TRAcking Non-small Cell Lung Cancer Evolution Through Therapy (Rx) EVO

TRACERx EVO is a programme of work using a prospective observational cohort study of participants with early- and late-stage non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

Inclusion Criteria:Cohort A, B and C :Written Informed consentAgreement to be followed up (including on-study assessments and sample collection) every 3 months in the first 2 years and then 6 monthly.Agreement to be followed up at a TRACERx EVO siteCohort A:Participants ≥18 years of age, with early stage I-IIIB NSCLC disease who are eligible for primary surgeryPathologically confirmed NSCLC, or a strong suspicion of cancer on lung imaging necessitating surgery (e.g., diagnosis determined from frozen section in theatre)Primary surgery in keeping with NICE guidelines in (lobectomy, either open or thoracoscopic), lung parenchymal-sparing operations (segmentectomy or wedge resection) if a complete resection can be achieved, extensive surgery (bronchoangioplastic surgery, bilobectomy, pneumonectomy) if necessary to obtain clear margins, hilar and mediastinal lymph node sampling or en bloc resection)Minimum tumour diameter at least 10mm to allow for sampling of at least two tumour regions (if 10mm, a high likelihood of nodal involvement on pre-operative imaging required to meet eligibility according to stage, i.e., T1 N1-3)Deemed to be fit for surgeryConsidered sufficiently fit for standard of care adjuvant therapy if indicatedPerformance status 0 to 1Cohort B:Participants ≥18 years of age, with late-stage unresectable stage IIIB and above NSCLC disease (TNM 8th edition) or presenting with stage IV de novo metastatic disease.Sufficient tissue (at least 1 region/biopsy), either FFPE or fresh frozenDeemed to be fit for anti-cancer treatmentPerformance status 0 to 2Cohort C:Participants ≥18 years of age, with any stage SCLC.Sufficient tissue (at least 1 region/biopsy), either FFPE or fresh frozenDeemed to be fit for anti-cancer treatmentPerformance status 0 to 2Exclusion Criteria:Cohort A, B and C:Other active malignancyAny other* malignancy diagnosed or relapsed at any time, which is currently being treated (including by hormonal therapy).Any other* current malignancy or malignancy diagnosed or relapsed within the past 3 years**.*Exceptions are: non-melanomatous skin cancer, stage 0 melanoma in situ, and in situ cervical cancer**An exception will be made for malignancies diagnosed or relapsed more than 2, but less than 3, years ago only if a pre-operative biopsy of the lung lesion has confirmed a diagnosis of NSCLC.Psychological condition that would preclude informed consentDiagnosis other than NSCLC or SCLC confirmed following surgery or biopsyHistory of intravenous drug abuse within the last 5 yearsConfirmed diagnosis of known high-risk infections (e.g., Human Immunodeficiency Virus) (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or syphilis infection, tuberculosis and Creutzfeldt-Jacob disease) unless participant case is of a particular scientific interest and agreed in advance with research staff, local mortuary staff and pathologist.Contra-indicated co-morbid conditionsWomen who are pregnant or breast feedingCohort A:Positive margins, incomplete resection or insufficient nodal samplingParticipation in a neo-adjuvant or adjuvant therapeutic trial with non-standard of care therapyInsufficient tissue, i.e., a minimum of two tumour regions unlikely to be obtained for the study based on pre-operative imagingParticipant found to have pre-invasive lesions rather than invasive cancer following surgery, such as adenocarcinoma in situ or minimally invasive lesions will be withdrawn. However, the surgical tissue and baseline blood already collected will be sent to the central laboratory. These participants will not be followed-up in the study or required to provide any further blood samples. If these participants subsequently develop invasive cancer, the date of diagnosis and the tumour histology will be reported on the electronic data capture system.Cohort B/C:• Insufficient tissue, i.e., at least one tissue biopsy to be obtained (Fresh Frozen or FFPE)