicity scale by comparison to the RTOG scale, Response rate at different times: week 6-8, 1 year and 2 years after the end of irradiation, Progression-free survival rate at 1 year and 2 years after the end of irradiation Confirmation of the predictive value of serum cytokine levels (IL-6 and IL-10) during irradiation for the occurrence of early radiation toxicity, and analysis of the correlation between these serum levels at inclusion and the expression polymorphism of candidate genes.

Official Title
-----------------
Evaluation of the Interest of Breath Holding for the Prevention of Radiation Pneumonitis Following Conformal Radiation Therapy

Conditions
-----------------
Carcinoma, Non-small-cell Lung

Intervention / Treatment
-----------------
* Radiation: Free breathing
* Radiation: Breath holding


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Non-metastatic cytologically or histologically proven non-small-cell lung cancer (NSCLC) Operated NSCLC patients requiring post-surgical irradiation or non-operated NSCLC patients requiring curative irradiation Conformational thoracic radiotherapy with curative intent Age >= 18 Complete functional respiratory evaluation (FRE) performed less than 2 months before inclusion, demonstrating a maximum expiratory flow-volume/second > 1 l (in case surgery, the FRE must have been realized in the post-surgery period) Thoracic CT-scan performed less than 2 months before inclusion for non-operated patient PET-scan performed less than 2 months before inclusion for non-operated patient Performance status (PS) ECOG <= 1 Possible training on breath holding technique Female patients of childbearing potential: effective method of contraception necessary Mandatory affiliation with a social security system Written, signed, informed consent Exclusion Criteria: Small-cell lung cancer Metastatic disease Infiltrating pulmonary disease Previous thoracic irradiation Indication of irradiation with palliative intent Previous or concurrent primary malignancies at other sites (except basocellular skin cancer or cervical cancer in situ or complete remission for more than 5 years) Life expectancy < 6 months Patient understanding incompatible with the breath-hold technique (patients with major presbycusis are not eligible) Pregnant or lactating woman Patient included in another clinical trial Follow-up difficult Patient deprived of freedom

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Free breathing during conformal radiation | Radiation: Free breathing<br>* Free breathing during conformal radiation<br>* Other names: Lung cancer;|
| Experimental: B<br>Breath holding during conformal radiation | Radiation: Breath holding<br>* Breath holding during conformal radiation<br>* Other names: Lung cancer;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical, functional and radiological evaluations at 6-8 weeks and 10-12 weeks after the end of irradiation |  | 6-8 and 10-12 weeks after the end of irradiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RTOG and LENT-SOMA scores at 6-8 weeks and 10-12 weeks after the end of irradiation, response rates at 6-8 weeks, 1 year and 2 years after irradiation |  | 6-8 and 10-12 weeks after the end of irradiation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non-small-cell lung cancer, Breath-hold, Radiation pneumonitis, Serum cytokines, LENT-SOMA scale, Non-metastatic non-small-cell lung cancer