Lung Cancer Organoids and Patient Derived Tumor Xenografts

Lung (tumor) material obtained from biopsies or surgical resection material that is not needed by the pathologist for diagnosis (i.e. to stage the patient or to perform molecular diagnosis) will be collected and used for the generation of matched normal and lung cancer organoids and/or PDX.

Biopsy material: Patients with (suspected) lung cancer will undergo a bronchoscopy or endobronchial ultrasound guided transbronchial needle aspiration (EBUS/EUS-TBNA) bronchoscopy for the collection of a lung / lymph node biopsy. Biopsies are collected according to standard of care procedures for i.e. the initial diagnosis and staging of lung cancer, and molecular profiling of recurrent tumors. During the standard of care biopsy procedure, an extra biopsy (lung and/or lymph node) will be collected and used for the generation of lung (cancer) organoids:

* Bronchoscopy: biopsy-derived lung (tumor) tissue from endobronchial tumors
* EBUS/EUS-TBNA bronchoscopy: cytology-derived lung (tumor) cells from mediastinal lymph nodes

A 10 ml blood sample will only be collected at the moment blood must be drawn according to standard of care procedures or when the patient has received an intravenous drip. The patient therefore does not require to undergo additional procedures.

Resection material: Patients who are selected to undergo surgical removal of a primary lung cancer will be included. The (tumor) material that will be used to make organoids and PDX will be derived from remaining healthy and tumor tissue that is not needed for the pathologist to make a diagnosis, to stage the patient or to perform a molecular diagnosis. The patient therefore does not require to undergo additional treatments or procedures. A 10 ml blood sample will be collected at the moment blood must be drawn pre-operatively according to standard of care procedures or from the intravenous drip the patient will receive before start surgery. The patient therefore does not require to undergo additional procedures.

Collection of clinical data: Clinical data will be collected from existing standard of care data:

* Histology
* Date diagnosis lung cancer
* TNM classification (eight edition)
* If performed, molecular analysis data such as Epidermal Growth Factor Receptor (EGFR) mutation, Anaplastic Lymphoma Kinase (ALK) translocation, Kirsten Rat Sarcoma (KRAS) viral oncogene homolog mutation etc. (Type of test, results)
* PD-L1 status if available. If available, type of test and PD-L1%
* Type, dose, and date of treatment the patient received before and/or after the collection tumor biopsy (chemotherapy, radiotherapy, tyrosine kinase inhibitors, immunotherapy). If applicable, also the date and dose of all cycles.

• Tissue and blood (Other): Tissue and blood will be derived from patient during a standard of care procedure

Primary outcomes

• Lung cancer organoids [1 year]: Establishing matched normal and primary human lung cancer organoids from patient-derived (tumor) tissue material by establishing long term culturing and bio-banking conditions for matched normal and primary lung cancer organoids from patient-derived lung (tumor) material. From these, we will In the established organoids we will: • the rate of proliferation and cell death (turnover) will be calculated
• Lung cancer organoids [1 year]: Establishing matched normal and primary human lung cancer organoids from patient-derived (tumor) tissue material by establishing long term culturing and bio-banking conditions for matched normal and primary lung cancer organoids from patient-derived lung (tumor) material. From these, we will In the established organoids we will: • the size distribution of the organoids
• Lung cancer organoids [1 year]: Establishing matched normal and primary human lung cancer organoids from patient-derived (tumor) tissue material by establishing long term culturing and bio-banking conditions for matched normal and primary lung cancer organoids from patient-derived lung (tumor) material. From these, we will In the established organoids we will: • determine the frequency of primary, secondary and tertiary organoid formation

Secondary outcomes

• Oncogenetic drivers [1 year]: To define oncogenic drivers in lung cancer organoids
• Tumor heterogeneity [1 year]: To investigate the stability of (epi-) genetic and phenotypic tumor heterogeneity of cultured organoids compared to a primary/secondary biopsy
• Molecular biology [1 year]: To predict sensitivity and to get insight in the molecular biology of the response to immunotherapy, radiotherapy, cytotoxic and targeted agents
• Treatment response [1 year]: To compare treatment response in normal lung organoids and lung cancer organoids
• Xenografts [1 year]: To establish and characterize patient-derived tumor xenografts
• Therapeutic approaches [1 year]: To test novel therapeutic approaches in lung cancer organoids and clinically relevant PDX models, including radiotherapy combined with hypoxia activated prodrugs and immunotherapies
• Developing biomarkers [1 year]: To develop biomarker(s) of tumor response to be able to select patients who will benefit from novel treatment strategies.
• Analysing blood [1 year]: To analyze (ct)DNA in organoid-derived culture supernatants and corresponding patient-derived blood samples
• Analysing blood [1 year]: To analyze metabolites in organoid-derived culture supernatants and corresponding patient-derived blood samples
• Analysing blood [1 year]: To analyze RNA in organoid-derived culture supernatants and corresponding patient-derived blood samples
• Analysing blood [1 year]: To analyze proteins in organoid-derived culture supernatants and corresponding patient-derived blood samples
• Analysing blood [1 year]: To analyze microvesicles secreted by lung cancer cells in organoid-derived culture supernatants and corresponding patient-derived blood samples

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* All patients selected to undergo primary surgical resection of a primary lung cancer. All types of resection are eligible, e.g. wedge resection, segmental resection, lobectomy, pneumonectomy.
* All patients with (suspected) lung cancer that will undergo a bronchoscopy or endobronchial ultrasound guided transbronchial needle aspiration (EBUS/EUS-TBNA) bronchoscopy.

Exclusion Criteria:

There are no exclusion criteria