lung_cancer_slides.pdf

Respiratory cancer, smokingrelated and interstitial lung disease, and a mention of COVID-19 2023 Learning objectives • • • • • • • • • • Introduction to head and neck cancer Be aware of interstitial lung disease & COVID pathology How lung cancer is diagnosed Know what kinds of neoplasms occur in...

Respiratory cancer, smokingrelated and interstitial lung disease, and a mention of COVID-19 2023 Learning objectives • • • • • • • • • • Introduction to head and neck cancer Be aware of interstitial lung disease & COVID pathology How lung cancer is diagnosed Know what kinds of neoplasms occur in lung Classify lung cancer Read about paraneoplastic syndromes Know what TNM means Appreciate the evolving treatment of lung cancer Understand why molecular pathology is important Appreciate the ongoing importance of asbestos in mesothelioma Head & neck cancer • • • • • • Male: female 5:1 Tobacco Alcohol HPV Hygiene Repeated trauma • Squamous carcinoma • Lymph node spread • Local recurrence • HPV – 10-50% positive • p16 or HPV as biomarker • Non-HPV, p53 mutant cases more aggressive COVID-19 Is it a viral or immunological disease? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874430/ Backdrop – smoking related disease COPD – Emphysema – Chronic bronchitis Pharmacogenomics and Inter-individual susceptibility eg AAT, CYP1A1, GSTM1, mEPH • Passive smoking • E-cigarettes and heat not burn products • Vitamin E acetate Interstitial lung disease • Hypersensitivity pneumonitis (extrinsic allergic alveolitis) – Type III and IV – Bird fancier – Farmer’s lung Interstitial lung disease • Sarcoidosis – Cell mediated – US black>white – Granulomas – Hilar lymphadenopathy – Raised angiotensin converting enzyme Interstitial lung disease • Idiopathic pulmonary fibrosis (UIP) – Post viral? – Other systemic disease – Part of a spectrum? – Honeycomb lung http://www.cancerresearchuk.org/cancerinfo/cancerstats/keyfacts/lung-cancer/ • Benign • Malignant – Primary – Secondary Benign • Mesenchymoma • Papilloma • Inflammatory myoblastic tumour Primary malignant • Epithelium – importance of metaplasia & dysplasia • • • • • Vessels Muscle Cartilage Lymphoid Pleura Secondary • • • • Sarcoma Renal carcinoma Lymphoma and many more Primary epithelial • Squamous • Adeno • Small cell undifferentiated • Carcinoid • Large cell undifferentiated • Molecular Making the diagnosis • Radiology – size change • Cytology • EBUS • Biopsy • Circulating tumour DNA • Grade • Stage TNM Squamous (NSCLC) Approx 40% Smoking Air pollution Asbestos Fibrosing lung disease TNM staging Adenocarcinoma (NSCLC) Approx 40% Smoking Lung scar Air pollution Asbestos May be more amenable to immune checkpoint treatment Adenocarcinoma – bronchoalveolar (NSCLC) Variant of adenocarcinoma Pattern of spread - intrapulmonary dissemination Small cell undifferentiated (SCLC) • Neuroendocrine • Paraneoplastic effects May produce bioactive amines or peptides eg ADH, PTN-like peptides, ACTH. • Neurological – eg demyelination Carcinoid • Malignant spectrum • “Typical”- towards less aggressive end of spectrum • “Atypical” – smoking related, tends towards malignant end of spectrum Paraneoplastic syndromes • A set of signs and symptoms not directly caused by the cancer • May be related to factors produced • May be immunological • Neurological - various • Endocrine - various • Skin – acanthosis nigricans (EGF) • Connective tissue/bone finger clubbing • Haematological – eg EPO • Kidney disease – immune complex GN Molecular pathology and treatment Lung EGFR amplification BRAF RAS ALK rearrangements Assessment of PDL-1 (immune checkpoints) • Circulating tumour cells • Circulating tumour DNA PD1 and PDL1 – checkpoint inhibition Current treatments • Conventional chemotherapy • Targeted, small molecule • Immuno-oncology and checkpoint inhibitors • Mechanisms of resistance • Mutational burden • Immunologically “cold” tumours • Value of monitoring circulating tumour DNA - ctDNA Mesothelioma Asbestos - crocidolite Incidence rising Long lag period: 20-40 years Male:female 5:1 Significance of fibrous pleural plaques Learning objectives • • • • • • • • • • Introduction to head and neck cancer Be aware of interstitial lung disease & COVID pathology Know what kinds of neoplasms occur in lung How lung cancer is diagnosed Classify lung cancer Read about paraneoplastic syndromes Know what TNM means Appreciate the evolving treatment of lung cancer Understand why molecular pathology is important Appreciate the ongoing importance of asbestos in mesothelioma