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Lung cancer

Lung cancer arises from the cells of the respiratory epithelium
 
They are broadly divided into 2 categories -
 Small cell lung cancer ( SLCL ) which is highly malignant tumour of the cells exhibiting neuroendocrine characteristics and accounts for 15 % of lung cancer cases
 Non-small cell lung cancer ( NSCLC ) constitute the majority ( 85 % ) of cases and are further subdivided into 3 groups – adenocarcinoma , squamous cell carcinoma and large cell carcinoma

 

How common – 2nd most common cancer by diagnosis by gender behind prostate and breast cancer Commoner in men ( 60 % ) but commonest cause of cancer death in both sexes Rare under age of 40 and people who have never smoked Majority in people over 65 with highest incidence between 80-84 yrs and lowest in people less than 40 In the US lung cancer accounts for 14 % of new cancers in men and 13 % in women In the UK lung cancer is the 3rd most common cancer accounting for 13 % of all new cancer cases and it is the most common cause of cancer death responsible for 21 % of all cancer deaths in 2017 ( Cancer Research UK ) It has been noted that as smoking rates peak – generally in men first followed by women , lung cancer incidence and mortality rise in subsequent decades before declining following the initiation of comprehensive tobacco control programmes.

 

Risk factors – Smoking is the biggest cause (80-90 % ) including passive smoking
This has been shown in epidemiological studies since early1950s Risk proportional to patients pack years , age they started and the type of cigarette smoked ( ↑ risk with unfiltered and high nicotine ) ie duration of smoking should be considered the strongest determinant of lung cancer risk in smokers Studies have shown that smokers have a 15-30 fold increased risk of developing lung cancer compared with non smokers This has also been shown for cigars , cigarillos and pipes < 10 % occurs in never smokers , usually women In the US exposure to indoor radon ( a naturally occurring radioactive gas ) is thought to be the 2nd most important environmental risk factor for lung cancer A family h/o lung cancer -has been found to be a risk factor in several registry based studies Asbestos exposure Previous radiotherapy to chest Inhalation of polycyclic aromatic hydrocarbons , nickel chromate or inorganic arsenic – Rare causes Air pollution & occupational exposures COPD -Bergen COPD Cohort study has shown that COPD is an independent risk factor for lung cancer but the underlying mechanisms are poorly understood It has been shown that a diet rich in vegetable and fruits and particularly cruciferous vegetables may exert some protective effect against lung cancers.

 

Presentation – Persistent cough , haemoptysis , dyspnoe Pleural effusion Recurrent chest infections Hoarseness of voice ( recurrent laryngeal nerve ) Dyspnoe Chest pain Wheeze , stridor Anorexia Weight loss Fatigue SVC obstruction Paraneoplastic syndromes Horners syndrome ( Pancoast )

 

Imaging – XR – low cost , easily accessible and low radiation dose

It should be noted that although chest X-ray remains the first line investigation for suspected lung cancer in the primary care in UK , a study by Stephen H Bradley et al have shown that highest quality studies suggest that the sensitivity of chest X ray for symptomatic lung cancer diagnosis is only 77 % to 80 %

That implies that if you suspect lung cancer and the CXR has been reported as normal in a high risk patient you should consider further investigation for e.g CT Thorax It has been shown in studies that in instances in which only CXR is relied on diagnosis of lung cancers alone 
22 % to 63 % of the lung cancers would be missed at a stage of the disease at which they could be detected with CT Digital chest radiography has 94 % detection rates of lung cancer but that is achievable only at the expense of an excessive number of work up CT examinations
 CT Scan
- is more sensitive than chest radiography for the detection of early lung cancers presenting as small , non calcified , solitary pulmonary nodules ( SPN’s )
- assess tumour size , spread , L node involvment , chest wall invasion or metastasis to other sites

 

CXR findings that suggest lung cancer or mesothelioma Aged 40 and over with unexplained haemoptysis- refer USC.

 

Aged 40 and over 

+ two or more of the following unexplained symptoms
 OR

if they have ever smoked and have 1 or more of the following unexplained symptoms Cough Fatigue SOB Chest pain Weight loss Appetite loss

 

People aged 40 and over with any of the following Persistent recurrent chest infection Finger clubbing Supraclavicular lymphadenopathy or persistent cervical lymphadenopathy Chest signs consistent with lung cancer Thrombocytosis.

 

People aged 40 and over if

 Two or more of the following unexplained symptoms They have 1 or more of the following unexplained symptoms and have ever smoked or They have 1 or more of the following unexplained symptoms and have been exposed to asbestos


 cough fatigue SOB chest pain weight loss appetite loss


Aged 40 and over with
 Finger clubbing Chest signs compatible with pleural disease

 

Non-small cell – Adenocarcinoma ( 35-40 % )

♦ most common cell type overall
♦ ↑ common in women
♦ most common cell type in non smokers
♦ peripheral
♦ even small resectible lesions carry a risk of occult metastases
♦ site of metastatic spread includes 
 ○ regional lymph nodes
 ○ bone
 ○ liver
 ○ adrenal
 ○ lung
 ○ CNS and skin
 Squamous cell carcinoma (25-30 % )

♦ strongly associated with smoking
♦ commonest histological diagnosis
♦ most common carcinoma to cavitate
♦ often associated with hypercalcaemia
♦ poor prognosis
♦ central
 Large-cell carcinoma
♦ Histologically speaking the cancer does not look like squamous cell carcinoma , adenocarcinoma , small cell carcinoma or any other rare variant
♦ peripherally located- large peripheral mass on CXR
♦ can have neurosecretory elements → paraneoplastic features
♦ grow rapidly and metastasize early
♦ very large usually > 4 cm

 

Small cell – also known as oat cell carcinoma almost always smoking related aggressive – metastasises early most patients present with systemic dis spread to liver , skeleton , bone marrow , brain and adrenal glands ( haematogenous ) can cause paraneoplastic syndromes and SVC obstruction central location treatment – chemo or radiotherapy

 

Mesothelioma – Peak age 60-70 yrs typically 25-50 yrs post asbestos exposure ( ie prolonged latent period ) Incidence in UK- rare Malignant mesothelioma – highly aggressive , poor survival rate irrespective of treatment 90 % have occupational history (builders , shipyard workers ) All types of asbestos fibre implicated Often leads to encasement/compression of lung by a solid tumour

References

  1. Early Detection of Lung Cancer – Information for General Practitioners Cancer Research UK Document accessed via
http://www.cancerresearchuk.org/prod_consump/groups/
cr_common/@nre/@hea/documents/generalcontent/cr_043915.pdf
  2. Non-Small Cell Lung Cancer Clinical Presentation Winston W Tan et al Updated Nov 17 2016 Medscape accesses via http://emedicine.medscape.com/article/279960-clinical
  3. Lung Cancer A.Prof Frank Gaillard et al accessed via https://radiopaedia.org/articles/lung-cancer-3
  4. Metastatic Non-Small-Cell Lung Cancer : ESMO Clinical Practice Guidelines Ann Oncol 9 ( 2016 ) 27 (supply 5 ) : v1-v27
  5. Oncology at a Glance – Graham G. Dark.
  6. Suspected cancer : recognition and referral NICE guideline [ NG 12 ] June 2015
  7. Oxford Handbook of Oncology – Edited by Jim Cassidy et al
  8. Dela Cruz, Charles S et al. “Lung cancer: epidemiology, etiology, and prevention.” Clinics in chest medicine vol. 32,4 (2011): 605-44. doi:10.1016/j.ccm.2011.09.001 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864624/
  9. de Groot, Patricia M et al. “The epidemiology of lung cancer.” Translational lung cancer research vol. 7,3 (2018): 220-233. doi:10.21037/tlcr.2018.05.06 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037963/
  10. The International Epidemiology of Lung Cancer
    Geographical Distribution and Secular Trends
    Danny R. Youlden, BSc, Susanna M. Cramb, MPH, and Peter D. Baade, PhD Journal of Thoracic Oncology • Volume 3, Number 8, August 2008 https://www.jto.org/article/S1556-0864(15)30445-7/pdf
  11. Cancer Research UK Lung cancer –https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-One
  12. Bradley SH, Abraham S, Callister ME, Grice A, Hamilton WT, Lopez RR, Shinkins B, Neal RD. Sensitivity of chest X-ray for detecting lung cancer in people presenting with symptoms: a systematic review. Br J Gen Pract. 2019 Nov 28;69(689):e827-e835. doi: 10.3399/bjgp19X706853. PMID: 31636130; PMCID: PMC6805164. ( Abstract ) https://pubmed.ncbi.nlm.nih.gov/31636130/
  13. Screening and early detection of lung cancer
    J. Vansteenkiste1*, C. Dooms1, C. Mascaux2 & K. Nackaerts1
    1
    Respiratory Oncology Unit (Pulmonology) and Leuven Lung Cancer Group, University Hospital Gasthuisberg, Leuven, Belgium; 2
    Division of Medical Oncology,
    Department of Medicine, University of Colorado, Aurora, USA Annals of Oncology 23 (Supplement 10): x320–x327, 2012
    doi:10.1093/annonc/mds303
  14. Bartjan de HoopCornelia Schaefer-ProkopHester A. GietemaPim A. de JongBram van GinnekenRob J. van Klaveren, and Mathias Prokop

    Radiology 2010 255:2629-637

  15. Risk factors for lung cancer worldwide
    Jyoti Malhotra1,2, Matteo Malvezzi3,4, Eva Negri4
    , Carlo La Vecchia3 and
    Paolo Boffetta ERJ Express. Published on May 12, 2016 as doi: 10.1183/13993003.00359-2016 https://erj.ersjournals.com/content/erj/early/2016/05/12/13993003.00359-2016.full.pdf
  16. Gunnar R. Husebø, Rune Nielsen, Jon Hardie, Per Sigvald Bakke, Lorena Lerner, Corina D’Alessandro-Gabazza, Jeno Gyuris, Esteban Gabazza, Pål Aukrust, Tomas Eagan,
    Risk factors for lung cancer in COPD – results from the Bergen COPD cohort study,
    Respiratory Medicine,
    Volume 152,
    2019,
    Pages 81-88,
    ISSN 0954-6111,
    https://doi.org/10.1016/j.rmed.2019.04.019.
    (http://www.sciencedirect.com/science/article/pii/S0954611119301477) Abstract

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