Prediciting Radiation-Induced lung injury through patient-specific lung epithelial ORganoids

Recruiting

Conditions: Pulmonale fibrose en pneumontis na radiotherapie
Radiation damage
Radiation induced lung damage
Radiation Induced Lung Injury
10029107

Registration Number: NL-OMON52503

Lead Sponsor: eids Universitair Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 65

Inclusion Criteria

* Age * 18-85 years;
* Clinical suspicion of lung tumor with mediastinal lymph node involvement
based on enlarged lymph nodes on CT thorax or FDG uptake on PET-CT conform ESMO
guidelines;
* Planned bronchoscopy with endobronchial ultrasound (EBUS) with sedation
(Propofol or benzodiazepine) for standard diagnostic work-up;
* Clinical performance adequate for undergoing EBUS (according to pulmonary
physician ordering the diagnostic procedure).

Exclusion Criteria

* Clinical performance too low to undergo EBUS according to pulmonary physician
ordering the diagnostic procedure;
* Suspicion of metastasis or stage IV disease on PET-CT or CT-thorax;
* Inadequate understanding of the Dutch language in speech and writing.
* Clinical performance too low to receive chemoradiotherapy or proton therapy;
* Significant co-morbidities such as end stage renal disease, severe
cardiovascular disease, severe psychiatric disease, end stage COPD, or other
comorbidity with limited expected survival (<1 year) or WHO performance status
>3
* Known pre-existent diagnosis of lung fibrosis or newly diagnosed lung
fibrosis before start of the study;
* Previous thoracic radiation-treatment.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>A significant difference in the number of H2AX foci (double strand DNA damage)<br /><br>per cell induced by in vitro radiation between patient-specific normal<br /><br>epithelial cells from patients with grade 2 pneumonitis or fibrosis following<br /><br>chemoradiation or proton therapy based on CTCAE scoring system and patients<br /><br>with grade * 1 pneumonitis or fibrosis. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>In vitro:<br /><br>* Measurement of in vitro-induced changes in EMT (e.g. TGF-beta,<br /><br>alpha-SM-actin, SLUG, vimentin), -oxidative stress (e.g. HMOX1), or<br /><br>-inflammation (e.g. IL-6) by ionizing radiation in normal lung epithelial cell<br /><br>cultures derived from bronchoalveolar lavage fluid.<br /><br>Changes in the following clinical parameters following radiation:<br /><br>* Performance, symptoms and QOL as measured by questionnaires;<br /><br>* Lung function (VC, FVC, FEV1) and diffusion capacity (DLCOc, KCO);<br /><br>* Respiratory resistance (Rrs) and reactance (Xrs) as measured by forced<br /><br>oscillation technique;<br /><br>* Lung structure as measured by CTCAE grading on CT thorax;<br /><br>* Lung density measured by quantitative densitometry using CT-thorax.<br /><br>- The *-H2AX decay ratio in peripheral lymphocytes by measuring the difference<br /><br>in foci at 30 min and 24 hours after 1Gy radiation of peripheral lymphocytes. </p><br>