To demonstrate the validity of using patient-derived lung epithelial organoids, as a model of normal lung tissue, we aim to assess lung epithelial cell responses to ionizing radiation exposure and relate these to clinical outcome. In addition,…
ID
Source
Brief title
Condition
- Other condition
- Respiratory tract neoplasms
Synonym
Health condition
Pulmonale fibrose en pneumontis na radiotherapie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A significant difference in the number of *H2AX foci (double strand DNA damage)
per cell induced by in vitro radiation between patient-specific normal
epithelial cells from patients with * grade 2 pneumonitis or fibrosis following
chemoradiation or proton therapy based on CTCAE scoring system and patients
with grade * 1 pneumonitis or fibrosis.
Secondary outcome
In vitro:
* Measurement of in vitro-induced changes in EMT (e.g. TGF-beta,
alpha-SM-actin, SLUG, vimentin), -oxidative stress (e.g. HMOX1), or
-inflammation (e.g. IL-6) by ionizing radiation in normal lung epithelial cell
cultures derived from bronchoalveolar lavage fluid.
Changes in the following clinical parameters following radiation:
* Performance, symptoms and QOL as measured by questionnaires;
* Lung function (VC, FVC, FEV1) and diffusion capacity (DLCOc, KCO);
* Respiratory resistance (Rrs) and reactance (Xrs) as measured by forced
oscillation technique;
* Lung structure as measured by CTCAE grading on CT thorax;
* Lung density measured by quantitative densitometry using CT-thorax.
- The *-H2AX decay ratio in peripheral lymphocytes by measuring the difference
in foci at 30 min and 24 hours after 1Gy radiation of peripheral lymphocytes.
Background summary
Standard of care for patients with stage III non-small cell lung cancer (NSCLC)
is chemotherapy combined with concurrent or sequential radiotherapy.
Radiation-induced lung injury (RILI) of normal lung tissue is one of the main
dose-limiting factors during radiation treatment. Therefore, it is important to
identify which patients are at risk for RILI to be able to create a
personalized radiation treatment and prevent reduction in quality of life (QOL)
in cancer survivors. So far, no reliable biomarkers have been found that can be
used for this identification. This study aims to use patient-derived airway
epithelial organoids to search for individual predictors for RILI.
Study objective
To demonstrate the validity of using patient-derived lung epithelial organoids,
as a model of normal lung tissue, we aim to assess lung epithelial cell
responses to ionizing radiation exposure and relate these to clinical outcome.
In addition, clinical outcome parameters will be combined to create a better
understanding of RILI.
Study design: This study is a prospective cross-sectional study.
Study design
This study is a prospective cross-sectional study.
Study burden and risks
The eligible patient group has a severe disease with an intensive treatment
regimen. However, since the burden and risk of the measurements is low and the
possible outcome of this study may benefit future patients with comparable
disease, we have concluded that the benefit-risk ratio is acceptable. Most
measurements are part of standard clinical care and follow-up. Additional
measurements are questionnaires, lung function and additional low-dose CT
images at baseline and 3 times after that. Bronchoalveolar lavage will be added
to a planned diagnostic procedure under sedation, therefore not giving
additional burden to the patient. It has a minimal risk of fever, bleeding or
bronchospasm, none requiring specific therapy.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
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.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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In other registers
| Register | ID |
|---|---|
| CCMO | NL73109.058.20 |