PAN-study: Pan-Cancer Early Detection Study (PAN)

5.1. General inclusion criteria

1. Aged 30 years or over
2. Ability to provide informed consent

5.2. General exclusion criteria

1. (Anticipated) inability to complete the breath sampling procedure due to e.g. inability to maintain adequate ventilation unaided or claustrophobia
2. Participation in a Clinical Trial Investigational Medicinal Product (CTIMP) during the 28 days prior to breath biopsy.
3. Any biopsy or endoscopic procedure conducted during the past 48 hours. A breath sample can be collected \>48 hours post procedure.
4. Any disorder that is not stable in the opinion of the investigator. Specifically, subjects should be excluded if:

   4.1. Currently in the process of investigation for a malignancy other than the tumours of interest to this study.

   4.2. A history of malignancy, unless treated with curative intent and cancer-free at least 2 years prior to inclusion. Patients previously treated for highly localised disease e.g. basal cell carcinoma, localised squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that curative therapy was completed at least 12 months prior to inclusion.

   4.3. A history of the malignancy the patient is currently being investigated for. E.g. a patient suspected of gastric cancer with previous gastric cancer in medical history 4.4. Known active bacterial, fungal or viral infection including but not limited to upper respiratory tract infection, tuberculosis, pneumonia, cystitis, pyelonephritis, gastritis, prostatitis or viral hepatitis. Patients can be recruited after being symptom free for at least 2 weeks for mild infections and 6 weeks if admitted to the hospital and/or treated with i.v. antibiotics.

   4.5. Documented history of a clinically important lung condition other than asthma or COPD e.g., active lung infection, , bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, allergic bronchopulmonary aspergillosis/mycosis, pulmonary fibrosis or hypersensitivity pneumonitis, α1- antitrypsin deficiency. If α1- antitrypsin deficiency is diagnosed after a breath sample has been taken, the patient sample may still be used for analysis. α1- antitrypsin carriers are eligible for the study.

   4.6. Asthma or COPD exacerbation requiring hospitalisation and/or administration of oral prednisolone in past 6 weeks.

   4.7. Renal failure stages 3b and above (eGFR 45ml/min or less) 4.8. Any hospitalisation for symptoms unrelated to the clinical presentation of the tumour under investigation during the past 6 weeks.
5. Immunocompromised patients: specifically, patients with Acquired Immune Deficiency Syndrome (AIDS) (HIV with normal blood counts is eligible), inborn or acquired severe immune-deficiency including those caused by pharmacological treatment.
6. Documented history of pulmonary surgery or endobronchial interventional procedures other than biopsy, lavage or bronchial brushings. These include surgical resection, VATS, bronchial thermoplasty and coiling.
7. Applicable for the limonene sub-study only (see section 4.1): Non-abstinent participants with alcohol related liver disease or participants who drink to excess daily.
8. Applicable for the limonene sub-study only (see section 4.1): Current smokers (or e-cigarette users) or participants who have smoked (or used e-cigarettes) in the past 6 months prior to baseline sample.