lung cancer

see also:

• neoplasia / cancer / tumours
• palliative care
• lung lesions
• lung / pulmonary mass on CT or CXR

• the vast majority of primary lung cancers are carcinomas which are divided into:
  • non small cell carcinoma (NSCLC) - accounts for 80%
  • small cell carcinoma (SMLC) “oat cell” - accounts for 17%
• other primary lung cancers include:
  • carcinoid - accounts for < 1%
  • sarcoma - accounts for 0.1%
  • mesothelioma
• > 85% of lung cancers occur in smokers
  • smokers have a 13% lifetime risk of lung cancer but this is doubled if they have a c.9976T BRCA2 gene mutation
• lung cancers in never smokers is increasing (see below)
• overall 5 year survival for lung cancer even with Rx is poor at ~14%
• LungVax lung cancer vaccine targeting neoantigens on lung cancer cells developed in 2024 and will be trialed

• accounts for 80%
• tends to be Rx surgically
• ~50% are squamous cell and the other 50% are adenocarcinomas
• some may metastasise to the brain in which case Ix workup of this possibility usually entails:
  • CT brain with iv contrast
  • plus MRI scan if either:
    • CT findings may represent other pathology such as infarcts instead of tumour
    • when surgical resection is being considered and thus there is need to exclude other metastases to brain or meninges

• accounts for 17%
• tends to respond better to chemoRx and radioRx
• most grow in the larger airways and grow rapidly and contain dense neurosecretory granules which may result in a variety of paraneoplastic neuroendocrine features including:
  • syndrome of inappropriate ADH secretion (SIADH) in 5-10% ⇒ hyponatraemia
  • ectopic secretion of ACTH in 5% ⇒ hypokalaemic nephropathy
  • atrial natriuretic factor
  • Eaton-Lambert reverse myasthenic syndrome 5-6%
  • Subacute cerebellar degeneration
  • Subacute sensory neuropathy - it seems to be related to the loss of the dorsal root ganglia with early involvement of major fibers responsible for detecting vibration and position.
  • Limbic encephalopathy via Anti-Hu, Anti-Yo antibodies and characterized by rapid onset of depression, seizures, irritability, and short-term memory loss
• see also emedicine

• an uncommon cancer (3% of all cancers) which is almost exclusively related to exposure to asbestos with a synergistic effect of smoking
• it has a latency period of 20-50 years following exposure to asbestos
• Australia has one of the highest incidences of mesothelioma in the world, largely due to its extensive use and mining of asbestos.
• currently ~500 Australians die each year with cases expected to peak this decade as cases hit 18,000 by 2020.
• mesothelioma may affect pleura (75%), peritoneum (20%), pericardium (5%) and rarely testicles.
• see mesothelioma

• lung cancer occurring in never smokers (LCINS) is increasing, more common in women and in Asian populations, and is a distinct biological and clinical entity attributed to either¹⁾:
  • passive smoking
    • second-hand smoke increases lung cancer risk in never smokers by approximately 20–25%
    • indirect tobacco exposure may act synergistically with other biological processes, such as APOBEC-related mutagenesis
  • genetic factors
    • first-degree family history of lung cancer
    • variants in EGFR, TP53, ATM, and members of the APOBEC3 family
    • certain mutations, such as EGFR p.Thr790Met (T790M), confer a particularly high lifetime risk and may lead to the development of multifocal lung lesions at younger ages
      • among never smokers, those with EGFR T790M were more than 25 times as likely to develop lung cancer - the variant was present in 1 of 15,850 individuals and became enriched in the United States with a regional carrier frequency of 1 in 2078 through a founder event in the Southern Appalachian region approximately 200 years ago²⁾
    • population-specific genetic factors, such as the APOBEC3A/B germline deletion, significantly increase the risk of certain lung cancers in some ethnic groups
    • clonal hematopoiesis of indeterminate potential (CHIP) represents another emerging risk factor.
      • CHIP involves somatic mutations in hematopoietic stem cells, commonly affecting genes such as DNMT3A, TET2, and ASXL1.
      • Individuals with high variant allele fractions may experience a higher risk of solid tumors, including lung cancer, independent of smoking status
      • may promote tumorigenesis through chronic inflammation, including elevated interleukin-1β (IL-1β) signaling
  • viruses - perhaps human papilloma virus (HPV)
  • radon gas - 50% increased risk if levels exceed EPA recommended levels as they do in Cornwall, UK and in 1 of 15 homes in the US
  • air pollution
    • ultrafine particulate matter - an increase in air concentration of only 1% leads to 14% increase in cancer
    • high PM2.5 exposure correlates with a greater mutation burden, TP53 mutations, telomere shortening, and inflammatory activation within the lung microenvironment
  • mesothelioma (asbestos exposure) - 2-3% of all male deaths from lung cancer
  • perhaps ultra-processed food diets
    • a 2025 study showed those in the highest quarter of energy-adjusted UPF consumption were 41% more likely to be diagnosed with lung cancer than those in the lowest quarter ³⁾
  • those hospitalised due to severe COVID-19 coronavirus (2019-nCoV / SARS-CoV-2) or influenza appear to have increased risk - perhaps hazard ratio of 1.24 ⁴⁾

• unexplained haemoptysis, or,
• any of the following lasting more than 3 weeks in the adult (or < 3 weeks if risk factors)⁵⁾:
  • cough
  • chest pain and/or shoulder pain
  • SOB
  • abnormal chest signs
  • hoarseness
  • clubbing
  • cervical and/or supraclavicular lymphadenopathy
  • weight loss or anorexia
  • features suggestive of metastasis (eg. brain, bone, liver or skin)
  • signs of pleural effusion

• FH lung cancer
• smokers, ex-smokers, passive smokers
• Aboriginal or Torres Strait Islander people
• smoking-related COPD
• PH exposure to asbestos
• previous lung disease
• PH cancer, especially head and neck cancer

• NB. sputum cytology has a low sensistivity and is no longer recommended for the Ix of lung cancer
• massive haemoptysis or stridor then emergency admission for Ix
• urgent CT scan and referral to spscialist services if any of the following:
  • persistent haemoptysis in smokers or ex-smokers, aged > 40 years, or who have other risk factors, or,
  • signs of superior vena cava obstruction
• all other patients should have an urgent CXR and Mx according to findings:
  • CXR suspicious for lung cancer or normal but high risk ⇒ CT chest and urgent referral to specialist services
  • lower risk patients:
    • consolidation consistent with clinical picture:
      • Rx accordingly, repeat CXR in 6 weeks and if persistent consolidation ⇒ chest CT
    • pulmonary nodule
      • if no change from previous then monitor
      • if change then CT chest
    • those low risk patients having CT chest:
      • if scan suggests cancer or visible change in a nodule, then urgent referral to specialist services
      • otherwise, consider other diagnoses, and consider monitoring for 2 years.